Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

PubMed Central

Salacz, Michael E; Kast, Richard E; Saki, Najmaldin; Brüning, Ansgar; Karpel-Massler, Georg; Halatsch, Marc-Eric

2016-01-01

To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs) (monocyte, macrophage, microglia, dendritic cells) that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low drug cost. Four core observations support this approach: 1) malignant glioblastoma cells require a reciprocal trophic relationship with nonmalignant macrophages or microglia to thrive; 2) glioblastoma cells secrete MCP-1 to start the cycle, attracting MLCs, which subsequently also secrete MCP-1 perpetuating the recruitment cycle; 3) increasing cytokine levels in the tumor environment generate further immunosuppression and tumor growth; and 4) MTZ regimen may impede MCP-1-driven processes, thereby interfering with glioblastoma growth. PMID:27175087

Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process.

PubMed

Park, Junsung; Cho, Wonkyung; Cha, Kwang-Ho; Ahn, Junhyun; Han, Kang; Hwang, Sung-Joo

2013-01-30

Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability. Because of its unique characteristics, the supercritical anti-solvent (SAS) process was used to BCS class II drug in a variety of ways including micronization, amorphization and solid dispersion. Solid dispersions were prepared using hydroxypropylmethylcellulose/polyvinylpyrrolidone (HPMC/PVP) at 1:0.5, 1:1, and 1:2 weight ratios of drug to polymer, and pure telmisartan was also treated using the SAS process. Processed samples were characterized for morphology, particle size, crystallinity, solubility, dissolution rate and polymorphic stability. After the SAS process, all samples were converted to the amorphous form and were confirmed to be hundreds nm in size. Solubility and dissolution rate were increased compared to the raw material. Solubility tended to increase with increases in the amount of polymer used. However, unlike the solubility results, the dissolution rate decreased with increases in polymer concentration due to gel layer formation of the polymer. Processed pure telmisartan showed the best drug release even though it had lower solubility compared to other solid dispersions; however, because there were no stabilizers in processed pure telmisartan, it recrystallized after 1 month under severe conditions, while the other solid dispersion samples remained amorphous form. We conclude that after controlling the formulation of solid dispersion, the SAS process could be a promising approach for improving the solubility and dissolution rate of telmisartan. Copyright © 2012 Elsevier B.V. All rights reserved.

Left ventricular hypertrophy induced by abdominal aortic banding and its prevention by angiotensin receptor blocker telmisartan--a proteomic analysis.

PubMed

Liu, Li; Wang, Wen; Meng, Xianmin; Gao, Jiuming; Wu, Haiying; Wang, Peihe; Wu, Weichun; Wang, Linlin; Ma, Liyuan; Zhang, Weiguo

2010-12-01

Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood pressure or hypertension) and can lead to heart failure. The major objective of the present study was to investigate the proteomic changes in response to the development of left ventricular hypertrophy (LVH) induced by abdominal aortic banding (AB) and its prevention by antihypertensive treatment with angiotensin II receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were assigned into three groups: SHAM-control, aortic banding without treatment (AB-Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8 weeks). Echocardiography, hemodynamics, and pathology were performed to assess LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins from myocardium was performed by two-dimensional gel electrophoresis and MALDI-TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood pressure, left ventricular end systolic pressure, interventricular septal thickness at diastole, posterior wall thickness in diastole, heart weight (HW) and HW/body weight (BW) were increased, indicating that both hypertension and LVH developed. Telmisartan prevented hypertension and LVH. Concurrently, among numerous proteins, there were 17 that were differentially expressed among hypertrophic hearts, normal hearts, and the hearts where hypertrophic response was suppressed by ARB treatment. Primarily, proteins involved in cell structure, metabolism, stress and signal transduction exhibited up-regulations in LVH, providing cellular and molecular mechanism for hypertrophic development. These changes were prevented or greatly attenuated by telmisartan regimen. Interestingly, antioxidative-related heat shock protein 2 was detected neither in SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes of protein expression. Both LVH and proteomic changes can be prevented by blockade of renin-angiotensin system with telmisartan. These protein alterations may constitute mechanistic pathways leading to hypertrophy development and experimental targets for novel therapeutic strategy.

Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions.

PubMed

Nenicu, Anca; Gu, Yuan; Körbel, Christina; Menger, Michael D; Laschke, Matthias W

2017-08-01

Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone. Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg -1 ), parecoxib (5 mg·kg -1 ), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high-resolution ultrasound imaging as well as immunohistochemical and Western blot analyses. Telmisartan-treated lesions exhibited a significantly reduced lesion volume when compared with vehicle-treated controls and parecoxib-treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67-positive cells and higher numbers of apoptotic cleaved caspase-3-positive stromal cells within the lesions. This was associated with a lower expression of COX-2, MMP-9 and p-Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions. Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis. © 2017 The British Pharmacological Society.

In a Subgroup of High-Risk Asians, Telmisartan Was Non-Inferior to Ramipril and Better Tolerated in the Prevention of Cardiovascular Events

PubMed Central

Dans, Antonio L.; Teo, Koon; Gao, Peggy; Chen, Jyh-Hong; Jae-Hyung, Kim; Yusoff, Khalid; Chaithiraphan, Suphachai; Zhu, Jun; Lisheng, Liu; Yusuf, Salim

2010-01-01

Background and Objectives Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) showed that telmisartan (80 mg/day) was non-inferior to ramipril (10 mg/day) in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare Asians and non-Asians with respect to the following: 1) Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events; 2) Proportions who reached the full dose of telmisartan, ramipril or placebo; and 3) Proportions of overall discontinuations, and discontinuations due to adverse effects. Method The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies) and ramipril (given in ONTARGET). Results 1) Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2) more Asians achieved the full dose of either drug; 3) less withdrew (overall); and 4) less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians. Conclusion and Significance Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data in ethnic subgroups can help assess applicability of results to specific populations. Trial Registration ClinicalTrials.gov NCT00153101 PMID:21200437

Double blockade of angiotensin II (AT1)-receptors and ACE does not improve weight gain and glucose homeostasis better than single-drug treatments in obese rats

PubMed Central

Miesel, Anja; Müller-Fielitz, Helge; Jöhren, Olaf; Vogt, Florian M; Raasch, Walter

2012-01-01

BACKGROUND AND PURPOSE Combination therapies are becoming increasingly important for the treatment of high blood pressure. Little is known about whether double blockade of angiotensin II (AT1) receptors and angiotensin-converting enzyme (ACE) exert synergistic metabolic effects. EXPERIMENTAL APPROACH Spontaneously hypertensive rats were allowed to choose between palatable chocolate bars and standard chow and were simultaneously treated with the AT1 blocker telmisartan (8 mg·kgbw−1·day−1), the ACE inhibitor ramipril (4 mg·kgbw−1·day−1) or a combination of the two (8 + 4 mg·kgbw−1·day−1) for 12 weeks. KEY RESULTS Although food-dependent energy intake was increased by telmisartan and telmisartan + ramipril compared with ramipril or controls, body weight gain, abundance of fat and plasma leptin levels were decreased. Increased insulin levels in response to an oral glucose tolerance test were comparably attenuated by telmisartan and telmisartan + ramipril, but not by ramipril. During an insulin tolerance test, glucose utilization was equally as effectively improved by telmisartan and telmisartan + ramipril. In response to a stress test, ACTH, corticosterone and glucose increased in controls. These stress reactions were attenuated by telmisartan and telmisartan + ramipril. CONCLUSIONS AND IMPLICATIONS The combination of telmisartan + ramipril was no more efficacious in regulating body weight and glucose homeostasis than telmisartan alone. However, telmisartan was more effective than ramipril in improving metabolic parameters and in reducing body weight. The association between the decrease in stress responses and the diminished glucose levels after stress supports our hypothesis that the ability of telmisartan, as an AT1 receptor blocker, to alleviate stress reactions may contribute to its hypoglycaemic actions. PMID:22014027

Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

PubMed

Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

2016-05-01

Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients.

Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.

PubMed

Oh, Gyu Chul; Han, Jung-Kyu; Han, Ki Hoon; Hyon, Min-Su; Doh, Joon Hyung; Kim, Moo Hyun; Jeong, Jin-Ok; Bae, Jang-Ho; Kim, Sang Hyun; Yoo, Byung-Su; Baek, Sang Hong; Rhee, Moo-Yong; Ihm, Sang-Hyun; Sung, Jung Hoon; Choi, Young Jin; Kim, Soo-Joong; Hong, Kyung-Soon; Lee, Byoung Kwon; Cho, JangHyun; Shin, Eun Seok; Rhew, Jay Young; Kim, Hyunsu; Kim, Hyo-Soo

2018-05-01

Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432. Copyright © 2018. Published by Elsevier Inc.

Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study.

PubMed

Son, Mijeong; Guk, Jinju; Kim, Yukyung; Woo Chae, Dong; Heo, Young-A; Soh, Dongjun; Park, Kyungsoo

2016-08-01

Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population. In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations. Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0.9940 to 1.5940; amlodipine, 0.9705 to 1.0636 and 0.9813 to 1.0779. There were no significant differences in the prevalences of AEs between the treatments, and all reported AEs were mild or moderate. These results demonstrate that when rosuvastatin, telmisartan, and amlodipine are coadministered to healthy male subjects, pharmacokinetic exposure increases with respect to rosuvastatin and telmisartan, whereas no change occurs with respect to amlodipine. However, based on previous analyses, the degree of increase in the exposure observed was not regarded as clinically significant. All treatments were well-tolerated. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Telmisartan improves survival and ventricular function in SHR rats with extensive cardiovascular damage induced by dietary salt excess.

PubMed

Susic, Dinko; Frohlich, Edward D

2014-05-01

Excessive dietary salt intake induces extensive cardiovascular and renal damage in spontaneously hypertensive rats (SHR) that may be prevented by antihypertensive agents. This study examines whether salt-induced cardiac damage may be reversed by angiotensin II (type 1) receptor blockade (telmisartan). Eight-week-old male SHRs were divided into four groups; Group 1 (NS) was fed regular rat chow, and Group 2 (HS) received high-salt diet (HS; 8% NaCl). After 8 weeks on their respective diets, systemic hemodynamics and indices of left ventricular (LV) function were determined. Group 3 (HSnoT) was given HS for 8 weeks and then switched to a regular chow (0.6% NaCl) diet with no other treatment, and Group 4 (HSArb) received HS for 8 weeks and was then given regular diet plus telmisartan. Rats from these latter two groups were monitored for the ensuing 30 days. Compared with the NS group, rats in the HS group exhibited increased mean arterial pressure (161 ± 7 vs. 184 ± 8 mm Hg) and LV diastolic dysfunction, as evidenced by a decreased rate of LV pressure decline (-8754 ± 747 vs. -4234 ± 754 mmHg/sec) at the end of the 8 weeks of their respective treatment. After switching to regular chow, only one of 11 rats in the HSnoT group survived for the 30 days, whereas 10 died within 18 days; in the HSArb group only one of nine rats died; eight survived 30 days (P < .01). Telmisartan significantly improved LV function and survival in those SHR rats having extensive cardiovascular damage induced by dietary salt excess. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model.

PubMed

Rosselli, Maria Soledad; Burgueño, Adriana L; Carabelli, Julieta; Schuman, Mariano; Pirola, Carlos J; Sookoian, Silvia

2009-09-01

To evaluate the effect of losartan-an angiotensin II type 1 receptor (AT1R) antagonist- and telmisartan-an AT1R blocker with insulin-sensitizing properties-, on the hepatic expression of plasminogen activator inhibitor-1 (PAI-1) in a rat model of nonalcoholic fatty liver disease (NAFLD). Rats were given a high-fat diet (HFD) for 8 weeks and after this period were randomly divided into 3 groups. For 12 weeks along with the same access to HFD, one group (9 rats) received losartan and another group received telmisartan (10 rats), both at 10mg/kg intraperitoneally (ip) every 24h. The third group (8 rats) received saline ip along with the HFD. Finally, a control group (6 rats) was fed with standard chow diet for 20 weeks. Fatty liver was reverted by both losartan and telmisartan. Both drugs had beneficial effects on insulin resistance, reaching statistical significance in telmisartan group. Expression of hepatic mRNA of PAI-1 showed a 42% decrease in losartan-treated rats in comparison with both HFD group and telmisartan-treated rats. To further evaluate this differential effect on PAI-1 expression, we explored the effect of the drugs on liver expression of TNFalpha, PEPCK-C and PPARalpha, and no significant differences were observed. These results indicate that AT1R blockers could be eligible drugs for reducing hepatic lipid accumulation in patients with NAFLD. However, only 12 weeks of losartan treatment strongly reduced hepatic PAI-1 gene expression. These differences could provide even more effective options for preventing fatty liver disease and its cardiovascular complications.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Interactions between angiotensin AT1 receptor antagonists and second-generation antiepileptic drugs in the test of maximal electroshock.

PubMed

Łukawski, Krzysztof; Janowska, Agnieszka; Jakubus, Tomasz; Czuczwar, Stanisław J

2014-06-01

The anticonvulsant activity of angiotensin AT1 receptor antagonists, losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'(1H-tetrazol-5-yl)-biphenil-4-yl)methyl]imidazole) and telmisartan (49-[(1,49-dimethyl-29-propyl[2,69-bi-1H-benzimidazo]-19-yl)methyl]-[1,19-biphenyl]-2-carboxylic acid), has been reported recently. It is suggested that AT1 receptor antagonists may affect the protective action of antiepileptic drugs. The aim of this study was to determine the influence of losartan and telmisartan on the anticonvulsant activity of some second-generation antiepileptics (lamotrigine - LTG, oxcarbazepine - OXC, and topiramate - TPM). For this purpose, the maximal electroshock seizure (MES) test in mice was used. Additionally, the drug combinations were checked for adverse effects in the passive avoidance and chimney tests. In the MES test, losartan at the doses of 30 and 50 mg/kg, administered intraperitoneally (i.p.), potentiated the protective action of LTG (P < 0.01). This interaction was not accompanied by a significant change of LTG level either in plasma or in the brain. Telmisartan at the dose of 30 mg/kg i.p. enhanced the anticonvulsant action of TPM (P < 0.01). However, this interaction was pharmacokinetic in nature, as telmisartan significantly increased plasma and total brain concentrations of TPM (P < 0.001). The combinations of AT1 receptor antagonists with antiepileptic drugs did not affect retention in the passive avoidance test or motor coordination in the chimney test. The potentiation of the anticonvulsant action of LTG by losartan probably on account of pharmacodynamic interactions, make this combination important for further experimental and clinical studies. The combination of telmisartan and TPM is less beneficial due to pharmacokinetic interactions. © 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique.

Prospective virtual screening for novel p53-MDM2 inhibitors using ultrafast shape recognition

NASA Astrophysics Data System (ADS)

Patil, Sachin P.; Ballester, Pedro J.; Kerezsi, Cassidy R.

2014-02-01

The p53 protein, known as the guardian of genome, is mutated or deleted in approximately 50 % of human tumors. In the rest of the cancers, p53 is expressed in its wild-type form, but its function is inhibited by direct binding with the murine double minute 2 (MDM2) protein. Therefore, inhibition of the p53-MDM2 interaction, leading to the activation of tumor suppressor p53 protein presents a fundamentally novel therapeutic strategy against several types of cancers. The present study utilized ultrafast shape recognition (USR), a virtual screening technique based on ligand-receptor 3D shape complementarity, to screen DrugBank database for novel p53-MDM2 inhibitors. Specifically, using 3D shape of one of the most potent crystal ligands of MDM2, MI-63, as the query molecule, six compounds were identified as potential p53-MDM2 inhibitors. These six USR hits were then subjected to molecular modeling investigations through flexible receptor docking followed by comparative binding energy analysis. These studies suggested a potential role of the USR-selected molecules as p53-MDM2 inhibitors. This was further supported by experimental tests showing that the treatment of human colon tumor cells with the top USR hit, telmisartan, led to a dose-dependent cell growth inhibition in a p53-dependent manner. It is noteworthy that telmisartan has a long history of safe human use as an approved anti-hypertension drug and thus may present an immediate clinical potential as a cancer therapeutic. Furthermore, it could also serve as a structurally-novel lead molecule for the development of more potent, small-molecule p53-MDM2 inhibitors against variety of cancers. Importantly, the present study demonstrates that the adopted USR-based virtual screening protocol is a useful tool for hit identification in the domain of small molecule p53-MDM2 inhibitors.

Telmisartan as metabolic modulator: a new perspective in sports doping?

PubMed

Sanchis-Gomar, Fabian; Lippi, Giuseppe

2012-03-01

The World Antidoping Agency (WADA) has introduced some changes in the 2012 prohibited list. Among the leading innovations to the rules are that both 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (peroxisome proliferator-activated receptor-δ [PPAR-δ]-5' adenosine monophosphate-activated protein kinase [AMPK] agonist) and GW1516 (PPAR-δ-agonist) are no longer categorized as gene doping substances in the new 2012 prohibited list but as metabolic modulators in the class "Hormone and metabolic modulators." This may also be valid for the angotensin II receptor blocker telmisartan. It has recently been shown that telmisartan might induce similar biochemical, biological, and metabolic changes (e.g., mitochondrial biogenesis and changes in skeletal muscle fiber type) as those reported for the former call of substances. We suspect that metabolic modulators abuse such as telmisartan might become a tangible threat in sports and should be thereby targeted as an important antidoping issue. The 2012 WADA prohibited list does not provide telmisartan for a potential doping drug, but arguments supporting the consideration to include them among "metabolic modulators" are at hand.

Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude.

PubMed

Caravita, Sergio; Faini, Andrea; Baratto, Claudia; Bilo, Grzegorz; Macarlupu, Josè Luis; Lang, Morin; Revera, Miriam; Lombardi, Carolina; Villafuerte, Francisco C; Agostoni, Piergiuseppe; Parati, Gianfranco

2018-06-09

Acute exposure to high-altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. Fifty-five subjects with mild hypertension, double-blindly randomized to placebo or to a fixed-dose combination of an angiotensin-receptor blocker (telmisartan 80 mg) and a calcium-channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High-altitude exposure caused both an 8 mm Hg upward shift ( P <0.01) and a 0.4 mm Hg/mL/kg per minute steepening ( P <0.05) of the systolic blood pressure/oxygen consumption relationship during exercise, independent of treatment. Telmisartan/nifedipine did not modify blood pressure reactivity to exercise (blood pressure/oxygen consumption slope), but downward shifted ( P <0.001) the relationship between systolic blood pressure and oxygen consumption by 26 mm Hg, both at sea level and at altitude. Muscle oxygen delivery was not influenced by altitude exposure but was higher on telmisartan/nifedipine than on placebo ( P <0.01). In hypertensive subjects exposed to high altitude, we observed a hypoxia-driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Quality-by-design approach for the development of telmisartan potassium tablets.

PubMed

Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

2018-05-01

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats.

PubMed

Sharma, Ashish Kumar; Kanawat, Devendra Singh; Mishra, Akanksha; Dhakad, Prashant Kumar; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi

2014-12-01

The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system. © The Author(s) 2013.

Arterial Stiffness and Pharmacological Interventions – The TRanscend Arterial stiffNess Substudy (TRANS study)

PubMed Central

Topouchian, Jirar; El Feghali, Ramzi; Pannier, Bruno; Wang, Shuyu; Zhao, Feng; Smetana, Karel; Teo, Koon; Asmar, Roland

2007-01-01

The degree of arterial stiffness is correlated with the risk of cardiovascular diseases and it is a powerful predictor for morbidity and mortality. Studies have shown that arterial stiffness reduction is associated with an improvement in survival. Reduction of arterial stiffness by pharmacological drugs varies according to the drugs and doses used and duration of treatment. This effect on the arteries differs among the various classes of drugs and among individual drugs in the same class. Quantification of the stiffness and other properties of the arterial wall can be used to monitor the responses to therapy in individuals with hypertension and other cardiovascular diseases. These measures can then be used as surrogate markers for the risk of clinical events. Inhibition of the renin-angiotensin system (RAS) is associated with an important decrease in cardiovascular risk. Findings from clinical trials support the hypothesis that the protective effects of RAS inhibition are partly independent from blood pressure reduction and related to several mechanisms including vascular protective effects. The aim of the TRanscend Arterial stiffNess Substudy (TRANS) is to assess the effect of an angiotensin II receptor blocker (ARB), telmisartan, on the arterial stiffness in a subgroup of patients from the Telmisartan Randomized Assessment Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) trial. The TRANSCEND trial is an international, multicenter, randomized double blind placebo controlled trial of telmisartan that enrolled patients at high risk for cardiovascular events. Some clinical baseline data of the TRANS substudy are reported. When completed, the results of the TRANS substudy will show whether the beneficial effects of treatment with telmisartan on cardiovascular outcome may be related to an improvement in arterial stiffness. PMID:17969367

Extensive Diminution of Particle Size and Amorphization of a Crystalline Drug Attained by Eminent Technology of Solid Dispersion: A Comparative Study.

PubMed

Singh, Gurjeet; Sharma, Shailesh; Gupta, Ghanshyam Das

2017-07-01

The present study emphasized on the use of solid dispersion technology to triumph over the drawbacks associated with the highly effective antihypertensive drug telmisartan using different polymers (poloxamer 188 and locust bean gum) and methods (modified solvent evaporation and lyophilization). It is based on the comparison between selected polymers and methods for enhancing solubility through particle size reduction. The results showed different profiles for particle size, solubility, and dissolution of formulated amorphous systems depicting the great influence of polymer/method used. The resulting amorphous solid dispersions were characterized using x-ray diffraction (XRD), differential scanning calorimetry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and particle size analysis. The optimized solid dispersion (TEL 19) prepared with modified locust bean gum using lyophilization technique showed reduced particle size of 184.5 ± 3.7 nm and utmost solubility of 702 ± 5.47 μg/mL in water, which is quite high as compared to the pure drug (≤1 μg/mL). This study showed that the appropriate selection of carrier may lead to the development of solid dispersion formulation with desired solubility and dissolution profiles. The optimized dispersion was later formulated into fast-dissolving tablets, and further optimization was done to obtain the tablets with desired properties.

Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

PubMed

Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

2011-08-01

In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

Study of effect of variables on particle size of telmisartan nanosuspensions using box-Behnken design.

PubMed

Rao, M R P; Bajaj, A

2014-12-01

Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent precipitation technique to improve the saturation solubility and dissolution rate of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated of which TPGS was found to provide maximum decrease in particle size and accord greater stability to the nanosuspensions. Box-Behnken design was used to investigate the effect of independent variables like stabilizer concentration, time and speed of stirring on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of the drug. Concentration of TPGS and speed of rotation were found to play an important role in particle size of the nanosuspensions whereas time of stirring displayed an exponential relationship with particle size. Freeze dried nanocrystals obtained from nanosuspension of least particle size were found to have increased saturation solubility of telmisartan in different dissolution media. The reconstituted nanosuspension was found to reduce both systolic and diastolic blood pressure without affecting pulse pressure and heart rate. Statistical tools can be used to identify key process and formulation parameters which play a significant role in controlling the particle size in nanosuspensions. © Georg Thieme Verlag KG Stuttgart · New York.

Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor.

PubMed

Khallaf, Waleed A I; Messiha, Basim A S; Abo-Youssef, Amira M H; El-Sayed, Nesrine S

2017-07-01

Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy.

PubMed

Albayrak, Bülent; Cankaya, Erdem; Cetinkaya, Ramazan; Cerrah, Serkan; Bilen, Yusuf

2016-05-01

Diabetic nephropathy (DN) is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males) with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan), Group II (n: 20, trandolapril + verapamil), Group III (n: 20, trandolapril +telmisartan + verapamil), and Group IV (n: 20, telmisartan + verapamil). At the end of a three-month therapy, within and between group comparisons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR), electrolytes, serum albumin, low-density lipoprotein (LDL)- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in proteinuria and mean arterial blood pressure (MABP) were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P <0.001) in Group I, 37% (P <0.001) in Group II, 42% (P <0.001) in Group III, and 43% (P <0.001) in Group IV; the reduction rate in MABP was 10.6% (P <0.001) in Group I, 13.7% (P <0.001) in Group II, 17.5% (P <0.001) in Group III, and 15.4% (P <0.001) in Group IV]. Decrease in HbA1C (before and after treatment) was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients tolerated the drugs well. In conclusion, in patients with DN, both double or triple combinations of trandolapril, telmisartan and verapamil resulted in significant decreases in proteinuria and MABP. Triple combinations did not have any superiority over double combinations. Therefore, the suitable drug combinations may be chosen according to the clinical status of a patient.

Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection.

PubMed

Attia, Yasmeen M; Elalkamy, Essam F; Hammam, Olfat A; Mahmoud, Soheir S; El-Khatib, Aiman S

2013-07-05

Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice. To achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed. Telmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive properties, yet it did not affect the anti-schistosomal activity of PZQ. These results suggest potential anti-fibrotic effects of telmisartan, an AT1 receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni-induced liver fibrosis in mice.

Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-{gamma}-dependent activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toyama, Kensuke; Nakamura, Taishi; Kataoka, Keiichiro

2011-07-08

Highlights: {yields} Telmisartan, an angiotensin receptor blocker, acts as a partial PPAR{gamma} agonist. {yields} The protective effects of telmisartan against diabetic vascular injury were associated with attenuation of vascular NF{kappa}B activation and TNF {alpha}. {yields} PPAR{gamma} activity of telmisartan was involved in the normalization of vascular PPAR{gamma} downregulation in diabetic mice. {yields} We provided the first evidence indicating that PPAR{gamma} activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. -- Abstract: Experimental and clinical data support the notion that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) activation is associated with anti-atherosclerosis as well as anti-diabetic effect. Telmisartan,more » an angiotensin receptor blocker (ARB), acts as a partial PPAR{gamma} agonist. We hypothesized that telmisartan protects against diabetic vascular complications, through PPAR{gamma} activation. We compared the effects of telmisartan, telmisartan combined with GW9662 (a PPAR{gamma} antagonist), and losartan with no PPAR{gamma} activity on vascular injury in obese type 2 diabetic db/db mice. Compared to losartan, telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of telmisartan than losartan were associated with greater anti-inflammatory effects of telmisartan, as shown by attenuation of vascular nuclear factor kappa B (NF{kappa}B) activation and tumor necrosis factor {alpha}. Coadministration of GW9662 with telmisartan abolished the above mentioned greater protective effects of telmisartan against vascular injury than losartan in db/db mice. Thus, PPAR{gamma} activity appears to be involved in the vascular protective effects of telmisartan in db/db mice. Moreover, telmisartan, but not losartan, prevented the downregulation of vascular PPAR{gamma} in db/db mice and this effect of telmisartan was cancelled by the coadministration of GW9662. Our data provided the first evidence indicating that PPAR{gamma} activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. PPAR{gamma} activity of telmisartan was involved in the normalization of vascular PPAR{gamma} downregulation in diabetic mice. Thus, telmisartan seems to exert vascular protective effects in hypertensive patients with diabetes.« less

Do socioeconomic disparities affect accessing and keeping antihypertensive drug therapy? Evidence from an Italian population-based study.

PubMed

Corrao, G; Zambon, A; Parodi, A; Mezzanzanica, M; Merlino, L; Cesana, G; Mancia, G

2009-04-01

We conducted this population-based cohort study by linking several databases to explore the role of socioeconomic position for accessing and keeping antihypertensive drug therapy. A total of 71 469 patients, residents in the city of Milan (Italy) aged 40-80 years, who received an antihypertensive drug during 1999-2002 were followed for 1 year starting from the first dispensation. Socioeconomic position and drug prescriptions were respectively obtained from tax registry and outpatient prescription database. The effect of socioeconomic characteristics on standardized incidence rate (SIR) of new users of antihypertensive agents, odds ratio (OR) of using combined antihypertensive agents and non-antihypertensive drugs and hazard ratio (HR) of discontinuing antihypertensive therapy were estimated after adjustment for potential confounders. SIRs were 3.7 and 4.2 per 1000 person-months among persons at the lowest and intermediate income, respectively, and 2.4 and 3.0 among immigrants and Italians, respectively. Compared to persons at the highest income, those at the lowest income had increased chances of starting with combined antihypertensive drugs (OR: 1.1; 95% confidence intervals (CIs): 1.0, 1.2), and of using drugs for heart failure (OR:1.5; CIs:1.3, 1.6) and diabetes (OR: 1.7; CIs: 1.6, 1.9). Compared with Italians, non-western immigrants had increased chances of starting with combined antihypertensive agents (OR: 1.2; CIs: 1.0, 1.3), of using drugs for heart failure (OR: 1.2; CIs: 1.0, 1.4) and for diabetes (OR: 1.8; CIs: 1.6, 2.1), and of interrupting antihypertensive therapy (HR: 1.1; 95% CIs: 1.0, 1.2). Despite the universal health coverage of the Italian National Health Service (NHS), social disparities affect accessing and keeping antihypertensive therapy.

Neurorestoration after traumatic brain injury through angiotensin II receptor blockage.

PubMed

Villapol, Sonia; Balarezo, María G; Affram, Kwame; Saavedra, Juan M; Symes, Aviva J

2015-11-01

See Moon (doi:10.1093/awv239) for a scientific commentary on this article.Traumatic brain injury frequently leads to long-term cognitive problems and physical disability yet remains without effective therapeutics. Traumatic brain injury results in neuronal injury and death, acute and prolonged inflammation and decreased blood flow. Drugs that block angiotensin II type 1 receptors (AT1R, encoded by AGTR1) (ARBs or sartans) are strongly neuroprotective, neurorestorative and anti-inflammatory. To test whether these drugs may be effective in treating traumatic brain injury, we selected two sartans, candesartan and telmisartan, of proven therapeutic efficacy in animal models of brain inflammation, neurodegenerative disorders and stroke. Using a validated mouse model of controlled cortical impact injury, we determined effective doses for candesartan and telmisartan, their therapeutic window, mechanisms of action and effect on cognition and motor performance. Both candesartan and telmisartan ameliorated controlled cortical impact-induced injury with a therapeutic window up to 6 h at doses that did not affect blood pressure. Both drugs decreased lesion volume, neuronal injury and apoptosis, astrogliosis, microglial activation, pro-inflammatory signalling, and protected cerebral blood flow, when determined 1 to 3 days post-injury. Controlled cortical impact-induced cognitive impairment was ameliorated 30 days after injury only by candesartan. The neurorestorative effects of candesartan and telmisartan were reduced by concomitant administration of the peroxisome proliferator-activated receptor gamma (PPARγ, encoded by PPARG) antagonist T0070907, showing the importance of PPARγ activation for the neurorestorative effect of these sartans. AT1R knockout mice were less vulnerable to controlled cortical impact-induced injury suggesting that the sartan's blockade of the AT1R also contributes to their efficacy. This study strongly suggests that sartans with dual AT1R blocking and PPARγ activating properties have therapeutic potential for traumatic brain injury. Published by Oxford University Press on behalf of the Guarantors of Brain 2015. This work is written by US Government employees and is in the public domain in the US.

Interactions between antihypertensive drugs and food.

PubMed

Jáuregui-Garrido, B; Jáuregui-Lobera, I

2012-01-01

A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antihypertensive drugs, altering their therapeutic efficacy and causing toxic effects. The aim of this study was to conduct a review of available data about interactions between antihypertensive agents and food. The purpose of this review was to report an update of main findings with respect to the interactions between food and antihypertensive drugs by way of a search conducted in PubMed, which yielded a total of 236 articles initially. After excluding different articles, which were not focusing on the specific objective, the main results refer to interactions between antihypertensive drugs and food (in general) as well as between antihypertensive agents and grapefruit juice. Food may affect the bioavailability of antihypertensive drugs and this should be carefully considered. Advising patients to remove the grapefruit juice from their diet when treatment with these drugs seems to be the best recommendation. Given these interactions and the associated potential adverse effects the anamnesis must include detailed information about the specific eating habits of the patients.

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease--a cost-effectiveness analysis.

PubMed

Wisløff, Torbjørn; Selmer, Randi M; Halvorsen, Sigrun; Fretheim, Atle; Norheim, Ole F; Kristiansen, Ivar Sønbø

2012-04-04

Hypertension is one of the leading causes of cardiovascular disease (CVD). A range of antihypertensive drugs exists, and their prices vary widely mainly due to patent rights. The objective of this study was to explore the cost-effectiveness of different generic antihypertensive drugs as first, second and third choice for primary prevention of cardiovascular disease. We used the Norwegian Cardiovascular Disease model (NorCaD) to simulate the cardiovascular life of patients from hypertension without symptoms until they were all dead or 100 years old. The risk of CVD events and costs were based on recent Norwegian sources. In single-drug treatment, all antihypertensives are cost-effective compared to no drug treatment. In the base-case analysis, the first, second and third choice of antihypertensive were calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor. However the sensitivity and scenario analyses indicated considerable uncertainty in that angiotensin receptor blockers as well as, angiotensin-converting enzyme inhibitors, beta blockers and thiazides could be the most cost-effective antihypertensive drugs. Generic antihypertensives are cost-effective in a wide range of risk groups. There is considerable uncertainty, however, regarding which drug is the most cost-effective.

Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

PubMed

Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

2015-04-01

Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Design and Optimization of a Chemometric-Assisted Spectrophotometric Determination of Telmisartan and Hydrochlorothiazide in Pharmaceutical Dosage Form

PubMed Central

Lakshmi, KS; Lakshmi, S

2010-01-01

Two chemometric methods were developed for the simultaneous determination of telmisartan and hydrochlorothiazide. The chemometric methods applied were principal component regression (PCR) and partial least square (PLS-1). These approaches were successfully applied to quantify the two drugs in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range of 200-350 nm with the intervals Δλ = 1 nm. The calibration of PCR and PLS-1 models was evaluated by internal validation (prediction of compounds in its own designed training set of calibration) and by external validation over laboratory prepared mixtures and pharmaceutical preparations. The PCR and PLS-1 methods require neither any separation step, nor any prior graphical treatment of the overlapping spectra of the two drugs in a mixture. The results of PCR and PLS-1 methods were compared with each other and a good agreement was found. PMID:21331198

Design and optimization of a chemometric-assisted spectrophotometric determination of telmisartan and hydrochlorothiazide in pharmaceutical dosage form.

PubMed

Lakshmi, Ks; Lakshmi, S

2010-01-01

Two chemometric methods were developed for the simultaneous determination of telmisartan and hydrochlorothiazide. The chemometric methods applied were principal component regression (PCR) and partial least square (PLS-1). These approaches were successfully applied to quantify the two drugs in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range of 200-350 nm with the intervals Δλ = 1 nm. The calibration of PCR and PLS-1 models was evaluated by internal validation (prediction of compounds in its own designed training set of calibration) and by external validation over laboratory prepared mixtures and pharmaceutical preparations. The PCR and PLS-1 methods require neither any separation step, nor any prior graphical treatment of the overlapping spectra of the two drugs in a mixture. The results of PCR and PLS-1 methods were compared with each other and a good agreement was found.

Telmisartan Therapy Does Not Improve Lymph Node or Adipose Tissue Fibrosis More Than Continued Antiretroviral Therapy Alone.

PubMed

Utay, Netanya S; Kitch, Douglas W; Yeh, Eunice; Fichtenbaum, Carl J; Lederman, Michael M; Estes, Jacob D; Deleage, Claire; Magyar, Clara; Nelson, Scott D; Klingman, Karen L; Bastow, Barbara; Luque, Amneris E; McComsey, Grace A; Douek, Daniel C; Currier, Judith S; Lake, Jordan E

2018-05-05

Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection. In this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug. Collagen I, fibronectin, and phosphorylated SMAD3 (pSMAD3) deposition in lymph nodes, as well as collagen I, collagen VI, and fibronectin deposition in adipose tissue, were quantified by immunohistochemical analysis at weeks 0 and 48. Two-sided rank sum and signed rank tests compared changes over 48 weeks. Forty-four participants enrolled; 35 had paired adipose tissue specimens, and 29 had paired lymph node specimens. The median change overall in the percentage of the area throughout which collagen I was deposited was -2.6 percentage points (P = 0.08) in lymph node specimens and -1.3 percentage points (P = .001) in adipose tissue specimens, with no between-arm differences. In lymph node specimens, pSMAD3 deposition changed by -0.5 percentage points overall (P = .04), with no between-arm differences. Telmisartan attenuated increases in fibronectin deposition (P = .06). In adipose tissue, changes in collagen VI deposition (-1.0 percentage point; P = .001) and fibronectin deposition (-2.4 percentage points; P < .001) were observed, with no between-arm differences. In adults with treated HIV infection, lymph node and adipose tissue fibrosis decreased with continued ART alone, with no additional fibrosis reduction with telmisartan therapy.

Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan

PubMed Central

Narra, Nataraj; Rama Rao, Tadikonda

2014-01-01

The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement (P < 0.005) in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months. PMID:25371826

Tai Chi for Essential Hypertension

PubMed Central

Wang, Jie; Feng, Bo; Yang, Xiaochen; Liu, Wei; Teng, Fei; Li, Shengjie; Xiong, Xingjiang

2013-01-01

Objectives. To assess the current clinical evidence of Tai Chi for essential hypertension (EH). Search Strategy. 7 electronic databases were searched until 20 April, 2013. Inclusion Criteria. We included randomized trials testing Tai Chi versus routine care or antihypertensive drugs. Trials testing Tai Chi combined with antihypertensive drugs versus antihypertensive drugs were also included. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 18 trials were included. Methodological quality of the trials was low. 14 trials compared Tai Chi with routine care. 1 trial compared Tai Chi with antihypertensive drugs. Meta-analysis all showed significant effect of TaiChi in lowering blood pressure (BP). 3 trials compared Tai Chi plus antihypertensive drugs with antihypertensive drugs. Positive results in BP were found in the other 2 combination groups. Most of the trials did not report adverse events, and the safety of Tai Chi is still uncertain. Conclusions. There is some encouraging evidence of Tai Chi for EH. However, due to poor methodological quality of included studies, the evidence remains weak. Rigorously designed trials are needed to confirm the evidence. PMID:23986780

Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double-blind placebo-controlled multicenter clinical study.

PubMed

Zhu, Hanyu; Chen, Xiangmei; Cai, Guangyan; Zheng, Ying; Liu, Moyan; Liu, Wenhu; Yao, Hebin; Wang, Yaping; Li, Wenge; Wu, Hua; Lun, Lide; Zhang, Jianrong; Guan, Xiaohong; Yin, Shinan; Zhuang, Xiaoming; Li, Jijun; Liu, Yanjun; Zhou, Chunhua

2016-09-01

Persistent proteinuria is an important factor contributing to the progression of diabetic nephropathy. The present randomized double-blind placebo-controlled multicenter clinical study evaluated the efficacy and safety of telmisartan combined with the antioxidant probucol in reducing urinary protein levels in patients with type 2 diabetes (T2D). Patients with T2D and 24-h proteinuria 0.5-3 g were enrolled in the study and randomly assigned to one of two groups: a telmisartan or a probucol + telmisartan group. Both groups were given telmisartan 80 mg q.d. for 48 weeks. The probucol + telmisartan group was given probucol 500 mg b.i.d. for the first 24 weeks, with the dosage then reduced to 250 mg b.i.d. for the remaining 24 weeks. The telmisartan group was given probucol placebo. In all, 160 patients were enrolled in the present study. The 24-h proteinuria levels were significantly reduced in the probucol + telmisartan compared with telmisartan group. For patients with baseline 24-h proteinuria levels <1.0 g, both treatments resulted in significant reductions in 24-h proteinuria levels after 48 weeks treatment. However, in patients with baseline 24-h proteinuria levels ≥1.0 g, 24-h proteinuria levels after 48 weeks treatment were only reduced in the probucol + telmisartan group. There was no significant difference between the two groups for either adverse cardiovascular or other events. In patients with diabetic nephropathy, probucol combined with telmisartan more effectively reduces urinary protein levels than telmisartan alone. © 2015 The Authors. Journal of Diabetes published by Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

A selective peroxisome proliferator-activated receptor-gamma modulator, telmisartan, binds to the receptor in a different fashion from thiazolidinediones.

PubMed

Tagami, Tetsuya; Yamamoto, Hiroyuki; Moriyama, Kenji; Sawai, Kuniko; Usui, Takeshi; Shimatsu, Akira; Naruse, Mitsuhide

2009-02-01

Angiotensin type 1 receptor blockers are widely used for the treatment of hypertension, and one angiotensin type 1 receptor blocker, telmisartan, specifically activates the peroxisome proliferator-activated receptor (PPAR)-gamma. We studied the impact of PPARgamma mutants on transcriptional control and interaction with cofactors to elucidate differences in the molecular mechanism between telmisartan and other PPARgamma agonists, thiazolidinediones (TZDs). We created several amino acid substitutions in the ligand binding domain of PPARgamma that, based on molecular modeling, may affect the binding of these agents. In transient expression experiments, wild-type PPARgamma-mediated transcription stimulated by telmisartan was more than one third of that stimulated by TZDs. The activation stimulated by TZDs was impaired, whereas activation stimulated by telmisartan was retained, in the H323Y, S342A, and H449A mutants. In the Y473A mutant, the TZD-induced activation was further impaired and lower than that of telmisartan-induced activation. Coexpression of coactivators enhanced the activation by both telmisartan and TZDs, but activation by telmisartan always exceeded that of TZDs in the Y473A mutant. Based on a mammalian two-hybrid assay, the interaction with corepressors was retained in Y473A. Telmisartan and TZDs, but not 9cis retinoic acid, dissociated corepressors from the wild-type PPARgamma. Telmisartan most effectively dissociated corepressors from Y473A. The interaction with coactivators was enhanced by TZD activation of wild-type PPARgamma and both telmisartan and TZD activation of Y473A. Thus, the Y473A mutant is selectively stimulated by telmisartan but not TZDs, suggesting that telmisartan and TZDs have differential effects on the transcriptional control. In conclusion, these PPARgamma mutants could be powerful tools for developing novel therapeutic agents that retain the metabolic efficacy of PPARgamma activation with fewer adverse effects, such as the increase in body weight associated with TZDs.

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

PubMed Central

2013-01-01

Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

Persistence with Antihypertensive Drugs in Patients with Hypertension and Dementia in Germany.

PubMed

Jacob, Louis; Adam-Schnepf, Leonie; Kostev, Karel

2017-01-01

Hypertension, a chronic disease resulting from aging and its related physiopathological dysregulations, is often associated with dementia. The goal was to analyze the persistence with antihypertensive drugs in patients affected by both hypertension and dementia in Germany. This study included hypertension patients who were initially treated with antihypertensive drugs in 1,262 general practices in Germany between January 2013 and December 2015 (index date). Patients with hypertension and comorbid dementia were matched (1 : 1) to patients without dementia by age, gender, type of residence (nursing home versus home-care setting), physician, and initial antihypertensive therapy, using a propensity score method. The primary outcome was the rate of patients without treatment discontinuation with antihypertensive drugs in cases and controls in the 12 months following the index date. Cox regressions were used to determine the impact of dementia on persistence with antihypertensive treatment. This study included 2,191 patients with hypertension and comorbid dementia and 2,191 patients with hypertension but without dementia. The mean age was 79.3 years (SD = 10.3 years) in both groups. Twelve months after initiation of antihypertensive therapy, 73.5% of cases and 69.5% of controls were persistent (p < 0.001). Dementia was associated with a significant decrease in the risk of non-persistence with antihypertensive drugs in the entire population (HR = 0.86, 95% CI: 0.79-0.93). This finding was corroborated in five different subgroups (age ≤60 years, age 61-70 years, men, women, and patients living in home-care settings). Dementia was found to be a protective factor for persistence with antihypertensive drugs in Germany.

Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose.

PubMed

Wohl, Petr; Krusinová, Eva; Hill, Martin; Kratochvílová, Simona; Zídková, Katerina; Kopecký, Jan; Neskudla, Tomás; Pravenec, Michal; Klementová, Marta; Vrbíková, Jana; Wohl, Pavel; Mlejnek, Petr; Pelikánová, Terezie

2010-10-01

Telmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome. Twelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed. Fasting plasma glucose was lower after telmisartan compared with placebo (P<0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor α (TNFα), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P<0.05), leptin and resistin (P<0.001) were increased, whereas TNFα was decreased (P<0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFα and leptin was increased after telmisartan treatment. Despite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFα during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.

Effects of aerobic dance training on blood pressure in individuals with uncontrolled hypertension on two antihypertensive drugs: a randomized clinical trial.

PubMed

Maruf, Fatai Adesina; Akinpelu, Aderonke Omobonike; Salako, Babatunde Lawal; Akinyemi, Joshua Odunayo

2016-04-01

There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Telmisartan regresses left ventricular hypertrophy in caveolin-1 deficient mice

PubMed Central

Kreiger, Marta H; Di Lorenzo, Annarita; Teutsch, Christine; Kauser, Katalin; Sessa, William C.

2011-01-01

The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known, however the role of the Ang II in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav- KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan, and cardiac function assessed by echocardiography. Treatment of Cav-1 KO mice with telmisartan significantly improved cardiac function compared to age-matched, vehicle treated Cav-1 KO mice, while telmisartan did not affected cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by telmisartan in Cav-1 KO but not WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides-A and –B, β-myosin heavy chain and TGF-β and telmisartan treatment normalized the expression of these genes. Telmisartan reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, telmisartan treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy. PMID:20585312

Effects of drug price reduction and prescribing restrictions on expenditures and utilisation of antihypertensive drugs in Korea

PubMed Central

Yoo, Ki-Bong; Lee, Sang Gyu; Park, Sohee; Kim, Tae Hyun; Ahn, Jeonghoon; Cho, Mee-Hyun; Park, Eun-Cheol

2015-01-01

Objectives To evaluate the quantitative effects of the drug price reduction on pharmaceutical expenditures and the new guidelines to restrict prescribing on drug utilisation for antihypertensive drugs. Design We used an interrupted time series design with the National patient sample data of Health Insurance Review and Assessment Service in South Korea. Methods 54 295 participants who were with primary hypertension from the National patient sample data of Health Insurance Review and Assessment Service were included. The study period was from March 2011 to December 2013. The dependent variables were antihypertensive drug costs, antihypertensive drug cost per prescribing day, daily drug utilisation, average number of drugs per month, percentage of original drugs per prescription, drug overutilisation and prohibited combinations. Segmented regression analysis was used. Results The drug price reduction reduced expenditure (US$−1.51, −10.2%), and the new guidelines reduced expenditures even more (US$−2.13; −16.2%). These policies saved US$4.22 (28%) of antihypertensive drug costs per patient in December 2013 compared to March 2012. Drug price reduction policy was introduced in April 2012. We established the policy effect by comparing it before (March 2012) with after(21 months later-December 2012). The effects of the guidelines decreased expenditures, daily drug utilisation and the average number of drugs per month more than did the drug price reduction. Conclusions Both policies saved money. The guidelines were more effective over time and had fewer side effects such as increasing daily drug utilisation and number of drugs than the effects of drug price reduction. PMID:26179644

Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

PubMed Central

Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

2013-01-01

A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations are provided. PMID:23620485

Assessing the Effects of Non-steroidal Anti-inflammatory Drugs on Antihypertensive Drug Therapy Using Post-Marketing Surveillance Database

PubMed Central

Ishiguro, Chieko; Fujita, Toshiharu; Omori, Takashi; Fujii, Yosuke; Mayama, Takeshi; Sato, Tosiya

2008-01-01

Background Antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat many common diseases. However, it has been suspected that interactions between these drugs exist. Here, we assessed the interactions between non-selective NSAIDs and several classes of antihypertensive drugs. Methods The study design was a cohort study using “The Antihypertensive Drug Database,” which is a collection of data accumulated from Drug Use Investigations. Subjects newly starting antihypertensive drug therapy were identified in the database. We compared the “User” group, who were co-administered NSAIDs, with the “Non-user” group, who were not. The outcome measure was the change in systolic blood pressure from the baseline after 2 months of treatment. We estimated the non-adjusted and adjusted differences in the change in systolic blood pressure between the “User” and “Non-user” groups. Results Data were collected for a total of 1,204 subjects, of whom 364 were prescribed beta blockers, 60 were prescribed diuretics, 628 were prescribed angiotensin-converting enzyme inhibitors, and 152 were prescribed calcium channel blockers. The adjusted difference in the change in systolic blood pressure between the User (n = 301) and Non-user (n = 903) groups was 2.88 mmHg (95% confidence interval: 0.89, 4.87); thus, systolic blood pressure in the Non-User group decreased further from the baseline than that in the User group. In subjects administered beta blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers, the corresponding differences were 0.37 mmHg (-3.24, 3.98), 6.11 mmHg (-3.16, 15.37), 3.85 mmHg (1.16, 6.66), and 3.50 mmHg (-2.03, 9.02). Conclusion The effectiveness of antihypertensive drugs was attenuated by the co-administration of NSAIDs. The differences in the effects of NSAIDs varied with different classes of antihypertensive drugs. PMID:18469490

Do advertisements for antihypertensive drugs in Australia promote quality prescribing? A cross-sectional study.

PubMed

Montgomery, Brett D; Mansfield, Peter R; Spurling, Geoffrey K; Ward, Alison M

2008-05-20

Antihypertensive medications are widely prescribed by doctors and heavily promoted by the pharmaceutical industry. Despite strong evidence of the effectiveness and cost-effectiveness of thiazide diuretics, trends in both promotion and prescription of antihypertensive drugs favour newer, less cost-effective agents. Observational evidence shows correlations between exposure to pharmaceutical promotion and less ideal prescribing. Our study therefore aimed to determine whether print advertisements for antihypertensive medications promote quality prescribing in hypertension. We performed a cross-sectional study of 113 advertisements for antihypertensive drugs from 4 general practice-oriented Australian medical publications in 2004. Advertisements were evaluated using a quality checklist based on a review of hypertension management guidelines. Main outcome measures included: frequency with which antihypertensive classes were advertised, promotion of thiazide class drugs as first line agents, use of statistical claims in advertisements, mention of harms and prices in the advertisements, promotion of assessment and treatment of cardiovascular risk, promotion of lifestyle modification, and targeting of particular patient subgroups. Thiazides were the most frequently advertised drug class (48.7% of advertisements), but were largely promoted in combination preparations. The only thiazide advertised as a single agent was the most expensive, indapamide. No advertisement specifically promoted any thiazide as a better first-line drug. Statistics in the advertisements tended to be expressed in relative rather than absolute terms. Drug costs were often reported, but without cost comparisons between drugs. Adverse effects were usually reported but largely confined to the advertisements' small print. Other than mentioning drug interactions with alcohol and salt, no advertisements promoted lifestyle modification. Few advertisements (2.7%) promoted the assessment of cardiovascular risk. Print advertisements for antihypertensive medications in Australia provide some, but not all, of the key messages required for guideline-concordant care. These results have implications for the regulation of drug advertising and the continuing education of doctors.

Assessing the effects of non-steroidal anti-inflammatory drugs on antihypertensive drug therapy using post-marketing surveillance database.

PubMed

Ishiguro, Chieko; Fujita, Toshiharu; Omori, Takashi; Fujii, Yosuke; Mayama, Takeshi; Sato, Tosiya

2008-01-01

Antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat many common diseases. However, it has been suspected that interactions between these drugs exist. Here, we assessed the interactions between non-selective NSAIDs and several classes of antihypertensive drugs. The study design was a cohort study using "The Antihypertensive Drug Database," which is a collection of data accumulated from Drug Use Investigations. Subjects newly starting antihypertensive drug therapy were identified in the database. We compared the "User" group, who were co-administered NSAIDs, with the "Non-user" group, who were not. The outcome measure was the change in systolic blood pressure from the baseline after 2 months of treatment. We estimated the non-adjusted and adjusted differences in the change in systolic blood pressure between the "User" and "Non-user" groups. Data were collected for a total of 1,204 subjects, of whom 364 were prescribed beta blockers, 60 were prescribed diuretics, 628 were prescribed angiotensin-converting enzyme inhibitors, and 152 were prescribed calcium channel blockers. The adjusted difference in the change in systolic blood pressure between the User (n = 301) and Non-user (n = 903) groups was 2.88 mmHg (95% confidence interval: 0.89, 4.87); thus, systolic blood pressure in the Non-User group decreased further from the baseline than that in the User group. In subjects administered beta blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers, the corresponding differences were 0.37 mmHg (-3.24, 3.98), 6.11 mmHg (-3.16, 15.37), 3.85 mmHg (1.16, 6.66), and 3.50 mmHg (-2.03, 9.02). The effectiveness of antihypertensive drugs was attenuated by the co-administration of NSAIDs. The differences in the effects of NSAIDs varied with different classes of antihypertensive drugs.

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis.

PubMed

Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Fitzmaurice, David; Cheng, K K; Marshall, Tom

2016-11-01

Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients' adherence to medication or medication targets, such as blood pressure levels. In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA.

Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mogi, Masaki; Li Jianmei; Tsukuda, Kana

Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was notmore » affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.« less

Antihypertensive drugs.

PubMed

Laurent, Stéphane

2017-10-01

Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated. In addition, side effects are described and explained through their pharmacological mechanisms, in order to better understand their mechanism of occurrence and in which patients drugs are contra-indicated. This review does not address the effectiveness of monotherapies in large randomized clinical trials and combination therapies, since these are the matters of other articles of the present issue. Five major pharmacological classes of antihypertensive drugs are detailed here: beta-blockers, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers. Four additional pharmacological classes are described in a shorter manner: renin inhibitors, alpha-adrenergic receptor blockers, centrally acting agents, and direct acting vasodilators. Copyright © 2017. Published by Elsevier Ltd.

Effects of telmisartan and losartan on cardiovascular protection in Japanese hypertensive patients.

PubMed

Hasegawa, Hiroshi; Takano, Hiroyuki; Narumi, Hiroya; Ohtsuka, Masashi; Mizuguchi, Tadahiko; Namiki, Takao; Kobayashi, Yoshio; Komuro, Issei

2011-11-01

The Telmisartan and Losartan Cardiac Evaluation Trial, a multicenter, prospective, randomized, open-labeled, blinded-endpoint trial, was designed to compare the effects of two angiotensin II receptor blockers (ARBs), telmisartan and losartan, on cardiovascular protection in Japanese patients with mild to moderate essential hypertension. We compared the effects of telmisartan and losartan on left ventricular (LV) hypertrophy, cardiac function, atherosclerosis of carotid arteries and surrogate markers related to the actions of peroxisome proliferator-activated receptor-γ. A total of 58 patients were enrolled in the present trial and the follow-up period was 1 year. There were no significant differences in blood pressure (BP) levels between the telmisartan group and the losartan group throughout the trial. The percentage of the patients treated with ARB monotherapy was significantly higher in the telmisartan group compared with the losartan group. In addition, the progression of intima-media thickness of common carotid artery was significantly inhibited in the telmisartan group compared with the losartan group. Neither group experienced significant changes in cardiac function and LV mass index. There were no differences between the groups with respect to changes in surrogate markers such as serum adiponectin, creatinine, homeostasis model assessment index, plasminogen activator inhibitor-1 and high sensitivity C-reactive protein. Although BP levels were equal and well controlled in both groups, telmisartan showed more protective vascular effects than losartan.

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway

PubMed Central

Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

2011-01-01

Abstract Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. PMID:20477906

Dietary flavonoids added to pharmacological antihypertensive therapy are effective in improving blood pressure.

PubMed

de Jesús Romero-Prado, Marina María; Curiel-Beltrán, Jesús Aarón; Miramontes-Espino, María Viviana; Cardona-Muñoz, Ernesto Germán; Rios-Arellano, Angeles; Balam-Salazar, Lol-Be

2015-07-01

Epidemiological studies have suggested that the daily intake of flavonoids is associated with a decreased risk of developing cardiovascular disease. Our purpose was to evaluate the effect of the addition of dietary flavonoids (DF) to antihypertensive treatment (AHT), based on telmisartan (Tms) or captopril (Cpr), on blood pressure (BP), body mass index (BMI), waist/hip ratio, leptin, lipid profile and inflammation in hypertensive young patients. An open-label, randomized, controlled trial was performed among 79 patients aged 20-55 years with grade I or grade II systemic arterial hypertension. The subjects were assigned to one of four groups for AHT plus DF during 6 months: Cpr (n = 14), Cpr + DF (n = 19), Tms (n = 25) and Tms + DF (n = 21). DF consisted of dark chocolate, dehydrated red apple and green tea in an infusion to obtain a daily dose of 425.8 ± 13.9 mg epicatechin equivalents. The BP and anthropometric parameters were measured every 2 weeks. Lipid profile, leptin and hsCRP were determined by standard methods. The combination AHT-DF produced an additional and significant reduction in (i) SBP/DBP of -5/-4 mmHg, being -7/-5 for Cpr + DF and -4/-3 for Tms + DF; (ii) triglyceride levels (-30.6%) versus AHT alone (-9.6%); and (iii) leptin: Cpr + DF versus Tms + DF (p < 0.005). Finally, C-reactive protein plasma levels were reduced significantly in all groups independently of the applied treatment. We conclude that the addition of flavonoids to pharmacological antihypertensive therapy shows additional benefits on BP, lipid profile, leptin, obesity and inflammation. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Imputing Observed Blood Pressure for Antihypertensive Treatment: Impact on Population and Genetic Analyses

PubMed Central

2014-01-01

BACKGROUND Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts. METHODS We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs. RESULTS Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20–0.50) and 0.44 (95% CI = 0.22–0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP. CONCLUSIONS This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors. PMID:24532572

Current prescription status of antihypertensive drugs with special reference to the use of diuretics in Japan.

PubMed

Ibaraki, Ai; Goto, Wataru; Iura, Rie; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

2017-02-01

The guidelines for the management of hypertension recommend the inclusion of diuretics, especially when three or more antihypertensive drugs are used. The present study investigated the current prescription status of antihypertensive drugs with a particular focus on the use of diuretics in a local district in Japan. Prescriptions, including antihypertensive drugs, were collected from a dispensing pharmacy of the Yahata Pharmacist Association, located in Kitakyushu City, in October 2014. Of the 10 585 prescriptions, calcium channel blockers (CCBs) were prescribed in 73.5%, followed by angiotensin II receptor blockers (ARB, 62.7%), diuretics (16.5%) and β-blockers (13.6%). The average number of drugs used was 1.80. The rates of prescription of diuretics for patients with one, two, three and four drugs were 0.6%, 13.1%, 55.2% and 82.6%, respectively. Diuretics were more frequently prescribed in elderly patients, and the prescription rate of doctors in hospitals was significantly higher than that of general practitioners (19.1% vs. 15.7%, P<0.01). In addition, 40% of patients with thiazide diuretics were prescribed combination tablets of hydrochlorothiazide with ARB, whereas trichlormethiazide (34.9%) and indapamide (19.8%) were used in other patients. Based on these findings, the use of diuretics remains limited, even among patients taking multiple antihypertensive drugs.

Using Clinical Data, Hypothesis Generation Tools and PubMed Trends to Discover the Association between Diabetic Retinopathy and Antihypertensive Drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senter, Katherine G; Sukumar, Sreenivas R; Patton, Robert M

Diabetic retinopathy (DR) is a leading cause of blindness and common complication of diabetes. Many diabetic patients take antihypertensive drugs to prevent cardiovascular problems, but these drugs may have unintended consequences on eyesight. Six common classes of antihypertensive drug are angiotensin converting enzyme (ACE) inhibitors, alpha blockers, angiotensin receptor blockers (ARBs), -blockers, calcium channel blockers, and diuretics. Analysis of medical history data might indicate which of these drugs provide safe blood pressure control, and a literature review is often used to guide such analyses. Beyond manual reading of relevant publications, we sought to identify quantitative trends in literature from themore » biomedical database PubMed to compare with quantitative trends in the clinical data. By recording and analyzing PubMed search results, we found wide variation in the prevalence of each antihypertensive drug in DR literature. Drug classes developed more recently such as ACE inhibitors and ARBs were most prevalent. We also identified instances of change-over-time in publication patterns. We then compared these literature trends to a dataset of 500 diabetic patients from the UT Hamilton Eye Institute. Data for each patient included class of antihypertensive drug, presence and severity of DR. Graphical comparison revealed that older drug classes such as diuretics, calcium channel blockers, and -blockers were much more prevalent in the clinical data than in the DR and antihypertensive literature. Finally, quantitative analysis of the dataset revealed that patients taking -blockers were statistically more likely to have DR than patients taking other medications, controlling for presence of hypertension and year of diabetes onset. This finding was concerning given the prevalence of -blockers in the clinical data. We determined that clinical use of -blockers should be minimized in diabetic patients to prevent retinal damage.« less

Context-Awareness Based Personalized Recommendation of Anti-Hypertension Drugs.

PubMed

Chen, Dexin; Jin, Dawei; Goh, Tiong-Thye; Li, Na; Wei, Leiru

2016-09-01

The World Health Organization estimates that almost one-third of the world's adult population are suffering from hypertension which has gradually become a "silent killer". Due to the varieties of anti-hypertensive drugs, patients are interested in how these drugs can be selected to match their respective conditions. This study provides a personalized recommendation service system of anti-hypertensive drugs based on context-awareness and designs a context ontology framework of the service. In addition, this paper introduces a Semantic Web Rule Language (SWRL)-based rule to provide high-level context reasoning and information recommendation and to overcome the limitation of ontology reasoning. To make the information recommendation of the drugs more personalized, this study also devises three categories of information recommendation rules that match different priority levels and uses a ranking algorithm to optimize the recommendation. The experiment conducted shows that combining the anti-hypertensive drugs personalized recommendation service context ontology (HyRCO) with the optimized rule reasoning can achieve a higher-quality personalized drug recommendation service. Accordingly this exploratory study of the personalized recommendation service for hypertensive drugs and its method can be easily adopted for other diseases.

Potential utility of combination therapy with nateglinide and telmisartan for metabolic derangements in Zucker Fatty rats.

PubMed

Kajioka, T; Miura, K; Kitahara, Y; Yamagishi, S

2007-12-01

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular disease. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial hyperglycemia. In this study, we investigated the potential utility of combination therapy with telmisartan, an angiotensin II receptor blocker and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial hyperglycemia and metabolic derangements in Zucker Fatty (ZF) rats. ZF rats fed twice daily were given vehicle, 50 mg/kg of nateglinide, 5 mg/kg of telmisartan, or both for 6 weeks. Combination therapy with nateglinide and telmisartan for 2 weeks ameliorated postprandial hyperglycemia in ZF rats fed twice daily. Furthermore, 6-week treatment with nateglinide and telmisartan not only decreased fasting plasma insulin, triglycerides, and free fatty acid levels, but also improved the responses of blood glucose to insulin and subsequently reduced the decremental glucose areas under the curve in the ZF rats. Combination therapy also restored the decrease of plasma adiponectin levels in the ZF rats. Monotherapy with nateglinide or telmisartan alone didnot significantly improve these metabolic parameters. These observations demonstrate that combination therapy with nateglinide and telmisartan may improve the metabolic derangements by ameliorating early phase of insulin secretion as well as insulin resistance in ZF rats fed twice daily. Our present findings suggest that the combination therapy with nateglinide and telmisartan could be a promising therapeutic strategy for the treatment of the metabolic syndrome.

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

PubMed

Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

2011-07-01

Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice.

PubMed

Blakely, Pennelope K; Huber, Amanda K; Irani, David N

2016-08-25

Alphaviruses can cause fatal encephalitis in humans. Natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. Central nervous system (CNS) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. We investigated whether reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity within the CNS contributes to fatal alphavirus encephalitis in mice. Infected animals were treated systemically with the angiotensin receptor-blocking drug, telmisartan, given its ability to cross the blood-brain barrier, selectively block type-1 angiotensin receptors (AT1R), and inhibit Nox-derived ROS production in vascular smooth muscle and other extraneural tissues. Clinical, virological, biochemical, and histopathological outcomes were followed over time. The importance of the angiotensin II (Ang II)/AT1R axis in disease pathogenesis was confirmed by demonstrating increased Ang II levels in the CNS following infection, enhanced disease survival when CNS Ang II production was suppressed, increased AT1R expression on microglia and tissue-infiltrating myeloid cells, and enhanced disease survival in AT1R-deficient mice compared to wild-type (WT) controls. Systemic administration of telmisartan protected WT mice from lethal encephalitis caused by two different alphaviruses in a dose-dependent manner without altering virus replication or exerting any anti-inflammatory effects in the CNS. Infection triggered up-regulation of multiple Nox subunits in the CNS, while drug treatment inhibited local Nox activity, ROS production, and oxidative neuronal damage. Telmisartan proved ineffective in Nox-deficient mice, demonstrating that this enzyme is its main target in this experimental setting. Nox-derived ROS, likely arising from CNS myeloid cells triggered by AT1R signaling, are pathogenic during fatal alphavirus encephalitis in mice. Systemically administered telmisartan at non-hypotensive doses targets Nox activity in the CNS to exert a neuroprotective effect. Disruption of this pathway may have broader implications for the treatment of related infections as well as for other CNS diseases driven by oxidative injury.

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis

PubMed Central

Fitzmaurice, David; Cheng, K. K.; Marshall, Tom

2016-01-01

Background Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. Methods and Findings We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients’ adherence to medication or medication targets, such as blood pressure levels. Conclusions In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA. PMID:27846215

Consumption and costs of antihypertensive drugs in Mexico: are diuretic agents a standing technological trajectory?

PubMed

Altagracia-Martínez, M; Kravzov-Jinich, J; Guadarrama-Atrizco, M D; Rubio-Poo, C; Wertheimer, A I

2006-03-01

Little is known about hypertension medication consumption and costs in Mexico. Hypertension control is a pharmacological challenge and a public health issue. (a) To compare drug sales, number of written prescriptions, and monthly treatment costs among 5 classes of antihypertensive drugs and (b) to analyze diuretic drug sales and prescriptions to determine whether these antihypertensive agents represent an established technological trajectory. A retrospective time series data study from 1999 to 2003. Data sources used were International Marketing Services of Mexico drug sales and the Mexico Prescription Audit databases. The 5 different classes of antihypertensive drugs were accommodated into 4 main technological trajectories according to their main biological mechanisms of action. Each technological trajectory was assessed using consumption and prescription data. Daily defined dose was used to calculate drug treatment costs. The market for cardiovascular agents is one of the largest, and in 2003 accounted for a value market share of 59 billion US dollar and a unit share of 40.7 million. Among cardiovascular agents, antihypertensive drugs made up a large percentage of market shares. Calcium channel blockers and angiotensin-converting enzyme inhibitors I had the biggest share value of the total cardiovascular market. Amlodipine had the highest share among calcium channel blockers, and enalapril and captopril had the largest share among angiotensin-converting enzyme inhibitors I. The top-selling diuretic drug was furosemide. The trend in number of prescriptions was parallel to that in sales. The diuretic spironolactone was the most expensive drug treatment (59 US dollar). Treatment with spironolactone might represent 47% of the income of a Mexican family if their household income was close to minimum wage (124 US dollar). The most effective and least expensive drugs-diuretics-had the smallest market share of all antihypertensive agents in Mexico. Nevertheless, diuretic agents are still in use and kept over time a steady market share both in value and in units.

How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure

PubMed Central

Digne-Malcolm, Holly; Frise, Matthew C.; Dorrington, Keith L.

2016-01-01

Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents. PMID:27524972

[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research].

PubMed

Rajzer, Marek; Kawecka-Jaszcz, Kalina; Wojciechowska, Wiktoria

2003-01-01

The frequency of arterial hypertension occurrence in polish population amounts to 30-40%, among diabetics is significantly higher-70%. According to the WHO/ISH Guidelines all hypertensive patients with diabetes are included into the "high risk group" independent of hypertension stage. Pharmacological treatment of hypertension is this group of patients has a particular meaning. Among hypertensive patients the degree of blood pressure lowering is more effective for cardiovascular risk reduction than choice of drug. This fact is well documented in clinical trials comparing antihypertensive efficacy of old and new antihypertensive drugs (for example UKPDS, STOP 2, INSIGHT). From the other point of view renal protection and metabolic benefits, as well as reduction of target organ damage are more advantageous for angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium antagonists than for diuretics and beta-blockers. Despite fast progress in clinical research on new antihypertensive drugs (especially AT1 receptor inhibitors) ACE-I seem to still remain still the "first choice" for hypertensive diabetics. Adequate blood pressure control among diabetic hypertensives is of special importance and usually needs appropriate combined antihypertensive therapy. Our review presents detailed information about treatment advantages and disadvantages of drugs from different antihypertensive classes in light of current clinical trials and international guidelines.

In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

PubMed

Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

2017-06-16

Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

[Clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives].

PubMed

Villa, Juan; Cano, Alejandra; Franco, David; Monsalve, Mauricio; Hincapié, Jaime; Amariles, Pedro

2014-11-01

To establish the clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the interaction severity and probability of occurrence. Systematic review. A PubMed/Medline search was made using the MeSH terms: NSAIDs, Antihypertensive drugs, and Drug interactions. Articles between 2002 and 2012, human studies, in Spanish and English and full text access were included. Found articles were included and some of the references used in this works. Studies with in vitro methods, effects on ocular hypertension and those who do not consider the interaction NSAIDs, antihypertensives were excluded. For the selection of the papers included three independent reviewers were involved. We used a tool for data extraction and for assess of the interaction clinical relevance. Nineteen of 50 papers found were included. There were identified 21 interactions with pharmacodynamic mechanism, classified by their clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%). In addition, evidence of 16 combinations of no interaction were found. Some NSAIDs may attenuate the effectiveness of antihypertensive drugs when used concurrently, especially with angiotensin converting enzyme inhibitors, diuretics, beta blockers and angiotensin receptorsii blockers. There was no evidence of effect modification of calcium channel antagonists, especially dihydropyridine, by concurrent use of NSAIDs. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

PubMed Central

Mukhopadhyay, Sutirtho; Kadam, Kiran; Sawant, Laxman; Nachane, Dhanashree; Pandita, Nancy

2011-01-01

Objective: Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT1) receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC) method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods: Simultaneous determination of related substances was performed on Kromasil C18 analytical column (250 × 4.6 mm; 5μm pertical size) column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid) and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v) was used at a flow rate of 1.0 ml min–1. UV detection was performed at 270 nm. Results: During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions: HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets. PMID:21966158

Intramyocellular lipid content in subjects with impaired fasting glucose after telmisartan treatment, a randomised cross-over trial.

PubMed

Kratochvílová, Simona; Škoch, Antonín; Wohl, Petr; Švehlíková, Eva; Dezortová, Monika; Hill, Martin; Hájek, Milan; Pelikánová, Terezie

2016-04-01

Ectopic lipid accumulation in skeletal muscle is associated with insulin resistance. Telmisartan improves metabolic parameters in type 2 diabetic patients. The aim of our study was to evaluate the in vivo effect of telmisartan on intramyocellular lipid content (IMCL) in subjects with impaired fasting glucose (IFG) by magnetic resonance spectroscopy (MRS). We enrolled 10 subjects with IFG in a cross-over, placebo-controlled, randomized, double-blind trial, treated with 3 weeks of telmisartan (160 mg daily) or placebo. After completing each treatment, a hyperinsulinaemic euglycaemic clamp (1 mU/kg per min; 5 mmol/l; 120 min) to assess insulin action (metabolic clearance rate of glucose, MCR) and (1)H MRS of the m. tibialis anterior using a MR Scanner Siemens Vision operating at 1.5 T to evaluate IMCL content, were performed. Plasma adipokine levels were determined simultaneously. Telmisartan treatment resulted in a lower fasting plasma glucose (FPG) (p < 0.05), but insulin action was comparable to after placebo. Telmisartan did not affect IMCL content. After placebo, IMCL correlated negatively with total cholesterol (p < 0.001), MCR (p < 0.05) and adiponectin (p < 0.05) and positively with FPG (p < 0.05). After telmisartan treatment there was only a positive correlation between IMCL and TNFα (p < 0.05). IMCL content is related to parameters of glucose metabolism and insulin action in sedentary IFG subjects. A short telmisartan treatment did not affect the IMCL content despite its positive effect on FPG. The improvement in FPG was probably mediated through interference with other metabolic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Baseline Antihypertensive Drug Count and Patient Response to Hypertension Medication Management.

PubMed

Crowley, Matthew J; Olsen, Maren K; Woolson, Sandra L; King, Heather A; Oddone, Eugene Z; Bosworth, Hayden B

2016-04-01

Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well-established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Coffee consumption and the incidence of antihypertensive drug treatment in Finnish men and women.

PubMed

Hu, Gang; Jousilahti, Pekka; Nissinen, Aulikki; Bidel, Siamak; Antikainen, Riitta; Tuomilehto, Jaakko

2007-08-01

Only 2 prospective studies have previously investigated the association between coffee consumption and incident hypertension, and the findings are equivocal. The objective was to determine the relation between coffee consumption and the incidence of antihypertensive drug treatment. We prospectively followed 24 710 Finnish subjects aged 25-64 y without a history of antihypertensive drug treatment, coronary heart disease, or stroke at baseline. Daily coffee consumption was assessed by questionnaires. During a mean follow-up period of 13.2 y, 2505 participants started antihypertensive drug treatment. The multivariate-adjusted (age, sex, study year, education, leisure-time physical activity, smoking, body mass index, high total cholesterol, history of diabetes, and alcohol, tea, fruit, vegetable, sausage, and bread consumption) hazard ratios for antihypertensive drug treatment associated with the amount of coffee consumed daily (0-1, 2-3, 4-5, 6-7, or >or=8 cups) were 1.00, 1.29 (95% CI: 1.09, 1.54), 1.26 (95% CI: 1.06, 1.49), 1.24 (95% CI: 1.04, 1.48), and 1.14 (95% CI: 0.94, 1.37) (P for trend = 0.024), respectively. This trend became marginally significant after additional adjustment for baseline systolic blood pressure (P for trend = 0.077). The results indicate that coffee drinking seems to increase the risk of antihypertensive drug treatment, and this risk was higher in subjects with low-to-moderate coffee intakes; however, there was no significantly increased trend in drinkers of approximately 1 cup (100 mL)/d or >or=8 cups/d.

Generic substitution of antihypertensive drugs: does it affect adherence?

PubMed

Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

2006-01-01

Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. To assess the association between generic substitution and nonadherence to antihypertensive drugs. We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Telmisartan to prevent recurrent stroke and cardiovascular events.

PubMed

Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

TELMISARATAN PROVIDES BETTER RENAL PROTECTION THAN VALSARTAN IN A RAT MODEL OF METABOLIC SYNDROME

PubMed Central

Khan, Abdul Hye; Imig, John D.

2013-01-01

BACKGROUND Angiotension receptor blockers (ARB), telmisartan and valsartan were compared for renal protection in spontaneously hypertensive rats (SHR) fed high fat diet. We hypothesized that in cardiometabolic syndrome, telmisartan an ARB with PPAR-γ activity will offer better renal protection. METHODS SHR were fed either normal (SHR-NF, 7% fat) or high fat (SHR-HF, 36% fat) diet and treated with an ARB for 10 weeks. RESULTS Blood pressure was similar between SHR-NF (190±3 mmHg) and SHR-HF (192±4 mmHg) at the end of the 10 week period. Telmisartan and valsartan decreased blood pressure to similar extents in SHR-NF and SHR-HF groups. Body weight was significantly higher in SHR-HF (368±5g) compared to SHR-NF (328±7g). Telmisartan but not valsartan significantly reduced the body weight gain in SHR-HF. Telmisartan was also more effective than valsartan in improving glycemic and lipid status in SHR-HF. Monocyte chemoattractant protein-1 (MCP-1), an inflammatory marker, was higher in SHR-HF (24±2 ng/d) compared to SHR-NF (14±5 ng/d). Telmisartan reduced MCP-1 excretion in both SHR-HF and SHR-NF to a greater extent than valsartan. An indicator of renal injury, urinary albumin excretion increased to 85±8 mg/d in SHR-HF compared to 54±9 mg/d in SHR-NF. Telmisartan (23±5 mg/d) was more effective than valsartan (45±3 mg/d) in lowering urinary albumin excretion in SHR-HF. Moreover, telmisartan reduced glomerular damage to a greater extent than valsartan in the SHR-HF. CONCLUSIONS Collectively, our data demonstrate that telmisartan was more effective than valsartan in reducing body weight gain, renal inflammation, and renal injury in a rat model of cardiometabolic syndrome. PMID:21415842

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.

PubMed

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-10-01

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

More hypotension in patients taking antihypertensives preoperatively during shoulder surgery in the beach chair position.

PubMed

Trentman, Terrence L; Fassett, Sharon L; Thomas, Justin K; Noble, Brie N; Renfree, Kevin J; Hattrup, Steven J

2011-11-01

Hypotension is common in patients undergoing surgery in the sitting position under general anesthesia, and the risk may be exacerbated by the use of antihypertensive drugs taken preoperatively. The purpose of this study was to compare hypotensive episodes in patients taking antihypertensive medications with normotensive patients during shoulder surgery in the beach chair position. Medical records of all patients undergoing shoulder arthroscopy during a 44-month period were reviewed retrospectively. The primary endpoint was the number of moderate hypotensive episodes (systolic blood pressure ≤ 85 mmHg) during the intraoperative period. Secondary endpoints included the frequency of vasopressor administration, total dose of vasopressors, and fluid administered. Values are expressed as mean (standard deviation). Of 384 patients who underwent shoulder surgery, 185 patients were taking no antihypertensive medication, and 199 were on at least one antihypertensive drug. The antihypertensive medication group had more intraoperative hypotensive episodes [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of vasopressors and volume of fluids administered were similar between groups. The timing of the administration of angiotensin-converting enzyme inhibitors and of angiotensin receptor antagonists (≤ 10 hr vs > 10 hr before surgery) had no impact on intraoperative hypotension. Preoperative use of antihypertensive medication was associated with an increased incidence of intraoperative hypotension. Compared with normotensive patients, patients taking antihypertensive drugs preoperatively are expected to require vasopressors more often to maintain normal blood pressure.

Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats

PubMed Central

Müller-Fielitz, Helge; Lau, Margot; Geißler, Cathleen; Werner, Lars; Winkler, Martina; Raasch, Walter

2015-01-01

Background and Purpose AT1 receptor blockers (ARBs) represent an approach for treating metabolic syndrome due to their potency in reducing hypertension, body weight and onset of type 2 diabetes. The mechanism underlying ARB-induced weight loss is still unclear. Experimental Approach Leptin resistance tests (LRTs) in diet-induced obese or lean rats were conducted to determine whether telmisartan (8 mg·kg−1·day−1, 14 days) enhances leptin sensitivity. Phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) staining was performed in hypothalami to determine leptin transport across the blood–brain barrier. Key Results Telmisartin reduced weight gain, food intake and plasma leptin but blood pressure remained unchanged. The 24 h profiles of plasma leptin after saline injections were similar in controls and telmisartan-treated rats, but after leptin injections were higher in controls and slightly lower in telmisartan-treated animals. After telmisartan, energy intake during LRT was lower in leptin-than in saline-pretreated rats, but remained unchanged in controls, irrespectively of whether rats received saline or leptin. Leptin minimized the gain in body weight during LRT in telmisartan-treated rats as compared with saline-treated animals. pSTAT3 staining was reduced in cafeteria diet-fed rats as compared with chow-fed rats but this was normalized by telmisartan. Telmisartin reduced hypothalamic mRNA levels of the orexigenic peptides melanin-concentrating hormone and prepro-orexin. Conclusions and Implications Rats fed a cafeteria diet develop leptin resistance after 2 weeks. Leptin sensitivity was preserved by telmisartan treatment even in rats fed a cafeteria diet. This pleiotropic effect is not related to the hypotensive action of telmisartan. PMID:25258168

[Use of antihypertensive drug therapy and risk of development of congestive heart failure].

PubMed

Sobrino, Javier; Plana, Jaume; Felip, Angela; Doménech, Mónica; Reth, Peter; Adrián, María Jesús; de la Sierra, Alejandro

2004-09-18

It has been suggested that the use of some antihypertensive agents may favour the development of congestive heart failure. The aim of the present study was to evaluate such a possible association in patients who had a new diagnosis of congestive heart failure. This was a retrospective case-control study of 81 patients who had a first hospital admission with a new diagnosis of congestive heart failure (cases) and 162 patients admitted for other hypertensive complications (controls). Previous antihypertensive drug use was registered and the possible association with congestive heart failure was evaluated. The presence of congestive heart failure was not associated with the use of any antihypertensive drug class. When treatments were grouped in classic (diuretics and betablockers) or modern (calcium channel blockers, angiotensin-converting-enzyme inhibitors, alphablockers or angiotensin receptor blockers), a negative association was observed with the latter group, which was observed in 48.1% of cases and 63.6% of controls (odds ratio: 0.532; 95% confidence interval, 0.310-0.913). This association was lost after adjustment for other cardiovascular risk factors or previous hypertensive complications. The development of congestive heart failure was not associated with the use of any specific antihypertensive drug class. From the present evidence, it is not possible to recommend a specific antihypertensive agent in patients at risk of developing congestive heart failure but without evidence of such disease.

Antihypertensive drug prescription trends at the primary health care centres in Bahrain.

PubMed

Jassim al Khaja, K A; Sequeira, R P; Wahab, A W; Mathur, V S

2001-05-01

To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.

PubMed

Jin, Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

PubMed

Tomas, Ana; Tomić, Zdenko; Milijasević, Boris; Ban, Milica; Horvat, Olga; Vukmirović, Sasa; Sabo, Ana

2016-06-01

Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices. This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology. Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension. Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE inhibitors is unjustifiable. There is a potential for large savings with switching to low-price ACEi, modeling the practice of Scandinavian countries.

How Ghanaian, African-Surinamese and Dutch patients perceive and manage antihypertensive drug treatment: a qualitative study.

PubMed

Beune, Erik J A J; Haafkens, Joke A; Agyemang, Charles; Schuster, John S; Willems, Dick L

2008-04-01

To explore and compare how Ghanaian, African-Surinamese (Surinamese), and White-Dutch patients perceive and manage antihypertensive drug treatment in Amsterdam, the Netherlands. Qualitative study was conducted using detailed interviews with a purposive sample of 46 hypertensive patients without comorbidity who were prescribed antihypertensives. Patients in all the ethnic groups actively decided how to manage their prescribed antihypertensive regimens. In all the groups, confidence in the doctor and beneficial effects of medication were reasons for taking prescribed antihypertensive dosage. Particularly, ethnic-minority patients reported lowering or leaving off the prescribed medication dosage. Explanations for altering prescribed dosage comprised disliking chemical medications, fear of side effects and preference for alternative treatment. Surinamese and Ghanaian men also worried about the negative effects of antihypertensives on their sexual performance. Some Ghanaians mentioned fear of addiction or lack of money as explanations for altering prescribed dosage. Surinamese and Ghanaians often discontinued medication when visiting their homeland. Some respondents from all ethnic groups preferred natural treatments although treatment type varied. Patients' explanations for their decisions regarding the use of antihypertensives are often influenced by sociocultural issues and in ethnic-minority groups also by migration-related issues. Self-alteration of prescribed medication among Surinamese and Ghanaians may contribute to the low blood pressure (BP) control rate and high rate of malignant hypertension reported among these populations in the Netherlands. This study provides new information, which can help clinicians to understand how patients of diverse ethnic populations think about managing antihypertensive drug treatment and to address ethnic disparities in medication adherence and BP control.

Effect of pranayama on rate pressure product in mild hypertensives.

PubMed

Goyal, Rajni; Lata, Hem; Walia, Lily; Narula, Manjit K

2014-07-01

The modern living life-style is known to produce various physical and psychological stresses resulting in increased blood pressure (BP) and heart rate (HR). This can lead to increased myocardial oxygen demand (MVO2). MVO2 correlated best with rate pressure product (RPP). RPP is a product of HR and systolic BP. The present study was conducted to evaluate the effect of relaxation in the form of pranayama on RPP in mild hypertensives. Mild hypertensive patients were divided into two groups. Group A received antihypertensive drugs for 6 weeks and Group B received antihypertensive drugs along with pranayama training for 6 weeks. BP decreased significantly in Group B (148 ± 8.09-127 ± 12.10 mm of Hg) where pranayama was added. The decrease was significant as compared to Group A. HR decreased significantly in both the groups as compared to baseline, however the decrease was similar in both groups. RPP decreased significantly in both groups as compared to baseline, however the decrease was significantly more (P < 0.01) when pranayama was added to antihypertensive drugs (96.73 ± 20.53) when compared to antihypertensive drugs alone (114.66 ± 26.30). The pranayama produces relaxed state and in this state parasympathetic activity overrides sympathetic activity. Hence, addition of pranayama can be a useful addition to antihypertensive drugs for better control of hypertension in mild hypertensives.

Long-term Effects of Antihypertensive Drug Use and New-onset Osteoporotic Fracture in Elderly Patients: A Population-based Longitudinal Cohort Study.

PubMed

Chen, Hung-Yi; Ma, Kai-Yan; Hsieh, Pei-Ling; Liou, Yi-Sheng; Jong, Gwo-Ping

2016-12-20

Antihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up. In this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65-80 years from January 2002 to December 2012 and non-NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HR s) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group. A total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01-2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49-0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF. Elderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

Potentially Inappropriate Antihypertensive Prescriptions to Elderly Patients: Results of a Prospective, Observational Study.

PubMed

Márquez, Paola H Ponte; Torres, Olga H; San-José, Anonio; Vidal, Xavier; Agustí, Antonia; Formiga, Francesc; López-Soto, Alfonso; Ramírez-Duque, Nieves; Fernández-Moyano, Antonio; Garcia-Moreno, Juana; Arroyo, Juan A; Ruiz, Domingo

2017-06-01

Previous studies of antihypertensive treatment of older patients have focused on blood pressure control, cardiovascular risk or adherence, whereas data on inappropriate antihypertensive prescriptions to older patients are scarce. The aim of the study was to assess inappropriate antihypertensive prescriptions to older patients. An observational, prospective multicentric study was conducted to assess potentially inappropriate prescription of antihypertensive drugs, in patients aged 75 years and older with arterial hypertension (HTN), in the month prior to hospital admission, using four instruments: Beers, Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert Doctors to the Right Treatment (START) and Assessing Care of Vulnerable Elders 3 (ACOVE-3). Primary care and hospital electronic records were reviewed for HTN diagnoses, antihypertensive treatment and blood pressure readings. Of 672 patients, 532 (median age 85 years, 56% female) had HTN. 21.6% received antihypertensive monotherapy, 4.7% received no hypertensive treatment, and the remainder received a combination of antihypertensive therapies. The most frequently prescribed antihypertensive drugs were diuretics (53.5%), angiotensin-converting enzyme inhibitors (ACEIs) (41%), calcium antagonists (32.2%), angiotensin receptor blockers (29.7%) and beta-blockers (29.7%). Potentially inappropriate prescription was observed in 51.3% of patients (27.8% overprescription and 35% underprescription). The most frequent inappropriately prescribed drugs were calcium antagonists (overprescribed), ACEIs and beta-blockers (underprescribed). ACEI and beta-blocker underprescriptions were independently associated with heart failure admissions [beta-blockers odds ratio (OR) 0.53, 95% confidence interval (CI) 0.39-0.71, p < 0.001; ACEIs OR 0.50, 95% CI 0.36-0.70, p < 0.001]. Potentially inappropriate prescription was detected in more than half of patients receiving antihypertensive treatment. Underprescription was more frequent than overprescription. ACEIs and beta-blockers were frequently underprescribed and were associated with heart failure admissions.

Advertising of antihypertensive medicines and prescription sales in Australia.

PubMed

Vitry, A; Lai, Y H

2009-11-01

Drug promotion is one of the main factors that influence prescribing practices, but there are limited data available to quantify the relationship between drug advertising and prescription sales. To investigate the relationship between advertising for antihypertensive medicines and prescription sales in Australia between 1993 and 2002. Retrospective observational study. Advertising trends were monitored by counting the number of advertisements published in three Australian medical journals. Monthly prescription dispensing data were obtained from Drug Utilisation Sub-Committee and expressed as numbers of defined daily doses/1000 inhabitants/day. Linear regression and cross-correlations of time series were used in the analysis. The drug classes the most heavily advertised, angiotensin-converting enzyme inhibitors and calcium channel blockers, were also the most prescribed during the study period, while the drugs the least advertised, thiazide diuretics and beta-blockers, were the least used. In 5 of the 7 main antihypertensive classes, the product the most advertised was also the most prescribed. Other factors, such as the publication of large clinical trials, may have also influenced prescribing patterns. Prescription sales of antihypertensives in Australia are correlated with promotional advertising. The newest and most expensive medicines may be chosen over older effective drugs by prescribers. New policies on drug promotion control need to be developed.

Pharmacological interventions for hypertension in children.

PubMed

Chaturvedi, Swasti; Lipszyc, Deborah H; Licht, Christoph; Craig, Jonathan C; Parekh, Rulan

2014-02-01

Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender.  Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies.Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

PubMed

Holmqvist, Lina; Boström, Kristina Bengtsson; Kahan, Thomas; Schiöler, Linus; Qvarnström, Miriam; Wettermark, Björn; Hjerpe, Per; Hasselström, Jan; Manhem, Karin

2018-03-01

To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (<140/90 mm Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood pressure. The proportion of patients with PDC ≥ 80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). Patients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of telmisartan and losartan on irradiated testes.

PubMed

da Silva Mansano, Naira; Jorge, Isabela Fernandes; Chies, Agnaldo Bruno; Viani, Gustavo Arruda; Spadella, Maria Angélica

2018-02-01

To analyze the effects of radiation on the reproductive tissue of male Wistar rats and to evaluate whether treatment with the Ang II AT1 receptor antagonists telmisartan and losartan mitigate the dysfunctions resulting from this exposure. Rats were randomly divided into groups: Control, Irradiated, Telmisartan, Losartan, Irradiated+Telmisartan, and Irradiated+Losartan. Single dose of 5Gy was administered directly into the scrotum, followed by treatment with telmisartan (12mg/kg/day) or losartan (34mg/kg/two times/day) for 60days. Testicular function parameters were evaluated from spermatozoa of the vas deferens. Testes were processed for histopathological and morphometric-stereological analysis. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was evaluated. Radiation significantly reduced sperm motility, concentration, vitality, and increased the number of abnormal spermatozoa. Telmisartan and losartan did not significantly prevent these radiation-induced disorders. Seminiferous tubules were atrophied in both untreated and treated irradiated testes, and exhibited vacuoles, increased interstitial tissue and high number of blood vessels. However, several seminiferous tubules in recuperation were founded among damaged tubules in the testes of treated animals. The PCNA immunohistochemistry confirmed these outcomes. PCNA-positive cells were detected in dividing spermatogonia and spermatocytes from irradiated telmisartan and losartan treated rats whereas in the only-irradiated group, PCNA staining was observed in the nuclei of only the surviving spermatogonia. Under these experimental conditions, the testicular function parameters showed that radiation produced marked damage that was not reversed by treatments. However, gonadal restructuring and recovery of spermatogenesis in treated animals may to reflect attenuation of radiation-induced damages and potential start of recovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.

PubMed

Teo, Koon; Yusuf, Salim; Sleight, Peter; Anderson, Craig; Mookadam, Farouk; Ramos, Barbara; Hilbrich, Lutz; Pogue, Janice; Schumacher, Helmut

2004-07-01

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

PubMed

Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

2018-01-01

A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study

PubMed Central

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; Keyser, Jacques De; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2009-01-01

Summary Background The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Methods Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NTC00153062. Findings 20 332 patients (mean age 66 years) were randomised and followed-up for a median of 2·4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0·38), or with telmisartan versus placebo (p=0·61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Interpretation Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan. Funding Boehringer Ingelheim; Bayer-Schering Pharma (in selected countries); GlaxoSmithKline (in selected countries). PMID:18757238

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis.

PubMed

Espinosa, Angel; Ripollés-Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug's ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05-0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.

Angiotensin converting enzyme inhibition in clinical practice. A re-examination of stepped-care: a retrospective and a prospective.

PubMed

Zanchetti, A

1985-01-01

Diuretics have so far enjoyed a prominent position in all stepped-care programs, as the preferred first choice drug in most American schemes or as an alternative first choice drug with respect to beta-blockers in the WHO scheme. Among various reasons for this prominence has been that antihypertensive drugs available until recently all gradually led to sodium and water retention, and therefore required to be combined with a diuretic. This is no longer true: several antihypertensive agents are available now that do not require combination with diuretics, these new agents including not only beta-blockers but also angiotensin-converting enzyme (ACE) inhibitors and calcium entry blockers. Furthermore, some concern about the metabolic effects of diuretics has recently been raised, especially because of the failure to prevent coronary heart disease by the current diuretic-based antihypertensive regimens. Without denying the importance that diuretics have had in the past in making antihypertensive therapy successful and their continuing essential role in treating severe hypertension, it is likely, in my opinion, that in future years diuretics are going to be more often used as agents of second choice, mostly in combination with beta-blockers, ACE inhibitors, and, perhaps, some of the calcium blockers. In conclusion, although opinions of various experts about the sequence of choices between antihypertensive drugs may obviously differ, there is no doubt that the addition of new classes of effective agents, such as the ACE inhibitors and the calcium entry blockers, is making antihypertensive therapy more flexible and more easily suitable to the needs of individual patients.

Antihypertensive drugs for elderly patients: a cross- sectional study

PubMed Central

Lim, Ka Keat; Sivasampu, Sheamini; Khoo, Ee Ming

2015-01-01

INTRODUCTION As the population ages, the prevalence of hypertension also increases. Although primary care is usually the patient’s first point of contact for healthcare, little is known about the management of hypertension among elderly patients at the primary care level. This study aimed to determine the antihypertensive prescription trend for elderly patients, the predictors of antihypertensive use and any inappropriate prescribing practices in both public and private primary care settings. METHODS Data on patient demographics, diagnosis, prescription pattern, payment mode and follow-up was extracted from a cross-sectional study involving 122 public primary care clinics and 652 private primary care clinics in Malaysia. Encounters with hypertensive patients aged ≥ 60 years were included. RESULTS A total of 1,017 antihypertensive medications were prescribed – calcium channel blockers (27.1%), beta blockers (25.5%), diuretics (23.3%), angiotensin-converting enzyme inhibitors (14.9%) and angiotensin receptor blockers (6.3%). Out of the 614 patient encounters, 53.1% of the patients were prescribed monotherapy, 31.6% were prescribed dual therapy, 12.2% triple therapy, 2.8% quadruple therapy and 0.3% quintuple therapy. Type of primary care clinic and payment mode were significant predictors for the prescription of combination therapy and fixed-dose combination therapy, respectively. Four types of inappropriate prescriptions were identified. CONCLUSION Calcium channel blockers were the most common antihypertensive drug prescribed and more than half of the elderly patients were on monotherapy. Antihypertensive drug prescription was found to be associated with the type of primary care clinic and the payment mode, suggesting that prescription is influenced by the cost of the drug. PMID:25597751

Changes in Antihypertensive Therapy After Renal Transplantation.

PubMed

Villanego, F; Moreno, A; Wu, J; Naranjo, J; Delgado, A; Cazorla, J M; Garcia, T; Mazuecos, A

2018-03-01

Post-transplant hypertension is extremely frequent, occurring in 60% to 90% of cases. It is involved in the pathogenesis of chronic graft dysfunction and patient survival. We sought to describe changes in antihypertensive therapy after renal transplantation (RT) depending on the type of pretransplant renal replacement therapy (RRT), hemodialysis (HD) or peritoneal dialysis (PD). We performed a retrospective cohort study of RT patients who were divided into 2 groups according to the type of pretransplant RRT (HD group: 69 patients; PD group: 38 patients). Patients with a diagnosis of nonessential hypertension etiology, diagnosis of renal artery stenosis of the graft, active urologic complications, and history of acute graft rejection were excluded. Variables related to chronic kidney disease and RT as well as antihypertensive therapy were studied. PD patients had reduced number of antihypertensive drugs at 1 month after RT (1.39 ± 1.03) compared with pre-RT (2.16 ± 1.30; P = .001), a trend that was maintained at 6 months (1.70 ± 1.18; P = .06). In HD group, the number of antihypertensive drugs increased at 6 months after RT (1.59 ± 1.17) compared with pretransplant (1.15 ± 1.13; P = .027). The use of calcium channel blockers increased by 10.2% by 1 month (P = .071) and 9.2% (P = .036) by 6 months after RT. By 1 month after RT, antihypertensive therapy was reduced. Calcium channel blockers were the most common drug group, although it is usually necessary to use more than 1 drug. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of salt supplementation on the albuminuric response to telmisartan with or without hydrochlorothiazide therapy in hypertensive patients with type 2 diabetes are modulated by habitual dietary salt intake.

PubMed

Ekinci, Elif I; Thomas, Georgina; Thomas, David; Johnson, Cameron; Macisaac, Richard J; Houlihan, Christine A; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

2009-08-01

OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; <100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; >200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response.

Effects of Salt Supplementation on the Albuminuric Response to Telmisartan With or Without Hydrochlorothiazide Therapy in Hypertensive Patients With Type 2 Diabetes Are Modulated by Habitual Dietary Salt Intake

PubMed Central

Ekinci, Elif I.; Thomas, Georgina; Thomas, David; Johnson, Cameron; MacIsaac, Richard J.; Houlihan, Christine A.; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

2009-01-01

OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; <100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; >200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response. PMID:19549737

The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.

PubMed

Czechowska, G; Celinski, K; Korolczuk, A; Wojcicka, G; Dudka, J; Bojarska, A; Madro, A; Brzozowski, T

2016-08-01

It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone. Chronic treatment with losartan and telmisartan was associated with a significant reduction in the activity of alkaline phosphatase, and decreased concentrations of tumor necrosis factor-alpha and transforming growth factor beta-1 compared to controls. We also found a significant reduction interleukin-6 in rats receiving telmisartan (P < 0.05) but not losartan. Both treatments increased the concentration of liver glutathione along with a concomitant decrease of GSSG compared to controls. In addition, increased paraoxonase 1 activity was observed in the serum of rats receiving telmisartan group compared to the TAA alone controls. Finally, histological evaluation of liver sections revealed losartan and telmisartan treatment was associated with reduced inflammation and liver fibrosis. Taken together, these results indicate that both telmisartan and losartan have anti-inflammatory and anti-oxidative properties in the TAA model of liver fibrosis. These finding add support to a growing body of literature indicating a potentially important role for the angiotensin system in liver fibrosis and indicate angiotensin antagonists may be useful agents for fibrosis treatment.

Clinical and Demographic Characteristics Associated With Suboptimal Primary Stroke and Transient Ischemic Attack Prevention: Retrospective Analysis.

PubMed

Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Finnikin, Samuel; Marshall, Tom

2018-03-01

Primary prevention of stroke and transient ischemic attack (TIA) is important to reduce the burden of these conditions; however, prescribing of prevention drugs is suboptimal. We aimed to identify individual clinical and demographic characteristics associated with potential missed opportunities for prevention therapy with lipid-lowering, anticoagulant, or antihypertensive drugs before stroke/TIA. We analyzed anonymized electronic primary care records from a UK primary care database that covers 561 family practices. Patients with first-ever stroke/TIA, ≥18 years, with diagnosis between January 1, 2009, and December 31, 2013, were included. Missed opportunities for prevention were defined as people with clinical indications for lipid-lowering, anticoagulant, or antihypertensive drugs but not prescribed these drugs before their stroke/TIA. Mixed-effect logistic regression models evaluated the relationship between missed opportunities and individual clinical/demographic characteristics. The inclusion criteria were met by 29 043 people with stroke/TIA. Patients with coronary heart disease, chronic kidney disease, peripheral arterial disease, or diabetes mellitus were at less risk of a missed opportunity for prescription of lipid-lowering and antihypertensive drugs. However, patients with a 10-year cardiovascular disease risk ≥20% but without these diagnoses had increased risk of having a missed opportunity for prescription of lipid-lowering drugs or antihypertensive drugs. Women were less likely to be prescribed anticoagulants but more likely to be prescribed antihypertensive drugs. The elderly (≥85 years of age) were less likely to be prescribed all 3 prevention drugs, compared with people aged 75 to 79 years. Knowing the patient characteristics predictive of missed opportunities for stroke prevention may help primary care identify and appropriately manage these patients. Improving the management of these groups may reduce their risk and potentially prevent large number of future strokes and TIAs in the population. © 2018 American Heart Association, Inc.

Alpha1-adrenergic blockers: current usage considerations.

PubMed

Sica, Domenic A

2005-12-01

Alpha1-adrenergic-blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. These compounds are most effective in patients in the upright position, reducing systolic and diastolic pressures by 8%-10%. Alpha1-adrenergic-blocking drugs incrementally reduce blood pressure when combined with most drug classes and are the only antihypertensive drug class to improve plasma lipid profiles. Alpha1-adrenergic-blocking drugs are also accepted as important elements of the treatment plan for symptomatic benign prostatic hypertrophy. Dose escalation of an alpha1-adrenergic-blocking drug can trigger renal Na+ retention, and the ensuing volume expansion can attenuate its blood pressure-lowering effect. Orthostatic hypotension can occur with these compounds, particularly when a patient is volume-contracted. Dizziness, headache, and drowsiness are common side effects with alpha1-adrenergic blockers. A modest decline in the use of doxazosin and other alpha1-adrenergic-blocking drugs has occurred coincident to the early termination of the doxazosin treatment arm in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Effectiveness, safety and cost of drug substitution in hypertension

PubMed Central

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-01-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

Effectiveness, safety and cost of drug substitution in hypertension.

PubMed

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-09-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

PubMed Central

Espinosa, Angel; Ripollés–Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D.; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Background Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Methods Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Results Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Conclusions Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence. PMID:27018586

Applying a "Big Data" Literature System to Recommend Antihypertensive Drugs for Hypertension Patients with Diabetes Mellitus.

PubMed

Shu, Jing-Xian; Li, Ying; He, Ting; Chen, Ling; Li, Xue; Zou, Lin-Lin; Yin, Lu; Li, Xiao-Hui; Wang, An-Li; Liu, Xing; Yuan, Hong

2018-01-07

BACKGROUND The explosive increase in medical literature has changed therapeutic strategies, but it is challenging for physicians to keep up-to-date on the medical literature. Scientific literature data mining on a large-scale of can be used to refresh physician knowledge and better improve the quality of disease treatment. MATERIAL AND METHODS This paper reports on a reformulated version of a data mining method called MedRank, which is a network-based algorithm that ranks therapy for a target disease based on the MEDLINE literature database. MedRank algorithm input for this study was a clear definition of the disease model; the algorithm output was the accurate recommendation of antihypertensive drugs. Hypertension with diabetes mellitus was chosen as the input disease model. The ranking output of antihypertensive drugs are based on the Joint National Committee (JNC) guidelines, one through eight, and the publication dates, ≤1977, ≤1980, ≤1984, ≤1988, ≤1993, ≤1997, ≤2003, and ≤2013. The McNemar's test was used to evaluate the efficacy of MedRank based on specific JNC guidelines. RESULTS The ranking order of antihypertensive drugs changed with the date of the published literature, and the MedRank algorithm drug recommendations had excellent consistency with the JNC guidelines in 2013 (P=1.00 from McNemar's test, Kappa=0.78, P=1.00). Moreover, the Kappa index increased over time. Sensitivity was better than specificity for MedRank; in addition, sensitivity was maintained at a high level, and specificity increased from 1997 to 2013. CONCLUSIONS The use of MedRank in ranking medical literature on hypertension with diabetes mellitus in our study suggests possible application in clinical practice; it is a potential method for supporting antihypertensive drug-prescription decisions.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination

PubMed Central

Paz, Marco A.; de-La-Sierra, Alejandro; Sáez, Marc; Barceló, María Antonia; Rodríguez, Juan José; Castro, Sonia; Lagarón, Cristina; Garrido, Josep M; Vera, Pilar; Coll-de-Tuero, Gabriel

2016-01-01

Abstract Background: The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients’ characteristics associated with best performance of the drugs will improve management of hypertensive patients. Objective: To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. Study eligibility criteria: Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data. Study appraisal and synthesis methods: Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework. Main Outcome(s) and Measure(s): Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. Results: Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases. Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m2 were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats. Limitations: Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses. Conclusions and implications: Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised. PMID:27472680

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Haiyan; Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji, Jilin; Yamamoto, Naoki

2007-12-28

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions bymore » down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.« less

Telmisartan

MedlinePlus

... or in combination with other medications to treat high blood pressure. Telmisartan is also used to decrease the chance ... smoothly and the heart to pump more efficiently.High blood pressure is a common condition and when not treated, ...

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Prospectives of Antihypertensive Nano-ceuticals as Alternative Therapeutics.

PubMed

Niaz, Taskeen; Hafeez, Zeeshan; Imran, Muhammad

2017-01-01

Global death rate due to cardiovascular diseases (CVDs) is highest as compared to other ailments. Principal risk factor associated with CVDs is hypertension. Major classes of current antihypertensive (AHT) therapies include angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). All these antihypertensive therapeutic drugs have low oral bioavailability and can induce upper respiratory tract abstraction, angioedema, reflex tachycardia and extreme hypotensive effect after oral administration which can cause lethal effects in patients with heart diseases. Controlled and targeted release by using antihypertensive nano-medicines can provide better solution to overcome above-mentioned side effects. Scientific evolution towards the development of biopolymer based nano-carrier systems has unlocked new horizons for safe and/or edible nano drug delivery systems. In this article, we have reviewed in detail various mechanisms of AHT drugs, major draw backs associated with current therapeutic strategies, and the advantages of AHT nano-medicines over conventional drugs. Furthermore, recent reports of bio-based nano/micro -carrier systems with different AHT drugs have been analyzed with their key features. In depth review has been presented for chitosan as a potential carrier of AHT drugs due to its distinctive properties comprising muco-adhesive attribute, permeation enhancement as well as its biocompatible and biodegradable nature. Chitosan based novel AHT nano-ceuticals can improve oral bioavailability, reduce hydrophobicity and increase the plasma half-life of AHT drugs by their sustained release in lower part of the GIT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Generic drugs and the consumption trends of antihypertensives in Morocco].

PubMed

Berrada El Azizi, Ghizlane; Ahid, Samir; Ghanname, Imane; Ghannam, Imane; Belaiche, Abdelmajid; Hassar, Mohammed; Cherrah, Yahia

2013-01-01

To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population. © 2013 Société Française de Pharmacologie et de Thérapeutique.

A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations

PubMed Central

Alhazmi, Hassan A.; Alnami, Ahmed M.; Arishi, Mohammed A. A.; Alameer, Raad K.; Al Bratty, Mohammed; Rehman, Zia ur; Javed, Sadique A.; Arbab, Ismail A.

2017-01-01

The aim of this study was to develop and validate a fast and simple reversed-phase HPLC method for simultaneous determination of four cardiovascular agents—atorvastatin, simvastatin, telmisartan and irbesartan in bulk drugs and tablet oral dosage forms. The chromatographic separation was accomplished by using Symmetry C18 column (75 mm × 4.6 mm; 3.5 μ) with a mobile phase consisting of ammonium acetate buffer (10 mM; pH 4.0) and acetonitrile in a ratio 40:60 v/v. Flow rate was maintained at 1 mL/min up to 3.5 min, and then suddenly changed to 2 mL/min till the end of the run (7.5 min). The data was acquired using ultraviolet detector monitored at 220 nm. The method was validated for linearity, precision, accuracy and specificity. The developed method has shown excellent linearity (R2 > 0.999) over the concentration range of 1–16 µg/mL. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.189–0.190 and 0.603–0.630 µg/mL, respectively. Inter-day and intra-day accuracy and precision data were recorded in the acceptable limits. The new method has successfully been applied for quantification of all four drugs in their tablet dosage forms with percent recovery within 100 ± 2%. PMID:29257120

Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp; Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui; Mikami, Daisuke

Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area bymore » producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.« less

South African hypertension guideline 2011.

PubMed

Seedat, Y K; Rayner, B L

2011-12-14

Extensive data from randomised controlled trials have shown the benefit of treating hypertension. The target blood pressure (BP) for antihypertensive management is systolic <140 mmHg and diastolic <90 mmHg with minimal or no drug side-effects; however, stricter BP control is required for patients with end-organ damage, co-existing risk factors and co-morbidity, e.g. diabetes mellitus. The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month. Co-existent risk factors should also be controlled. Benefits of management include reduced risks of stroke, cardiac failure, chronic kidney disease and coronary heart disease. The correct BP measurement procedure is described, and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated. The total cardiovascular disease risk profile should be determined for all patients to inform management strategies. Lifestyle modification and patient education are cornerstones in the management of every patient. Major indications, precautions and contra-indications to each recommended antihypertensive drug are listed. Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg. First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics, calcium channel blockers (CCBs) or angiotensin-converting enzyme inhibitors (ACE-Is) (or ARBs - angiotensin II receptor blockers). If the target BP is not obtained, a second antihypertensive should be added from the aforementioned list. If the target BP is still not met, the third remaining antihypertensive agent should be used. In black patients either thiazide-like diuretics or CCBs can be used initially, because response rates are better than with ACE-Is or β-blockers. In treating resistant hypertension, a centrally acting drug, vasodilator, α-blocker, spironolactone or β-locker should be added. This guideline includes management of specific situations, i.e. hypertensive emergency and urgency, severe hypertension with target organ damage, hypertension in diabetes mellitus, resistant hypertension, fixed drug combinations, new trials in hypertension, and interactions of antihypertensive agents with other drugs. The guideline was developed by the Southern African Hypertension Society.

Short-term dietary salt supplementation blunts telmisartan induced increases in plasma renin activity in hypertensive patients with type 2 diabetes mellitus.

PubMed

Chen, Angela X; Jerums, George; Baqar, Sara; Lambert, Elisabeth; Somarajah, Goji; Thomas, Georgina; O'Callaghan, Christopher; MacIsaac, Richard J; Ekinci, Elif I

2015-09-01

Current guidelines recommend low dietary salt intake (LDS) in patients with diabetes to reduce blood pressure (BP). However, low salt intake has been associated with higher mortality rates in people with diabetes. Our aim is to examine the effect of angiotensin II receptor blocker (ARB), telmisartan, with and without dietary sodium chloride (NaCl) supplementation, on BP [mean arterial pressure (MAP)], plasma renin activity (PRA), serum aldosterone level and estimated glomerular filtration rate (eGFR) in hypertensive patients with type 2 diabetes. In a randomized, double-blind, placebo-controlled study (RCT), 28 patients with type 2 diabetes, treated with telmisartan (40 mg daily), received 2 weeks of placebo or NaCl capsules (100 mmol/24 h). Following a 6-week washout, the protocol was repeated in reverse. Twenty-four-hour urinary sodium excretion (24hUNa), ambulatory BP (ABP) monitoring and blood tests were performed before and after each study phase. The telmisartan-associated increase in PRA was blunted by approximately 50% during salt supplementation compared with placebo; median PRA was 2.3 μg/l/h with placebo compared with 1.7 μg/l/h with salt (P<0.001). A trend towards blunting of ARB induced increases in serum aldosterone was also demonstrated. Salt supplementation significantly reduced the MAP lowering effects of telmisartan (P<0.05). The present study demonstrates that salt supplementation blunts the telmisartan induced increase in PRA in patients with type 2 diabetes. © 2015 Authors; published by Portland Press Limited.

[What are the pharmacological options for treating resistant hypertension?

PubMed

Martell-Claros, N; Abad-Cardiel, M

2017-01-01

When treating a patient with resistant hypertension therapy should be optimize in order to prescribe three antihypertensive drugs at full doses, being powerful drugs, having 24-hour coverage, and showing synergistic effects. Diuretic therapy is of special relevance. The fourth drug should be an aldosterone antagonists. In the case of intolerance, or when control is not achieved, drugs from other type of antihypertensive drugs should be, sometimes allowing adequate blood pressure control. Copyright © 2017 Sociedad Española de Hipertension-Liga Española para la Lucha de la Hipertensión Arterial (SEH-LELHA). Publicado por Elsevier España, S.L.U. All rights reserved.

Statins, the renin-angiotensin-aldosterone system and hypertension - a tale of another beneficial effect of statins.

PubMed

Drapala, Adrian; Sikora, Mariusz; Ufnal, Marcin

2014-09-01

Statins, a class of lipid lowering drugs, decrease mortality associated with cardiovascular events. As hypercholesterolemia is often accompanied by hypertension, a large number of patients receive therapy with statins and antihypertensive drugs which act via the renin-angiotensin-aldosterone system (RAAS). New guidelines published by the American Heart Association and American College of Cardiology on the treatment of dyslipidaemia and the reduction of atherosclerotic cardiovascular risk, which use a risk prediction algorithm based on risk factors such as hypertension but not low-density lipoprotein (LDL) level, may even further increase the number of patients receiving such concomitant therapy. In this paper we review studies on an interaction between statins, the RAAS and antihypertensive drugs acting via the RAAS. Accumulating evidence suggests that the combination of statins and drugs affecting the RAAS exerts a synergistic effect on the circulatory system. For example, statins may lower arterial blood pressure and augment the effect of antihypertensive drugs acting via the RAAS. Statins may interact with the RAAS in a number of ways i.e. to decrease the expression of receptors for angiotensin II (Ang II), inhibit the Ang II-dependent intracellular signalling, reduce the RAAS-dependent oxidative stress and inflammation as well as inhibit the synthesis of Ang II and aldosterone. Although statins given either alone or together with antihypertensive drugs acting via the RAAS may lower arterial blood pressure, further research is needed to evaluate the mechanisms and their therapeutic significance. © The Author(s) 2014.

Psychiatric side effects of antihypertensive drugs other than reserpine.

PubMed

Paykel, E S; Fleminger, R; Watson, J P

1982-02-01

The psychiatric side effects of the major antihypertensive drugs other than reserpine are reviewed, including centrally acting drugs such as methyldopa and clonidine, peripheral adrenergic drugs such as guanethidine, beta-adrenoceptor blockers such as propranolol, and diuretics. Problems with differential diagnosis and with the interpretation of case reports make assessment of psychiatric side effects difficult. Sedation and sleep disturbances are the most common side effects, occurring with methyldopa, clonidine, and propranolol. Only methyldopa is clearly associated with depression. Other reported effects are toxic confusional states and psychotic reactions. These are rare, however, and no clear patterns of development have been recognized.

Can Walmart make us healthier? Prescription drug prices and health care utilization.

PubMed

Borrescio-Higa, Florencia

2015-12-01

This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in-differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent. Copyright © 2015 Elsevier B.V. All rights reserved.

Angiotensin-converting enzyme inhibitor use by older adults is associated with greater functional responses to exercise.

PubMed

Buford, Thomas W; Manini, Todd M; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D; Nayfield, Susan; Stafford, Randall S; Church, Timothy S; Pahor, Marco; Carter, Christy S

2012-07-01

To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. Four academic research centers within the United States. Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91).The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Angiotensin-Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise

PubMed Central

Buford, Thomas W.; Manini, Todd M.; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D.; Nayfield, Susan; Stafford, Randall S.; Church, Timothy S.; Pahor, Marco; Carter, Christy S.

2013-01-01

OBJECTIVES To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. DESIGN Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. SETTING Four academic research centers within the United States. PARTICIPANTS Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. INTERVENTION A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). MEASUREMENTS Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). RESULTS Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). CONCLUSION For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. PMID:22726232

Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

A convergent approach to the total synthesis of telmisartan via a Suzuki cross-coupling reaction between two functionalized benzimidazoles.

PubMed

Martin, Alex D; Siamaki, Ali R; Belecki, Katherine; Gupton, B Frank

2015-02-06

A direct and efficient total synthesis has been developed for telmisartan, a widely prescribed treatment for hypertension. This approach brings together two functionalized benzimidazoles using a high-yielding Suzuki reaction that can be catalyzed by either a homogeneous palladium source or graphene-supported palladium nanoparticles. The ability to perform the cross-coupling reaction was facilitated by the regio-controlled preparation of the 2-bromo-1-methylbenzimidazole precursor. This convergent approach provides telmisartan in an overall yield of 72% while circumventing many issues associated with previously reported processes.

Effects of antihypertensive agents on sexual function.

PubMed

Weiss, R J

1991-12-01

Patient compliance with antihypertensive therapy can be improved by minimizing drug-induced sexual dysfunction. Impotence, decreased libido, impaired ejaculation and gynecomastia are potential side effects, depending on the agent prescribed. Centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers and potassium-sparing diuretics are the drugs most often associated with sexual dysfunction. Thiazide diuretics cause impotence but may otherwise play a minimal role in sexual dysfunction. Alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel blockers have little adverse effect on sexual function. It is important to obtain an adequate history before and after initiating therapy. If sexual dysfunction develops in a patient, a different class of medication can be tried.

Pharmacotherapy of Hypertension in Chronic Dialysis Patients

PubMed Central

Georgianos, Panagiotis I.

2016-01-01

Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area. PMID:27797886

Nonsteroidal anti-inflammatory drugs and antihypertensives: how do they relate?

PubMed

Khatchadourian, Zovinar Der; Moreno-Hay, Isabel; de Leeuw, Reny

2014-06-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available as over-the-counter medications, despite their numerous side effects and drug interactions. The aim of this article is to increase awareness of the hypertensive potential of NSAIDs and their interference with antihypertensives. Patients with hypertension appear to be more susceptible than normotensive individuals to the blood pressure-increasing effect of NSAIDs. Most studies have found that short-term use of NSAIDs does not pose a major risk for hypertension or increase in cardiovascular disease in healthy individuals. The calcium channel blockers and β-blockers seem to be least affected by the concomitant use of NSAIDs. A dentist must weigh the benefits and disadvantages of using NSAIDs in patients taking antihypertensive drugs. For those who may be at greater risk, such as patients with hypertension and the elderly, careful selection of the class of NSAID and close monitoring are appropriate measures, especially if long-term use is anticipated. Copyright © 2014 Elsevier Inc. All rights reserved.

The economic returns of pediatric clinical trials of anti-hypertensive drugs

PubMed Central

Baker-Smith, Carissa M.; Benjamin, Daniel K.; Grabowski, Henry G.; Reid, Elizabeth D.; Mangum, Barry; Goldsmith, John V.; Murphy, M. Dianne; Edwards, Rex; Eisenstein, Eric L.; Sun, Jessica; Califf, Robert M.; Li, Jennifer S.

2012-01-01

Background Congress has authorized the U.S. Food and Drug Administration (FDA) to provide industry sponsors with a 6-month extension of drug marketing rights under the Pediatric Exclusivity Provision if FDA-requested pediatric drug trials are conducted. The cost and economic return of pediatric exclusivity to industry sponsors has been shown to be highly variable. We sought to determine the cost of performing pediatric exclusivity trials within a single therapeutic area and the subsequent economic return to industry sponsors. Methods We evaluated 9 orally administered anti-hypertensive drugs submitted to the FDA under the Pediatric Exclusivity Provision from 1997–2004 and obtained key elements of the clinical trial designs and operations. Estimates of the costs of performing the studies were generated and converted into after-tax cash outflow. Market sales were obtained and converted into after-tax inflows based on 6 months of additional patent protection. Net economic return and net return-to-cost ratios were determined for each drug. Results Of the 9 anti-hypertensive agents studied, an average of 2 studies per drug was performed, including at least 1 pharmacokinetic study and a safety and efficacy study. The median cost of completing a pharmacokinetic trial was $862,000 (range: $556,000–1.8 million). The median cost of performing safety and efficacy trials for these agents was $4.3 million (range: $2.1 million–12.9 million). The ratio of net economic return to cost was 17 (range: 4–64.7). Conclusion We found that, within a cohort of anti-hypertensive drugs, the Pediatric Exclusivity Provision has generated highly variable, yet lucrative returns to industry sponsors. PMID:18926149

ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

EPA Science Inventory

Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

Angiotensin II receptor type 1--a novel target for preventing neonatal meningitis in mice by Escherichia coli K1.

PubMed

Krishnan, Subramanian; Shanmuganathan, Muthusamy V; Behenna, Douglas; Stoltz, Brian M; Prasadarao, Nemani V

2014-02-01

The increasing incidence of Escherichia coli K1 meningitis due to escalating antibiotic resistance warrants alternate treatment options to prevent this deadly disease. We screened a library of small molecules from the National Institutes of Health clinical collection and identified telmisartan, an angiotensin II receptor type 1 (AT1R) blocker, as a potent inhibitor of E. coli invasion into human brain microvascular endothelial cells (HBMECs). Immunoprecipitation studies revealed that AT1R associates with endothelial cell gp96, the receptor in HBMECs for E. coli outer membrane protein A. HBMECs pretreated with telmisartan or transfected with AT1R small interfering RNA were resistant to E. coli invasion because of downregulation of protein kinase C-α phosphorylation. Administration of a soluble derivative of telmisartan to newborn mice before infection with E. coli prevented the onset of meningitis and suppressed neutrophil infiltration and glial cell migration in the brain. Therefore, telmisartan has potential as an alternate treatment option for preventing E. coli meningitis.

Thiazide diuretics in the treatment of hypertension: an update.

PubMed

Salvetti, Antonio; Ghiadoni, Lorenzo

2006-04-01

Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.

Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: a population-based cohort study

PubMed Central

Antoniou, Tony; Camacho, Ximena; Yao, Zhan; Gomes, Tara; Juurlink, David N.; Mamdani, Muhammad M.

2013-01-01

Background: Telmisartan, unlike other angiotensin-receptor blockers, is a partial agonist of peroxisome proliferator–activated receptor-γ, a property that has been associated with improvements in surrogate markers of cardiovascular health in small trials involving patients with diabetes. However, whether this property translates into a reduced risk of cardiovascular events and death in these patients is unknown. We sought to explore the risk of myocardial infarction, stroke and heart failure in patients with diabetes who were taking telmisartan relative to the risk of these events occurring in patients taking other angiotensin-receptor blockers. Methods: We conducted a population-based, retrospective cohort study of Ontario residents with diabetes aged 66 years and older who started treatment with candesartan, irbesartan, losartan, telmisartan or valsartan between Apr. 1, 2001, and Mar. 31, 2011. Our primary outcome was a composite of admission to hospital for acute myocardial infarction, stroke or heart failure. We examined each outcome individually in secondary analyses, in addition to all-cause mortality. Results: We identified 54 186 patients with diabetes who started taking an angiotensin-receptor blocker during the study period. After multivariable adjustment, patients who took either telmisartan (adjusted hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74–0.97) or valsartan (adjusted HR 0.86, 95% CI 0.77–0.95) had a lower risk of the composite outcome compared with patients who took irbesartan. In contrast, no significant difference in risk was seen between other angiotensin-receptor blockers and irbesartan. In secondary analyses, we found a reduced risk of admission to hospital for heart failure with telmisartan compared with irbesartan (adjusted HR 0.79, 95% CI 0.66–0.96), but no significant differences in risk were seen between angiotensin-receptor blockers in our other secondary analyses. Interpretation: Compared with other angiotensin-receptor blockers, telmisartan and valsartan were both associated with a lower risk of admission to hospital for acute myocardial infarction, stroke or heart failure among older adults with diabetes and hypertension. Telmisartan and valsartan may therefore be the preferred angiotensin-receptor blockers for use in these patients. PMID:23836857

Interventional procedures and future drug therapy for hypertension

PubMed Central

Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

PubMed

Azizi, Michel; Pereira, Helena; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Michel Halimi, Jean; Zannad, Faiez; Ormezzano, Olivier; Vaïsse, Bernard; Herpin, Daniel; Ribstein, Jean; Chamontin, Bernard; Mourad, Jean-Jacques; Ferrari, Emile; Plouin, Pierre-François; Jullien, Vincent; Sapoval, Marc; Chatellier, Gilles

2016-09-20

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2016 American Heart Association, Inc.

Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis

PubMed Central

2013-01-01

Background The prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction. In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs. Methods Claims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers’ characteristics. Results There were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers’ characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5). Conclusions For hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs. PMID:23552327

Caloric restriction or telmisartan control dyslipidemia and nephropathy in obese diabetic Zücker rats

PubMed Central

2014-01-01

Background The obese Zücker diabetic fatty male rat (ZDF:Gmi™-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy. In addition, diabetic dyslipidaemia has been linked to vascular and glomerular damage too. Dietary fat restriction is a current strategy to tackle obesity and, telmisartan, as a renoprotective agent, may mediate cholesterol efflux by activating PPARγ. To test the hypothesis that both therapeutical alternatives may influence dyslipidaemia and nephropathy in the ZDF rat, we studied their effect on development of diabetes. Methods Male Zücker Diabetic Fatty (ZDF) rats received a low-calorie diet, vehicle or telmisartan for 9 weeks. Blood samples were obtained for analyses of lipids and lipoproteins, LDL-oxidisability, HDL structural and functional properties. Urinalysis was carried out to estimate albumin loss. At the end of the experimental period, rats were sacrificed, liver extracted and APOA1 mRNA quantified. Results Results indicated that low-calorie diet and telmisartan can slower the onset of overt hyperglycaemia and renal damage assessed as albuminuria. Both interventions decreased the oxidative susceptibility of LDL and hepatic APOA1 mRNA expression but only dietary restriction lowered hyperlipidaemia. Conclusion Either a dietary or pharmacologic interventions with telmisartan have important beneficial effects in terms of LDL oxidative susceptibility and progression of albuminuria in obesity related type II diabetes. PMID:24468233

Calcium channel blockers in hypertension. Is there still a controversy?

PubMed

Izzo, Joseph L

2005-08-01

There are several reasons why no single antihypertensive drug class is ideal in all clinical situations. First, pathophysiologic heterogeneity in hypertension and diversity of mechanisms of antihypertensive drugs dictate that no single drug class can be optimally effective in all subpopulations. Second, sustained blood pressure control generally requires combination therapy to block the reflex stimulation of physiologic mechanisms that attempt to restore blood pressure to pretreatment levels. Third, while effective blood pressure control is more important than choice of initial drug in the prevention of hypertension-related morbidity and mortality, specific drug classes are indicated for optimal treatment of complications of hypertension (e.g. heart failure, kidney disease). Fourth, although antihypertensive drug side effects are uncommon, alternative strategies are required in some patients. Given these principles, past controversies regarding whether calcium channel blockers (CCBs) should be used in the treatment of hypertension become moot. CCBs are extremely effective in lowering blood pressure and in preventing stroke and cardiovascular disease. When additional blood pressure lowering is necessary to meet strict targets, CCBs may be added, even in heart failure or chronic kidney disease, where CCBs alone may not achieve optimal outcomes. Combinations of CCBs with "anti-neurohumoral" drugs such as ACE inhibitors are particularly useful to achieve sustained blood pressure control, reduce adverse effects such as edema, and improve outcomes.

Use of medications and lifestyles of hypertensive patients with high risk of cardiovascular disease in rural China.

PubMed

Zou, Guanyang; Zhang, Zhitong; Walley, John; Gong, Weiwei; Yu, Yunxian; Hu, Ruying; Yin, Jia; Yu, Min; Wei, Xiaolin

2015-01-01

Hypertension, with a global prevalence of 40%, is a risk factor for cardiovascular diseases (CVD). We conducted an exploratory study in Zhejiang China to understand the prevention of CVD among hypertensive patients with a 10 year CVD risk of 20% or higher. We assessed current practices in a rural 'township hospital' (a primary care facility), and compared them with international evidence-based practice. A questionnaire survey was conducted to examine the use of modern drugs (antihypertensive drugs, statins and aspirin) and traditional drugs, compliance to medications and lifestyle among 274 hypertensive patients aged 40-74, with a CVD risk of 20% or higher (using the Asian Equation). The majority (72%) were diagnosed with hypertension at township hospitals. Only 15% of study participants used two anti-hypertensive drugs, 0.7% took statin and 2.9% aspirin. Only 2.9% combined two types of modern drugs, while 0.4% combined three types (antihypertensives, statins and aspirin). Herbal compounds, sometimes with internationally rarely recommended drugs such as Reserpine were taken by 44%. Analysis of drug adherence showed that 9.8% had discontinued their drug therapy by themselves. 16% had missed doses and these were on less anti-hypertensive drugs than those who did not (t=-5.217, P=0.003). Of all participants, 28% currently smoked, 39% drank regularly and only 21% exercised frequently. The average salt intake per day was 7.1 (±3.8) g, while the national recommended level is 6g. The study revealed outdated and inadequate treatment and health education for hypertensive patients, especially for those who have high risk scores for CVD. There is a need to review the community-based guidelines for hypertension management. Health providers and patients should make a transition from solely treating hypertension, towards prevention of CVD. Health system issues need addressing including improving rural health insurance cover and primary care doctors' capacity to manage chronic disease patients.

Medications during pregnancy: antihypertensives and immunosuppressives.

PubMed

Umans, Jason G

2007-04-01

Use of prescription and nonprescription medications is common during pregnancy and is required in many women with underlying kidney disease or hypertension and in all with solid-organ allografts. Systematic assessment of drug safety during pregnancy is lacking, as are rigorous and comprehensive studies of pharmacokinetics and pharmacodynamics to guide drug selection and dosing across pregnancy. Renal and hepatic clearances of many drugs change markedly during pregnancy and pitfalls may complicate routine therapeutic monitoring of some drugs during pregnancy. However, available data and clinical experience allow reasonable strategies for selection and dosing of immunosuppressive agents in pregnant transplant recipients and of antihypertensive agents in women with mild or more severe hypertension complicating their pregnancies.

Accuracy of pharmaceutical advertisements in medical journals.

PubMed

Villanueva, Pilar; Peiró, Salvador; Librero, Julián; Pereiró, Inmaculada

2003-01-04

Because of the effect of the ever-growing evidence-based medicine movement on prescribing behaviour of doctors, the pharmaceutical industry incorporates bibliographical references to clinical trials that endorse their products in their advertisements. We aimed to assess whether the references about efficacy, safety, convenience, or cost of antihypertensive and lipid-lowering drugs included in advertisements supported the promotional claims. We assessed all advertisements for antihypertensive and lipid-lowering drugs published in six Spanish medical journals in 1997 that had at least one bibliographical reference. Two pairs of investigators independently reviewed the advertisements to see whether the studies quoted to endorse the advertising messages supported the corresponding claims. We identified 264 different advertisements for antihypertensive drugs and 23 different advertisements for lipid-lowering drugs. We recorded at least one reference in 31 advertisements in the antihypertensive group and at least one reference in every seven advertisements in the lipid-lowering group, providing a total of 125 promotional claims with references. We could not retrieve 23 (18%) references from monographic works and non-published data on file. 79 (63%) of the 125 references were from journals with a high impact factor; 84 (82%) of the 102 references retrieved were from randomised clinical trials. In 45 claims (44.1%; 95% CI 34.3-54.3) the promotional statement was not supported by the reference, most frequently because the slogan recommended the drug in a patient group other than that assessed in the study. Doctors should be cautious in assessment of advertisements that claim a drug has greater efficacy, safety, or convenience, even though these claims are accompanied by bibliographical references to randomised clinical trials published in reputable medical journals and seem to be evidence-based.

Medication persistence and the use of generic and brand-name blood pressure-lowering agents.

PubMed

Corrao, Giovanni; Soranna, Davide; La Vecchia, Carlo; Catapano, Alberico; Agabiti-Rosei, Enrico; Gensini, Gianfranco; Merlino, Luca; Mancia, Giuseppe

2014-05-01

Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents. The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses. Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings. Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

Relative effects of telmisartan, candesartan and losartan on alleviating arterial stiffness in patients with hypertension complicated by diabetes mellitus: an evaluation using the cardio-ankle vascular index (CAVI).

PubMed

Uehara, G; Takeda, H

2008-01-01

Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed improvement of arterial stiffness in 95 outpatients with hypertension complicated by type 2 diabetes mellitus who were treated orally for >or= 12 months with telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in the telmisartan and losartan groups CAVI did not change whereas in the candesartan group CAVI showed a statistically significant decrease of 2.70%. Although telmisartan is believed to enhance the activity of peroxisome proliferator-activated receptor (PPAR-gamma) in vitro, it did not ameliorate arterial stiffness in our patients. Candesartan, however, improved arterial stiffness independently of blood pressure lowering and without PPAR-gamma agonist action, possibly by direct action resulting from its potent affinity and binding capacity for the angiotensin II type 1 receptor. We conclude that candesartan is a potentially useful therapy against arterial stiffness in hypertensive patients with type 2 diabetes mellitus.

Angiotensin II Receptor Type 1—A Novel Target for Preventing Neonatal Meningitis in Mice by Escherichia coli K1

PubMed Central

Krishnan, Subramanian; Shanmuganathan, Muthusamy V.; Behenna, Douglas; Stoltz, Brian M.; Prasadarao, Nemani V.

2014-01-01

The increasing incidence of Escherichia coli K1 meningitis due to escalating antibiotic resistance warrants alternate treatment options to prevent this deadly disease. We screened a library of small molecules from the National Institutes of Health clinical collection and identified telmisartan, an angiotensin II receptor type 1 (AT1R) blocker, as a potent inhibitor of E. coli invasion into human brain microvascular endothelial cells (HBMECs). Immunoprecipitation studies revealed that AT1R associates with endothelial cell gp96, the receptor in HBMECs for E. coli outer membrane protein A. HBMECs pretreated with telmisartan or transfected with AT1R small interfering RNA were resistant to E. coli invasion because of downregulation of protein kinase C-α phosphorylation. Administration of a soluble derivative of telmisartan to newborn mice before infection with E. coli prevented the onset of meningitis and suppressed neutrophil infiltration and glial cell migration in the brain. Therefore, telmisartan has potential as an alternate treatment option for preventing E. coli meningitis. PMID:24041786

Perception of stress, depression, hypertension and myocardial infarction as predictors of adherence to hypertension drug treatment.

PubMed

Ljubotina, Aleksandar; Mićović, Vladimir; Kapović, Miljenko; Ljubotina, Maja; Popović, Branislava; Materljan, Eris

2014-12-01

This survey was performed to determine the relationship between the adherence to hypertension drug treatment and the perception of stress, depression, hypertension, and myocardial infarction. 300 patients with uncomplicated hyperten- sion from Rijeka, Croatia, were included (131 women, 169 men, mean age 53.5 years). Adherence to hypertension drug treatment as criterion, and the perception of stress, depression hypertension and myocardial infarction as prediclors were determined by self-assessment. Collected data were analysed using factor analysis, regression analysis, Kolmogorov-Smirnov test, chi2-test and t-test. The statistical significance was set at a probability rate of less than 5% (p < 0.05). 45.09% of women (p=0.479), and 64.08% of men (p = 0.032) were motivated to take antihypertensives. 55.79% of women (p = 0.382) and 64.78% of men (p = 0.028) had sufficient knowledge about drug treatment of hypertension. The positive predictors of motivation for taking antihypertensives were physiological disturbances and perceived potency of hypertension and the negative were perceived helplessness in stress control and negative thoughts and emotions. The positive predictors of knowledge about taking antihypertensives were perceived helplessness in stress control, perceived potency of hypertension and myocardial infarction and the negative predictors were perceived self-efficacy in stress control, physiological disturbances and evaluation of hypertension. Both the motivation as well as the knowledge about taking antihypertensives should be improved, especially in women. The perception of stress, depression, hypertension and myocardial infarction can be used to predict adherence to hypertension drug treatment.

Interventional procedures and future drug therapy for hypertension.

PubMed

Lobo, Melvin D; Sobotka, Paul A; Pathak, Atul

2017-04-14

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

State-of-the-art treatment of hypertension: established and new drugs.

PubMed

Burnier, Michel; Vuignier, Yann; Wuerzner, Gregoire

2014-03-01

The treatment of essential hypertension is based essentially on the prescription of four major classes of antihypertensive drugs, i.e. blockers of the renin--angiotensin system, calcium channel blockers, diuretics and beta-blockers. In recent years, very few new drug therapies of hypertension have become available. Therefore, it is crucial for physicians to optimize their antihypertensive therapies with the drugs available on the market. In each of the classes of antihypertensive drugs, questions have recently been raised: are angiotensin-converting enzyme (ACE) inhibitors superior to angiotensin II receptor blockers (ARB)? Is it possible to reduce the incidence of peripheral oedema with calcium antagonists? Is hydrochlorothiazide really the good diuretic to use in combination therapies? The purpose of this review is to discuss these various questions in the light of the most recent clinical studies and meta-analyses. These latter suggest that ACE inhibitors and ARB are equivalent except for a better tolerability profile of ARB. Third generation calcium channel blockers enable to reduce the incidence of peripheral oedema and chlorthalidone is certainly more effective than hydrochlorothiazide in preventing cardiovascular events in hypertension. At last, studies suggest that drug adherence and long-term persistence under therapy is one of the major issues in the actual management of essential hypertension.

AT1-receptor blockade attenuates outward aortic remodeling associated with diet-induced obesity in mice.

PubMed

Krueger, Friedrich; Kappert, Kai; Foryst-Ludwig, Anna; Kramer, Frederike; Clemenz, Markus; Grzesiak, Aleksandra; Sommerfeld, Manuela; Paul Frese, Jan; Greiner, Andreas; Kintscher, Ulrich; Unger, Thomas; Kaschina, Elena

2017-08-01

The renin-angiotensin system (RAS) and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are not yet understood. We investigated the effect of the angiotensin receptor type 1 (AT1-receptor) antagonist telmisartan on aortic outward remodeling in a diet-induced obesity model in mice. C57/Black6J mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) for 14 weeks. One group of HFD mice was additionally exposed to telmisartan (3 mg/kg per day) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibers and decreased elastin content. Vascular damage was associated with up-regulation of matrix metalloproteinase (MMP)-2 (MMP-2), MMP-3, MMP-12, cathepsin D, and cathepsin B. HFD aortae exhibited an enhanced inflammatory status, characterized by tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) colocalized with adipocytes in the adventitia. HFD resulted in a significant increase in aortic dimensions, evident by ultrasound measurements. Telmisartan abolished aortic dilatation and preserved elastin content. HFD induced enhanced expression of aortic MMP-2, MMP-9, and TNF-α was abrogated by telmisartan. Adventitial proteolytic and inflammatory factors were also examined in samples from human abdominal aneurysms. The expression of TNF-α, IL-1β, and MMP-9 was higher in the adventitial fat of diseased vessels compared with healthy tissues. Finally, adipocytes treated with TNF-α showed enhanced MMP-2, MMP-3, and cathepsin D, which was prevented by telmisartan. Taken together, HFD in mice induced aortic dilatation with up-regulation of matrix degrading and inflammatory pathways similar to those seen in human aortic aneurysmatic tissue. The HFD-induced vascular pathology was reduced by AT1-receptor antagonist telmisartan. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Arterial hypertension in children].

PubMed

Mota-Hernández, F

1993-07-01

It is considered hypertension in children, the persistent increase of the blood pressure values above percentile 95 for age and sex, in no less than three determinations, with adequate register techniques. Blood pressure is maintained mainly by the regulation of metabolism of sodium and water in the intravascular space, through the adequate balance of intake, filtration, reabsorption and renal throughout. It is also regulated by hormonal factors. Weight gain control in teen-agers could be useful to prevent high blood pressure in adults. In children, it is generally secondary to renal, reno-vascular, endocrinological or tumoral diseases. Clinical manifestations and the recommended diagnostic procedures are analysed to detect the most frequent causes of hypertension at different ages. Most cases response with antihypertensive drugs in combination with hyposodic diet. For the hypertensive crisis, asa diuretics and powerful antihypertensive drugs may be employed. Patients with chronic renal insufficiency could also need dialytic treatments. Renovascular diseases require almost always invasive treatments. Better prognosis in children with severe high blood pressure is related with recent diagnostic procedures, surgical techniques and antihypertensive drugs improvements.

Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease.

PubMed

Zhu, Carolyn W; Livote, Elayne E; Kahle-Wrobleski, Kristin; Scarmeas, Nikolaos; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Sano, Mary; Stern, Yaakov

2011-01-01

This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

PubMed Central

Nunes, A.D.C.; Souza, A.P.S.; Macedo, L.M.; Alves, P.H.; Pedrino, G.R.; Colugnati, D.B.; Mendes, E.P.; Santos, R.A.S.; Castro, C.H.

2017-01-01

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases. PMID:28355350

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.

PubMed

Nunes, A D C; Souza, A P S; Macedo, L M; Alves, P H; Pedrino, G R; Colugnati, D B; Mendes, E P; Santos, R A S; Castro, C H

2017-03-23

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Seventeen-Year Nationwide Trends in Antihypertensive Drug Use in Denmark.

PubMed

Sundbøll, Jens; Adelborg, Kasper; Mansfield, Kathryn E; Tomlinson, Laurie A; Schmidt, Morten

2017-12-15

Recent trends in use of antihypertensive drugs are unknown. From Danish nationwide prescription data, we obtained information on primary care use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, aldosterone receptor antagonists, and calcium channel blockers. During 1999 to 2015, the use of antihypertensive drugs per 1,000 inhabitants/day increased from 184 to 379 defined daily doses (DDD), corresponding to a rise in the prevalence proportion of users from ≈20% to ≈35%. From 1999 to 2015, a notable increase was observed for angiotensin-converting enzyme inhibitors (from 29 to 105 DDD per 1,000 inhabitants/day ≈260%) and angiotensin II receptor blockers (from 13 to 73 DDD per 1,000 inhabitants/day ≈520%). For diuretics the use remained stable, with a slight decrease (from 89 to 81 DDD per 1,000 inhabitants/day ≈-10%). The use of aldosterone receptor antagonists increased until 2007 and remained unchanged at around 3.5 DDD per 1,000 inhabitants/day thereafter (average change ≈65%). The use of beta blockers doubled during the study period (from 17 to 34 DDD per 1,000 inhabitants/day ≈100%), entirely driven by increasing use of metoprolol. Similar trends were observed for calcium channel blockers (from 34 to 82 DDD per 1,000 inhabitants/day ≈140%), where amlodipine drove the overall increase. In conclusion, antihypertensive drug use has increased remarkably during the past 2 decades. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

PubMed

Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Bayat, Zeynep; Aras, Bekir; Metineren, Mehmet Huseyin; Yucel, Mehmet; Simsek, Hasan

2016-02-01

Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-ɣ (PPAR-ɣ), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects. © 2016 John Wiley & Sons Australia, Ltd.

Review: Medicinal plants combating against hypertension: A green antihypertensive approach.

PubMed

Sultana, Sabira; Asif, Hafiz Muhammad

2017-11-01

Hypertension (HTN) or high blood pressure is a medical condition that accounts 9.4 million deaths all over the world every year. It is leading cause of morbidity and mortality worldwide. It increases the risk of cardiovascular diseases, including heart failure, diffuse atherosclerosis, cognitive impairment and dementia. Clinically, synthetic antihypertensive drugs have been used to treat hypertension. However, the efficacy of these drugs is low and also produces side effects which include dry mouth, dizziness, emotional distress, gastrointestinal disturbance, visual disorders etc. These distressing side effects adversely affect health-related quality of life. Therefore, there is a need to search natural, cheaper and non-toxic compound. Plant are widely use in traditional systems of medicine for the treatment of several diseases. About 80% of the world population relies on traditional medicine for primary healthcare. In the last three decades, a lot of research has been done on local medicinal plants for hypotensive and antihypertensive potentials. Plants are the rich source of secondary metabolites which have been found in vivo to have antihypertensive properties. The current study is focused on reviewing the antihypertensive property of medicinal plants and their metabolites. In the current review, we conducted a literature search using Elsevier, Science direct, Springer Link (Springer), Pub Med and Google Scholar. The search included the keywords "plants", "medicinal plants", "plant extracts", cross-referenced with the keywords "hypertension" "antihypertensive activity". The use of plant origin natural compounds as cardio protective and antihypertensive agents is an interesting strategy for discovering bioactive products. Plants are rich in a variety of secondary metabolites, such as flavonoids, alkaloids, tannins and terpenoids. These have been found in vivo to have antihypertensive effects. The present review therefore; stand for a good basis to choose exact molecules belonging to the indicated categories that in the forthcoming future will become useful therapeutic tools.

Efficacy and Tolerability of Antihypertensive Drugs in Diabetic and Nondiabetic Patients.

PubMed

Aslam, Maria; Ahmad, Mobasher; Mobasher, Fizza

2017-01-01

The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs) with essential hypertension. The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals) diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP) above 130 mmHg and diastolic blood pressure (DBP) above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI), beta-blocker (βB), calcium-channel blocker (CCB), diuretics (D), angiotensin receptor blocker (ARB) as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July-October). After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP) and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Significant control in mean BP by all drug groups was observed in "both groups that is patients with diabetes and without diabetes." The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well as DBP. Adverse effects observed were dry cough, pedal edema, dizziness, muscular cramps, constipation, palpitations, sweating, vertigo, tinnitus, paresthesia, and sexual dysfunction. All classes of antihypertensives were found to control blood pressure significantly in both groups of patients that is diabetic patients with hypertesion and non-diabetic patients with hypertension.

[Hypertensive crisis: pathogenesis, clinic, treatment].

PubMed

Vertkin, A L; Topolianskiĭ, A V; Abdullaeva, A U; Alekseev, M A; Shakhmanaev, Kh A

2013-01-01

Contemporary data on mechanisms of development, types, and clinical picture of hypertensive crisis (HC) are presented. Algorithms of rational therapy of uncomplicated and complicated HC are considered. Appropriateness of the use in HC of antihypertensive drugs with multifactorial action is stressed. These drugs include urapidil - an antihypertensive agent with complex mechanism of action. Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates vasoconstrictor effect of catecholamines and decreases total peripheral resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center promotes lowering of elevated vascular tone and prevents development of reflex tachycardia.

Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension.

PubMed

Nedogoda, Sergey V; Ledyaeva, Alla A; Chumachok, Elena V; Tsoma, Vera V; Mazina, Galina; Salasyuk, Alla S; Barykina, Irina N

2013-08-01

Obesity exacerbates hypertension and stimulates the renin-angiotensin-aldosterone system (RAAS). Full-dose RAAS inhibition could be a therapeutic option in overweight or obese patients with hypertension. This study compared four RAAS inhibitors at full therapeutic doses to determine their effect on blood pressure (BP) and cardiovascular risk factors in these patients. We conducted a 24-week, single-blind, randomized, parallel-group study in 120 overweight or obese patients (body mass index ≥27 kg/m(2)) with hypertension, aged 18-60 years. The primary endpoint was the change in mean 24-h systolic BP and diastolic BP from baseline to study end. Central BP, arterial stiffness, and metabolic and cardiac indices were also investigated. Patients were randomly allocated to perindopril 10 mg/day, enalapril 20 mg/day, losartan 100 mg/day or telmisartan 80 mg/day. Nonpharmacological interventions were also recommended. Reductions in mean 24-h systolic BP (and diastolic BP) were all significant (p < 0.05 versus baseline) for perindopril, enalapril, losartan and telmisartan: systolic BP -22, -11, -12 and -15 mmHg, respectively; (and diastolic BP -13, -6, -13 and -12 mmHg, respectively). Aortic elasticity improved with perindopril and telmisartan. Perindopril was associated with the greatest reductions in central aortic BP and leptin levels [30 % versus 2 %, 7 % and 14 % with enalapril, losartan and telmisartan, respectively (all p < 0.05 versus perindopril)]. Reductions in other BP, echocardiographic, metabolic and anthropometric parameters occurred with all treatments. Full-dose RAAS inhibition, particularly with perindopril, effectively reduces BP, improves arterial structure and regulates cardiovascular risk factors in overweight or obese patients with hypertension.

Protective effect of telmisartan against progressive oxidative brain damage and synuclein phosphorylation in stroke-resistant spontaneously hypertensive rats.

PubMed

Fukui, Yusuke; Yamashita, Toru; Kurata, Tomoko; Sato, Kota; Lukic, Violeta; Hishikawa, Nozomi; Deguchi, Kentaro; Abe, Koji

2014-07-01

Previously, we reported that reactive oxygen species and signaling molecules of angiotensin II produced lipid peroxides, degenerated proteins, and injured DNA after cerebral ischemia in normotensive Wistar rats. Here, we investigated the long-term effect of the angiotensin II type I receptor blocker telmisartan on oxidative stress and hyperphosphorylated α-synuclein accumulation in stroke-resistant spontaneously hypertensive rats (SHR-SR). At the age of 3 months, SHR-SR were divided into 3 treatment groups: SHR-SR vehicle (SHR/Ve), SHR-SR low-dose telmisartan (.3 mg/kg/day) (SHR/low), and SHR-SR high-dose telmisartan (3 mg/kg/day) (SHR/high). Immunohistologic analyses were conducted in these groups and Wistar rats at the age of 6, 12, and 18 months. The SHR/Ve group demonstrated more progressive increase in advanced glycation end product (AGE)-, 4-hydroxy-2-nonenal (4-HNE)-, and phosphorylated α-synuclein (pSyn)-positive cells in the cerebral cortex and hippocampus compared with the Wistar group at 18 months. These expressions were reduced in the SHR/low group even without lowering blood pressure (BP), and expressions were dramatically suppressed in the SHR/high group with lowering of BP. These data suggest that persistent hypertension in SHR-SR strongly potentiate the markers of oxidative damage (AGEs and 4-HNE) and abnormal accumulation of pSyn, which were greatly suppressed by telmisartan in a dose-dependent manner without and with lowering of BP. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis.

PubMed

Gandini, Sara; Palli, Domenico; Spadola, Giuseppe; Bendinelli, Benedetta; Cocorocchio, Emilia; Stanganelli, Ignazio; Miligi, Lucia; Masala, Giovanna; Caini, Saverio

2018-02-01

Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach. Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07-1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05-1.40), with acceptable between-studies heterogeneity (I 2  < 50%). There was no association between thiazide diuretics, ACEi or ARB use and skin cancer risk. We found no evidence of publication bias affecting the results. Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the impact of budget controls on the prescribing behaviours of physicians treating dialysis-dependent patients.

PubMed

Chang, Ray-E; Tsai, Ya-Hsing; Myrtle, Robert C

2015-11-01

This study examined whether outpatient haemodialysis providers changed their treatment practices with the establishment of an outpatient dialysis global budget (ODGB) through analysing the outpatient visits and medication received by those patients. A sample of 4668 observations (patient year) of 1350 haemodialysis with hypertension (HH) patients and 4668 observations of 1436 non-HH (NHH) patients were drawn from the National Health Insurance Research Database over the years from 1999 to 2005. The impact of ODGB on hypertension-related outpatient utilization of HH was estimated using the difference in difference (DID) method and examined in three stages: (1) the fee for service stage, the pre-ODGB (2000), (2) the phase-in stage (2001-2002) and (3) the post-ODGB stage (2003-2005). ODGB implementation did not affect the number of dialysis visits for HH patients. However, it did lead to a reduction in fees for antihypertension drugs used by haemodialysis facilities. There was an increase of 4.06 visits per patient per year (P < 0.001) in the number of non-dialysis outpatient with antihypertensive drugs visits for HH patients compared with the control group. The total fees for antihypertensive drugs for HH patients increased by New Taiwan Dollars (NT$)13 008 (P < 0.001) per patient per year relative to the control group after the implementation of ODGB. As ODGB was implemented, HH patients received fewer antihypertensive drugs during their dialysis visit. In addition, there was an increase in the number of non-dialysis outpatient visits by HH patients as well as increased payment in the drugs associated with their non-dialysis outpatient visits compared with the control group. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

A retrospective study of antihypertensives in pemphigus: a still unchartered odyssey particularly between thiols, amides and phenols

PubMed Central

Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Dmochowski, Marian

2015-01-01

Introduction Autoimmune pemphigus diseases comprise several entities with serious prognoses, including the pemphigus vulgaris (PV) group and pemphigus foliaceus (PF) group. Antihypertensives are suspected to be one of the factors triggering/sustaining pemphigus. Here, the data of pemphigus patients regarding arterial hypertension (AH) and taking potentially noxious drugs were statistically analyzed in a setting of a Polish university dermatology department. Material and methods Medical histories of pemphigus patients (40 admissions of 24 female patients – 13 PV, 11 PF; and 102 admissions of 38 male patients – 24 PV, 14 PF), diagnosed at both immunopathological and biochemical-molecular levels, were studied. Results Ten of 16 (62.50%) AH-positive PV patients received known PV triggers/sustainers 11 times (1–3 per patient). Fourteen of 15 (93.33%) AH-positive PF patients received known PF triggers/sustainers 21 times (1–3 per patient). No differences in numbers of patients taking potentially culprit drugs were shown between PV and PF (Fisher's exact test: p = 0.0829; Yates’ χ2 test: p = 0.1048). The most frequently used culprit drugs were ramipril in PV and enalapril in PF. On average, each PV/PF AH-positive patient received 3.161 different antihypertensives in his/her history of admissions (2.155 antihypertensives per admission). Conclusions Drug triggering should be suspected in every case of newly diagnosed or exacerbated pemphigus, as eliminating possible PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. Eliminating possible drug PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. PMID:26528346

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study.

PubMed

Yank, Veronica; Rennie, Drummond; Bero, Lisa A

2007-12-08

To determine whether financial ties to one drug company are associated with favourable results or conclusions in meta-analyses on antihypertensive drugs. Retrospective cohort study. Meta-analyses published up to December 2004 that were not duplicates and evaluated the effects of antihypertensive drugs compared with any comparator on clinical end points in adults. Financial ties were categorised as one drug company compared with all others. The main outcomes were the results and conclusions of meta-analyses, with both outcomes separately categorised as being favourable or not favourable towards the study drug. We also collected data on characteristics of meta-analyses that the literature suggested might be associated with favourable results or conclusions. 124 meta-analyses were included in the study, 49 (40%) of which had financial ties to one drug company. On univariate logistic regression analyses, meta-analyses of better methodological quality were more likely to have favourable results (odds ratio 1.16, 95% confidence interval 1.07 to 1.27). Although financial ties to one drug company were not associated with favourable results, such ties constituted the only characteristic significantly associated with favourable conclusions (4.09, 1.30 to 12.83). When controlling for other characteristics of meta-analyses in multiple logistic regression analyses, meta-analyses that had financial ties to one drug company remained more likely to report favourable conclusions (5.11, 1.54 to 16.92). Meta-analyses on antihypertensive drugs and with financial ties to one drug company are not associated with favourable results but are associated with favourable conclusions.

Systemic delivery of β-blockers via transdermal route for hypertension

PubMed Central

Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

2014-01-01

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

A prospective study on pulse wave velocity (PWV) and response to anti-hypertensive treatments: PWV determines BP control.

PubMed

Zheng, Meili; Huo, Yong; Wang, Xiaobin; Xu, Xin; Qin, Xianhui; Tang, Genfu; Xing, Houxun; Fan, Fangfang; Li, Jianping; Zhang, Yan; Wang, Binyan; Xu, Xiping; Yang, Xinchun; Chen, Yundai; Qian, Geng

2015-01-15

Recent data indicate that hypertension is not well controlled in many populations throughout the world. The factors that influence individual response to anti-hypertensive treatment need to be clarified. Pulse wave velocity (PWV), as a marker of arterial stiffness, has been demonstrated to have important relationships with BP progression; however, little information is available on the role of PWV in blood pressure (BP) control. We aimed to assess BP control during the run-in treatment period in the China Stroke Primary Prevention Trial (CSPPT). These analyses included a total of 3056 treated hypertensive subjects (age: 59.6±7.5years, male/female 1339/1717) with PWV measured at baseline. The average BP at enrollment was 166/95mmHg, and declined to 141/85mmHg after short-term antihypertensive treatment (a median follow-up of 20days). There was an inverse relationship between PWV level and BP reduction during the treatment, most notably for systolic BP (with estimated coefficients of -9.01 (P<0.001) for the top quartile, as compared to the bottom quartile). The association did not differ significantly by gender or types of antihypertensive drugs. Factors related to smaller BP decline were low baseline BP, high baseline PWV, high body mass index, high creatinine, use of fewer types of antihypertensive drug, high heart rate (only for SBP), high homocysteine and low age (only for DBP). PWV appears to be an independent determinant of individual response to anti-hypertensive treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of traditional Chinese patent medicine on essential hypertension: a systematic review.

PubMed

Xiong, Xingjiang; Wang, Pengqian; Zhang, Yuqing; Li, Xiaoke

2015-02-01

Traditional Chinese patent medicine (TCPM) is widely used for essential hypertension (EH) in China. However, there is no critically appraised evidence, such as systematic reviews or meta-analyses, regarding the potential benefits and disadvantages of TCPM to justify their clinical use and recommendation. The aim of this review was to systematically evaluate and meta-analyze the effects of TCPM for EH. Seven databases, the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Chinese Biomedical Literature Database, and the Wanfang Database, were searched from their inception to August 2014 for relevant studies that compared one TCPM plus antihypertensive drugs versus antihypertensive drugs alone. The methodological quality of the included trials was assessed using the Cochrane risk-of-bias tool. The primary outcome measures were mortality or progression to severe complications and adverse events. The secondary outcome measures were blood pressure (BP) and quality of life (QOL). Seventy-three trials, which included 8138 patients, on 17 TCPMs were included. In general, the methodological quality was low. Two trials evaluated the effects of TCPMs on mortality and the progression to severe complications after treatment, and no significant difference was identified compared with antihypertensive drugs alone. No severe adverse events were reported. Thirteen TCPMs used in complementary therapy significantly decreased systolic BP by 3.94 to 13.50 mmHg and diastolic BP by 2.28 to 11.25 mmHg. QOL was significantly improved by TCPM plus antihypertensive drugs compared with antihypertensive drugs alone. This systematic review provided the first classification of clinical evidence for the effectiveness of TCPM for EH. The usage of TCPMs for EH was supported by evidence of class level III. As a result of the methodological drawbacks of the included studies, more rigorously designed randomized controlled trials that focus on mortality and cardiovascular events during long-term follow-up are warranted before TCPM can be recommended for hypertensive patients. Two TCPMs, Song ling xue mai kang capsules and Yang xue qing nao granules, should be prioritized for further research.

Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

PubMed

Alba-Leonel, Adela; Carvajal, Alfonso; Fierro, Immaculada; Castillo-Nájera, Fernando; Campos-Ramos, Oscar; Villa-Romero, Antonio; Molina-Guarneros, Juan

2016-06-01

Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged. © 2016 The Authors Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

NON-COMPLIANCE TO ANTI-HYPERTENSIVE MEDICATION AND ITS ASSOCIATED FACTORS AMONG HYPERTENSIVES.

PubMed

Bilal, Arshia; Riaz, Mehwish; Shafiq, Noor-ulain; Ahmed, Mariam; Sheikh, Sadaf; Rasheed, Sobia

2015-01-01

Non-compliance to anti-hypertensive drugs can have negative impact on cardiovascular outcome. Various studies have been conducted on the issue but the factors are not yet explored properly, particularly in Pakistan. This study was conducted to determine the frequency and factors associated with non-compliance to anti-hypertensive medications in Karachi. This descriptive cross sectional study was conducted on 113 indoor hypertensive patients included by purposive sampling, aged 30 years and above diagnosed at least 6 months back in public sector tertiary care institutes of Karachi from March to October 2011. Data was collected through a questionnaire in Urdu. Demographic data, hypertension diagnosis, medical co-morbidity, current number of anti-hypertensive medicines, frequency of missing prescribed antihypertensive therapy and other factors affecting compliance pertaining to medicines, patient, physician and health care centre were included in the questionnaire. This study revealed that 68.14% patients were non-compliant. Non-compliance was found to be associated with gender and socioeconomic status. Duration of hypertension, duration between follow up visits to physician, number of drugs, careless attitude, role of physician and limiting access to health care center are found to be important factors in non-compliance. Multiple factors including patients, medicine and health care system related, which can be prevented with simple measures, were found responsible for higher prevalence of non-compliance against anti-hvnertensive medicines.

Long weekly working hours and ischaemic heart disease: a follow-up study among 145 861 randomly selected workers in Denmark

PubMed Central

Hannerz, Harald; Larsen, Ann Dyreborg; Garde, Anne Helene

2018-01-01

Objectives The aim of the present study was to test if incidences of ischaemic heart disease (IHD) and usage of antihypertensive drugs are independent of weekly working hours (WWH) among full-time employees in Denmark. Design and participants Data on WWH from participants of the Danish labour force surveys, 1999–2013, were linked on an individual level to national registers with data on socioeconomic status (SES), industry, emigrations, redeemed prescriptions, hospital contacts and deaths. Participants were followed until the end of 2014 (on average 7.7 years). Poisson regression was used to model incidence rates as a function of WWH. The analyses were controlled for calendar time, time passed since start of follow-up, employment in the healthcare industry, age, sex, SES and night work. Results In total, we found 3635 cases of IHD and 20 648 cases of antihypertensive drug usage. The rate ratio of IHD was 0.95 (95% CI 0.85 to 1.06) for 41–48 compared with 32–40 WWH and 1.07 (0.94 to 1.21) for >48 compared with 32–40 WWH. The corresponding rate ratios for antihypertensive drug usage were 0.99 (0.95 to 1.04) and 1.02 (0.97 to 1.08). No statistically significant interactions between WWH and sex, SES and night work, respectively, were found. Conclusion In this Danish sample, we did not find any statistically significant association between WWH and IHD or antihypertensive drug usage. PMID:29909368

[Classical antihypertensive drugs: diuretics].

PubMed

Nagy, Viktor László

2017-03-01

The diuretics are essential medicaments of antihypertensive therapy. They reduce blood pressure and cardiovascular events optimally. With increasing doses of thiazides and thiazide analogs do not come further powerful effect of reducing blood pressure or cardiovascular mortality and morbidity, but clearly elevate the side effects. Because of it, the minimum effective dose level and the fixed-dose combination therapy should be preferred. The use these drugs leads to especially positive outcome in elder patients, isolated systolic hypertension, heart failure, after stroke and in black population. Loop diuretics as antihypertensive therapy can be used only by renal impairment. The use of aldosterone antagonists can have a good effect not only on heart failure but also on prevention of atrial fibrillation. Furthermore, using it in a combination therapy with thiazides, it reduces the risk of hypokalemia. Therefore, the diuretic treatment in hypertension is flourishing again. Orv. Hetil., 2017, 158(11), 403-408.

Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Liu, Yongmei; Zhang, Yun; Wang, Pengqian; Wang, Jie

2013-01-01

Hypertension, which directly threatens quality of life, is a major contributor to cardiovascular and cerebrovascular events. Over the past two decades, domestic and foreign scholars have agreed upon various standards in the treatment of hypertension, and considerable progress has been made in the field of antihypertensive drugs. Oral antihypertensive drugs represent a milestone in hypertension therapy. However, the blood pressure standard for patients with hypertension is far from satisfactory. The study of Chinese herbal formulas for treating hypertension has received much research attention. These studies seek to integrate traditional and Western medicine in China. Currently, Chinese herbal formulas are known to have an outstanding advantage with regard to bodily regulation. Research shows that Chinese medicine has many protective mechanisms. This paper addresses the process of the antihypertensive mechanisms in Chinese herbal formulas for treating hypertension. These mechanisms are to be discussed in future research. PMID:23552514

[Achievements and problems of modern trials of antihypertensive drugs].

PubMed

Kobalava, Zh D; Kotovskaia, Iu V

2011-01-01

Most important value of lowering of substantially elevated arterial pressure (AP) for improvement of outcomes in patients with arterial hypertension (AH) was convincingly confirmed by large truly placebo controlled randomized clinical trials (RCT) with the use of mainly diuretics, and/or beta-adrenoblockers in the 60-80ths. Later comparative RCT confirmed equal antihypertensive efficacy of 5 main drug classes relative to AP level in brachial artery. In this review we discuss merit of auxiliary class-specific properties of antihypertensive agents potentially affecting prognosis besides AP lowering. We also discuss problems related to decline of significance of quantitative criteria of AH and consideration of AP level in general context of cardiovascular risk; problems of external validity of RCT; extrapolation of RCT results obtained in patients with complicated AH and very high cardiovascular risk on young patients with uncomplicated AH; significance of hard and surrogate end points.

Systolic hypertension: an increasing clinical challenge in Asia

PubMed Central

Park, Jeong Bae; Kario, Kazuomi; Wang, Ji-Guang

2015-01-01

Systolic hypertension, the predominant form of hypertension in patients aged over 50–60 years, is a growing health issue as the Asian population ages. Elevated systolic blood pressure is mainly caused by arterial stiffening, resulting from age-related vascular changes. Elevated systolic pressure increases the risk of cardiovascular disease, mortality and renal function decline, and this risk may increase at lower systolic pressure levels in Asian than Western subjects. Hence, effective systolic pressure lowering is particularly important in Asians yet blood pressure control remains inadequate despite the availability of numerous antihypertensive medications. Reasons for poor blood pressure control include low awareness of hypertension among health-care professionals and patients, under-treatment, and tolerability problems with antihypertensive drugs. Current antihypertensive treatments also lack effects on the underlying vascular pathology of systolic hypertension, so novel drugs that address the pathophysiology of arterial stiffening are needed for optimal management of systolic hypertension and its cardiovascular complications. PMID:25503845

Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Liu, Yongmei; Zhang, Yun; Wang, Pengqian; Wang, Jie

2013-07-01

Hypertension, which directly threatens quality of life, is a major contributor to cardiovascular and cerebrovascular events. Over the past two decades, domestic and foreign scholars have agreed upon various standards in the treatment of hypertension, and considerable progress has been made in the field of antihypertensive drugs. Oral antihypertensive drugs represent a milestone in hypertension therapy. However, the blood pressure standard for patients with hypertension is far from satisfactory. The study of Chinese herbal formulas for treating hypertension has received much research attention. These studies seek to integrate traditional and Western medicine in China. Currently, Chinese herbal formulas are known to have an outstanding advantage with regard to bodily regulation. Research shows that Chinese medicine has many protective mechanisms. This paper addresses the process of the antihypertensive mechanisms in Chinese herbal formulas for treating hypertension. These mechanisms are to be discussed in future research.

What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

PubMed

Seedat, Yackoob K; Brewster, Lizzy M

2014-02-01

This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic blockers (ARB). Response was superior in African ancestry patients on a thiazide like diuretic or indapamide and CCB, while the response to β-adrenergic blockers and ACEI are attenuated. Available data are very limited but self-defined ancestry seems to be the best predictor of individual responses to antihypertensive drugs. Knowledge of the factors like economic and social consideration affect the lower rate of detection, treatment and control of hypertension in the African ancestry population of the USA. For regions in which health care resources are particularly scarce, investment in population-based primary prevention strategies may yield the largest benefit.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

PubMed

Gueyffier, F; Subtil, F; Bejan-Angoulvant, T; Zerbib, Y; Baguet, J P; Boivin, J M; Mercier, A; Leftheriotis, G; Gagnol, J P; Fauvel, J P; Giraud, C; Bricca, G; Maucort-Boulch, D; Erpeldinger, S

2015-01-01

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

Mobile Device-Based Electronic Data Capture System Used in a Clinical Randomized Controlled Trial: Advantages and Challenges.

PubMed

Zhang, Jing; Sun, Lei; Liu, Yu; Wang, Hongyi; Sun, Ningling; Zhang, Puhong

2017-03-08

Electronic data capture (EDC) systems have been widely used in clinical research, but mobile device-based electronic data capture (mEDC) system has not been well evaluated. The aim of our study was to evaluate the feasibility, advantages, and challenges of mEDC in data collection, project management, and telemonitoring in a randomized controlled trial (RCT). We developed an mEDC to support an RCT called "Telmisartan and Hydrochlorothiazide Antihypertensive Treatment (THAT)" study, which was a multicenter, double-blinded, RCT, with the purpose of comparing the efficacy of telmisartan and hydrochlorothiazide (HCTZ) monotherapy in high-sodium-intake patients with mild to moderate hypertension during a 60 days follow-up. Semistructured interviews were conducted during and after the trial to evaluate the feasibility, advantage, and challenge of mEDC. Nvivo version 9.0 (QSR International) was used to analyze records of interviews, and a thematic framework method was used to obtain outcomes. The mEDC was successfully used to support the data collection and project management in all the 14 study hospitals. A total of 1333 patients were recruited with support of mEDC, of whom 1037 successfully completed all 4 visits. Across all visits, the average time needed for 141 questions per patient was 53 min, which were acceptable to both doctors and patients. All the interviewees, including 24 doctors, 53 patients, 1 clinical research associate (CRA), 1 project manager (PM), and 1 data manager (DM), expressed their satisfaction to nearly all the functions of the innovative mEDC in randomization, data collection, project management, quality control, and remote monitoring in real time. The average satisfaction score was 9.2 (scale, 0-10). The biggest challenge came from the stability of the mobile or Wi-Fi signal although it was not a problem in THAT study. The innovative mEDC has many merits and is well acceptable in supporting data collection and project management in a timely manner in clinical trial. ©Jing Zhang, Lei Sun, Yu Liu, Hongyi Wang, Ningling Sun, Puhong Zhang. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.03.2017.

[Effect of RAAS antagonist on the expression of gap junction cx43 in myocardium of spontaneously hypertensive rat].

PubMed

Tan, Li-Li; Li, Lu; Liu, Li-Min; Zhao, Hong-Li

2013-07-01

OBJECTIVE To investigate the expression of gap junction protein Cx43 in the cardiac muscle of spontaneous hypertensive rat and the effects of various antagonists against renin angiotensin aldosterone system (RAAS) on Cx43 expression. METHODS 70 spontaneous hypertensive rats of 8-week age, 200-gram weight were separated into 7 groups, as hypertension, ramipril, telmisartan, eplerenone, ramipril + telmisartan, telmisartan + eplerenone, and ramipril+eplerenone treatment group. Another 10 healthy Wistar rats of the same age and weight were used as control group. All the rats were given intragastric administration at 8 a. m. every morning, and measured arteria caudilis pressure at 0, 4 and 8 week, respectively. 8 weeks later, all the rats were sacrificed, and the hearts were taken to measure the weight of left ventricle and the ratio of left ventricle to body weight. Myocardial fibrosis was observed by H&E staining of paraffin embedded sections, and Cx43 expression was examined by RT-PCR and western blot. The arteria caudilis pressure of spontaneous hypertensive rats was significantly higher than that of healthy control Wistar rats (P < 0.01). The decreased blood pressure was observed in RAAS antagonists treated rats, compared with hypertension group (P < 0.05). The combined treatment of telmisartan and eplerenone had the best effect of lowering blood pressure. Moreover, the weight of left ventricle, the ratio of left ventricle to body weight, myocardial fibrosis and angiotensin 11 were all prominently decreased in telmisartan and eplerenone combination group (P < 0.01). The expression of Cx43 in spontaneous hypertensive rats was significantly lower than that of healthy control Wistar rats (P < 0.01). Increased Cx43 expression was observed in RAAS antagonists treated rats, compared with hypertension group (P < 0.05). The expression of gap junction protein Cx43 was significantly down-regulated in spontaneous hypertensive rats, while RAAS antagonists increased Cx43 expression. The combination of telmisartan and eplerenone effectively recovered the expression of Cx43 and probably reversed hypertension.

The KCNH2 genetic polymorphism (1956, C>T) is a novel biomarker that is associated with CCB and α,β-ADR blocker response in EH patients in China.

PubMed

He, Fazhong; Luo, Jianquan; Luo, Zhiying; Fan, Lan; He, Yijing; Zhu, Dingliang; Gao, Jinping; Deng, Sheng; Wang, Yan; Qian, Yuesheng; Zhou, Honghao; Chen, Xiaoping; Zhang, Wei

2013-01-01

KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs.

Sexual function in hypertensive patients receiving treatment.

PubMed

Reffelmann, Thorsten; Kloner, Robert A

2006-01-01

In many forms of erectile dysfunction (ED), cardiovascular risk factors, in particular arterial hypertension, seem to be extremely common. While causes for ED are related to a broad spectrum of diseases, a generalized vascular process seems to be the underlying mechanism in many patients, which in a large portion of clinical cases involves endothelial dysfunction, ie, inadequate vasodilation in response to endothelium-dependent stimuli, both in the systemic vasculature and the penile arteries. Due to this close association of cardiovascular disease and ED, patients with ED should be evaluated as to whether they may suffer from cardiovascular risk factors including hypertension, cardiovascular disease or silent myocardial ischemia. On the other hand, cardiovascular patients, seeking treatment of ED, must be evaluated in order to decide whether treatment of ED or sexual activity can be recommended without significantly increased cardiac risk. The guideline from the first and second Princeton Consensus Conference may be applied in this context. While consequent treatment of cardiovascular risk factors should be accomplished in these patients, many antihypertensive drugs may worsen sexual function as a drug specific side-effect. Importantly, effective treatment for arterial hypertension should not be discontinued as hypertension itself may contribute to altered sexual functioning; to the contrary, alternative antihypertensive regimes should be administered with individually tailored drug regimes with minimal side-effects on sexual function. When phosphodiesterase-5 inhibitors, such as sildenafil, tadalafil and vardenafil, are prescribed to hypertensive patients on antihypertensive drugs, these combinations of antihypertensive drugs and phosphodiesterase 5 are usually well tolerated, provided there is a baseline blood pressure of at least 90/60 mmHg. However, there are two exceptions: nitric oxide donors and alpha-adrenoceptor blockers. Any drug serving as a nitric oxide donor (nitrates) is absolutely contraindicated in combination with phosphodiesterase 5 inhibitors, due to significant, potentially life threatening hypotension. Also, a-adrenoceptor blockers, such as doxazosin, terazosin and tamsulosin, should only be combined with phosphodiesterase 5 inhibitors with special caution and close monitoring of blood pressure.

Sexual dysfunction with antihypertensive and antipsychotic agents.

PubMed

Smith, P J; Talbert, R L

1986-05-01

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

Hypertension Treatment in Patients with Metabolic Syndrome and/or Type 2 Diabetes Mellitus: Analysis of the Therapy Effectivity and the Therapeutic Inertia in Outpatient Study

PubMed Central

Strišková, Andrea; Borčin, Marián

2018-01-01

We have analysed the database of 1,595 consecutive patients visiting our department of cardiology and internal medicine clinic in 2005–2014. The analysis included 13,990 visit records, and the average number of visits per patient was 8.5 ± 7.0. Our goals were to evaluate the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in patients with metabolic syndrome and/or diabetes mellitus. The final number of patients for analysis who fulfilled the inclusion criteria for interpenetration of both diagnostic circles was 570. Results. 15% of patients were treated using hypertension monotherapy, 70% of patients were treated using 2- to 4-drug combination therapy, and 15% of patients were treated using 5- to 6-drug combination. The drugs used most frequently were perindopril (perin), nitrendipine (nitre), amlodipine (amlo), telmisartan (telmi), hydrochlorothiazide (hydro), rilmenidine, and nebivolol (used in >100 patients). The most significant decrease of sBP was associated with treatment by nitre, hydro, telmi, and urapidil (>19 mmHg). The most significant decrease of dBP was associated with treatment by nitre, hydro, telmi, and verapamil (>10 mmHg). The most significant decrease of both sBP and dBP was associated with treatment using 3-drug combination of telmi + hydro + spironolactone (41 and 16 mmHg, resp.), telmi + hydro + nitre (34 and 15 mmHg, resp.), and telmi + hydro + urapidil (34 and 15 mmHg, resp.). At the last visit, 281 out of 413 patients at the first visit had sBP >140 mmHg (68%); that is, sBP control was 32%. At the last visit, 76 patients out of 217 at the first visit had dBP >90 mmHg (35%); that is, dBP control was 65%. Therapeutic inertia was calculated by evaluating the proportion of visits at which sBP was above the target for eligible visits minus the proportion of visits where the change was made in antihypertensive treatment (AHT), either medication type or dose, over the number of eligible visits, with the resultant value multiplied by the mean of the difference between the actual sBP and the target value at clinic visits. TIQ was counted at first 200 consecutive patients, and the average value was 57.30 ± 147.20. Conclusion. The study presents the real-life data concerning the difficulties in hypertension treatment in patients with concomitant metabolic syndrome and/or type 2 diabetes mellitus. sBP was controlled at 32% patients only. The study results allow evaluating the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in these patients. PMID:29805801

Hypertension Treatment in Patients with Metabolic Syndrome and/or Type 2 Diabetes Mellitus: Analysis of the Therapy Effectivity and the Therapeutic Inertia in Outpatient Study.

PubMed

Farský, Štefan; Strišková, Andrea; Borčin, Marián

2018-01-01

We have analysed the database of 1,595 consecutive patients visiting our department of cardiology and internal medicine clinic in 2005-2014. The analysis included 13,990 visit records, and the average number of visits per patient was 8.5 ± 7.0. Our goals were to evaluate the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in patients with metabolic syndrome and/or diabetes mellitus. The final number of patients for analysis who fulfilled the inclusion criteria for interpenetration of both diagnostic circles was 570. Results . 15% of patients were treated using hypertension monotherapy, 70% of patients were treated using 2- to 4-drug combination therapy, and 15% of patients were treated using 5- to 6-drug combination. The drugs used most frequently were perindopril (perin), nitrendipine (nitre), amlodipine (amlo), telmisartan (telmi), hydrochlorothiazide (hydro), rilmenidine, and nebivolol (used in >100 patients). The most significant decrease of sBP was associated with treatment by nitre, hydro, telmi, and urapidil (>19 mmHg). The most significant decrease of dBP was associated with treatment by nitre, hydro, telmi, and verapamil (>10 mmHg). The most significant decrease of both sBP and dBP was associated with treatment using 3-drug combination of telmi + hydro + spironolactone (41 and 16 mmHg, resp.), telmi + hydro + nitre (34 and 15 mmHg, resp.), and telmi + hydro + urapidil (34 and 15 mmHg, resp.). At the last visit, 281 out of 413 patients at the first visit had sBP >140 mmHg (68%); that is, sBP control was 32%. At the last visit, 76 patients out of 217 at the first visit had dBP >90 mmHg (35%); that is, dBP control was 65%. Therapeutic inertia was calculated by evaluating the proportion of visits at which sBP was above the target for eligible visits minus the proportion of visits where the change was made in antihypertensive treatment (AHT), either medication type or dose, over the number of eligible visits, with the resultant value multiplied by the mean of the difference between the actual sBP and the target value at clinic visits. TIQ was counted at first 200 consecutive patients, and the average value was 57.30 ± 147.20. Conclusion . The study presents the real-life data concerning the difficulties in hypertension treatment in patients with concomitant metabolic syndrome and/or type 2 diabetes mellitus. sBP was controlled at 32% patients only. The study results allow evaluating the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in these patients.

Workplace Social Capital and Adherence to Antihypertensive Medication: A Cohort Study

PubMed Central

Oksanen, Tuula; Kawachi, Ichiro; Kouvonen, Anne; Suzuki, Etsuji; Takao, Soshi; Sjösten, Noora; Virtanen, Marianna; Pentti, Jaana

2011-01-01

Background While hypertension is a common and treatable health problem, adherence to antihypertensive medication remains a challenge. This study examines the hypothesis that workplace social capital may influence adherence to antihypertensive medication among hypertensive employees. Methodology/Principal Findings We linked survey responses to nationwide pharmacy records for a cohort of 3515 hypertensive employees (mean age 53.9 years, 76% women) who required continuous antihypertensive drug therapy (the Finnish Public Sector study). A standard scale was used to measure workplace social capital from co-workers' assessments and self-reports in 2000–2004. Non-adherence to antihypertensive medication was determined based on the number of days-not-treated at the year following the survey using comprehensive prescription records. Negative binomial regression models were conducted adjusting for socio-demographic characteristics, duration of hypertension, behaviour-related risk factors, and co-morbid conditions. The overall rate of days-not-treated was 20.7 per person-year (78% had no days-not-treated). Higher age, obesity, and presence of somatic co-morbidities were all associated with better adherence, but this was not the case for co-worker-assessed or self-reported workplace social capital. The rate of days-not-treated was 19.7 per person-year in the bottom fourth of co-worker-assessed workplace social capital, compared to 20.4 in the top fourth. The corresponding rate ratio from the fully-adjusted model was 0.95 (95% confidence interval (CI) 0.58–1.56). In a subgroup of 907 new users of antihypertensive medication this rate ratio was 0.98 (95% CI 0.42–2.29). Conclusions/Significance We found no consistent evidence to support the hypothesized effect of workplace social capital on adherence to drug therapy among employees with chronic hypertension. PMID:21931836

Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension.

PubMed

Reddi, A S; Nimmagadda, V R; Arora, R

2001-05-01

We have previously demonstrated that antihypertensive treatment with doxazosin (DZN), an alpha-adrenergic blocker, and lisinopril (LIS), an ACE inhibitor, reverse glomerular sclerosis in corpulent spontaneously hypertensive rats with type 2 diabetes. In this study, we examined the effects of the above-mentioned antihypertensive drugs alone and in combination on the structure of interlobular and arcuate arteries in these rats. Both male and female rats aged 6 months were treated with antihypertensive drugs for 16 weeks. Various structural parameters were evaluated by light microscopy, with the use of digital image analysis, in kidney sections stained with periodic acid-SCHIFF: Systolic blood pressure was significantly lower in treated than in untreated rats. Untreated diabetic rats had a significantly higher media/lumen ratio (smaller luminal diameter) of both arteries compared with the ratio in treated rats (for interlobular artery, 0.72+/-0.06 [no treatment], 0.49+/-0.03 [DZN treatment], 0.54+/-0.06 [LIS treatment], and 0.52+/-0.04 [combination therapy], P<0.05 to <0.001 for no treatment versus treatment; for arcuate artery, 0.66+/-0.11 [no treatment], 0.40+/-0.02 [DZN treatment], 0.39+/-0.04 [LIS treatment], and 0.40+/-0.03 [combination therapy], P<0.05 for no treatment versus treatment). Antihypertensive treatment caused significant increases in total arterial cross-sectional area, internal and external diameters, luminal and medial cross-sectional area, and medial thickness in both interlobular and arcuate arteries. The improvement in arterial structure after antihypertensive treatment was due to remodeling and growth of the vessels. Both DZN and LIS were equally efficacious, and combination therapy had no additive or synergistic effect.

Refractory Hypertension: Determination of Prevalence, Risk Factors and Comorbidities in a Large, Population-Based Cohort

PubMed Central

Calhoun, David A.; Booth, John N.; Oparil, Suzanne; Irvin, Marguerite R.; Shimbo, Daichi; Lackland, Daniel T.; Howard, George; Safford, Monika M.; Muntner, Paul

2014-01-01

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30,239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic ≥ 140/90 mm Hg) on ≥ 5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic ≥140/90 mm Hg on ≥ 3 or<140/90 mm Hg on ≥ 4 antihypertensive classes) and all treated hypertensive participants served as comparator groups. Of 14,809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension(n=2,144) and 41.7% among participants on 5 or more antihypertensive drug classes. Among all hypertensive participants, African American race, male gender, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes and history of stroke and coronary heart disease were associated with refractory hypertension. Compared to resistant hypertension, prevalence ratios for refractory hypertension were increased for African Americans (3.00, 95% CI 1.68 – 5.37) and those with albuminuria (2.22, 95% CI 1.40 – 3.52) and diabetes (2.09, 95% CI 1.32 – 3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension compared to either comparator group. These data indicate that while resistant hypertension is relatively common among treated hypertensive patients, true antihypertensive treatment failure is rare. PMID:24324035

Poor drug adherence and lack of awareness of hypertension among hypertensive stroke patients in Kampala, Uganda: a cross sectional study.

PubMed

Mugwano, Isaac; Kaddumukasa, Mark; Mugenyi, Levi; Kayima, James; Ddumba, Edward; Sajatovic, Martha; Sila, Cathy; DeGeorgia, Michael; Katabira, Elly

2016-01-02

Raised blood pressure (BP) remains an important risk factor for cardiovascular diseases such as stroke. Adherence to therapeutic recommendations especially antihypertensive drugs is important in BP control. The aim of the study was to assess the stroke risk factors and levels of adherence among hypertensive patients with stroke in Kampala Uganda. In a cross-sectional study we describe 112 hypertensive subjects with stroke from two Kampala city hospitals. A standardized pre-tested questionnaire was used to collect medical history, clinical details, radiological findings and laboratory data. A total of 112 hypertensive subjects with stroke were enrolled between May 2013 and April 2014. The median ages were 63.5 years (52.5-75.0) for the cases. Seventy percent (78/112) of the study participants had ischemic strokes. Only 17% were adherent to anti-hypertensive medications. The main cause of non-adherence appears to be lack of knowledge. Poor adherence of anti-hypertensive medications among hypertensive patients remains a big challenge in our setting. This has been attributed to lack of adequate knowledge and cost of the prescribed drugs. There is therefore an urgent need to promptly diagnose and educate hypertensive patients with emphasis on adherence to anti hypertensive drugs.

Blood pressure change and antihypertensive treatment in old and very old people: evidence of age, sex and cohort effects.

PubMed

Molander, L; Lövheim, H

2013-03-01

The epidemiology of blood pressure in very old age has not been thoroughly studied. The objective of this study was to study blood pressure changes throughout old age and changes in blood pressure and antihypertensive drug use from 1981 to 2005. The study includes 1133 blood pressure measurements from two studies carried out in Umeå, Sweden. The U70 study (1981-1990) included individuals aged 70-88 and the Umeå 85+/GERDA study (2000-2005) covered people aged 85, 90 or ≥95 years. The impact of age, sex and year of investigation on blood pressure was investigated using linear regression. Mean diastolic blood pressure (DBP) decreased by 0.35 mm Hg (P<0.001) for each year of age. An inverted U-shaped relation was found between age and systolic blood pressure (SBP), with SBP reaching its maximum at 74.5 years. Mean SBP and DBP also decreased over time (SBP by 0.44 mm Hg per year, P<0.001 and DBP by 0.34 mm Hg per year, P<0.001). The proportion of participants on antihypertensive drugs increased from 39.0% in 1981 to 69.4% in 2005. In this study of people aged ≥70 years, mean SBP and DBP decreased with higher age and later investigation year. Antihypertensive drug use increased with time, which might partly explain the observed cohort effect.

Targeting nocturnal hypertension in type 2 diabetes mellitus.

PubMed

Rossen, Niklas Blach; Knudsen, Søren Tang; Fleischer, Jesper; Hvas, Anne-Mette; Ebbehøj, Eva; Poulsen, Per Løgstrup; Hansen, Klavs Würgler

2014-11-01

Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention. © 2014 American Heart Association, Inc.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs.

PubMed

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = -19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

PubMed Central

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

Objective To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. Methods In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. Results 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average −4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = −19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Conclusion Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. PMID:27454447

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

PubMed

Burke, Valerie; Beilin, Lawrie J; Cutt, Hayley E; Mansour, Jacqueline; Wilson, Amy; Mori, Trevor A

2005-06-01

To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. Randomized controlled trial. Research studies unit. Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P < 0.01). At follow-up, changes in the two groups were not significantly different (4.1/1.3 +/- 1.1/1.0 mmHg in controls; 2.5/-0.1 +/- 1.1/0.8 mmHg in the programme group; P = 0.73). At 4 months, drug withdrawal differed significantly between the groups (P = 0.038) in men (control 44%; programme 66%) but not in women (65 and 64%, respectively; P = 0.964). At follow-up, sex-related differences were not significant, and 41% in the control group and 43% in the programme group maintained drug-withdrawal status. With the programme, net weight loss was 3.3 kg (P < 0.001) at 4 months and 3.0 kg (P < 0.001) at follow-up; respective net decreases in waist girth were 3.3 cm (P < 0.001) and 3.5 cm (P < 0.001). A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study.

PubMed

Heinze, Georg; Hronsky, Milan; Reichardt, Berthold; Baumgärtel, Christoph; Müllner, Marcus; Bucsics, Anna; Winkelmayer, Wolfgang C

2015-04-01

Healthcare systems spend considerable proportions of their budgets on pharmaceutical treatment of hypertension, hyperlipidemia, and diabetes mellitus. From data on almost all residents of Austria, a country with mandatory health insurance and universal health coverage, we estimated potential cost savings by substituting prescribed medicines with the cheapest medicines that were of the same chemical substance and strength, and available during the same time. Data from 8.3 million persons (98.5 % of the total Austrian insured population) from 2009-2012 were analyzed. Real prescription costs for antihypertensive, lipid-lowering, and hypoglycemic medicines achievable by same-substance, same-strength drug substitution were computed for each active ingredient, and per gender and 1-year age category of patients. In 2012, health insurance providers spent 231.3 million, 77.8 million, and 91.9 million for antihypertensive, lipid-lowering, and diabetes medications, of which 52.2 million (22.6 %), 15.9 million (20.5 %), and 4.1 million (4.5 %), respectively, could have been saved by same-substance drug substitution. Highest potential savings were calculated for amlodipine (8.0 million, 65.4 %), simvastatin (12.2 million, 59.3 %), and metformin (2.4 million, 54.6 %), respectively. Higher savings for men than for women resulted from differing prescribed cumulative dosages and proportions of patients with co-payment waiver. Potential cost savings in antihypertensive and lipid-lowering drugs increased from 2009-2012. Our study highlights the cost-savings potential from arguably the most acceptable of interventions, simply switching to the cheapest available same-substance, same-strength product. In 2012, this strategy could have reduced costs for antihypertensive, lipid-lowering, and hypoglycemic treatment by up to 18.0 %.

Systematic review: antihypertensive drug therapy in patients of African and South Asian ethnicity.

PubMed

Brewster, Lizzy M; van Montfrans, Gert A; Oehlers, Glenn P; Seedat, Yackoob K

2016-04-01

Despite the large differences in the epidemiology of hypertension across Europe, treatment strategies are similar for national populations of white European descent. However, hypertensive patients of African or South Asian ethnicity may require ethnic-specific approaches, as these population subgroups tend to have higher blood pressure at an earlier age that is more difficult to control, a higher occurrence of diabetes, and more target organ damage with earlier cardiovascular mortality. Therefore, we systematically reviewed the evidence on antihypertensive drug treatment in South Asian and African ethnicity patients. We used the Cochrane systematic review methodology to retrieve trials in electronic databases including CENTRAL, PubMed, and Embase from their inception through November 2015; and with handsearch. We retrieved 4596 reports that yielded 35 trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity patients. Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers, nebivolol was not more effective than placebo in reducing systolic blood pressure levels. Trials with morbidity and mortality outcomes indicated that lisinopril and losartan-based therapy were associated with a greater incidence of stroke and sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials with blood pressure outcomes in 1719 South Asian hypertensive patients. In contrast with the studies in African ethnicity patients, there were no significant differences in blood pressure lowering efficacy between drugs, and no trials available with mortality outcomes. In conclusion, in patients of African ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes. We found no evidence of different efficacy of antihypertensive drugs in South Asians, but there is a need for trials with morbidity and mortality outcomes. Screening for cardiovascular risk at a younger age, treating hypertension at lower thresholds, and new delivery models to find, treat and follow hypertensives in the community may help reduce the excess cardiovascular mortality in these high-risk groups.

Qigong for hypertension: a systematic review.

PubMed

Xiong, Xingjiang; Wang, Pengqian; Li, Xiaoke; Zhang, Yuqing

2015-01-01

The purpose of this review was to evaluate the efficacy and safety of qigong for hypertension.A systematic literature search was performed in 7 databases from their respective inceptions until April 2014, including the Cochrane Library, EMBASE, PubMed, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, Wanfang database, and Chinese National Knowledge Infrastructure. Randomized controlled trials of qigong as either monotherapy or adjunctive therapy with antihypertensive drugs versus no intervention, exercise, or antihypertensive drugs for hypertension were identified. The risk of bias was assessed using the tool described in Cochrane Handbook for Systematic Review of Interventions, version 5.1.0.Twenty trials containing 2349 hypertensive patients were included in the meta-analysis. The risk of bias was generally high. Compared with no intervention, qigong significantly reduced systolic blood pressure (SBP) (weighted mean difference [WMD] = -17.40 mm Hg, 95% confidence interval [CI] -21.06 to -13.74, P < 0.00001) and diastolic blood pressure (DBP) (WMD = -10.15 mm Hg, 95% CI -13.99 to -6.30, P < 0.00001). Qigong was inferior to exercise in decreasing SBP (WMD = 6.51 mm Hg, 95% CI 2.81 to 10.21, P = 0.0006), but no significant difference between the effects of qigong and exercise on DBP (WMD = 0.67 mm Hg, 95% CI -1.39 to 2.73, P = 0.52) was identified. Compared with antihypertensive drugs, qigong produced a clinically meaningful but not statistically significant reduction in SBP (WMD = -7.91 mm Hg, 95% CI -16.81 to 1.00, P = 0.08), but appeared to be more effective in lowering DBP (WMD = -6.08 mm Hg, 95% CI -9.58 to -2.58, P = 0.0007). Qigong plus antihypertensive drugs significantly lowered both SBP (WMD = -11.99 mm Hg, 95% CI -15.59 to -8.39, P < 0.00001) and DBP (WMD = -5.28 mm Hg, 95% CI, -8.13 to -2.42, P = 0.0003) compared with antihypertensive drugs alone. No serious adverse events were reported.The meta-analysis suggests that qigong is an effective therapy for hypertension. However, more rigorously designed randomized controlled trials with long-term follow-up focusing on hard clinical outcomes are required to confirm the results.

Yearly evolution of organ damage markers in diabetes or metabolic syndrome: data from the LOD-DIABETES study.

PubMed

Gomez-Marcos, Manuel A; Recio-Rodríguez, Jose I; Patino-Alonso, Maria C; Agudo-Conde, Cristina; Gomez-Sanchez, Leticia; Rodriguez-Sanchez, Emiliano; Gomez-Sanchez, Marta; Garcia-Ortiz, Luis

2011-10-14

Cardiovascular disease morbidity-mortality is greater in people with type 2 diabetes mellitus or metabolic syndrome. The purpose of this study was to evaluate the yearly evolution of organ damage markers in diabetes or metabolic syndrome, and to analyze the associated factors. An observational prospective study was carried out in the primary care setting, involving 112 patients: 68 diabetics and 44 subjects with metabolic syndrome, subjected to 12 months of follow-up. traditional cardiovascular risk factors (blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and) and non-traditional risk factors (waist circumference, hsC Reactive Protein and fibrinogen); subclinical vascular (carotid intima-media thickness, pulse wave velocity and ankle/brachial index), cardiac (Cornell voltage-duration product), renal organ damage (creatinine, glomerular filtration and albumin/creatinine index), and antihypertensive and lipid-lowering drugs. At baseline, the diabetics presented a mean age of 59.9 years, versus 55.2 years in the subjects with metabolic syndrome (p = 0.03). Diastolic blood pressure, total cholesterol and HDL-cholesterol were lower among the patients with diabetes, while blood glucose and HbA1c, as well as antihypertensive and lipid-lowering drug use, were greater. At evaluation after one year, the diabetics showed a decrease in BMI (-0.39), diastolic blood pressure (-3.59), and an increase in fibrinogen (30.23 mg/dL), ankle/brachial index (0.07) and the number of patients with ankle/brachial index pathologic decreased in 6. In turn, the patients with metabolic syndrome showed an increase in HDL-cholesterol (1-91 mg/dL), fibrinogen (25.54 mg/dL), Cornell voltage-duration product (184.22 mm/ms), ankle/brachial index (0.05) and the use of antihypertensive and lipid-lowering drugs, and a reduction in serum glucose (3.74 mg/dL), HOMA, systolic (-6.76 mmHg), diastolic blood pressure (-3.29 mmHg), and pulse wave velocity (-0.72 m/s). The variable that best predicted a decrease in pulse wave velocity in subjects with metabolic syndrome was seen to be an increase in antihypertensive drug use. The annual assessment of cardiovascular risk factors and the decrease in pulse wave velocity was more favorable in the patients with metabolic syndrome, probably influenced by the increased percentage of subjects treated with antihypertensive and lipid lowering drugs in this group.

Analytical Eco-Scale for Assessing the Greenness of a Developed RP-HPLC Method Used for Simultaneous Analysis of Combined Antihypertensive Medications.

PubMed

Mohamed, Heba M; Lamie, Nesrine T

2016-09-01

In the past few decades the analytical community has been focused on eliminating or reducing the usage of hazardous chemicals and solvents, in different analytical methodologies, that have been ascertained to be extremely dangerous to human health and environment. In this context, environmentally friendly, green, or clean practices have been implemented in different research areas. This study presents a greener alternative of conventional RP-HPLC methods for the simultaneous determination and quantitative analysis of a pharmaceutical ternary mixture composed of telmisartan, hydrochlorothiazide, and amlodipine besylate, using an ecofriendly mobile phase and short run time with the least amount of waste production. This solvent-replacement approach was feasible without compromising method performance criteria, such as separation efficiency, peak symmetry, and chromatographic retention. The greenness profile of the proposed method was assessed and compared with reported conventional methods using the analytical Eco-Scale as an assessment tool. The proposed method was found to be greener in terms of usage of hazardous chemicals and solvents, energy consumption, and production of waste. The proposed method can be safely used for the routine analysis of the studied pharmaceutical ternary mixture with a minimal detrimental impact on human health and the environment.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

PubMed

Shiga, Yuhei; Miura, Shin-Ichiro; Norimatsu, Kenji; Hitaka, Yuka; Nagata, Itsuki; Koyoshi, Rie; Morii, Joji; Kuwano, Takashi; Uehara, Yoshinari; Inoue, Asao; Shirotani, Tetsuro; Fujisawa, Kazuaki; Matsunaga, Eiyu; Saku, Keijiro

2015-12-01

We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients. © The Author(s) 2014.

Effect of the Medicare Part D coverage gap on medication use among patients with hypertension and hyperlipidemia.

PubMed

Li, Pengxiang; McElligott, Sean; Bergquist, Henry; Schwartz, J Sanford; Doshi, Jalpa A

2012-06-05

Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. Quasi-experimental study using pre-post design and contemporaneous control group. Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. Because this study was nonrandomized, unobserved differences may still exist between study groups. The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low-value medications may also increase. Penn-Pfizer Alliance and American Heart Association.

Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

PubMed

Kaneko, Reina; Sano, Kota; Ono, Shunsuke

2018-07-01

The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

Blood pressure as a therapeutic target in stroke.

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-01-01

Stroke, as a clinical manifestation of the cardiovascular diseases, is one of the leading causes of death and disability in both developed and developing countries. Hypertension is by far, the most important risk factor for stroke. Epidemiological data indicate that the risk of stroke increases with both systolic and diastolic blood pressure elevation, from levels of 115/75 mmHg. It is also evident that most adults worldwide have values above these limits, thus emphasizing the importance of blood pressure as a risk factor for stroke. Clinical trials of antihypertensive treatment, both in studies that have compared active drugs against placebo or in those comparing different types of drugs have clearly demonstrated a protective effect of blood pressure reduction in the prevention of stroke. The degree of protection is directly related to blood pressure reduction and, the lower the level, the better the prognosis. Although data on secondary stroke prevention are scarcer, studies also seem to indicate that lowering blood pressure with antihypertensive treatment protects against stroke recurrence. At the present moment there is still uncertainty on 2 different aspects regarding the relationship between antihypertensive treatment and stroke. First, the blood pressure management during acute stroke has not adequately investigated in clinical trials. Second, the possibility of a protective role of specific types of antihypertensive drugs beyond blood pressure reduction is a matter of debate. Independently of these unresolved issues, prevention of hypertension development by lifestyle changes and adequate treatment and control to the hypertensive population will be a very effective measure in reducing stroke incidence, stroke recurrence, and stroke mortality.

Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries.

PubMed

Dehghan, Mahshid; Mente, Andrew; Teo, Koon K; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Avezum, Alvaro; Probstfield, Jeffrey L; Dans, Tony; Yusuf, Salim

2012-12-04

Diet quality is strongly related to cardiovascular disease (CVD) incidence, but little is known about its impact on CVD events in older people at high risk of CVD and receiving effective drugs for secondary prevention. This study assessed the association between diet quality and CVD events in a large population of subjects from 40 countries with CVD or diabetes mellitus with end-organ damage receiving proven medications. Overall, 31 546 women and men 66.5±6.2 years of age enrolled in 2 randomized trials, the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND), were studied. We used 2 dietary indexes: the modified Alternative Healthy Eating Index and the Diet Risk Score. The association between diet quality and the primary composite outcome of CV death, myocardial infarction, stroke, or congestive heart failure was assessed with Cox proportional hazard regression with adjustment for age, sex, trial enrollment allocation, region, and other known confounders. During the 56-month follow-up, there were 5190 events. Patients in the healthier quintiles of modified Alternative Healthy Eating Index scores had a significantly lower risk of CVD (hazard ratio, 0.78; 95% confidence interval, 0.71-0.87, top versus lowest quintile of modified Alternative Healthy Eating Index). The reductions in risk for CV death, myocardial infarction, and stroke were 35%, 14%, and 19%, respectively. The protective association was consistent regardless of whether patients were receiving proven drugs. A higher-quality diet was associated with a lower risk of recurrent CVD events among people ≥55 years of age with CVD or diabetes mellitus. Highlighting the importance of healthy eating by health professionals would substantially reduce CVD recurrence and save lives globally.

Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

PubMed

Liu, Zhendong; Zhao, Yingxin; Wei, Fang; Ye, Lin; Lu, Fanghong; Zhang, Hua; Diao, Yutao; Song, Hongbin; Qi, Zaiwen

2014-03-01

To explore synergistic effect between angiotensin II receptor blockers (ARBs) and statins on Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. This study was a 2 × 2 factorial randomized, prospective, double-blind, placebo-controlled trial. One hundred and fifty nine hypertensive patients with carotid atherosclerosis were randomized to the administration of control group, telmisartan group, rosuvastatin group, and combination group (telmisartan plus rosuvastatin) base on hydrochlorothiazide treatment. Carotid ultrasonography, parameters of Th17/Treg functional axis, interleukin (IL)-1β, IL-2, interferon (IFN)-γ, hypersensitive C-reactive protein (hsCRP), monocyte chemotactic protein (MCP)-1 were evaluated. Blood pressure level markedly reduced in four groups. There was significantly synergistic effect of combination of telmisartan with rosuvastatin on reducing carotid imtima-media thickness (IMT), Th17 cells frequency, IL-17, IL-6, IL-23, tumor necrosis factor (TNF)-α, expression of retinoic acid receptor-related orphan receptor (ROR)γt mRNA, Th17/Treg ratio, IL-1β, IL-2, IFN-γ, hsCRP, and MCP-1, and increasing Treg cells frequency, IL-10, transforming growth factor(TGF)-β1, and expression of forkhead/winged helix transcription factor (Foxp3) mRNA (all P<0.05). Change rate of IMT statistical positively related to descent rates of Th17 cells frequency, IL-17, IL-6, IL-23, TNF-α, expression of RORγt mRNA, Th17/Treg ratio, IL-1β, IL-2, IFN-γ, hsCRP, and MCP-1, and negatively related to increased rates of Treg frequency, IL-10, TGF-β1, and expression of Foxp3 mRNA, respectively (all P<0.05). There is a synergistic effect of combination of telmisartan with rosuvastatin on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Improving Adherence to Treatment and Reducing Economic Costs of Hypertension: The Role of Olmesartan-Based Treatment.

PubMed

Costa, Francesco Vittorio

2017-09-01

Poor adherence to antihypertensive treatment is the single most important factor of unsatisfactory blood pressure (BP) control. This review focuses on therapy-related factors affecting adherence and suggests how to improve it with a wise choice of treatment schedule. Complex drug treatment schemes, poor tolerability and drug substitutions are frequent causes of poor adherence which, in turn, causes insufficient BP control, greater incidence of cardiovascular events and, finally, higher global health costs. The effects of prescribing generic drugs and of drug substitutions on adherence is also discussed. In terms of adherence, generic drugs do not seem to be better than branded drugs, unless patients have to bear very high "out of pocket" expenses to buy original drugs, suggesting no advantages in switching drug with the mere goal of reducing the cost of therapy. An important role in improving adherence (and thus cardiovascular events and health expenditure) is also played by the availability of fixed-dose combinations; among antihypertensive drugs, angiotensin receptor blockers (ARBs) are those associated with higher levels of adherence and persistence. Among ARBs, olmesartan stands out for a wide choice of effective fixed-dose combinations.

Simultaneous determination of multiple angiotensin type 1 receptor antagonists and its application to high-throughput pharmacokinetic study

NASA Astrophysics Data System (ADS)

Zhu, Xiaoyan; Sun, Jianguo; Hao, Haiping; Wang, Guangji; Hu, Xiaoling; Lv, Hua; Gu, Shenghua; Wu, Xiaoming; Xu, Jinyi

2008-05-01

A rapid and sensitive high performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) detection was developed for the simultaneous determination of multiple angiotensin type 1 receptor antagonists (AT1RAs) WX472, WX581, 1b and telmisartan in rat plasma for the purpose of high-throughout pharmacokinetic screening. The method was operated under selected reaction monitoring (SRM) mode in the positive ion mode. The analytes and the internal standard (pitavastatin) were extracted from 100 [mu]L rat plasma under acidic conditions by liquid-liquid extraction with ethyl acetate. The analytes and internal standard were baseline separated on a Gemini analytical column (3 [mu]m, 150 mm × 2.0 mm) with the adoption of a gradient elution using acetonitrile and 0.05% aqueous formic acid. The standard curves were linear in the concentration ranges of 4.5-900 ng/mL for WX472, 5-1000 ng/mL for WX581 and 0.5-100 ng/mL for 1b and telmisartan. Intra- and inter-batch precisions (R.S.D.%) were all within 15% and the method assessed a quite good accuracy (R.E.%). Recoveries were found to be >65% for all the compounds and no obvious matrix effects were found. This method has been successfully applied to the high-throughput pharmacokinetic screening study for both cassette dosing and cassette analysis of four compounds to rats. Significant drug-drug interactions were observed after cassette dosing. The study suggested that cassette analysis of pooled samples would be a better choice for the high-throughput pharmacokinetic screening of angiotensin type 1 receptor antagonists.

Randomised clinical trial of strategies for improving medication compliance in primary hypertension.

PubMed

Sackett, D L; Haynes, R B; Gibson, E S; Hackett, B C; Taylor, D W; Roberts, R S; Johnson, A L

1975-05-31

230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.

Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Kang, Kyung Koo; Kim, Jeong Hoon; Ahn, Byoung Ok; Yoo, Moohi

2009-03-01

A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3(rd) week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.

Methods of defining hypertension in electronic medical records: validation against national survey data

PubMed Central

Peng, Mingkai; Chen, Guanmin; Kaplan, Gilaad G.; Lix, Lisa M.; Drummond, Neil; Lucyk, Kelsey; Garies, Stephanie; Lowerison, Mark; Weibe, Samuel; Quan, Hude

2016-01-01

Background Electronic medical records (EMR) can be a cost-effective source for hypertension surveillance. However, diagnosis of hypertension in EMR is commonly under-coded and warrants the needs to review blood pressure and antihypertensive drugs for hypertension case identification. Methods We included all the patients actively registered in The Health Improvement Network (THIN) database, UK, on 31 December 2011. Three case definitions using diagnosis code, antihypertensive drug prescriptions and abnormal blood pressure, respectively, were used to identify hypertension patients. We compared the prevalence and treatment rate of hypertension in THIN with results from Health Survey for England (HSE) in 2011. Results Compared with prevalence reported by HSE (29.7%), the use of diagnosis code alone (14.0%) underestimated hypertension prevalence. The use of any of the definitions (38.4%) or combination of antihypertensive drug prescriptions and abnormal blood pressure (38.4%) had higher prevalence than HSE. The use of diagnosis code or two abnormal blood pressure records with a 2-year period (31.1%) had similar prevalence and treatment rate of hypertension with HSE. Conclusions Different definitions should be used for different study purposes. The definition of ‘diagnosis code or two abnormal blood pressure records with a 2-year period’ could be used for hypertension surveillance in THIN. PMID:26547088

ENALAPRIL: PHARMACOKINETIC/DYNAMIC INFERENCES FOR COMPARATIVE DEVELOPMENTAL TOXICITY

EPA Science Inventory

Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the ...

Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

PubMed Central

Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.

2013-01-01

Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student’s T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481

Translating data on antihypertensive drugs into clinical practice.

PubMed

Weber, M A

1998-06-01

Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma: should they choose drugs from older classes that have not provided full protection? Or, should they prescribe newer agents with exciting potential but with, as yet, unproved endpoint benefits in hypertension? Until currently ongoing prospective trials of antihypertensive therapy are completed, physicians must be guided by their own interpretations of the available data.

[Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance].

PubMed

Zhang, Qiuzan; Wang, Yanrong; Liu, Yingli; Yang, Qian; Wang, Xiuru; Wang, Qiang; Zhang, Chenming; Wang, Bangmao

2015-04-01

To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05). Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.

Unsuccessfully Treated Hypertension: A Major Public Health Problem With a Potential Solution.

PubMed

Furberg, Curt D; Sealey, Jean E; Blumenfeld, Jon D

2017-09-01

About one-half of all hypertensive adults do not have their blood pressure controlled. They are often prescribed medications that conform to national guidelines but they continue to have elevated blood pressure. This public health problem might be improved by applying plasma renin guided therapy. A contributor to the public health problem of unsuccessfully treated hypertension is that the circulating renin-angiotensin system (RAS) is not recognized in treatment guidelines as clinically relevant for the treatment of hypertension or as important as the body salt status for determining blood pressure levels. Another contributor to the problem is the lack of specificity in the package inserts for antihypertensive drugs. They do not specifically state under the heading "Indications" that RAS blockers are primarily most effective in hypertensive subjects with medium and high plasma renin levels; by contrast, natriuretic drugs are most effective in those with low plasma renin levels. Literature review. To address the problem of unsuccessfully treated hypertension, we recommend that the "Indications" section of package inserts for antihypertensive drugs be more specific. The primary indication for RAS blockers ought to be hypertension with medium and high plasma renin levels, and natriuretic agents for those with low plasma renin levels. Similar language ought to be added to treatment guidelines. Additionally, 3 other reasons for lack of blood pressure control also need to be addressed-failure to prescribe antihypertensive drugs to hypertensive subjects, failure of patients to fill prescriptions, and low drug adherence. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia Shengjie; Ni Zheming; Xu Qian

Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena{sup -}, Lis{sup -} (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap{sup -} and Ram{sup -} (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena{sup -}, Lis{sup -} were much longer compared with Cap{sup -}, Ram{sup -}more » in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented. - Graphical abstract: A series of antihypertensive drugs including Enalpril, Lisinopril, Captopril and Ramipril were intercalated into Zn/Al-NO{sub 3}-LDHs successfully by coprecipitation or ion-exchange technique. We focus on the structure, thermal property and low/controlled release property of as-synthesized drug-LDH composite intended for the possibility of applying these LDH-antihypertensive nanohybrids in drug delivery and controlled release systems.« less

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

PubMed Central

Diogo, Lucilia N.; Monteiro, Emília C.

2014-01-01

Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

Evaluation of polyherbal formulation (SJT-HT-03) for antihypertensive activity in albino rats.

PubMed

Ghelani, Hardik S; Patel, Bipin M; Gokani, Rina H; Rachchh, Manish A

2014-01-01

Hypertension is an incurable pathological condition and lifelong therapy is required. Long term use of conventional synthetic anti-hypertensive drugs is associated with a spectrum of toxic effects. However, therapeutic interventions using herbal drugs for hypertension have gained considerable attention worldwide. To evaluate the anti-hypertensive activity of polyherbal formulation (SJT-HT-03). The polyherbal formulation (SJT-HT-03) comprises of leaves of Aegle marmelos L., fruits of Benincasa hispida Thunb., Garcinia indica Thouars, and flowers of Musa paradiasica L., Rosa indica L., Hibiscus rosa sinensis L. Selected plants as mentioned above were collected, dried and extracted with different solvents. Formulation SJT-HT-03 (250 mg/kg, p.o.), was evaluated using two kidney one clip (2K1C) model and deoxycorticosterone acetate (DOCA)-salt-induced hypertension model using the enalapril (10 mg/kg, p.o.) and hydrochlorothiazide (5 mg/kg, p.o.) as a reference standard drug in respective models. SJT-HT-03 significantly reduced (P < 0.001, one-way analysis of variance followed by Turkey's multiple comparison tests) systolic as well as diastolic blood pressure (BP) in 2K1C and DOCA-salt model. Further, SJT-HT-03 has shown a significant reduction (P < 0.01) in angiotensin converting enzyme (ACE) activity in serum, clipped kidney as well as in lungs in 2K1C model, whereas significant reduction (P < 0.05) in serum Na(+) and increase in serum K(+) level in DOCA model. Polyherbal formulation SJT-HT-03 possess significant anti-hypertensive activity by producing direct depressant effect on heart, inhibition of ACE, aldosterone antagonistic as well as diuretic effect and thereby act on multiple targets to achieve optimal effect.

Health services research in the public healthcare system in Hong Kong: an analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data.

PubMed

Wong, Martin C S; Jiang, Johnny Y; Tang, Jin-ling; Lam, Augustine; Fung, Hong; Mercer, Stewart W

2008-06-25

Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example. Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients' demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients' demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > or = 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients.

Initial antihypertensive prescription and switching: a 5 year cohort study from 250,851 patients.

PubMed

Wong, Martin C S; Tam, Wilson W S; Cheung, Clement S K; Tong, Ellen L H; Sek, Antonio C H; John, George; Cheung, N T; Yan, Bryan P Y; Yu, C M; Leeder, Stephen; Griffiths, Sian

2013-01-01

Adverse effects of antihypertensive therapy incur substantial cost. We evaluated whether any major classes of antihypertensive drugs were significantly associated with switching as a proxy measure of medication side effects in a large Chinese population in Hong Kong. From a clinical database, all adult patients newly prescribed an antihypertensive mono-therapy in Hong Kong between the years 2001-2003 and 2005 were included. Those who paid only one visit, died or stayed in the cohort for <180 days after the prescription, or prescribed more than one antihypertensive agent were excluded. The factors associated with switching at 180 days were evaluated by multivariate regression analyses. Age, gender, payment status, service type, district of residence, drug class, systolic and diastolic blood pressure levels were predictor variables. From 250,851 subjects, 159,813 patients were eligible. A total of 6,163 (3.9%) switched their medications within 180 days. Patients prescribed thiazide diuretics had the highest switching rate (5.6%), followed by ACEIs (4.5%), CCBs (4.4%) and beta-blockers (3.2%). When compared with ACEIs, patients on thiazide diuretics were significantly more likely to be switchers (adjusted odds ratio [AOR] 1.49, 95% C.I. 1.31-1.69, p<0.001), whilst patients prescribed CCBs and beta-blockers were similarly likely to have switching. Following these patients up for 5 years showed that thiazide had the most marked increase in switching rate. The higher rates of switching among thiazide diuretics in this study might raise a probably greater incidence of their adverse effects in this Chinese population, yet other factors might also influence switching rates. Patients prescribed thiazide diuretics for longer term should be observed for their intolerability.

The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.

PubMed

Kandzari, David E; Kario, Kazuomi; Mahfoud, Felix; Cohen, Sidney A; Pilcher, Garrett; Pocock, Stuart; Townsend, Raymond; Weber, Michael A; Böhm, Michael

2016-01-01

Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation. Copyright © 2015 Elsevier Inc. All rights reserved.

[Arterial hypertension, antihypertensive therapy, and visit-to-visit blood pressure variability of elderly nursing home residents].

PubMed

Könner, F; Kuhnert, R; Budnick, A; Kolloch, R; Scholze, J; Dräger, D; Kreutz, R

2014-11-01

Arterial hypertension is a common health problem in older nursing home residents (NHR). The aim of this study was to prospectively analyze blood pressure (BP) patterns, antihypertensive therapy, and visit-to-visit BP variability in NHR. BP, visit-to-visit variability (estimated by standard deviation of means) of systolic BP (SBP) were analyzed in 12 nursing homes in Germany. NHR who were at least 65 years old and had no moderate or severe dementia were studied at baseline (T0), after 3 and 6 months, respectively. BP data were available for 177 NHR (mean age 83.8, 69.5% female) at T0.  A total of 90.4% NHR was affected by hypertension. Mean systolic/diastolic blood pressure was 130,1/75,5 mmHg. BP values of ≥ 140/90 mmHg were found in 29.9%, while 33.9% of NHR exhibited SBP values < 120 mmHg. At least one antihypertensive drug was used in 84.2%, and 40.7% of NHR were treated with at least three different drugs. The median of the visit-to-visit SBP variability was 9.05 (Min. 0, Max. 35.78); an influence of age, sex, and type of antihypertensive medication was not found. Elderly German NHR showed a high prevalence of hypertension and BP was controlled in 80%. However, a large proportion received intensive BP lowering pharmacotherapy and exhibited SBP values clearly lower than recommend target values between 140 and 150 mmHg particularly for elderly patients over 80 years. Thus, to avoid overtreatment BP should be monitored closely to adapt antihypertensive therapy in this population. © Georg Thieme Verlag KG Stuttgart · New York.

Postural Changes in Measures of Arterial Stiffness in Hypertensive Subjects on Antihypertensive Drug Therapy: A Prospective, Pilot Study.

PubMed

Sule, Ashish Anil; Jun, Du Qi; Cheong, Chin Yee

2017-06-01

Prospective study with a controlled arm to know if there are variations of measures of arterial stiffness with posture in subjects with hypertension on antihypertensive medications. We studied postural variations of measures of arterial stiffness in 21 subjects with diagnosed hypertension on antihypertensive medications and compared them with 21 normotensive subjects. All subjects underwent pulse-wave analysis on SphygmoCor in the morning between 8 am to 10 am initially in supine and then in sitting position after 3 minutes. Summary measures on demographics, and blood pressure characteristics at sitting and supine positions are obtained. Differences between characteristics at supine and sitting position are compared using nonparametric paired test of Wilcoxon signed-rank test. A value of p  < 0.05 was accepted as statistically significant. Antihypertensive medications decreased the supine aortic augmentation pressure (AAP) and augmentation index (AI) but not significantly. When subgroups of patients with antihypertensive treatment were analyzed, it was noted that angiotensin-converting enzyme inhibitor and angiotensin receptor blocker group (12) decreased AAP and AI significantly in supine position compared with patients on other antihypertensive medications (9) ( p -value 0.034 and 0.038, respectively). There was no significant difference in other groups of calcium channel blockers, β-blockers, or diuretics. However, in normotensive control arm, there was an increase in AAP and AI in the supine position. In hypertensive subjects, on antihypertensive, there was reduction in AAP and AI in supine position compared with those of normotensives. The significance of the decrease in AAP and AI in supine position on antihypertensive needs to be studied further.

Doxazosin in the current treatment of hypertension.

PubMed

Wykretowicz, Andrzej; Guzik, Przemyslaw; Wysocki, Henryk

2008-03-01

Evidence from various studies has shown that even a very small reduction in the blood pressure explains the majority of benefits in cardiovascular outcomes. Although doxazosin is a relatively old drug, it is a very effective add-on therapeutic agent. It has been used in a variety of clinical trials, including different groups of hypertensive patients such as diabetics, the elderly, patients with benign prostatic hyperplasia or hypercholesterolaemia, the obese or Afro-Americans and in combination with all major groups of antihypertensive drugs such as: calcium channel antagonists, diuretics, beta-adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers. The purpose of this article is to review the role of doxazosin in the current treatment of hypertension. English-language reports published in 1986 - 2007 were retrieved. Data extraction was based on articles reporting at least 15 or more patients treated with combination of doxazosin with other antihypertensive drugs. In these studies doxazosin in either standard or extended-release formulation was added as a second- or third-line agent. The two formulations of doxazosin, although chemically identical, appear to differ in some other effects. A large proportion of patients demonstrated a favourable blood pressure response with relatively few treatment-associated side effects showing that this drug appears to be a valuable add-on antihypertensive treatment option. Doxazosin reduces blood pressure and additionally influences other risk factors of coronary heart disease. However, it should be clearly stated that the clinical role of 'beyond blood pressure' effects of doxazosin are largely undetermined.

Recruitment of participants through community pharmacies for a pharmacogenetic study of antihypertensive drug treatment.

PubMed

van Wieren-de Wijer, Diane B M A; Maitland-van der Zee, Anke-Hilse; de Boer, Anthonius; Stricker, Bruno H Ch; Kroon, Abraham A; de Leeuw, Peter W; Bozkurt, O; Klungel, Olaf H

2009-04-01

To describe the design, recruitment and baseline characteristics of participants in a community pharmacy based pharmacogenetic study of antihypertensive drug treatment. Participants enrolled from the population-based Pharmaco-Morbidity Record Linkage System. We designed a nested case-control study in which we will assess whether specific genetic polymorphisms modify the effect of antihypertensive drugs on the risk of myocardial infarction. In this study, cases (myocardial infarction) and controls were recruited through community pharmacies that participate in PHARMO. The PHARMO database comprises drug dispensing histories of about 2,000,000 subjects from a representative sample of Dutch community pharmacies linked to the national registrations of hospital discharges. In total we selected 31010 patients (2777 cases and 28233 controls) from the PHARMO database, of whom 15973 (1871 cases, 14102 controls) were approached through their community pharmacy. Overall response rate was 36.3% (n = 5791, 794 cases, 4997 controls), whereas 32.1% (n = 5126, 701 cases, 4425 controls) gave informed consent to genotype their DNA. As expected, several cardiovascular risk factors such as smoking, body mass index, hypercholesterolemia, and diabetes mellitus were more common in cases than in controls. Furthermore, cases more often used beta-blockers and calcium-antagonists, whereas controls more often used thiazide diuretics, ACE-inhibitors, and angiotensin-II receptor blockers. We have demonstrated that it is feasible to select patients from a coded database for a pharmacogenetic study and to approach them through community pharmacies, achieving reasonable response rates and without violating privacy rules.

Pharmacy Use and Costs in Employer-Provided Health Plans. Insights for TRICARE Benefit Design from the Private Sector

DTIC Science & Technology

2005-01-01

non - steroidal anti - inflammatory drugs ( NSAIDs ), oral antihistamines, gastrointestinal agents, and oral...National Defense Authorization Act NSAID non - steroidal anti - inflammatory drug OLS ordinary least squares p-value probability value P&T Pharmacy...antihypertensives, non - steroidal anti - inflammatory drugs ( NSAIDs ), oral antihistamines, gastrointestinal agents, and oral hy-

Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

PubMed

Schiffrin, Ernesto L

2015-12-04

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

PubMed Central

Yu, Ting; Zhao, Shengnan; Li, Ziqiang; Wang, Yi; Xu, Bei; Fang, Dailong; Wang, Fazhan; Zhang, Zhi; He, Lili; Song, Xiangrong; Yang, Jian

2016-01-01

Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic-co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future. PMID:27898022

Number of daily antihypertensive drugs and the risk of osteoporotic fractures in older hypertensive adults: National health insurance service - Senior cohort.

PubMed

Kim, So Yeon; Kim, Sunyoung; Choi, Sung Eun; Kim, Byung Sung; Choi, Hyun Rim; Hwang, Deri; Won, Chang Won

2017-07-01

Antihypertensive medication represents one of the most common prescriptions for senior individuals. Numerous studies have assessed the influence of antihypertensive treatment on the risk for osteoporotic fracture, yet much controversy remains. We analyzed the relationship between the incidence of osteoporotic fracture and the average number of daily antihypertensive drugs (NDAD) included in the prescription of elderly hypertensive patients. The study population was derived from the National Health Insurance Service-Senior Cohort (2002-2013), and consisted of elderly patients (≥60 years) diagnosed with hypertension in 2009, who did not have osteoporotic fractures in 2008, and underwent at least one national health check-up between 2009 and 2013, and had complete records after 2010. The outcome measured was the incidence of osteoporotic fractures between 2010 and 2013. The study population was stratified into the three groups (low, moderate, and high), in terms of NDAD. A total of 137,304 hypertensive patients were included. A multivariate model corrected by age, gender, body mass index, systolic blood pressure, underlying disease, smoking status, and use of medicines showed that the groups with moderate and high NDAD exhibited, respectively, 12% and 16% lower risk of osteoporotic fracture compared to that in the group with low NDAD. In terms of the risk of osteoporotic fracture associated with the number of daily thiazide diuretics (NDTD), the adjusted odds ratios (aOR; 95%CI) were 0.89 (0.84-0.94) and 0.93 (0.84-1.02) in the groups with moderate and high NDTD, respectively compared to low NDTD as reference. As to NDADnotTD, the aOR (95%CI) were 0.90 (95%CI, 0.86-0.94) and 0.89 (95%CI, 0.84-0.95) in the groups with moderate and high NDADnotTD, respectively compared to low NDADnotTD as reference. In elderly hypertensive patients, the incidence of osteoporotic fracture decreased as the NDAD increased. The incidence rate of osteoporotic fracture also decreased with the increase in the number of daily non-thiazide antihypertensive drugs. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice.

PubMed

Wang, Xingxu; Ye, Yong; Gong, Hui; Wu, Jian; Yuan, Jie; Wang, Shijun; Yin, Peipei; Ding, Zhiwen; Kang, Le; Jiang, Qiu; Zhang, Weijing; Li, Yang; Ge, Junbo; Zou, Yunzeng

2016-08-01

Angiotensin II (AngII) type 1 receptor blockers (ARBs) have been effectively used in hypertension and cardiac remodeling. However, the differences among them are still unclear. We designed this study to examine and compare the effects of several ARBs widely used in clinics, including Olmesartan, Candesartan, Telmisartan, Losartan, Valsartan and Irbesartan, on the ACE-AngII-AT1 axis and the ACE2-Ang(1-7)-Mas axis during the development of cardiac remodeling after pressure overload. Although all of the six ARBs, attenuated the development of cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) for 2 or 4weeks in the wild-type mice evaluated by echocardiography and hemodynamic measurements, the degree of attenuation by Olmesartan, Candesartan and Losartan tended to be larger than that of the other three drugs tested. Additionally, the degree of downregulation of the ACE-AngII-AT1 axis and upregulation of the ACE2-Ang(1-7)-Mas axis was higher in response to Olmesartan, Candesartan and Losartan administration in vivo and in vitro. Moreover, in angiotensinogen-knockdown mice, TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan, Candesartan and Losartan but not by Telmisartan, Valsartan and Irbesartan administration. Furthermore, only Olmesartan and Candesartan could downregulate the ACE-AngII-AT1 axis and upregulate the ACE2-Ang(1-7)-Mas axis in vitro. Our data suggest that Olmesartan, Candesartan and Losartan could effectively inhibit pressure overload-induced cardiac remodeling even when with knockdown of Ang II, possibly through upregulation of the expression of the ACE2-Ang(1-7)-Mas axis and downregulation of the expression of the ACE-AngII-AT1 axis. In contrast, Telmisartan, Valsartan and Irbesartan only played a role in the presence of AngII, and Losartan had no effect in the presence of AngII in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypertension in the African American population: A succinct look at its epidemiology, pathogenesis, and therapy.

PubMed

Ortega, Luis M; Sedki, Emad; Nayer, Ali

2015-01-01

Arterial hypertension is prevalent in the black population in the United States. It is directly related to cardiovascular and kidney damage. Its pathogenesis is complex and includes the high incidence of obesity, salt sensitivity and the activation of the renin-angiotensin-aldosterone system. This complexity requires a therapeutic combination that includes changes in dietary habits and appropriate antihypertensive regimes. The International Society of Hypertension in Blacks recommends initiating dietary intervention for values of systolic/diastolic arterial blood pressure above 115/75 mmHg and maintaining arterial blood pressure below 135/85 mmHg using appropiate antihypertensive medication. The most adequate antihypertensive drug for this population has yet to be determined. Copyright © 2015. Published by Elsevier España, S.L.U.

Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates.

PubMed

Liu, Jie; Liu, Qin; Yang, Xue; Xu, Shengtao; Zhang, Hengyuan; Bai, Renren; Yao, Hequan; Jiang, Jieyun; Shen, Mingqin; Wu, Xiaoming; Xu, Jinyi

2013-12-15

A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50=0.4 nM) and 15e (IC50=5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of γ-cyclodextrin effect on permeation of lipophilic drugs: application of cellophane/fused octanol membrane.

PubMed

Muankaew, Chutimon; Jansook, Phatsawee; Loftsson, Thorsteinn

2017-06-01

According to the Biopharmaceutics Classification System, oral bioavailability of drugs is determined by their aqueous solubility and the ability of the dissolved drug molecules to permeate lipophilic biological membranes. Similarly topical bioavailability of ophthalmic drugs is determined by their solubility in the aqueous tear fluid and their ability to permeate the lipophilic cornea. Enabling pharmaceutical excipients such as cyclodextrins can have profound effect on the drug bioavailability. However, to fully appreciate such enabling excipients, the relationship between their effects and the physicochemical properties of the permeating drug needs to be known. In this study, the permeation enhancing effect of γ-cyclodextrin (γCD) on saturated drug solutions containing hydrocortisone (HC), irbesartan (IBS), or telmisartan (TEL) was evaluated using cellophane and fused cellulose-octanol membranes in a conventional Franz diffusion cell system. The flux (J), the flux ratio (J R ) and the apparent permeability coefficients (P app ) demonstrate that γCD increases drug permeability. However, its efficacy depends on the drug properties. Addition of γCD increased P app of HC (unionized) and IBS (partially ionized) through the dual membrane but decreased the P app of TEL (fully ionized) that displays low complexation efficacy. The dual cellophane-octanol membrane system was simple to use and gave reproducible results.

In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

PubMed

Guala, A; Leone, D; Milan, A; Ridolfi, L

2017-06-01

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

[Implementation of ontology-based clinical decision support system for management of interactions between antihypertensive drugs and diet].

PubMed

Park, Jeong Eun; Kim, Hwa Sun; Chang, Min Jung; Hong, Hae Sook

2014-06-01

The influence of dietary composition on blood pressure is an important subject in healthcare. Interactions between antihypertensive drugs and diet (IBADD) is the most important factor in the management of hypertension. It is therefore essential to support healthcare providers' decision making role in active and continuous interaction control in hypertension management. The aim of this study was to implement an ontology-based clinical decision support system (CDSS) for IBADD management (IBADDM). We considered the concepts of antihypertensive drugs and foods, and focused on the interchangeability between the database and the CDSS when providing tailored information. An ontology-based CDSS for IBADDM was implemented in eight phases: (1) determining the domain and scope of ontology, (2) reviewing existing ontology, (3) extracting and defining the concepts, (4) assigning relationships between concepts, (5) creating a conceptual map with CmapTools, (6) selecting upper ontology, (7) formally representing the ontology with Protégé (ver.4.3), (8) implementing an ontology-based CDSS as a JAVA prototype application. We extracted 5,926 concepts, 15 properties, and formally represented them using Protégé. An ontology-based CDSS for IBADDM was implemented and the evaluation score was 4.60 out of 5. We endeavored to map functions of a CDSS and implement an ontology-based CDSS for IBADDM.

Methods of defining hypertension in electronic medical records: validation against national survey data.

PubMed

Peng, Mingkai; Chen, Guanmin; Kaplan, Gilaad G; Lix, Lisa M; Drummond, Neil; Lucyk, Kelsey; Garies, Stephanie; Lowerison, Mark; Weibe, Samuel; Quan, Hude

2016-09-01

Electronic medical records (EMR) can be a cost-effective source for hypertension surveillance. However, diagnosis of hypertension in EMR is commonly under-coded and warrants the needs to review blood pressure and antihypertensive drugs for hypertension case identification. We included all the patients actively registered in The Health Improvement Network (THIN) database, UK, on 31 December 2011. Three case definitions using diagnosis code, antihypertensive drug prescriptions and abnormal blood pressure, respectively, were used to identify hypertension patients. We compared the prevalence and treatment rate of hypertension in THIN with results from Health Survey for England (HSE) in 2011. Compared with prevalence reported by HSE (29.7%), the use of diagnosis code alone (14.0%) underestimated hypertension prevalence. The use of any of the definitions (38.4%) or combination of antihypertensive drug prescriptions and abnormal blood pressure (38.4%) had higher prevalence than HSE. The use of diagnosis code or two abnormal blood pressure records with a 2-year period (31.1%) had similar prevalence and treatment rate of hypertension with HSE. Different definitions should be used for different study purposes. The definition of 'diagnosis code or two abnormal blood pressure records with a 2-year period' could be used for hypertension surveillance in THIN. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Influence of psychosocial factors on adherence to antihypertensive drug therapy: results from a Cardiovascular Health Program cohort followed in the Metropolitan Region of Santiago, Chile].

PubMed

Sandoval, Daniela; Chacón, Javier; Muñoz, Reinaldo; Henríquez, Óscar; Koch, Elard; Romero, Tomás

2014-10-01

Inadequate blood pressure control in hypertensive patients remains a persistent health problem in Chile and worldwide. Poor adherence to antihypertensive drug therapy is one of the frequently cited factors. To determine the influence of psychosocial factors in the adherence to drug therapy in hypertensive patients followed through a Cardiovascular Health Program (CHP) that provides free access to primary care centers located in the Metropolitan Region of Santiago, Chile. Cross sectional study. A randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from a universe of 1.484 patients. Adherence to treatment was determined by the Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood pressure were recorded. Validated questionnaires were utilized to assess the patient-physician relationship, awareness of being hypertensive, patient perception of social support, family cohesion, patient self-health assessment and symptoms of emotional stress and depression. The drug therapy adherence was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI 1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient-physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). Our study highlights the influence of inadequate patient-physician relation, high level of emotional stress and depression, low education level and income and male gender in the lack of adherence to antihypertensive drug therapy in hypertensive patients followed throughout the CHP.

Terbinafine-induced lichenoid drug eruption.

PubMed

Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

2017-03-01

Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study.

PubMed

Gu, Dongfeng; He, Jiang; Coxson, Pamela G; Rasmussen, Petra W; Huang, Chen; Thanataveerat, Anusorn; Tzong, Keane Y; Xiong, Juyang; Wang, Miao; Zhao, Dong; Goldman, Lee; Moran, Andrew E

2015-08-01

Hypertension is China's leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world's largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs. The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35-84 y over 2015-2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140-159/90-99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China. Expanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

PubMed

Mauri, Laura; Kario, Kazuomi; Basile, Jan; Daemen, Joost; Davies, Justin; Kirtane, Ajay J; Mahfoud, Felix; Schmieder, Roland E; Weber, Michael; Nanto, Shinsuke; Azizi, Michel

2018-01-01

Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

PubMed

Pavithran, Purushothaman; Prakash, E Sankaranarayanan; Dutta, Tarun K; Madanmohan, Trakroo

2010-02-01

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful MARRIAGE?

PubMed

Rayner, Brian

2004-03-01

Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.

New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

PubMed

Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

2013-12-01

There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.

Comparison of vasculoprotective effects of benidipine and losartan in a rat model of metabolic syndrome.

PubMed

Matsuzaki, Gen; Ishizaka, Nobukazu; Furuta, Kyoko; Hongo, Makiko; Saito, Kan; Sakurai, Ryota; Koike, Kazuhiko; Nagai, Ryozo

2008-06-10

Although antihypertensive drugs confer improvement in endothelial dysfunction and protection from atherogenesis in hypertension, different classes of antihypertensive drugs may elicit different degrees of vasculoprotective effects. We have investigated the effects of a long-acting calcium antagonist, benidipine, and an angiotensin AT(1) receptor antagonist, losartan, on the vascular damage observed in OLETF rats, an animal model of metabolic syndrome. At 34 weeks of age, OLETF rats were treated with either benidipine (3 mg/kg/day, per os) or losartan (25 mg/kg/day, per os) for 8 weeks. The extent of blood pressure reduction, restoration endothelium-dependent aortic relaxation, and elevation of serum nitrite/nitrate concentration did not differ significantly between benidipine- and losartan-treated OLETF rats. Benidipine and losartan also reduced the aortic expression of transforming growth factor-beta1 mRNA and thickening of the vascular wall to a similar extent. Increased cardiac fibrosis was also inhibited by both benidipine and losartan. These data suggest that, when used in an antihypertensive dose, benidipine is as effective as losartan in restoring vascular endothelial function and in suppressing of cardiovascular remodeling in an animal model of metabolic syndrome.

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

PubMed

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

Aliskiren: review of efficacy and safety data with focus on past and recent clinical trials.

PubMed

Sen, Selçuk; Sabırlı, Soner; Ozyiğit, Tolga; Uresin, Yağız

2013-09-01

Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. Clinical data have substantiated that the antihypertensive effectiveness of aliskiren is similar to that of the other major antihypertensive agents. Furthermore, aliskiren has a similar safety profile to placebo. Combination treatment with aliskiren showed significant blood pressure and proteinuria reductions compared with monotherapy. Aliskiren decreases plasma renin activity in contrast to other renin-angiotensin-aldosterone related drugs. The efficacy of aliskiren in treating major cardiovascular events and the prevention of end-organ damage are being investigated in the ASPIRE HIGHER program. Although the first studies of the ASPIRE HIGHER program such as ALOFT, AVOID, AGELESS showed favorable findings, ASPIRE and AVANT-GARDE studies provided contradictory results. Subsequently, the ALTITUDE study was terminated early because of safety issues and lack of beneficial effects. Most recently, the ASTRONAUT trial showed no reduction in cardiovascular death or heart failure rehospitalization with the addition of aliskiren to standard therapy in patients who were hospitalized for heart failure and with reduced left-ventricular ejection fraction. The results of ongoing studies in other patient groups such as the ATMOSPHERE trial are awaited.

Therapeutic strategies to improve control of hypertension.

PubMed

Armario, Pedro; Waeber, Bernard

2013-03-01

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

High blood pressure, Alzheimer disease and antihypertensive treatment.

PubMed

Marfany, Agustí; Sierra, Cristina; Camafort, Miguel; Doménech, Mónica; Coca, Antonio

2018-03-01

Alzheimer's disease (AD), the most common form of dementia, is a complex disease, the mechanisms of which are poorly understood. AD represents 70% of all dementia cases, affecting up to 50% of elderly persons aged 85 or older, with functional dependence, poor quality of life, institutionalization and mortality. Advanced age is the main risk factor of AD, that is why population ageing, due to life expectancy improvements, increases AD incidence and prevalence, as well as the economic, social, and emotional costs associated with this illness. Existing anti-AD drugs present some limitations, as they target specific downstream neurochemical abnormalities while the upstream underlying pathology continues unchecked. Chronic hypertension has been suggested as one of the largest modifiable risk factors for developing AD. At least 25% of all adults and more than 50% of those over 60 years of age have hypertension. Epidemiological studies have shown that hypertension is a risk factor for dementia and AD, but the association is complex. Some studies have demonstrated that antihypertensive drugs can reduce the risk of AD. This review focuses on current knowledge about the relationship between chronic hypertension and AD as well as antihypertensive treatment effect on AD pathogenesis and its clinical outcomes.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

PubMed Central

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. PMID:29489874

The latest development of antihypertensive medication

NASA Astrophysics Data System (ADS)

Nasution, S.; Rey, I.; Effendi-YS, R.

2018-03-01

Hypertension is the most common risk factor for cardiovascular disease, stroke, renal failure, and death. Recent drug monitoring studies found non-adherence to BP lowering therapy in 25% to 65% of patients with apparent treatment-resistant hypertension (TRH). This review focuses on the latest development of antihypertensive medication, such as vasopeptidase inhibitors, aldosterone synthase inhibitors, Soluble Epoxide Hydrolase Inhibitors, agonists of natriuretic peptide receptor, Vasoactive Intestinal Peptide Receptor Agonist, a novel mineralocorticoid receptor antagonist, inhibitors of aminopeptidase A, dopamine β-hydroxylase inhibitor, intestinal Na+/H+ exchanger 3 inhibitor and other agents.

[Evaluation of antihypertensive therapy by ambulatory blood pressure monitoring and establishment of the level of antihypertensive goal on the circadian rhythm of blood pressure].

PubMed

Fujioka, T; Tamaki, S; Fudo, T; Nakae, I; Sugawara, A; Kambara, H

1990-01-01

We have developed a new method for the evaluation of antihypertensive therapy on the circadian rhythm of blood pressure and attempted to determine the indications for antihypertensive therapy and the level of antihypertensive goal. Blood pressures were measured for 24 hours by the use of ambulatory blood pressure monitoring using 630 (ABPM-630) in 50 normotensives, 50 untreated hypertensives and 50 hypertensives undertreatment with various antihypertensive drugs (110 males and 40 females, with a mean age of 53.4 +/- 13.3 yrs). Blood pressure profiles were prepared for determination of the hyperbaric and hypobaric indexes. According to the WHO's definitions for blood pressure, the hyperbaric index was defined as the area above 140 mmHg in systolic blood pressure or 90 mmHg in diastolic blood pressure, and the hypobaric index, as the area below 100 mmHg or 60 mmHg, respectively. The criteria of the hypobaric index was obtained from the mean basal blood pressure (the lowest blood pressure during sleep) of the 50 normotensives. The mean hyperbaric index of the 50 normotensives was 20.4 +/- 40.2/5.5 +/- 15.3 (systole/diastole) mmHg.hour/day and the mean hypobaric index, 12.2 +/- 22.5/9.0 +/- 24.0 mmHg.hour/day. The 50 untreated hypertensives showed a mean hyperbaric index of 281.8 +/- 197.0/156.0 +/- 126.1 mmHg.hour/day and a mean hypobaric index of 0.1 +/- 0.6/0.3 +/- 1.5 mmHg.hour/day. Comparison of the indexes before and after treatment with various antihypertensives showed that a decrease in the hyperbaric index without an increase in the hypobaric index was the most optimal reduction of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Drugs affecting blood pressure variability: an update.

PubMed

Hocht, Christian; Del Mauro, Julieta Sofia; Bertera, Facundo Martín; Taira, Carlos Alberto

2015-01-01

Blood pressure variability (BPV) is considered nowadays a novel risk factor for cardiovascular disease. Clinical evidences support that short-term and long-term BPV independently contribute to target organ damage, cardiovascular events and mortality in patients with hypertension or diabetes. Attenuation of excessive fluctuations of systolic and diastolic BPV has been suggested as an additional therapeutic target in cardiovascular prevention. A growing number of preclinical and clinical studies have focused in the assessment of drug effects or other interventions on the different types of BPV and their contribution in the prevention of cardiovascular events. Prospective clinical trials have shown that antihypertensive classes differ in their ability to control excessive BP fluctuations with an impact in clinical outcomes. Current evidences suggest that calcium channel blockers are more effective than other blood pressure lowering drugs for the reduction of short-term, mid-term and long-term BPV. In order to increase actual knowledge regarding the therapeutic significance of BPV in cardiovascular disease, there is a need for additional clinical studies specifically designed for the study of the relevance of short-term and long-term BPV control by antihypertensive drugs.

The brain renin‐angiotensin system plays a crucial role in regulating body weight in diet‐induced obesity in rats

PubMed Central

Winkler, Martina; Schuchard, Johanna; Stölting, Ines; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Bader, Michael

2016-01-01

Background and Purpose Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain‐related mechanism. Here, we investigated the role of the brain renin‐angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan. Methods Transgenic rats with a brain‐specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild‐type, Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg−1·d−1, 3 months). Results Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain‐dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro‐opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats. Conclusions The brain renin‐angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet‐induced obesity and obesity‐related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS‐driven mechanism. PMID:26892671

Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.

PubMed

Clase, Catherine M; Barzilay, Joshua; Gao, Peggy; Smyth, Andrew; Schmieder, Roland E; Tobe, Sheldon; Teo, Koon K; Yusuf, Salim; Mann, Johannes F E

2017-03-01

Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

PubMed

Majumder, Kaustav; Wu, Jianping

2014-12-24

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

Arterial hypertension in the female world: pathophysiology and therapy.

PubMed

Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

2016-04-01

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.

Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

PubMed Central

Majumder, Kaustav; Wu, Jianping

2014-01-01

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides. PMID:25547491

Therapeutic Efficacy and Safety of Traditional Chinese Medicine Classic Herbal Formula Longdanxiegan Decoction for Hypertension: A Systematic Review and Meta-Analysis.

PubMed

Xiong, Xing-Jiang; Yang, Xiao-Chen; Liu, Wei; Duan, Lian; Wang, Peng-Qian; You, Hu; Li, Xiao-Ke; Wang, Shihan

2018-01-01

Background: The traditional Chinese medicine classic herbal formula Longdanxiegan decoction (LDXGD) is widely used for hypertensive patients in China. Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of LDXGD for hypertension. Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang Database were searched up to February 7, 2017 for randomized control trials in treating hypertension. Results: Nine trials were identified. Compared with antihypertensive drugs, Longdanxiegan decoction plus antihypertensive drugs (LPAD) significantly improved systolic blood pressure (BP) ( n = 138; MD = -4.82 mmHg; 95% CI: -7.89 to -1.76; P = 0.002), diastolic BP ( n = 138; MD = -2.42 mmHg; 95% CI: -3.22 to -1.62; P < 0.00001), categorical BP ( n = 509; RR: 1.26; 95% CI: 1.17 to 1.36; P < 0.00001), hypertension related symptoms ( n = 509; RR: 1.31; 95% CI: 1.15 to 1.49; P < 0.0001), and heart rate ( n = 138; MD = -2.40 bpm; 95% CI: -4.23 to -0.56; P = 0.01). Beneficial effects but no statistically significant reduction in total cholesterol ( n = 138; MD = -0.11 mmol/l; 95% CI: -0.65 to 0.44; P = 0.71), or triglyceride ( n = 138; MD = -0.20 mmol/l; 95% CI: -0.46 to 0.07; P = 0.14) was observed in LPAD. Compared with antihypertensive drugs, LDXGD used alone significantly improved systolic BP, diastolic BP, and hypertension related symptoms. But there was no difference between LDXGD and antihypertensive drugs on categorical BP ( n = 120; RR: 1.09; 95% CI: 0.96 to 1.23; P = 0.18). The safety of LDXGD were still unclear. Conclusions: Due to poor methodological quality of the included trials, as well as potential reporting bias, our review found no conclusive evidence for the effectiveness of LDXGD in treating hypertension. The potential beneficial effects and safety of LDXGD should be assessed in future properly designed trials.

Hypertension: management perspectives.

PubMed

Borghi, Claudio; Cicero, Arrigo F G

2012-10-01

The increasing worldwide prevalence of hypertension and the related increase in cost due to diagnosis, management and negative outcomes forces public health institutions and clinical researchers to find new strategies to improve blood pressure (BP) control. So what are the possible future perspectives for high BP management? Three main points are briefly discussed in this article: individualized therapy, the known genetic contribution to hypertension development and control, and the improvement of disease management, including perspectives on new antihypertensive drug development. It is likely that the integration of the best available current knowledge with recent diagnostic and therapeutic achievements for the management of hypertension prevention and treatment will lead to the early detection of at-risk conditions, early diagnosis, and individualized and efficacious treatment. The most promising antihypertensive drugs currently in development are innovative renin-angiotensin-aldosterone system modulators. Further drugs have potentially interesting mechanisms of action, but renalase analogs are in the very early phases of development, and available endothelin antagonists have a poor safety profile.

Role of dihydropyridinic calcium channel blockers in the management of hypertension.

PubMed

Coca, Antonio; Mazón, Pilar; Aranda, Pedro; Redón, Josep; Divisón, Juan Antonio; Martínez, Javier; Calvo, Carlos; Galcerán, Josep María; Barrios, Vivencio; Roca-Cusachs I Coll, Alexandre

2013-01-01

Dihydropyridinic calcium channel blockers are a subclass of antihypertensive drugs with growing significance in the therapeutic armamentarium. Early studies in the 1990s had aroused certain fears with regard to the safety of the first drugs from this class, since they had a fast onset of action and a short half-life, and thus they were associated with reflex adrenergic activation. New molecules with long half-lives and high lipophilia have shown safety and efficacy in the control of blood pressure, as well as in the reduction of several end points related to hypertension. Moreover, these new molecules, which block special subtypes of calcium channel receptors, provide drugs not only with an action profile that goes beyond the antihypertensive effect, but also with a lower rate of side effects. Therefore, in the light of new studies that include calcium channel blockers alone or in combination, these agents will probably be used even more extensively for the management of hypertension in the following years.

Guide of Hypertensive Crisis Pharmacotherapy.

PubMed

Wani-Parekh, Priyanka; Blanco-Garcia, Carlos; Mendez, Melissa; Mukherjee, Debabrata

2017-01-01

Cardiovascular diseases (CVD) are the number one cause of death globally compared to any other cause. CVD accounts for approximately 17.3 million deaths per year and are rising. Hypertension is the leading risk factor for cardiovascular diseases. Approximately, 80 million people suffer from hypertension in the U.S. While, majority of these individuals are on antihypertensive medications only 54% of individuals with hypertension are optimally controlled. Heart failure and stroke are some of the devastating complications of uncontrolled hypertension. Hypertensive crisis can be classified as either an urgency or emergency; difference between the two is the presence of end organ damage, which is noted in hypertensive emergency. Hypertensive crisis is usually treated by parenteral antihypertensive medications. The main drug classes of drugs for treatment are nitrates, calcium channel blockers, dopamine-1 agonists, adrenergic-blocking agents etc. In this review, we discuss approach to management of hypertensive crisis and each drug class with its physiology and complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study.

PubMed

Corrao, Giovanni; Soranna, Davide; Merlino, Luca; Mancia, Giuseppe

2014-10-01

Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0·86; 95% CI 0·63-1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1·19; 95% CI 0·86-1·63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96-1·47), 0·87 (0·63-1·21) and 1·08 (0·80-1·46). Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Pharmacogenetics and Stroke

PubMed Central

Meschia, James F.

2009-01-01

Genetic variations have been shown to influence drug metabolism, risk of adverse drug events, and pharmacodynamic responses for many drugs routinely used to treat patients with stroke or at risk for stroke. Examples include clopidogrel, statins, antihypertensive medications, and coumadin. Further validation studies are needed to assess the clinical utility of selecting drugs and doses based on genetic tests. Physicians, pharmaceutical companies, regulatory agencies, and health insurers continue to grapple with how best to translate this burgeoning field into effective individualized medicine. PMID:19762696

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed Central

Curtis, J R; Bateman, F J

1975-01-01

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure. PMID:811312

Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

PubMed Central

Kancirová, Ivana; Jašová, Magdaléna; Waczulíková, Iveta; Ravingerová, Táňa; Ziegelhöffer, Attila; Ferko, Miroslav

2016-01-01

Objective(s): Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. Conclusion: In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria. PMID:27482342

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed

Curtis, J R; Bateman, F J

1975-11-22

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.

Innovative lipid-based carriers containing cationic derivatives of polyisoprenoid alcohols augment the antihypertensive effectiveness of candesartan in spontaneously hypertensive rats.

PubMed

Gawryś, Olga; Baranowska, Iwona; Gawarecka, Katarzyna; Świeżewska, Ewa; Dyniewicz, Jolanta; Olszyński, Krzysztof H; Masnyk, Marek; Chmielewski, Marek; Kompanowska-Jezierska, Elżbieta

2018-04-01

Novel lipid-based carriers, composed of cationic derivatives of polyisoprenoid alcohols (amino-prenols, APrens) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), were designed. The carriers, which were previously shown to be nontoxic to living organisms, were now tested if suitable for administration of candesartan, an antihypertensive drug. Spontaneously hypertensive rats (SHR) received injections of candesartan (0.1 mg/kg body weight per day; s.c.) in freshly prepared carriers for two weeks. The rats' arterial pressure was measured by telemetry. Urine and blood collection were performed in metabolic cages. In a separate group of SHR, the pharmacokinetics of the new formulation was evaluated after a single subcutaneous injection. The antihypertensive activity of candesartan administered in DOPE dispersions containing APrens was distinctly greater than that of candesartan dispersions composed of DOPE only or administered in the classic solvent (sodium carbonate). The pharmacokinetic parameters clearly demonstrated that candesartan in APren carriers reached the bloodstream more rapidly and in much greater concentration (almost throughout the whole observation) than the same drug administered in dispersions of DOPE only or in solvent. Serum creatinine (P Cr ) decreased significantly only in the group receiving candesartan in carriers with APrens (from 0.80 ± 0.04 to 0.66 ± 0.09 mg/dl; p < 0.05), whereas in the other groups P Cr remained at the same level after treatment. Moreover, the new derivatives increased the loading capacity of the carriers, which is a valuable feature for any drug delivery system. Taken together, our findings led us to conclude that APrens are potentially valuable components of lipid-based drug carriers.

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

PubMed

Avanzini, F; Palumbo, G; Alli, C; Roncaglioni, M C; Ronchi, E; Cristofari, M; Capra, A; Rossi, S; Nosotti, L; Costantini, C; Pietrofeso, R

2000-06-01

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Anthropological Approach of Adherence Factors for Antihypertensive Drugs

PubMed Central

Sarradon-Eck, Aline; Egrot, Marc; Blance, Marie Anne; Faure, Muriella

2010-01-01

Objective: Uncontrolled high blood pressure leads clinicians to wonder about adherence degree among hypertensive patients. In this context, our study aims to describe and analyze patients' experience of antihypertensive drugs in order to shed light on the multiple social and symbolic logics, forming part of the cultural factors shaping personal medication practices. Methods: The medical inductive and comprehensive anthropological approach implemented is based on an ethnographic survey (observations of consultations and interviews). Semi-structured interviews were conducted with 68 hypertensive patients (39 women and 29 men, between the ages of 40 and 95, of whom 52 were over 60) who had been receiving treatment for over a year. Results: Antihypertensive drugs are reinterpreted when filtered through the cultural model of physiopathology (the body as an engine). This symbolic dimension facilitates acceptance of therapy but leads to a hierarchization of other prescribed drugs and of certain therapeutic classes (diuretics). Prescription compliance does not solely depend on the patient's perception of cardiovascular risk, but also on how the patient fully accepts the treatment and integrates it into his or her daily life; this requires identification with the product, building commitment and self-regulation of the treatment (experience, managing treatment and control of side effects, intake and treatment continuity). Following the prescription requires a relationship based on trust between the doctor and patient, which we have identified in three forms: reasoned trust, emotional trust and conceded trust. Conclusion: Consideration and understanding of these pragmatic and symbolic issues by the treating physician should aid practitioners in carrying out their role as medical educators in the management of hypertension. This paper was originally published in French, in the journal Pratiques et organisation des soins 39(1): 3-12. PMID:21532764

[Method of traditional Chinese medicine formula design based on 3D-database pharmacophore search and patent retrieval].

PubMed

He, Yu-su; Sun, Zhi-yi; Zhang, Yan-ling

2014-11-01

By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.

Cardioprotective peptides from marine sources.

PubMed

Harnedy, Padraigín A; FitzGerald, Richard J

2013-05-01

Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.

Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature

PubMed Central

Schiffrin, Ernesto L

2010-01-01

Abstract This review addresses the use of the different antihypertensive agents currently available and some in development, and their effects on the vasculature. The different classes of agents used in the treatment of hypertension, and the results of recent large clinical trials, dosing protocols and adverse effects are first briefly summarized. The consequences on blood vessels of the use of antihypertensive drugs and the differential effects on the biology of large and small arteries resulting in modulation of vascular remodelling and dysfunction in hypertensive patients are then described. Large elastic conduit arteries exhibit outward hypertrophic remodelling and increased stiffness, which contributes to raise systolic blood pressure and afterload on the heart. Small resistance arteries undergo eutrophic or hypertrophic inward remodelling, and impair tissue perfusion. By these mechanisms both large and small arteries may contribute to trigger cardiovascular events. Some antihypertensive agents correct these changes, which could contribute to improved outcome. The mechanisms that at the level of the vascular wall lead to remodelling and can be beneficially affected by antihypertensive agents will also be addressed. These include vasoconstriction, growth and inflammation. The molecular pathways contributing to growth and inflammation will be summarily described. Further identification of these signalling pathways should allow identification of novel targets leading to development of new and improved medications for the treatment of hypertension and cardiovascular disease. PMID:20345850

Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?

PubMed

Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Iaconianni, Paola; Gatti, Simona; Padula, Francesco

2016-01-01

Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several "acute" pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s) which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials) on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent) of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient's reproductive desire and possible risk for his fertility.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study

PubMed Central

Georgiopoulos, Georgios; Katsi, Vasiliki; Oikonomou, Dimitrios; Vamvakou, Georgia; Koutli, Evangelia; Laina, Aggeliki; Tsioufis, Constantinos; Nihoyannopoulos, Petros; Tousoulis, Dimitrios

2016-01-01

Background: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). Methods: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. Results: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. Conclusion: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research. PMID:27536242

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study.

PubMed

Georgiopoulos, Georgios; Katsi, Vasiliki; Oikonomou, Dimitrios; Vamvakou, Georgia; Koutli, Evangelia; Laina, Aggeliki; Tsioufis, Constantinos; Nihoyannopoulos, Petros; Tousoulis, Dimitrios

2016-01-01

Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.

[Exercise in arterial hypertension].

PubMed

Predel, Hans-Georg; Schramm, Thomas

2006-09-01

Regular endurance training has established itself as a major therapeutic principle in the specter of nonpharmacological measures in arterial hypertension. An initial medical check as well as an adequate technique, dosage and intensity of the prescribed exercise training are mandatory. With respect to the concomitant pharmacological treatment, it should be considered that the beneficial effects of lifestyle modification will not be counteracted by the chosen antihypertensive drug but, ideally, synergistically supported. Based on the individual clinical situation, principally all antihypertensive drugs recommended by the current European guidelines, may be prescribed as mono- or combination therapy.beta-receptor blockers are especially capable of controlling excessive exercise-induced blood pressure increase; however, they have metabolic and exercise physiological limitations. The neutrality concerning metabolic and exercise physiological parameters as well as the positive profile of side effects favor ACE inhibitors, long-acting calcium channel blockers and especially AT(1) antagonists in physically active hypertensive patients with concomitant metabolic syndrome.

Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking

PubMed Central

Sohn, Young In; Lee, Nathanael J.; Chung, Andrew; Saavedra, Juan M.; Turner, R. Scott; Pak, Daniel T. S.; Hoe, Hyang-Sook

2013-01-01

Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer’s Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKIIα and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling. PMID:24012668

Effects of catgut-embedding acupuncture technique on nitric oxide levels and blood pressure in patients with essential hypertension

NASA Astrophysics Data System (ADS)

Suhana; Srilestari, A.; Marbun, M. B. H.; Mihardja, H.

2017-08-01

Hypertension is common a health problem and its prevalence in Indonesia is quite high (31.7%). Catgut embedding—an acupuncture technique—is known to reduce blood pressure; however, no study has confirmed the underlying mechanism. This study examines the effect of catgut embedding on serum nitric oxide (NO) concentration and blood pressure in patients with essential hypertension. Forty hypertension patients were randomly assigned to two groups: the control group received anti-hypertensive drugs whereas the case group received anti-hypertensive drugs and catgut embedding. Results showed a statistically significant mean difference in NO concentration (p < 0.05) and statistically and clinically significant mean difference in systolic and diastolic blood pressure between the two groups (p < 0.05). The results confirm that catgut embedding can influence serum NO concentration and blood pressure in essential hypertension patients.

The effects of anti-hypertensives and type 2 diabetes on salivary flow and total antioxidant capacity.

PubMed

Djukić, L J; Roganović, J; Brajović, M D; Bokonjić, D; Stojić, D

2015-07-01

The present cross-sectional study aimed to determine the effect of first-line anti-hypertensive drugs (enalapril, metoprolol, and combinations of enalapril with metoprolol and/or hydrochlorothiazide) on salivary gland function and salivary total antioxidant capacity (TAC) in hypertensive patients with/without diabetes mellitus (DM) type 2. Salivary gland function was measured as xerostomia (interview) and unstimulated whole saliva flow rate (UWSFR) in 447 subjects (387 hypertensive and 60 healthy). Salivary TAC was evaluated by spectrophotometric assay. Enalapril is not xerogenic, while metoprolol and drug combinations are. In the presence of DM type 2, all drugs, except metoprolol, had pronounced xerogenic effect. Binary logistic regression analysis found enalapril to be significantly associated with decreased risk of xerogenic effect development, while DM type 2 with increased risk. In the presence of enalapril in hypertensive patients with/without DM type 2 salivary TAC was similar to that in healthy subjects, while for metoprolol was reduced. Enalapril is not xerogenic but is antioxidant, which moderately reduces the risk of xerogenic effect development even in the presence of DM type 2. However, metoprolol and drug combinations exhibit xerogenic effect. In DM type 2, xerogenic effect of all drugs was pronounced except of metoprolol. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Socioeconomic differences in prevalence, awareness, control and self-management of hypertension among four minority ethnic groups, Na Xi, Li Shu, Dai and Jing Po, in rural southwest China.

PubMed

Cai, L; Dong, J; Cui, W L; You, D Y; Golden, A R

2017-06-01

This study investigates socioeconomic differences in prevalence, awareness, control and self-management of hypertension in rural China. A cross-sectional survey was conducted among four ethnic minority groups in Yunnan Province: Na Xi, Li Shu, Dai and Jing Po. Approximately 5532 consenting individuals aged ⩾35 years (48.4% of whom were male) were selected to participate in the study using a stratified, multistage sampling technique. Information about participants' demographic characteristics and hypertension awareness, treatment, control and self-management practices was obtained using a standard questionnaire. The age-standardised prevalence of hypertension in the study population was 33.6%. In hypertensive subjects, the overall levels of awareness, treatment and control of hypertension were 42.1%, 28.5% and 6.7%, respectively. Approximately 58.7% of hypertensive patients regularly self-monitored blood pressure (BP), 64.7% adhered to their physician-prescribed anti-hypertensive drugs, and 88.0% took at least one measure to control BP. Hypertensive patients of Jing Po ethnicity had the lowest rates of awareness, treatment, control and self-management of hypertension among the four ethnic minority groups studied. Individuals with lower levels of education were more likely to be hypertensive. Further, individuals with lower levels of education had a lower probability of awareness of their hypertensive status and of treatment with antihypertensive medication. Access to medical services was positively associated with awareness of suffering from hypertension, being treated with antihypertensive medication, and compliance with antihypertensive drug treatment. This study suggests that effective strategies to enhance awareness, treatment and management of hypertension should focus on individuals with low levels of education and poor access to medical services.

Antihypertensive adherence and drug class among Asian Pacific Americans.

PubMed

Taira, Deborah A; Gelber, Rebecca P; Davis, James; Gronley, Krista; Chung, Richard S; Seto, Todd B

2007-06-01

Research on adherence has emphasized the need to consider patient ethnicity when developing adherence plans. The objective of this study is to identify predictors of adherence for specific groups, particularly Asian Americans and Pacific Islanders. We examined the factors, including drug class, associated with antihypertensive adherence for 28,395 adults in Hawaii (July 1999-June 2003) using health plan administrative data. The population included Japanese (n=13,836), Filipino (n=3,812), Chinese (n=2,280), Korean (n=450), part-Hawaiian (n=3,746) and white (n=3,920) patients. Members with antihypertensive medication in their possession >or=80% of the time were considered adherent. Multivariable logistic regression models were used to identify factors associated with adherence. Overall adherence rates were less than 65% among all racial/ethnic groups. After adjustment for patient age, gender, morbidity level, health plan type, isle of residence, comorbidities and year of treatment, Japanese were more likely than whites to adhere to antihypertensive therapy [OR=1.21 (1.14-1.29)], whereas Filipino [OR=0.69 (0.64-0.74)], Korean [OR=0.79 (0.67-0.93)] and Hawaiian [OR=0.84 (0.78-0.91)] patients were less likely to adhere. These results were consistent across therapeutic class. Other patient factors associated with lower adherence included younger age, higher morbidity and history of heart disease. Patient factors were also significantly related to adherence, including gender and seeing a sub-specialist. Seeing a physician of the same ethnicity did not appear to improve adherence. Our findings of substantial disparities among Asian Pacific American subgroups highlight the need to examine subgroups separately. Future qualitative research is needed to determine appropriate interventions, particularly for Filipino, Korean and Hawaiian patients.

Treatment of hypertension by increasing impaired endothelial TRPV4-KCa2.3 interaction.

PubMed

He, Dongxu; Pan, Qiongxi; Chen, Zhen; Sun, Chunyuan; Zhang, Peng; Mao, Aiqin; Zhu, Yaodan; Li, Hongjuan; Lu, Chunxiao; Xie, Mingxu; Zhou, Yin; Shen, Daoming; Tang, Chunlei; Yang, Zhenyu; Jin, Jian; Yao, Xiaoqiang; Nilius, Bernd; Ma, Xin

2017-11-01

The currently available antihypertensive agents have undesirable adverse effects due to systemically altering target activity including receptors, channels, and enzymes. These effects, such as loss of potassium ions induced by diuretics, bronchospasm by beta-blockers, constipation by Ca 2+ channel blockers, and dry cough by ACEI, lead to non-compliance with therapies (Moser, 1990). Here, based on new hypertension mechanisms, we explored a new antihypertensive approach. We report that transient receptor potential vanilloid 4 (TRPV4) interacts with Ca 2+ -activated potassium channel 3 (KCa2.3) in endothelial cells (ECs) from small resistance arteries of normotensive humans, while ECs from hypertensive patients show a reduced interaction between TRPV4 and KCa2.3. Murine hypertension models, induced by high-salt diet, N(G)-nitro-l-arginine intake, or angiotensin II delivery, showed decreased TRPV4-KCa2.3 interaction in ECs. Perturbation of the TRPV4-KCa2.3 interaction in mouse ECs by overexpressing full-length KCa2.3 or defective KCa2.3 had hypotensive or hypertensive effects, respectively. Next, we developed a small-molecule drug, JNc-440, which showed affinity for both TRPV4 and KCa2.3. JNc-440 significantly strengthened the TRPV4-KCa2.3 interaction in ECs, enhanced vasodilation, and exerted antihypertensive effects in mice. Importantly, JNc-440 specifically targeted the impaired TRPV4-KCa2.3 interaction in ECs but did not systemically activate TRPV4 and KCa2.3. Together, our data highlight the importance of impaired endothelial TRPV4-KCa2.3 coupling in the progression of hypertension and suggest a novel approach for antihypertensive drug development. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Effects of antihypertensive drugs losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension combined with isolated impaired fasting glucose.

PubMed

Xiao, Wei-Yin; Ning, Ning; Tan, Ming-Hong; Jiang, Xue-Shu; Zhou, Liang; Liu, Ling; Yi, Dong; Wei, Ping

2016-05-01

The objective of this study was to observe the antihypertensive effect of losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension (EH) combined with isolated impaired fasting glucose (i-IFG). Patients (n=244) were randomly assigned to losartan potassium tablets (50-100 mg per day) or levamlodipine besylate tablets (2.5-5.0 mg per day) for intensive antihypertensive treatment with no lifestyle interventions for 3 years. The changes in fasting plasma glucose, fasting insulin (FINS) and insulin sensitivity index (ISI) from before to after treatment were observed. Blood pressure (BP) in each group was significantly reduced by treatment (P<0.05). After 12 months of treatment, the FINS level in the losartan potassium group was significantly decreased and ISI was significantly increased compared with before treatment (P<0.05) and compared with the levamlodipine besylate group (P<0.05). After 24 and 36 months of treatment, FINS was significantly decreased and ISI was significantly improved in both groups compared with baseline (P<0.05), and there was no difference between the groups (P>0.05). The incidence of new-onset diabetes mellitus was not significantly different between two groups. The antihypertensive effect of losartan and levamlodipine besylate could amoliorate insulin resistance in patients with EH combined with i-IFG. The improvement of insulin resistance by losartan potassium at 12 months might be better than that by levamlodipine besylate; however, after 24 and 36 months of follow-up, both agents significantly alleviated insulin resistance. These results suggest that the effects of these two drugs on insulin resistance are not significantly different.

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

PubMed Central

Qiao, Liansheng; Li, Bin; Chen, Yankun; Li, Lingling; Chen, Xi; Wang, Lingzhi; Lu, Fang; Luo, Ganggang; Li, Gongyu; Zhang, Yanling

2016-01-01

Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE) was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM), was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC) assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM) proteins based on in silico proteolysis and virtual screening, which could be beneficial to reveal the pharmacological action of TCM proteins and provide new lead compounds for peptides-based drug design. PMID:27983650

Summer syncope syndrome redux.

PubMed

Huang, Jennifer Juxiang; Desai, Chirag; Singh, Nirmal; Sharda, Natasha; Fernandes, Aaron; Riaz, Irbaz Bin; Alpert, Joseph S

2015-10-01

While antihypertensive therapy is known to reduce the risk for heart failure, myocardial infarction, and stroke, it can often cause orthostatic hypotension and syncope, especially in the setting of polypharmacy and possibly, a hot and dry climate. The objective of the present study was to investigate whether the results of our prior study involving continued use of antihypertensive drugs at the same dosage in the summer as in the winter months for patients living in the Sonoran desert resulted in an increase in syncopal episodes during the hot summer months. All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. This is a 3-year retrospective chart review study. They were defined as "cases" if they presented during the summer months (May to September) and "controls" if they presented during the winter months (November to March). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher's exact test. A total of 834 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened: 477 in the summer months and 357 in the winter months. In patients taking antihypertensive medications, there was a significantly higher number of cases of syncope secondary to dehydration during the summer months (40.5%) compared with the winter months (29%) (P = .04). No difference was observed in the type of antihypertensive medication used and syncope rate. The number of antihypertensives used did not increase the cases of syncope in either summer or winter. An increased number of syncope events was observed in the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. The data confirm our earlier observations that demonstrated a greater number of cases of syncope among people who reside in a dry desert climate who were taking antihypertensive medications during summer months. We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months. Copyright © 2015 Elsevier Inc. All rights reserved.

[Differences in the reduction of blood pressure according to drug administration at activity hours or rest hours].

PubMed

Helena Ponte Márquez, Paola; José Solé, Maria; Arroyo, Juan Antonio; Matas, Laia; Benet, Maria Teresa; Roca-Cusachs, Àlex

2015-01-20

In this study, 123 recordings of blood pressure (BP) obtained by ambulatory BP monitoring were analyzed. These recordings were measured in 2011 in patients from a Spanish tertiary university hospital. All participating patients were treated with 2, 3 or 4 anti-hypertensive drugs. The main aim of this study was to determine differences in BP control, if any, depending on the medication schedule. Thus, BP levels were studied at 3 periods of the day: activity hours, rest hours and 24h. We compared subjects taking all anti-hypertensive agents during the day (n=70, group 1) with those taking at least one at night (n=53, group 2). Significant differences were found on diastolic BP, where group 2 patients had lower levels at activity, 24h periods and sleep-time. Even if it was not statistically significant, lower levels of systolic BP from group 2 were also observed at activity and 24h periods as well as lower levels of systolic, diastolic and mean BP at rest hours periods. There were also significant group differences in relation to the number of prescribed agents (with the mean being higher for group 2) and the type of agent (beta-blockers and calcium antagonists were more prevalent in group 2). Nevertheless, the multivariate regression analysis done taking into account these variables did not change the observed statistical significance. The administration of anti-hypertensive drugs at night could be associated with lower BP levels. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin.

PubMed

Pons, Zara; Margalef, Maria; Bravo, Francisca I; Arola-Arnal, Anna; Muguerza, Begoña

2016-03-01

The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS). Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration. GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin. GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

Effect of salt intake on blood pressure in patients receiving antihypertensive therapy: Shimane CoHRE Study.

PubMed

Ito, Tomoko; Takeda, Miwako; Hamano, Tsuyoshi; Kijima, Tsunetaka; Yamasaki, Masayuki; Isomura, Minoru; Yano, Shozo; Shiwaku, Kuninori; Nabika, Toru

2016-03-01

Salt intake is recognized as an important risk factor for hypertension in the general population. On the other hand, the availability of various classes of antihypertensive drugs means that it is generally not considered crucial to control the salt intake of hypertensive patients. In this study, we evaluated whether blood pressure (BP) was correlated with 24-hour salt intake in patients receiving antihypertensive therapy. A total of 1496 consecutive participants undergoing health screening examinations were recruited. Subjects were divided into two groups according to their antihypertensive medications checked on prescriptions: 1005 subjects without antihypertensive therapy (untreated subjects) and 491 subjects with antihypertensive therapy (treated subjects). The 24-hour urinary sodium excretion (24h-uNa), a surrogate marker for daily salt intake, was estimated with the formula proposed by Tanaka et al. in 2002. Univariate analysis indicated that 24h-uNa was positively correlated with the systolic BP of both untreated and treated subjects. This was confirmed by multiple linear regression analysis after adjustment for confounding factors (untreated subjects: partial regression coefficient β=1.45 ± 0.26, p<0.001; treated subjects: β=0.75 ± 0.27, p=0.01). Salt intake was also correlated with the pulse pressure in both treated subjects (β=0.55 ± 0.24, p=0.02) and untreated subjects (β=0.93 ± 0.19, p<0.001). These results suggest the importance of reducing salt intake in hypertensive patients on pharmacotherapy, as well as in the general population. Further studies of hypertensive patients employing 24-h urine collection are warranted to confirm the present findings. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

A Network-Based Classification Model for Deriving Novel Drug-Disease Associations and Assessing Their Molecular Actions

PubMed Central

Oh, Min; Ahn, Jaegyoon; Yoon, Youngmi

2014-01-01

The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug) was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively) in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer’s disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer’s disease. PMID:25356910

Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

DOE PAGES

Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; ...

2015-05-07

We report that angiotensin II type 1 receptor (AT 1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT 1R blockers (ARBs), the structural basis for AT 1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT 1R in complex with its selective antagonist ZD7155 atmore » 2.9 Å resolution. The AT 1R-ZD7155 complex structure revealed key structural features ofAT 1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT 1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT 1R structure-function relationship and structure-based drug design.« less

Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius

We report that angiotensin II type 1 receptor (AT 1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT 1R blockers (ARBs), the structural basis for AT 1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT 1R in complex with its selective antagonist ZD7155 atmore » 2.9 Å resolution. The AT 1R-ZD7155 complex structure revealed key structural features ofAT 1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT 1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT 1R structure-function relationship and structure-based drug design.« less

Physicochemical and microbiological stability studies of extemporaneous antihypertensive pediatric suspensions for hospital use.

PubMed

Mendes, Cassiana; Costa, Ana Paula; Oliveira, Paulo Renato; Tagliari, Monika Piazzon; Silva, Marcos Antônio Segatto

2013-01-01

Extemporaneous suspensions of the antihypertensive agents furosemide, spironolactone and hydrochlorothiazide for pediatric use have been prepared at University Hospital (Federal University of Santa Catarina - Brazil). The aim of this work was to investigate the physicochemical and microbiological stability of these suspensions over the estimated shelf-life period of seven days and, if necessary, to optimize the formulations by improving the chemical stability. The pediatric suspensions were prepared using drug raw material and were stored at 25 ± 2°C and 5 ± 3°C. Chemical stability was evaluated by HPLC assay of the suspensions for drug content. Physical stability was evaluated by sedimentation volume, redispersibility, particle size, and zeta potential. Viable bacterial and fungal contaminations were assessed according to the official compendium. Furosemide and spironolactone suspensions as prepared herein can be stored for 7 days. However, the hydrochlorothiazide suspension formulation at pH 6.5 demonstrated poor chemical stability and was optimized by adjusting the pH to 3.3 where the drug exhibited acceptable stability. The optimized formulation demonstrated to be stable over the required period of 7 days.

Repurposing and Rescuing of Mibefradil, an Antihypertensive, for Cancer: A Case Study.

PubMed

Krouse, Andrew J; Gray, Lloyd; Macdonald, Timothy; McCray, John

2015-12-01

The expanding "valley of death" in drug development is leaving potentially life-saving new chemical entities and molecular targets fallow. This situation is forcing early-stage companies to think creatively about moving their technologies forward, especially as institutional investors show more interest in later stages of development. Drug repurposing, a strategy to examine existing drugs for therapeutic value against different diseases, is an emerging method to bring an off-market drug back onto the market. Tau Therapeutics LLC identified the role of T-type calcium channel blockers (Cav3) in cancer proliferation, but the company was unable to attract funding while having both a nonvalidated drug target and new chemical entities. To change the risk profile of the company, Tau set out to repurpose the known Cav3 drug mibefradil as a proof of concept for the treatment of cancer. Mibefradil was launched for hypertension in the 1990s but withdrawn because of drug-drug interactions. A new sequential combination treatment, termed Interlaced Therapy™, uses short-term administration of mibefradil to enhance the overall therapeutic potential of conventional anticancer agents. Mibefradil is currently in a phase Ib clinical trial with the National Cancer Institute (NCI) Adult Brain Tumor Consortium. Mibefradil has been repurposed from an abandoned antihypertensive to a targeted solid tumor treatment, and it has been rescued from drug-drug interactions by using short-term dose exposure. Tau is using the early success of mibefradil as a proof of concept to build a platform technology of Cav3 blockers for broad antitumor applications in combination with new targeted cancer therapies, well-established chemotherapies, and radiation.

In Vitro Dissolution as a Tool for Formulation Selection: Telmisartan Two-Step IVIVC.

PubMed

Ruiz Picazo, Alejandro; Martinez-Martinez, Ma Teresa; Colón-Useche, Sarin; Iriarte, Ramon; Sánchez-Dengra, Bárbara; González-Álvarez, Marta; García-Arieta, Alfredo; González-Álvarez, Isabel; Bermejo, Marival

2018-05-17

The purpose of this investigation was to develop an exploratory two-step level A IVIVC for three telmisartan oral immediate release formulations, the reference product Micardis, and two generic formulations (X1 and X2). Correlation was validated with a third test formulation, Y1. Experimental solubility and permeability data were obtained to confirm that telmisartan is a class II compound under the Biopharmaceutic Classification System. Bioequivalence (BE) studies plasma profiles were combined using a previously published reference scaling procedure. X2 demonstrated in vivo BE, while X1 and Y1 failed to show BE due to the lower boundary of the 90% confidence interval for C max being outside the acceptance limits. Average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed ( f a ). Fractions dissolved ( f diss ) were obtained in several conditions in USP II and USP IV apparatus, and later, the results were compared in order to find the most biopredictive model, calculating the f 2 similarity factor. The apparatus and conditions showing the same rank order than in vivo data were selected for further refinement of conditions. A Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the different formulations of telmisartan employed the USP IV dissolution apparatus and a dissolution environment with a flow rate of 8 mL/min and a three-step pH change, from 1.2 to 4.5 and 6.8, with a 0.05% of Tween 80. Thus, these conditions gave rise to a biopredictive dissolution test. This new model is able to predict the formulation differences in dissolution that were previously observed in vivo, which could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Calcium channel antagonists in the treatment of hypertension.

PubMed

Weber, Michael A

2002-01-01

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease.

PubMed

Garrido-Gil, Pablo; Joglar, Belen; Rodriguez-Perez, Ana I; Guerra, Maria J; Labandeira-Garcia, Jose L

2012-02-22

Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662. The results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.

Drugs for metabolic conditions and prostate cancer death in men on GnRH agonists.

PubMed

Bosco, Cecilia; Wong, Chloe; Garmo, Hans; Crawley, Danielle; Holmberg, Lars; Hammar, Niklas; Adolfsson, Jan; Stattin, Pär; Van Hemelrijck, Mieke

2018-02-01

To evaluate whether drugs for metabolic conditions influence prostate cancer-specific mortality in men starting gonadotrophin-releasing hormone (GnRH) agonists, as it is unclear whether metabolic syndrome and its related drugs is affecting treatment response in men with prostate cancer on GnRH agonists. We selected all men receiving GnRH agonists as primary treatment in the Prostate Cancer data Base Sweden (PCBaSe) (n = 9267). Use of drugs for metabolic conditions (i.e. anti-diabetes, anti-dyslipidaemia, and antihypertension) in relation to all-cause, cardiovascular disease (CVD), and prostate cancer-specific death were studied using multivariate Cox proportional hazard and Fine and Gray competing regression models. In all, 6322 (68%) men used at least one drug for a metabolic condition at GnRH agonist initiation: 46% on antihypertensive drugs only, 32% on drugs for dyslipidaemia and hypertension, and ~10% on drugs for more than two metabolic conditions. Cox models indicated a weak increased risk of prostate cancer death in men who were on drugs for hypertension only (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.03-1.23) or drugs for hyperglycaemia (HR 1.19, 95% CI 1.06-1.35) at GnRH agonist initiation. However, upon taking into account competing risk from CVD death, none of the drugs for metabolic conditions were associated with an increased risk of prostate cancer death. We did not find evidence for a better or worse response to GnRH agonists in men with prostate cancer who were also on drugs for hypertension, dyslipidaemia, or hyperglycaemia. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Use of medications for secondary prevention in stroke patients at hospital discharge in Australia.

PubMed

Eissa, Ashraf; Krass, Ines; Bajorek, Beata V

2014-04-01

Stroke is one of the leading causes of death and disability. Significant proportions (33 %) of stroke presentations are by patients with a previous stroke or transient ischaemic attack. Consequently, the stroke management guidelines recommend that all ischaemic stroke patients should receive three key evidence-based preventive drug therapies: antihypertensive drug therapy, a statin and an antithrombotic drug therapy (anticoagulant and/or antiplatelet). To determine the rates of utilization of the three key evidence-based drug therapies for the secondary prevention of stroke and to identify factors associated with use of treatment at discharge. Five metropolitan hospitals in New South Wales, comprising two tertiary referral centres and three district hospitals. A retrospective clinical audit was conducted in the study hospitals. Patients discharged with a principal diagnosis of ischaemic stroke during a 12-month time period (July 2009-2010) were identified for review. The rate of utilization of each of the three key evidence-based drug therapies and the factors associated with use of treatment at discharge. A total of 521 medical records were reviewed. Of these, 469 patients were discharged alive with a mean age of 73.6 ± 14.4 years. Overall, 75.4 % were prescribed an antihypertensive agent at discharge versus only 65.7 % on admission (P < 0.05). Three hundred-sixty patients (77.6 % of the eligible patients) were prescribed a statin at discharge (compared to only 43.9 % on admission, P < 0.05), of whom 74.0 % received monotherapy. Almost all (97.6 %) eligible patients were prescribed an antithrombotic drug therapy at discharge, of whom 68.5 % were prescribed monotherapy and 28.2 % were prescribed dual therapy. Only 60.0 % of eligible patients were discharged on all three key guideline recommended secondary preventive drug therapies. Multivariate logistic regression analyses showed that hypertension (OR 6.67; 95 % CI 4.35-11.11), hypercholesterolemia (OR 2.04; 95 % CI 1.32-3.23), and discharge destination (OR 0.22; 95 % CI 0.10-0.48) were associated with the utilization of all three guideline recommended therapies. There is a scope for improvement in implementing the stroke management guidelines when it comes to prescribing secondary preventive drug therapies using antihypertensives, antithrombotics and statins. Appropriate risk/benefit assessment is indispensable for optimal prescribing and maximizing patient outcomes, particularly in older people.

Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS.

PubMed

Gundersen, Per Ole M; Helland, Arne; Spigset, Olav; Hegstad, Solfrid

2018-04-28

Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker. A 200 µL serum sample was handled automatically using a pipetting robot. Protein precipitation was performed with 600 µL of 1% formic acid in acetonitrile (v:v) and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. After evaporation and reconstitution the eluent was injected thrice with different inlet and mass spectrometric methods to cover the different physico-chemical properties of the drugs and the variations in therapeutic concentration ranges between drugs. Acquity UPLC BEH C18 (2.1x50mm, 1.7 µm) column equipped with a corresponding pre-column was used for chromatographic separation. For every analyte an isotopically labelled analogue served as internal standard, except for lisinopril where enalaprilat-d5 was used. Accuracies were in the range of -13.7 to 13.2% and intra-day and inter-day precisions in the range of 1.1 to 10.5%. The linearity within the calibration ranges expressed as coefficient of determination was higher than 0.995 for all compounds. Matrix effects and recovery efficiencies were within acceptable limits. The limits of quantitation varied from 0.02 to 10.7 µg/L. The stability of the drugs in serum at different conditions was tested. Diltiazem was not stable at 4-8 °C with up to 23.5 % loss after six days. Degradation of atenolol, irbesartan, bendroflumethiazide, hydrochlorothiazide and diltiazem was observed when stored at 30 °C. The suitability of the method was demonstrated in a routine TDM setting, analysing samples from 127 patients undergoing antihypertensive drug treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

L-type Ca2+ channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory

PubMed Central

Degoulet, Mickael; Stelly, Claire E.; Ahn, Kee-Chan; Morikawa, Hitoshi

2015-01-01

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca2+ channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA. PMID:26100537

L-type Ca²⁺ channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory.

PubMed

Degoulet, M; Stelly, C E; Ahn, K-C; Morikawa, H

2016-03-01

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca(2+) channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA.

Are SGLT2 inhibitors reasonable antihypertensive drugs and renoprotective?

PubMed

Lovshin, J A; Gilbert, R E

2015-06-01

By eliminating glucose in the urine, the sodium-glucose-linked cotransporter-2 (SGLT2) inhibitors act as osmotic diuretics to lower blood pressure in addition to reducing plasma glucose and assisting with weight loss. While not approved as antihypertensive agents, the ability of this new class of antihyperglycemic agents to lower blood pressure is not insubstantial, and while not used primarily for this indication, they may assist diabetic individuals in attaining currently recommended blood pressure targets. In addition to lowering systemic pressure, preclinical and exploratory human studies suggest that SGLT2 inhibitors may also lower intraglomerular pressure, potentially reducing the rate of GFR decline in patients with diabetic nephropathy. However, given the lack of clinically meaningful endpoint data, the use of SGLT2 inhibitors, primarily, as either antihypertensive or renoprotective agents would, at present, be premature. Fortunately, further insight will be garnered from large, randomized controlled trials that will assess the effects of various SGLT2 inhibitors on cardiovascular and renal outcomes.

Process versus outcome in hypertension: a positive result.

PubMed

Haynes, R B; Gibson, E S; Taylor, D W; Bernholz, C D; Sackett, D L

1982-01-01

We studied the association between the outcome of antihypertensive care and three items of that care among 230 hypertensive steelworkers who were referred to 83 physicians. The first item was the decision to treat some patients but not others: 63% of the patients were prescribed antihypertensive drugs and the mean decrease in their diastolic blood pressure (DBP) was greater than that among untreated patients (12.2 +/- 0.84 vs 7.8 +/- 0.83 mm Hg [+/- SEM], p less than 0.001). The second item was the vigor of prescribed medication: Patients prescribed more vigorous treatments had lower DBP (p less than 0.005). Third, patient compliance was related to achieving a goal DBP of less than 90 mm Hg (p less than 0.05) and the product of prescribed vigor and compliance was highly associated with DBP response (p less than 0.0001). These results stand in contrast to those of previous studies that failed to detect associations between various other items of the care process and the outcome of antihypertensive care.

Musical auditory stimulus acutely influences heart rate dynamic responses to medication in subjects with well-controlled hypertension.

PubMed

Martiniano, Eli Carlos; Santana, Milana Drumond Ramos; Barros, Érico Luiz Damasceno; do Socorro da Silva, Maria; Garner, David Matthew; de Abreu, Luiz Carlos; Valenti, Vitor E

2018-01-17

Music can improve the efficiency of medical treatment when correctly associated with drug action, reducing risk factors involving deteriorating cardiac function. We evaluated the effect of musical auditory stimulus associated with anti-hypertensive medication on heart rate (HR) autonomic control in hypertensive subjects. We evaluated 37 well-controlled hypertensive patients designated for anti-hypertensive medication. Heart rate variability (HRV) was calculated from the HR monitor recordings of two different, randomly sorted protocols (control and music) on two separate days. Patients were examined in a resting condition 10 minutes before medication and 20 minutes, 40 minutes and 60 minutes after oral medication. Music was played throughout the 60 minutes after medication with the same intensity for all subjects in the music protocol. We noted analogous response of systolic and diastolic arterial pressure in both protocols. HR decreased 60 minutes after medication in the music protocol while it remained unchanged in the control protocol. The effects of anti-hypertensive medication on SDNN (Standard deviation of all normal RR intervals), LF (low frequency, nu), HF (high frequency, nu) and alpha-1 scale were more intense in the music protocol. In conclusion, musical auditory stimulus increased HR autonomic responses to anti-hypertensive medication in well-controlled hypertensive subjects.

Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China.

PubMed

Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli

2017-04-07

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.

Memory is preserved in older adults taking AT1 receptor blockers.

PubMed

Ho, Jean K; Nation, Daniel A

2017-04-26

Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives. In post hoc analyses, we also examined (1) users of ARBs and angiotensin-converting enzyme inhibitors (ACEIs), (2) users of blood-brain barrier (BBB)-crossing ARBs and users of non-BBB-crossing ARBs, and (3) users of BBB-crossing ARBs and ACEIs (BBB crossers) and users of non-BBB-crossing ARBs and ACEIs (BBB noncrossers). Groups were compared regarding cognition and magnetic resonance imaging measures of brain volume and white matter hyperintensities (WMH), using analysis of covariance and multilevel models. At baseline, the HTN-Other group performed worse than normotensives on Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall (p = 0.002), Delayed Recall (p < 0.001), Recognition Memory (p = 0.001), and Trails A (p < 0.001) and B (p = 0.01). ARB users performed better than the HTN-Other group on Recognition Memory (p = 0.04) and worse than normotensives on Trails A (p = 0.04). The HTN-Other group performed worse than normotensives on Logical Memory Immediate (p = 0.02) and Delayed Recall over the 3-year follow-up (p = 0.007). Over the follow-up period, those taking BBB-crossing ARBs performed better than the HTN-Other group on AVLT Delayed Recall (p = 0.04), Logical Memory Immediate (p = 0.02), and Delayed Recall (p = 0.05). They also had fewer WMH than the HTN-Other group (p = 0.008) and those taking non-BBB-crossing ARBs (p = 0.05). There were no group differences in brain volume. Users of BBB-crossing medications (ARBs or ACEIs) showed better performance on AVLT Delayed Recall over time than all other groups, including normotensives (all p < 0.01), and had less WMH volume over time than the BBB noncrossers group (p = 0.03), although they had more WMH volume than normotensives (p = 0.01). The BBB noncrossers group performed worse than normotensives on Logical Memory Delayed Recall over time (p = 0.01), but the BBB crossers group was not significantly different (p = 0.13). Hypertensive participants demonstrated worse baseline memory and executive function, as well as greater memory decline, over the 3-year follow-up than normotensives, unless they were ARB users, who showed preserved memory compared with those taking other antihypertensive drugs. Users of BBB-crossing ARBs showed superior memory performance over time compared with other antihypertensive drug users and had less WMH volume. Users of BBB-crossing medications (ARBs or ACEIs) showed better list-learning memory performance over time than all other groups, including normotensives, and had less WMH volume over time than users of non-BBB-crossing medications. These findings demonstrate that ARBs, especially those of the BBB-crossing variety, are associated with greater memory preservation and less WMH volume than other antihypertensive medications.

Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

PubMed

Fournier, Jean-Pascal; Lapeyre-Mestre, Maryse; Sommet, Agnès; Dupouy, Julie; Poutrain, Jean-Christophe; Montastruc, Jean-Louis

2012-01-01

Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

Analysis of access to hypertensive and diabetic drugs in the Family Health Strategy, State of Pernambuco, Brazil.

PubMed

Barreto, Maria Nelly Sobreira de Carvalho; Cesse, Eduarda Ângela Pessoa; Lima, Rodrigo Fonseca; Marinho, Michelly Geórgia da Silva; Specht, Yuri da Silva; de Carvalho, Eduardo Maia Freese; Fontbonne, Annick

2015-01-01

To evaluate the access to drugs for hypertension and diabetes and the direct cost of buying them among users of the Family Health Strategy (FHS) in the state of Pernambuco, Brazil. Population-based, cross-sectional study of a systematic random sample of 785 patients with hypertension and 823 patients with diabetes mellitus who were registered in 208 randomly selected FHS teams in 35 municipalities of the state of Pernambuco. The selected municipalities were classified into three levels with probability proportional to municipality size (LS, large-sized; MS, medium-sized; SS, small-sized). To verify differences between the cities, we used the χ2 test. Pharmacological treatment was used by 91.2% patients with hypertension whereas 85.6% patients with diabetes mellitus used oral antidiabetic drugs (OADs), and 15.4% used insulin. The FHS team itself provided antihypertensive medications to 69.0% patients with hypertension, OADs to 75.0% patients with diabetes mellitus, and insulin treatment to 65.4%. The 36.9% patients with hypertension and 29.8% with diabetes mellitus that had to buy all or part of their medications reported median monthly cost of R$ 18.30, R$ 14.00, and R$ 27.61 for antihypertensive drugs, OADs, and insulin, respectively. It is necessary to increase efforts to ensure access to these drugs in the primary health care network.

Differences in pharmacology and their translation into differences in clinical efficacy--a comparison of the renin angiotensin blocking agents irbesartan and losartan.

PubMed

Bramlage, Peter; Schindler, Christoph

2010-03-01

Guidelines recommend five antihypertensive drug classes, but which particular drug to choose is up to the treating physician. We aimed at an in-depth comparison of two frequently used angiotensin receptor blockers to provide evidence for this decision. Pharmacology of irbesartan and losartan, their blood-pressure-lowering efficacy, their tolerability/safety, end-organ protective effects and economic evaluation. Both drugs differ in their oral bioavailability, potential for food interactions, degree of metabolism, dosing interval, time to peak, volume of distribution and terminal half-life. Irbesartan provides a greater and longer-lasting antihypertensive effect and was determined to be cost effective over losartan in Denmark and Sweden. Irbesartan was more effective in preventing deterioration of kidney function in patients with diabetic nephropathy, being cost effective from a German perspective. There is only one end point trial for either drug in patients with left ventricular hypertrophy, heart failure and atrial fibrillation, but no direct comparison. There is an incremental clinical benefit of irbesartan over losartan in the treatment of hypertension and diabetic nephropathy which can be substantiated by corresponding preclinical study evidence. This has translated into an economic benefit in a number of country-specific evaluations.

Predictors of postoperative bleeding after vitrectomy for vitreous hemorrhage in patients with diabetic retinopathy.

PubMed

Motoda, Saori; Shiraki, Nobuhiko; Ishihara, Takuma; Sakaguchi, Hirokazu; Kabata, Daijiro; Takahara, Mitsuyoshi; Kimura, Takekazu; Kozawa, Junji; Imagawa, Akihisa; Nishida, Kohji; Shintani, Ayumi; Iwahashi, Hiromi; Shimomura, Iichiro

2017-12-19

To clarify the association between perioperative variables and postoperative bleeding in pars plana vitrectomy for vitreous hemorrhage in diabetic retinopathy. The present retrospective study enrolled 72 eyes of 64 patients who were admitted to Osaka University Hospital between April 2010 and March 2014, and underwent vitrectomy for vitreous hemorrhage as a result of diabetic retinopathy. Postoperative bleeding developed in 12 eyes. Using binomial logistic regression analysis, we found that the duration of operation was the only significant variable associated with postoperative bleeding within 12 weeks after vitrectomy. Furthermore, Poisson regression analysis identified fasting blood glucose just before vitrectomy, no treatment with antiplatelet drugs and treatment with antihypertensive drugs, as well as duration of operation, to be significantly associated with the frequency of bleeding within 52 weeks after vitrectomy. Long duration of operation can be used to predict bleeding within both 12 and 52 weeks after vitrectomy. In addition, fasting blood glucose just before vitrectomy, no treatment with antiplatelet drugs and treatment with antihypertensive drugs might be risk factors for postoperative bleeding up to 1 year after vitrectomy. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Hypertension Vaccine may be a boon to millions in developing world.

PubMed

Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil

2014-01-01

Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQβ-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs.

The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS.

PubMed

de Mos, M; Huygen, F J P M; Stricker, B H Ch; Dieleman, J P; Sturkenboom, M C J M

2009-04-01

Antihypertensive drugs interact with mediators that are also involved in complex regional pain syndrome (CRPS), such a neuropeptides, adrenergic receptors, and vascular tone modulators. Therefore, we aimed to study the association between the use of antihypertensive drugs and CRPS onset. We conducted a population-based case-control study in the Integrated Primary Care Information (IPCI) database in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during an expert visit (using IASP criteria), or if they had been diagnosed by a medical specialist. Up to four controls per cases were selected, matched on gender, age, calendar time, and injury. Exposure to angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, beta-blockers, calcium channel blockers, and diuretics was assessed from the automated prescription records. Data were analyzed using multivariate conditional logistic regression. A total of 186 cases were matched to 697 controls (102 confirmed during an expert visit plus 84 with a specialist diagnosis). Current use of ACE inhibitors was associated with an increased risk of CRPS (OR(adjusted): 2.7, 95% CI: 1.1-6.8). The association was stronger if ACE inhibitors were used for a longer time period (OR(adjusted): 3.0, 95% CI: 1.1-8.1) and in higher dosages (OR(adjusted): 4.3, 95% CI: 1.4-13.7). None of the other antihypertensive drug classes was significantly associated with CRPS. We conclude that ACE inhibitor use is associated with CRPS onset and hypothesize that ACE inhibitors influence the neuro-inflammatory mechanisms that underlie CRPS by their interaction with the catabolism of substance P and bradykinin.

Cardiovascular risk in Mozambique: who should be treated for hypertension?

PubMed Central

Damasceno, Albertino; Padrão, Patricia; Silva-Matos, Carla; Prista, António; Azevedo, Ana; Lunet, Nuno

2014-01-01

Aim To estimate the proportion of Mozambicans eligible for pharmacological treatment for hypertension, according to single risk factor and total cardiovascular risk approaches. Methods A representative sample of Mozambicans aged 40–64 years (n = 1116) was evaluated according to the WHO STEPwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). We measured blood pressure (BP) and 12-h fasting blood glucose levels and collected data on sociodemographic characteristics, smoking, and use of antidiabetic and antihypertensive drugs. We estimated the 10-year risk of a fatal or nonfatal major cardiovascular event (WHO/lnternational Society of Hypertension risk prediction charts), and computed the proportion of untreated participants eligible for pharmacological treatment for hypertension, according to BP values alone and accounting also for the total cardiovascular risk (WHO guidelines for assessment and management of cardiovascular diseases). Results Among the Mozambicans aged 40–64 years and not taking antihypertensive drugs, less than 4% were classified as having cardiovascular risk at least 20% whereas the prevalence of SBP/DBP at least 140/90 mmHg was nearly 40%. A total of 19.8% of 40–64-year-olds would be eligible for pharmacological treatment of hypertension according to the WHO guidelines, all of whom had SBP/DBP at least 160/100 mmHg. Conclusion Among the Mozambicans aged 40–64 years not taking antihypertensive drugs and having SBP/DBP at least 140/90 mmHg, only half were eligible for pharmacological treatment according to the WHO guidelines. Taking the latter into account, when defining strategies to control hypertension at a population level, may allow a more efficient use of the scarce resources available in developing settings. PMID:24220589

Type 2 diabetes mellitus with hypertension at primary healthcare level in Malaysia: are they managed according to guidelines?

PubMed

Chan, G C

2005-03-01

A study was conducted at primary healthcare level in the Melaka Tengah district of Malaysia to determine whether hypertension in patients with type 2 diabetes mellitus were managed according to guidelines. A cross-sectional study involving 517 patients with diabetes mellitus from August to October 2003 was performed. All the subjects had type 2 diabetes mellitus. 350 (67.7 percent) patients had hypertension and about 25.7 percent of them were associated with microalbuminuria. The Malay ethnic group form the majority (54.6 percent), followed by Chinese (37.7 percent) and Indian (7.4 percent). Only 11 (3.1 percent) patients with type 2 diabetes mellitus and hypertension achieved the target blood pressure of less than 130/80 mmHg. For those who had not achieved the target goal, 39.5 percent of them were not on any antihypertensive drugs. 38.6 percent were on monotherapy and only 21.8 percent were on two or more antihypertensive drugs. Metoprolol was the most commonly used antihypertensive drug (22.4 percent), followed by Nifedipine (16.2 percent) and Prazosin (13.5 percent). Only 18.3 percent of patients with type 2 diabetes mellitus and hypertension were prescribed with angiotensin converting enzyme (ACE) inhibitors and 0.3 percent with angiotensin receptor blockers. For patients with type 2 diabetes mellitus, hypertension and microalbuminuria, only 14.1 percent of them were prescribed with ACE inhibitors. A significant proportion of patients with type 2 diabetes mellitus had associated hypertension but they were not managed optimally according to guidelines. More intensive management of hypertension among patients with diabetes is essential to reduce the morbidity and mortality at primary healthcare level.

Antihypertensive drug use in resistant and nonresistant hypertension and in controlled and uncontrolled resistant hypertension.

PubMed

de la Sierra, Alejandro; Armario, Pedro; Oliveras, Anna; Banegas, José R; Gorostidi, Manuel; Vinyoles, Ernest; de la Cruz, Juan J; Segura, Julián; Ruilope, Luis M

2018-07-01

Treatment-resistant hypertension (TRH) is associated with particular clinical features, nonadherence, and suboptimal treatment. We assessed possible associations of antihypertensive drug classes, specific agents inside each class, and types of combinations, with the presence of non-TRH vs. TRH, and with controlled vs. uncontrolled TRH. Comparisons were done in 14 264 patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974 treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591). Associations were adjusted for age, sex, and previous cardiovascular event. In both groups of patients treated with three or with at least four drugs, aldosterone antagonists among drug classes [adjusted odds ratio (OR): 1.82 and 1.41, respectively], and ramipril (OR: 1.28 and 1.30), olmesartan (OR: 1.31 and 1.37), and amlodipine (OR: 1.11 and 1.41) inside each class were significantly associated with blood pressure control (non-TRH or controlled TRH). In patients treated with three drugs, non-TRH was also associated with the use of chlorthalidone (OR: 1.50) and bisoprolol (OR: 1.19), whereas in patients treated with at least four drugs, controlled TRH was significantly associated with the triple combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic (OR: 1.17). The use of aldosterone antagonists is associated with blood pressure control in patients treated with three or more drugs. Similar results are observed with specific agents inside each class, being ramipril, olmesartan, chlorthalidone, amlodipine, and bisoprolol those exhibiting significant results. An increased use of these drugs might probably reduce the burden of TRH.

Treatment-associated change in apelin concentration in patients with hypertension and its relationship with left ventricular diastolic function.

PubMed

Baysal, Sadettin Selçuk; Pirat, Bahar; Okyay, Kaan; Bal, Uğur Abbas; Uluçam, Melek Zekiye; Öztuna, Derya; Müderrisoğlu, Haldun

2017-02-01

We examined the change in apelin concentration and its relationship with left ventricular diastolic function in patients treated for hypertension. Ninety treatment-naive patients with newly diagnosed hypertension and 33 age- and sex-matched control subjects were prospectively enrolled. Patients with hypertension were randomized to treatment either with telmisartan 80 mg or amlodipine 10 mg. Apelin concentration was measured and echocardiography was performed at baseline and after 1 month of treatment. The data of 77 patients and 33 controls were analyzed. Mean age, gender, baseline blood pressure, apelin levels, and echocardiographic measurements were similar between the treatment groups (p>0.05 for all). Apelin concentration was significantly lower in patients with hypertension than in controls. There was a significant increase in apelin level after 1 month of treatment in both groups (0.32±0.17 vs. 0.38±0.17 ng/dL in telmisartan group, p=0.009, and 0.27±0.13 vs. 0.34±0.18 ng/dL in amlodipine group, p=0.013). Diastolic function improved significantly in both groups (p<0.05) but was not significantly associated with change in apelin concentration. Apelin concentration increased significantly after 1 month of effective treatment with telmisartan or amlodipine to a similar extent. Change in apelin concentration was not associated with improvement in diastolic function.

Treatment-associated change in apelin concentration in patients with hypertension and its relationship with left ventricular diastolic function

PubMed Central

Baysal, Sadettin Selçuk; Pirat, Bahar; Okyay, Kaan; Bal, Uğur Abbas; Uluçam, Melek Zekiye; Öztuna, Derya; Müderrisoğlu, Haldun

2017-01-01

Objective: We examined the change in apelin concentration and its relationship with left ventricular diastolic function in patients treated for hypertension. Methods: Ninety treatment-naive patients with newly diagnosed hypertension and 33 age- and sex-matched control subjects were prospectively enrolled. Patients with hypertension were randomized to treatment either with telmisartan 80 mg or amlodipine 10 mg. Apelin concentration was measured and echocardiography was performed at baseline and after 1 month of treatment. Results: The data of 77 patients and 33 controls were analyzed. Mean age, gender, baseline blood pressure, apelin levels, and echocardiographic measurements were similar between the treatment groups (p>0.05 for all). Apelin concentration was significantly lower in patients with hypertension than in controls. There was a significant increase in apelin level after 1 month of treatment in both groups (0.32±0.17 vs. 0.38±0.17 ng/dL in telmisartan group, p=0.009, and 0.27±0.13 vs. 0.34±0.18 ng/dL in amlodipine group, p=0.013). Diastolic function improved significantly in both groups (p<0.05) but was not significantly associated with change in apelin concentration. Conclusion: Apelin concentration increased significantly after 1 month of effective treatment with telmisartan or amlodipine to a similar extent. Change in apelin concentration was not associated with improvement in diastolic function. PMID:27599667

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

PubMed Central

2011-01-01

Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include β-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation. PMID:21849624

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

A new synthesis and preliminary evaluation of some analogues of mecamylamine - a compound with anti-addiction properties.

PubMed

Mangan, David; McNabola, Neasa; Clark, Emily H; Bermudez, Isabel; Wonnacott, Susan; Southern, J Mike

2016-11-22

A new synthesis of mecamylamine - a known anti-hypertensive drug with anti-addictive properties is described. The new route allowed access to two novel analogues whose activity at two nicotinic acetylcholine receptor subtypes was assessed.

Should African Americans have a lower blood pressure goal than other ethnic groups to prevent organ damage?

PubMed

Flack, John M; Okwuosa, Tochukwi; Sudhakar, Rajeev; Ference, Brian; Levy, Phillip

2012-12-01

African Americans manifest an inordinately high burden of hypertension, pressure-related target-organ injury (eg, left ventricular hypertrophy, stroke), and sub-optimal hypertension control rates to conventional levels (<140/90 mm Hg). A substantive proportion of the excessive premature mortality in African Americans relative to Whites is pressure-related. Randomized prospective pharmacologic hypertension end-point trials have shown invariable cardiovascular disease (CVD) risk reduction across a broad range of pre-treatment BP levels down to 110/70 mm Hg with the magnitude of CVD risk reduction across the 5 major antihypertensive drug classes being directly linked to degree of blood pressure (BP) lowering. Pooled endpoint data from pharmacologic hypertension trials in African Americans showed that CVD risk reduction was the same with major antihypertensive drug classes when similar levels of BP were achieved. A lower than conventional BP target for African Americans seems justified and prudent because attainment of lower BP should incrementally lower CVD risk in this high-risk population.

The critical role of the central nervous system (pro)renin receptor in regulating systemic blood pressure

PubMed Central

Xu, Quanbin; Jensen, Dane D.; Peng, Hua; Feng, Yumei

2016-01-01

The systemic renin–angiotensin system (RAS) has long been recognized as a critically important system in blood pressure (BP) regulation. However, extensive evidence has shown that a majority of RAS components are also present in many tissues and play indispensable roles in BP regulation. Here, we review evidence that RAS components, notably including the newly identified (pro)renin receptor (PRR), are present in the brain and are essential for the central regulation of BP. Binding of the PRR to its ligand, prorenin or renin, increases BP and promotes progression of cardiovascular diseases in an angiotensin II-dependent and -independent manner, establishing the PRR a promising antihypertensive drug target. We also review the existing PRR blockers, including handle region peptide and PRO20, and propose a rationale for blocking prorenin/PRR activation as a therapeutic approach that does not affect the actions of the PRR in vacuolar H+-ATPase and development. Finally, we summarize categories of currently available antihypertensive drugs and consider future perspectives. PMID:27113409

Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

PubMed Central

Papanagnou, Panagiota; Baltopoulos, Panagiotis; Tsironi, Maria

2015-01-01

Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. PMID:26056460

TRPM8 and RAAS-mediated hypertension is critical for cold-induced immunosuppression in mice.

PubMed

Chan, Hao; Huang, Hsuan-Shun; Sun, Der-Shan; Lee, Chung-Jen; Lien, Te-Sheng; Chang, Hsin-Hou

2018-02-27

Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin-angiotensin-aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP). Essential roles of TRPM8 and Ig in cold-induced immunosuppression are supported by the cold-mediated amelioration of ITP and the cold-mediated suppression of bacterial clearance, which were observed in wild-type mice but not in Ig- and TRPM8-deficient mutants. Treatment with antihypertensive drugs aliskiren and losartan drastically reversed high plasma Ig levels and ameliorated cold-induced immunosuppression, indicating the involvement of the RAAS and hypertension. These results indicated that the natively increased plasma Ig level is associated with immunosuppression during periods of cold exposure, and antihypertensive drugs can be useful to manage cold-induced immunosuppression.

Identification of a novel selective PPARγ ligand with a unique binding mode and improved therapeutic profile in vitro

PubMed Central

Yi, Wei; Shi, Jingjing; Zhao, Guanguan; Zhou, X. Edward; Suino-Powell, Kelly; Melcher, Karsten; Xu, H. Eric

2017-01-01

Thiazolidinediones (TZD) function as potent anti-diabetic drugs through their direct action on the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), but their therapeutic benefits are compromised by severe side effects. To address this concern, here we developed a potent “hit” compound, VSP-51, which is a novel selective PPARγ-modulating ligand with improved therapeutic profiles in vitro compared to the multi-billion dollar TZD drug rosiglitazone (Rosi). Unlike Rosi, VSP-51 is a partial agonist of PPARγ with improved insulin sensitivity due to its ability to bind PPARγ with high affinity without stimulating adipocyte differentiation and the expression of adipogenesis-related genes. We have determined the crystal structure of the PPARγ ligand-binding domain (LBD) in complex with VSP-51, which revealed a unique mode of binding for VSP-51 and provides the molecular basis for the discrimination between VSP-51 from TZDs and other ligands such as telmisartan, SR1663 and SR1664. Taken together, our findings demonstrate that: a) VSP-51 can serve as a promising candidate for anti-diabetic drug discovery; and b) provide a rational basis for the development of future pharmacological agents targeting PPARγ with advantages over current TZD drugs. PMID:28128331

Adherence to treatment, emotional state and quality of life in patients with end-stage renal disease undergoing dialysis.

PubMed

García-Llana, Helena; Remor, Eduardo; Selgas, Rafael

2013-02-01

A low rate of adherence to treatment is a widespread problem of great clinical relevance among dialysis patients. The objective of the present study is to determine the relationship between adherence, emotional state (depression, anxiety, and perceived stress), and health-related quality of life (HRQOL) in renal patients undergoing dialysis. Two patient groups (30 in hemodialysis and 31 in peritoneal dialysis) participated in this study. We evaluated aspects of adherence, depression, anxiety, perceived stress, and HRQOL with self-report and standardized instruments. Peritoneal dialysis patients reported significantly higher levels of adherence to treatment and better HRQOL in Physical Function and Bodily Pain domains. Depression level is associated with HRQOL indicators. We did not find any differences regarding specific adherence to antihypertensive and phosphate binder drugs or in psychological variables depending on the modality of dialysis. Patients with adherence to antihypertensive drugs show better physical HRQOL. The predictors of HRQOL in dialysis patients were: work, gender and depression. Our results suggest that the modality of dialysis does not differentially affect the emotional state or specific adherence to drugs, but it is nevertheless related to their overall adherence to treatment and to their HRQOL.

Fungal biotransformation of diuretic and antihypertensive drug spironolactone with Gibberella fujikuroi, Curvularia lunata, Fusarium lini, and Aspergillus alliaceus.

PubMed

Al-Aboudi, Amal; Kana'an, Belal Muneeb; Zarga, Musa Abu; Bano, Saira; Atia-Tul-Wahab; Javed, Kulsoom; Choudhary, M Iqbal

2017-12-01

Derivatives of spironolactone (1), a diuretic and antihypertensive drug, were synthesized by using fungal cells for the first time. Ten different fungi were screened for their ability to biotransform 1, four of which were able to produce metabolites 2-8. Gibberella fujikuroi produced canrenone (2), 1-dehydrocanrenone (3), Curvularia lunuta provided compound 2, and 7α-thio-spironolactone (4), Fusarium lini yielded compounds 2, 3, 1β-hydroxycanrenone (5), 1α-hydroxycanrenone (6), 1-dehydro-15α-hydroxycanrenone (7), and 15α-hydroxycanrenone (8), while Aspergillus alliaceus was able to produce all the seven metabolites. Metabolites 5, 6, and 7 were identified as new compounds. Their structures were elucidated by using different spectroscopic techniques. Substrate 1 and its metabolites 2, 3, and 5-8 were also evaluated for α-glucosidase inhibitory activity in vitro. Substrate 1 was found to be strongly active with IC 50  = 335 ± 4.3 μM as compared to the standard drug acarbose IC 50  = 840 ± 1.73 μM, whereas all of resulting metabolites were found to be inactive. Copyright © 2017 Elsevier Inc. All rights reserved.

The management of hypertensive crises: a clinical review.

PubMed

Pergolini, M S

2009-01-01

Hypertension is an exceedingly common disorder in Western societies; but, thanks to improved management of chronic hypertension, the number of patients who present with hypertensive crisis (HC) is less than 1%. However, critical elevation of blood pressure (BP) obliges to a proper and immediate management in order to prevent serious injury to organ target of hypertension (brain, heart, kidney and vessels). Moreover, the so called hypertensive emergencies (HE) and the hypertensive urgencies (HU) expect a several therapeutic approach. The HE warrant both prompt admission to an intensive care unit, where it is available a continuous monitoring of BP, and a prompt starting of a therapy with parenteral anti-hypertensive drugs. The treatment of HU can be managed choosing oral anti-hypertensive agents followed by a tight observation of the patient also in ambulatory system, lowering the BP more gradually over 12 to 24-48 hours. The present clinical review is aimed at reporting the current opinions on the management of HC, examining as well the drugs of largest use. Any drug that lowers BP precipitously should be avoided. Choice of the appropriate agent should be based on the underlying pathophysiological and clinical findings, on the mechanism of action, and on its potential side effects.

Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1–7)/ Mas-dependent pathway

PubMed Central

Schuchard, Johanna; Winkler, Martina; Stölting, Ines; Schuster, Franziska; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Santos, Robson A; Bader, Michael; Raasch, Walter

2015-01-01

Background and Purpose Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II. As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects. Experimental Approach We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1). Key Results In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. Conclusions and Implications Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity. PMID:25906670

Outpatient use of cardiovascular drugs during pregnancy.

PubMed

Andrade, Susan E; Raebel, Marsha A; Brown, Jeffrey; Lane, Kimberly; Livingston, James; Boudreau, Denise; Rolnick, Sharon J; Roblin, Douglas; Smith, David H; Dal Pan, Gerald J; Scott, Pamela E; Platt, Richard

2008-03-01

To provide information on the prevalence of use of cardiovascular drugs, some of which may have fetotoxic or teratogenic effects, in the outpatient setting among pregnant women in the United States. A retrospective study was conducted using the automated databases of seven health plans participating in the HMO Research Network Center for Education and Research on Therapeutics (CERT). Women who delivered an infant from 1 January 2001 to 31 December 2005 were identified. Cardiovascular drug use was evaluated assuming a gestational duration of 270 days. During the period 2001 through 2005, 118,935 deliveries were identified that met the criteria for study; 3.1% of women (N = 3672) were dispensed an antihypertensive medication and 0.12% of women (N = 146) were dispensed an antihyperlipidemic medication at any time during pregnancy. The most common antihypertensive drugs dispensed during pregnancy were nifedipine (1219 deliveries; 1.0%), methyldopa (961 deliveries; 0.8%), atenolol (593 deliveries; 0.5%), and labetalol (576 deliveries; 0.5%). Overall, 134 women (0.11%) received an angiotensin converting enzyme (ACE) inhibitor and 7 women (0.006%) received an angiotensin II receptor blocker (ARB) during pregnancy. Statins were the most commonly dispensed antihyperlipidemic drugs (71 deliveries; 0.06%). The prevalence of use of cardiovascular drugs that are suspected to be fetotoxic or teratogenic (ACE inhibitors, ARBs, and statins) was low in this cohort of pregnant women. Differing patterns of use across health plans suggests that further research is needed to evaluate the potential differential effects of cardiovascular drugs to assist prescribers and patients in making informed treatment decisions. Copyright 2008 John Wiley & Sons, Ltd.

Section II: Reviews. Antihypertensive Drugs in Aircrew

DTIC Science & Technology

2001-06-01

Sleep 1997;20:806-11. utility in treating hypertensive emergencies. Only hydralazine and minoxidil are suitable for 7. Hampton JR. Comparative efficacy...like trials. European Heart J 1992;13(Suppl G):85- syndrome, the frequency of occurrence depending 91. on dose and duration. 4 Minoxidil causes severe

Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery.

PubMed

Duceppe, Emmanuelle; Lussier, Anne-Renee; Beaulieu-Dore, Roxane; LeManach, Yannick; Laskine, Mikhael; Fafard, Josee; Durand, Madeleine

2018-06-01

Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI. We performed a retrospective cohort study of hypertensive patients undergoing elective major vascular surgery to determine the association between the number of antihypertensive medications continued on the morning of surgery and AKI at 48 hours postoperatively. A total of 406 patients who had undergone suprainguinal vascular surgery were included, and 10.3% suffered postoperative AKI. In multivariable analysis, the number of antihypertensive medications taken on the morning of surgery was independently associated with AKI (P = .026). Compared with patients who took no medication, taking one medication (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.68-3.75) and taking two or more medications (aOR, 2.70; 95% CI, 1.13-6.44) were associated with a 1.6-fold and 2.7-fold increased risk of postoperative AKI, respectively. Other predictors of AKI were suprarenal surgery (aOR, 3.37; 95% CI, 1.53-7.44), age (aOR, 2.29 per 10 years; 95% CI, 1.40-3.74), length of surgery (aOR, 1.40 per 1 hour; 95% CI, 1.10-1.76), hemoglobin drop (aOR, 1.37 per 10 g/L; 95% CI, 1.10-1.74), and history of coronary artery disease (aOR, 2.33; 95% CI, 1.08-5.00). In patients undergoing major vascular surgery who are treated with chronic antihypertensive therapy, the administration of antihypertensive drugs on the morning of surgery is independently associated with an increased risk of postoperative AKI. Further prospective studies are needed to confirm this finding. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis

PubMed Central

Tomaszewski, Maciej; White, Christobelle; Patel, Prashanth; Masca, Nicholas; Damani, Ravi; Hepworth, Joanne; Samani, Nilesh J; Gupta, Pankaj; Madira, Webster; Stanley, Adrian; Williams, Bryan

2014-01-01

Objectives Non-adherence to therapy is an important cause of suboptimal blood pressure control but few practical tools exist to accurately and routinely detect it. We used a simple urine-based assay to evaluate the prevalence of antihypertensive treatment non-adherence and its impact on blood pressure in a specialist hypertension centre. Methods 208 hypertensive patients (125 new referrals, 66 follow-up patients with inadequate blood pressure control and 17 renal denervation referrals) underwent assessment of antihypertensive drug intake using high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis at the time of clinical appointment. A total of 40 most commonly prescribed antihypertensive medications (or their metabolites) were screened for in spot urine samples. Results Overall, 25% of patients were totally or partially non-adherent to antihypertensive treatment (total non-adherence 10.1%, partial non-adherence 14.9%). The highest prevalence of partial and total non-adherence was among follow-up patients with inadequate blood pressure control (28.8%) and those referred for consideration of renal denervation (23.5%), respectively. There was a linear relationship between blood pressure and the numerical difference in detected/prescribed antihypertensive medications—every unit increase in this difference was associated with 3.0 (1.1) mm Hg, 3.1 (0.7) mm Hg and 1.9 (0.7) mm Hg increase in adjusted clinic systolic blood pressure, clinic diastolic blood pressure (DBP) and 24 h mean daytime DBP (p=0.0051, p=8.62×10−6, p=0.0057), respectively. Conclusions Non-adherence to blood pressure lowering therapy is common, particularly in patients with suboptimal blood pressure control and those referred for renal denervation. HP LC-MS/MS urine analysis could be used to exclude non-adherence and better stratify further investigations and intervention. PMID:24694797

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

PubMed Central

2012-01-01

Background The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. Methods Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. Results At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m2), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. Conclusions NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible. PMID:22594907

Drug-induced sexual dysfunction.

PubMed

Aldridge, S A

1982-01-01

Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

Resistant hypertension revisited: a comparison of two university-based cohorts.

PubMed

Garg, Jay P; Elliott, William J; Folker, Amy; Izhar, Munavvar; Black, Henry R

2005-05-01

More than a decade ago, we found that a suboptimal medication regimen was the leading cause of resistant hypertension (RH) among patients referred to a tertiary care clinic. Since then, lower blood pressure (BP) goals have been recommended, suggesting that more patients may have RH. To assess whether the reasons for and treatment of RH have changed, we determined the frequency of various causes of resistance, the proportion of patients achieving goal BP, and the changes made in antihypertensive regimens. The charts of all new patients seen at the RUSH University Hypertension Center between January 1, 1993, and November 1, 2001, were reviewed for strict criteria for RH: 1) physician referral for uncontrolled hypertension; 2) BP > or =140/90 mmHg despite use of three antihypertensive drugs; and 3) at least one follow-up visit. Patients were followed-up until goal BP was achieved on two consecutive visits or their last visit or until March 2002. Of 1281 patients, 141 met criteria for RH. A cause of resistance was found in 94% of cases, including the following: drug-related causes (58%); nonadherence (16%); psychological causes (9%); office resistance (ie, in-clinic BP readings that were higher than goal despite treatment with antihypertensive medications and despite normotensive BP outside of the clinic as demonstrated by 24-h ambulatory BP monitoring) (6%); and secondary hypertension (5%). Overall, 53% of patients had their BP controlled to <140/90 mmHg, largely from regimen optimization and intensification, proper use of diuretics, and on average 4.1 +/- 1 antihypertensive medications (3.7 +/- 0.9 on referral). These data are strikingly similar to those from our previous study of RH, in which a suboptimal medication regimen was the most common reason for resistance. Goal BP was most commonly achieved after optimizing the diuretic regimen and increasing the number of medications, suggesting that physicians should use these measures to attain the recommended lower BP goals If goal BP is not reached, referral to a clinical hypertension specialist may be appropriate.

Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

PubMed

Salvi, Erika; Wang, Zhiying; Rizzi, Federica; Gong, Yan; McDonough, Caitrin W; Padmanabhan, Sandosh; Hiltunen, Timo P; Lanzani, Chiara; Zaninello, Roberta; Chittani, Martina; Bailey, Kent R; Sarin, Antti-Pekka; Barcella, Matteo; Melander, Olle; Chapman, Arlene B; Manunta, Paolo; Kontula, Kimmo K; Glorioso, Nicola; Cusi, Daniele; Dominiczak, Anna F; Johnson, Julie A; Barlassina, Cristina; Boerwinkle, Eric; Cooper-DeHoff, Rhonda M; Turner, Stephen T

2017-01-01

This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10 - 8 ), and the suggestive regions (P<10 -5 ) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein α1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10 - 4 ). HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment. © 2016 American Heart Association, Inc.

Antihypertensive Agents and Risk of Parkinson's Disease: A Nationwide Cohort Study

PubMed Central

Wu, Ruey-Meei; Lin, Jou-Wei; Chang, Chia-Hsuin; Lai, Mei-Shu

2014-01-01

Background and Purpose Hypertension has been associated with Parkinson's disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients. Methods Hypertensive patients who were free of PD, dementia and stroke were recruited from 2005–2006 using Taiwan National Health Insurance Database. We examined the association between the use of calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and the incidence of PD using beta-blockers as the reference. Cox regression model with time-varying medication use was applied. Results Among 65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a reduced risk of PD (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.57–0.90). Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was associated with a decreased risk of PD (aHR = .69 [55–0.87]. Further decreased association was observed for higher cumulative doses of felodipine (aHR = 0.54 [0.36–0.80]) and amlodipine (aHR = 0.60 [0.45–0.79]). There was no association between the use of ACEIs (aHR = 0.80 [0.64–1.00]) or ARBs (aHR = 0.86 [0.69–1.08]) with PD. A potentially decreased association was only found for higher cumulative use of ACEIs (HR = 0.52 [0.34–0.80]) and ARBs (HR = 0.52 [0.33–0.80]). Conclusions Our study suggests centrally-acting dihydropyridine CCB use and high cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD in hypertensive patients. Further long-term follow-up studies are needed to confirm the potential beneficial effects of antihypertensive agents in PD. PMID:24910980

Mobile phone text messaging improves antihypertensive drug adherence in the community.

PubMed

Varleta, Paola; Acevedo, Mónica; Akel, Carlos; Salinas, Claudia; Navarrete, Carlos; García, Ana; Echegoyen, Carolina; Rodriguez, Daniel; Gramusset, Lissette; Leon, Sandra; Cofré, Pedro; Retamal, Raquel; Romero, Katerine

2017-12-01

Antihypertensive drug adherence (ADA) is a mainstay in blood pressure control. Education through mobile phone short message system (SMS) text messaging could improve ADA. The authors conducted a randomized study involving 314 patients with hypertension with <6 months of antihypertensive treatment from the Preventive Health Program of 12 different primary care centers in Santiago, Chile. Patients were randomly assigned to receive or not receive SMS related to ADA and healthy lifestyle. Adherence was assessed by the self-reported four-item scale Morisky-Green-Levine questionnaire at baseline and after 6 months of follow-up, with four of four positive questions classified as good adherence. Group comparison for adherence was performed by means of a logistic regression model, adjusting by baseline adherence, age older than 60 years, and sex. A total of 163 patients were randomized to receive and 151 to not receive SMS. After 6 months of follow-up, ADA in the non-SMS group decreased from 59.3% to 51.4% (P=.1). By contrast, adherence increased from 49% to 62.3% (P=.01) in the SMS group. Text messaging intervention improved ADA (risk ratio, 1.3; 95% confidence interval, 1.0-1.6 [P<.05]). At 6-month follow-up, text messaging resulted in an increase in reporting ADA in this hypertensive Latino population. This approach could become an effective tool to overcome poor medication adherence in the community. ©2017 Wiley Periodicals, Inc.

Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness

PubMed Central

Halabi, Carmen M.; Broekelmann, Thomas J.; Knutsen, Russell H.; Ye, Li; Mecham, Robert P.

2015-01-01

Increased arterial stiffness is a common characteristic of humans with Williams-Beuren syndrome and mouse models of elastin insufficiency. Arterial stiffness is associated with multiple negative cardiovascular outcomes, including myocardial infarction, stroke, and sudden death. Therefore, identifying therapeutic interventions that improve arterial stiffness in response to changes in elastin levels is of vital importance. The goal of this study was to determine the effect of chronic pharmacologic therapy with different classes of antihypertensive medications on arterial stiffness in elastin insufficiency. Elastin-insufficient mice 4–6 wk of age and wild-type littermates were subcutaneously implanted with osmotic micropumps delivering a continuous dose of one of the following: vehicle, losartan, nicardipine, or propranolol for 8 wk. At the end of treatment period, arterial blood pressure and large artery compliance and remodeling were assessed. Our results show that losartan and nicardipine treatment lowered blood pressure and pulse pressure in elastin-insufficient mice. Elastin and collagen content of abdominal aortas as well as ascending aorta and carotid artery biomechanics were not affected by any of the drug treatments in either genotype. By reducing pulse pressure and shifting the working pressure range of an artery to a more compliant region of the pressure-diameter curve, antihypertensive medications may mitigate the consequences of arterial stiffness, an effect that is drug class independent. These data emphasize the importance of early recognition and long-term management of hypertension in Williams-Beuren syndrome and elastin insufficiency. PMID:26232234

Laboratory Monitoring of Patients Treated with Antihypertensive Drugs and Newly Exposed to Non Steroidal Anti-Inflammatory Drugs: A Cohort Study

PubMed Central

Fournier, Jean-Pascal; Lapeyre-Mestre, Maryse; Sommet, Agnès; Dupouy, Julie; Poutrain, Jean-Christophe; Montastruc, Jean-Louis

2012-01-01

Background Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. Methods We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. Results General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3–86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5–11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. Conclusion Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions. PMID:22479557

[Abpm and duration of the antihypertensive effect: a study with a new formulation of sustained release losartan (CRONOS)].

PubMed

Bendersky, Mario; Juncos, Luis; Waisman, Gabriel Dario; Piskorz, Daniel; Lopez-Santi, Ricardo; Montaña, Oscar; Caruso, Gustavo; Kotetzky, Martin; Penna, Maria; Gomez, Roberto

2012-01-01

Antihypertensive drugs action should last at least 24 h in order to enhance adherence, with positive impact on CV morbimortality. ABPM allow us to evaluate duration of action of drugs, against placebo, using Trough:Peak Ratio, antihypertensive effect in the last 4 h interdosis, and calculating the rate of BP morning surge. Losartán is an Antagonist At1 with good antihypertensive efficacy and renal, cardiac and cerebrovascular protection. Some studies shows less than 24 hs of action, that suggest twice a day dosing. The merge of a new formulation, Losartan Cronos, a bilayer tablet containing 50 mg of Losartan immediate release (IR) and 50 mg extended release (ER) would allow 24 h coverage, maintaining the previous advantages. To assess antihypertensive duration of action of Losartán Cronos in patients with essential hypertension throughout a 24-h dosing interval, using ABPM and response rates, AASI and Smoothness Index. 97 essential hypertensives, where included and received a single morning dose of Losartán Cronos (50 mg of regular release and 50 mg of controlled and retarded release) during 8 weeks. Performed valid ABPM post placebo and post active treatment. Results Mean age 58 (26-86), 60% women. 63% treatment naïve. The mean reduction in BP from baseline to week 8 (end of treatment) was statistically significant for all times analyzed (24 hours, daytime, night-time, and last 4 hours monitoring). There were no significant changes in 24h heart rate. BP morning surge (mmHg/hour) decreased from 4.53 to 3,68 (p=0.03).T:P Ratio was 0.91 for SBP and 1.14 for DBP. Smoothness Index: SBP 2.86 (95% CI 1.84-3.7) - DBP 3.17 (95% CI 2.03-3.9) 19 patients had adverse events, no-one cough, all mild, without discontinuations. Conclusion Losartán Cronos demonstrated efficacy and safety, decreases BP without significant effects in heart rate, it reduces the pulse pressure, and its effect lasts for 24 hs, assessed by T:P ratio, last 4 hours effects, decreasing morning surge, also presenting homogeneous effect, since its Smoothness Index is high. Our results suggests daily monodose administration.

Effects of nighttime single-dose administration of vasodilating vs sympatholytic antihypertensive agents on sleep blood pressure in hypertensive patients with sleep apnea syndrome.

PubMed

Kario, Kazuomi; Kuwabara, Mitsuo; Hoshide, Satoshi; Nagai, Michiaki; Shimpo, Masahisa

2014-06-01

Obstructive sleep apneas syndrome (OSAS) is associated with nocturnal hypertension with higher sleep blood pressure (BP) and its variability, both of which increase cardiovascular risk. In this crossover design study, the effect of nighttime single-dose administration of vasodilating (nifedipine 40 mg) vs sympatholytic (carvedilol 20 mg) antihypertensive agents on sleep BP in 11 hypertensive OSAS patients was evaluated. The authors recently developed a trigger sleep BP monitor with an oxygen-triggered function that initiates BP measurement when oxygen desaturation falls. The BP-lowering effects of nifedipine on the mean (P<.05) and minimum sleep systolic BPs (SBPs) (P<.01) were stronger than those of carvedilol. Sleep SBP surge (difference between the hypoxia-peak SBP measured by oxygen-triggered function and SBPs within 30 minutes before and after the peak SBP) was only significantly reduced by carvedilol (P<.05). The nighttime dosing of both vasodilating and sympatholytic antihypertensive drugs is effective to reduce sleep BP but with different BP-lowering profiles. ©2014 Wiley Periodicals, Inc.

Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers.

PubMed

De Luca, Michele; Ioele, Giuseppina; Spatari, Claudia; Ragno, Gaetano

2016-05-30

1,4-dihydropyridine antihypertensives (DHPs) are almost all dispensed in solid pharmaceutical formulations for their easy lability when exposed to light. This paper reports a study on the photoprotective effect of containers in different glassy or polymeric matrices with regard to four known DHPs when in solutions. The samples were subjected to forced degradation by means of a Xenon lamp, in accordance with the international rules on drug stability evaluation. The simultaneous determination of the drugs and their photoproducts was carried out by applying the multivariate curve resolution (MCR) methodology to the spectral data recorded along the irradiation test. This technique was able to determine the kinetic parameters and resolve the spectra of the photoproducts. The time required to reduce by 10% the concentration of the drug (t0.1) was adopted as a criterion to compare the protective ability of the containers. A significant photoprotection for all drugs tested was obtained by the use of polyethylene terephthalate (PET) containers. The best result was achieved for the felodipine solution in blue PET transparent bottle of 0.6mm thickness, reaching an almost complete stabilization up to six hours under stressing irradiation. In contrast, the glass containers, whether or not coloured, did not provide a satisfactory photoprotection of the drugs, showing in any case t0.1 values under 24min. These results can be a good opportunity to design new photoprotective pharmaceutical packaging for DHPs in liquid dosage form. Copyright © 2016 Elsevier B.V. All rights reserved.

[Control of blood pressure in hypertensive patients on combination therapy].

PubMed

de la Sierra, Alejandro; Oliveras, Anna; Armario, Pedro; Lucas, Silvia

2015-02-20

The impact of antihypertensive treatment on blood pressure (BP) control is fairly unknown. The aim of the study was to evaluate the degree of BP control and its relationship with treatment-related factors in hypertensive patients treated with 2 or 3 agents and attended in referral units. We studied 1,337 hypertensive subjects (41% women) with a mean age (SD) of 63 (12) years, who were receiving 2 or 3 antihypertensive drugs. The degree of BP control was estimated in a single visit by the proportion of patients with BP below 140/90mmHg. BP was controlled in 767 patients (57%). Lack of BP control was related to older age (12% risk for each 10-year increase) and the presence of microalbuminuria (64% risk increase). In those treated with 2 agents, BP control was 61%, without differences between those treated with fixed-drug or free combinations. BP control in those treated with 3 agents was 55%, higher in those receiving 3 agents in a fixed-drug combination (68%) compared with those on 3 agents administered separately (52%; P=.025). Drug classes used in combinations did not influence the degree of BP control. The degree of BP control in patients treated with 2 or 3 agents is 57%. Microalbuminuria is related to a lack of BP control. In those receiving 3 agents, the use of fixed-drug combinations is associated with better BP control. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Effect of hypotensive therapy combined with modified diet or zinc supplementation on biochemical parameters and mineral status in hypertensive patients.

PubMed

Suliburska, Joanna; Skrypnik, Katarzyna; Szulińska, Monika; Kupsz, Justyna; Bogdański, Paweł

2018-05-01

Hypotensive therapy leads to a number of trace elements metabolism disturbances. Zinc balance is frequently affected by antihypertensive treatment. To evaluate the effect of a hypotensive treatment, modified diet and zinc supplementation on mineral status and selected biochemical parameters in newly diagnosed hypertensive patients on monotherapy. In the first stage, arterial hypertension in ninety-eight human subjects was diagnosed. In the second stage, antihypertensive monopharmacotherapy was implemented. In the third stage, patients were randomized into three groups and continued antihypertensive monotherapy: group D received an optimal-mineral-content diet, group S received zinc supplementation, and group C had no changes in diet or zinc supplementation. Iron, zinc, and copper concentrations in serum, erythrocytes, urine, and hair were determined. Lipids, glucose, ceruloplasmin, ferritin, albumin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT) were assayed in serum. Antihypertensive monotherapy decreased zinc concentration in serum and erythrocytes and increased the level of zinc in urine, decreased CAT and SOD activity, TNF-α concentration in serum, and increased the level of NO in the serum. Zinc supply led to an increase in zinc concentration in serum, erythrocytes, and hair (in group S only). In the groups with higher zinc intake, decreased glucose concentration in the serum was observed. Significant correlation was seen between the zinc and glucose serum concentrations. Hypotensive drugs disturb zinc status in newly diagnosed hypertensive patients. Antihypertensive monotherapy combined with increased zinc supply in the diet or supplementation favorably modify zinc homeostasis and regulate glucose status without blood pressure affecting in patients with hypertension. Copyright © 2018 Elsevier GmbH. All rights reserved.

Hepatic Expression of Serum Amyloid A1 Is Induced by Traumatic Brain Injury and Modulated by Telmisartan

PubMed Central

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G.; Campbell, Ashley M.; Saavedra, Juan M.; Shewmaker, Frank P.; Symes, Aviva J.

2016-01-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

Retrospective analysis of drug photosensitivity in Norway

NASA Astrophysics Data System (ADS)

Selvaag, Edgar

1999-02-01

Reports on adverse drug reactions, as they were recorded at the Norwegian Medicines Control Authority beginning in the year 1970 up to 1994 were analyzed especially with regard to cutaneous reactions and photosensitivity reactions. During the time period, almost 13.000 side effects were reported. Out of these 799 reports involved the skin and appendages, and 64 out of these reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs which most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the background of experimental data and the prescription rates of these substances.

The Pharmacogenomics of Anti-Hypertensive Therapy.

PubMed

Padmanabhan, Sandosh; Paul, Laura; Dominczak, Anna F

2010-06-01

Hypertension is a major public health problem, but measures to reduce blood pressure and thus cardiovascular risk are complicated by the high prevalence of treatment resistance, despite the availability of multiple drugs. Drug side-effects contribute considerably to suboptimal blood pressure control. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenomics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice. In this review we summarise the current status of hypertension pharmacogenetics from monogenic hypertension to essential hypertension and discuss the issues that need to be considered in a hypertension pharmacogenomic study.

Leveraging prior quantitative knowledge in guiding pediatric drug development: a case study.

PubMed

Jadhav, Pravin R; Zhang, Jialu; Gobburu, Jogarao V S

2009-01-01

The manuscript presents the FDA's focus on leveraging prior knowledge in designing informative pediatric trial through this case study. In developing written request for Drug X, an anti-hypertensive for immediate blood pressure (BP) control, the sponsor and FDA conducted clinical trial simulations (CTS) to design trial with proper sample size and support the choice of dose range. The objective was to effectively use prior knowledge from adult patients for drug X, pediatric data from Corlopam (approved for a similar indication) trial and general experience in developing anti-hypertensive agents. Different scenarios governing the exposure response relationship in the pediatric population were simulated to perturb model assumptions. The choice of scenarios was based on the past observation that pediatric population is less responsive and sensitive compared with adults. The conceptual framework presented here should serve as an example on how the industry and FDA scientists can collaborate in designing the pediatric exclusivity trial. Using CTS, inter-disciplinary scientists with the sponsor and FDA can objectively discuss the choice of dose range, sample size, endpoints and other design elements. These efforts are believed to yield plausible trial design, qrational dosing recommendations and useful labeling information in pediatrics. Published in 2009 by John Wiley & Sons, Ltd.

TRPM8 and RAAS-mediated hypertension is critical for cold-induced immunosuppression in mice

PubMed Central

Lien, Te-Sheng; Chang, Hsin-Hou

2018-01-01

Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin–angiotensin–aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP). Essential roles of TRPM8 and Ig in cold-induced immunosuppression are supported by the cold-mediated amelioration of ITP and the cold-mediated suppression of bacterial clearance, which were observed in wild-type mice but not in Ig- and TRPM8-deficient mutants. Treatment with antihypertensive drugs aliskiren and losartan drastically reversed high plasma Ig levels and ameliorated cold-induced immunosuppression, indicating the involvement of the RAAS and hypertension. These results indicated that the natively increased plasma Ig level is associated with immunosuppression during periods of cold exposure, and antihypertensive drugs can be useful to manage cold-induced immunosuppression. PMID:29560109

The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells

PubMed Central

Ruiz-Magaña, María J.; Martínez-Aguilar, Rocío; Lucendo, Estefanía; Campillo-Davo, Diana; Schulze-Osthoff, Klaus; Ruiz-Ruiz, Carmen

2016-01-01

Epigenetic therapies have emerged as promising anticancer approaches, since epigenetic modifications play a major role in tumor initiation and progression. Hydralazine, an approved vasodilator and antihypertensive drug, has been recently shown to act as a DNA methylation inhibitor. Even though hydralazine is already tested in clinical cancer trials, its mechanism of antitumor action remains undefined. Here, we show that hydralazine induced caspase-dependent apoptotic cell death in human p53-mutant leukemic T cells. Moreover, we demonstrate that hydralazine triggered the mitochondrial pathway of apoptosis by inducing Bak activation and loss of the mitochondrial membrane potential. Hydralazine treatment further resulted in the accumulation of reactive oxygen species, whereas a superoxide dismutase mimetic inhibited hydralazine-induced cell death. Interestingly, caspase-9-deficient Jurkat cells or Bcl-2- and Bcl-xL-overexpressing cells were strongly resistant to hydralazine treatment, thereby demonstrating the dependence of hydralazine-induced apoptosis on the mitochondrial death pathway. Furthermore, we demonstrate that hydralazine treatment triggered DNA damage which might contribute to its antitumor effect. PMID:26942461

Combined use of molindone and guanethidine in patients with schizophrenia and hypertension.

PubMed

Simpson, L L

1979-11-01

Human sympathetic nerves have a high-affinity norepinephrine uptake system. This uptake system is inhibited competitively by chlorpromazine but not by molindone, which suggests that molindone will not interact adversely with guanethidine, an antihypertensive drug that enters sympathetic nerves via the high-affinity uptake system. Accordingly, patients with concomitant schizophrenia and hypertension were treated simultaneously with molindone and guanethidine; there was no evidence of an adverse drug interaction. The data indicate that molindone and guanethidine can be used in combination safely and effectively.

Intermittent blood pressure control: potential consequences for outcome.

PubMed

Leenen, F H

1999-05-01

Although both blood pressure (BP) and left ventricular (LV) mass at initial evaluation predict future cardiovascular risk, the actual BP and LV mass achieved over years of treatment more clearly relate to cardiovascular event rates. Intermittent compliance or noncompliance is the major reason for uncontrolled hypertension and presumably persistent LV hypertrophy. In general, drugs with rapid onset and short duration of action are not desirable because this profile may lead to large variations in BP lowering effect during actual drug intake and rapid disappearance of the antihypertensive effect with missed doses. In addition, intermittent compliance per se introduces the potential for adverse events. For drugs requiring several dose-titrations (e.g., alpha1-blockers), restarting at full doses may lead to excessive drug action and symptomatic hypotension. For other drugs (e.g., short acting beta-blockers or clonidine-like drugs), sudden discontinuation with intermittent compliance may lead to rebound-enhanced sympathetic responsiveness after one to two days, resulting not only in side effects, but also in adverse events, particularly in patients with (silent) coronary artery disease. The rapid onset, short acting dihydropyridines cause intermittent BP control at each dosing, particularly at higher doses. This intermittent control of BP is even more apparent at dosing intervals that are long relative to the duration of action. Thus, sympathetic activation and potential for adverse events can be anticipated at each dosing unless these drugs are being taken frequently at relatively low doses. For diuretics, angiotensin-converting enzyme inhibitors and angiotensin I receptor blockers, no adverse effects have been identified with intermittent compliance. Intermittent BP control is, in general, not an appropriate approach to the management of hypertension and introduces additional risks depending on the type of antihypertensive drug. In contrast, drugs with slow onset and long duration of action provide a more consistent effect during actual drug intake and a more persistent effect during short periods of noncompliance.

Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

PubMed

Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

2014-05-01

We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

PubMed

Barrios, Vivencio; Navarro, Angel; Esteras, Antonio; Luque, Manuel; Romero, Joaquima; Tamargo, Juan; Prieto, Luis; Carrasco, Jose Luis; Herranz, Inmaculada; Navarro-Cid, Josefa; Ruilope, Luis M

2002-01-01

Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

Hypertensive crisis in children: an experience in a single tertiary care center in Korea.

PubMed

Lee, Geum Hwa; Lee, I Re; Park, Se Jin; Kim, Ji Hong; Oh, Ji Young; Shin, Jae Il

2015-01-01

Hypertensive crisis is a medical emergency that can cause acute damage to multiple end-organs. However, relatively little is known on the etiology, treatment, and outcomes of hypertensive crisis in Korean children. The aim of this study was to determine the etiologies and efficacy of drugs for hypertensive crisis in children during the past 5 years at a single center in Korea. We analyzed data from 51 children with hypertensive crisis during the period between January 1, 2010 and April 1, 2014. The patients were divided into two groups: those diagnosed with a hypertensive emergency (hypertension with organ injury, n = 31) and those diagnosed with a hypertensive urgency (hypertension without organ injury, n = 20). Baseline etiologies and risk factors were compared between the two groups. In addition, systolic and diastolic blood pressures were evaluated at 1, 2, 4, and 5 hours after the administration of intravenous antihypertensive drugs. Kidney injury and cancer were the common causes in patients with hypertensive crisis. Cardiovascular complications (cardiac hypertrophy) (p = 0.002), central nervous system complications (p = 0.004), and retinopathy (p = 0.034) were more frequently observed in children with hypertensive emergency than those with hypertensive urgency. However, the proportion of renal complications was similar in both groups. Hydralazine was most commonly used in both groups to control acute increasing blood pressure at first. However, it was often ineffective for controlling abrupt elevated blood pressure. Therefore, intravenous antihypertensive drugs were changed from hydralazine to nicardipine, labetalol, or nitroprusside to control the high blood pressure in 45.1 % of the patients. Particularly, in patients with hypertensive crisis, there was no significant difference in reduction of systolic and diastolic blood pressure and in improvement of clinical outcomes between nicardipine and labetalol administration. Close blood pressure monitoring and careful examinations should be mandatory in children with underlying disease, especially renal diseases and cancer. Furthermore, both nicardipine and labetalol may be effective antihypertensive drug in lowering high blood pressure in children with hypertensive crisis.

Minoxidil-associated anorexia in an infant with refractory hypertension.

PubMed

Vesoulis, Zachary A; Attarian, Stephanie J; Zeller, Brandy; Cole, Francis Sessions

2014-12-01

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients. © 2014 Pharmacotherapy Publications, Inc.

Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness.

PubMed

Halabi, Carmen M; Broekelmann, Thomas J; Knutsen, Russell H; Ye, Li; Mecham, Robert P; Kozel, Beth A

2015-09-01

Increased arterial stiffness is a common characteristic of humans with Williams-Beuren syndrome and mouse models of elastin insufficiency. Arterial stiffness is associated with multiple negative cardiovascular outcomes, including myocardial infarction, stroke, and sudden death. Therefore, identifying therapeutic interventions that improve arterial stiffness in response to changes in elastin levels is of vital importance. The goal of this study was to determine the effect of chronic pharmacologic therapy with different classes of antihypertensive medications on arterial stiffness in elastin insufficiency. Elastin-insufficient mice 4-6 wk of age and wild-type littermates were subcutaneously implanted with osmotic micropumps delivering a continuous dose of one of the following: vehicle, losartan, nicardipine, or propranolol for 8 wk. At the end of treatment period, arterial blood pressure and large artery compliance and remodeling were assessed. Our results show that losartan and nicardipine treatment lowered blood pressure and pulse pressure in elastin-insufficient mice. Elastin and collagen content of abdominal aortas as well as ascending aorta and carotid artery biomechanics were not affected by any of the drug treatments in either genotype. By reducing pulse pressure and shifting the working pressure range of an artery to a more compliant region of the pressure-diameter curve, antihypertensive medications may mitigate the consequences of arterial stiffness, an effect that is drug class independent. These data emphasize the importance of early recognition and long-term management of hypertension in Williams-Beuren syndrome and elastin insufficiency. Copyright © 2015 the American Physiological Society.

The effect of different antihypertensive drugs on cavernous tissue in experimental chronic renal insufficiency.

PubMed

Toblli, Jorge E; Stella, Inés; Mazza, Osvaldo N; Ferder, León; Inserra, Felipe

2006-01-01

Male erectile dysfunction increases in prevalence in patients with severe chronic renal failure. Since arterial hypertension induces significant damage in cavernous tissue (CT), and considering that hypertension is extremely common in patients with end-stage renal disease (ESRD), the aim of this study was to evaluate the effect of the most conventionally employed antihypertensive drugs on CT in a rat model of renal insufficiency. Five groups of male rats with subtotal nephrectomy (STNx) and 1 with sham operations were studied over 6 months: STNx without treatment, STNx with benazepril (BZ), STNx with losartan (LS), STNx with amlodipine (AML) and STNx with atenolol (AT) plus the sham group. All rats were sacrificed at 6 months after STNx, and penises processed for LM and immunohistochemical studies. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries and the amount of collagen type III were evaluated. All groups with antihypertensive drugs showed similar control in blood pressure throughout the study. Un-treated STNx, STNx with AML and STNx with AT presented significant (p<0.01) hypertrophy in both VSM and CSM, together with an increased amount of collagen type III in CT. Conversely, STNx with either BZ or LS showed a substantial (p<0.01) reduction in all of these variables, with values not different from the sham group. There was a significant (p<0.01) negative correlation between creatinine clearance and the amount of VSM, CSM and collagen type III deposition in CT in untreated STNx, STNx with AML and STNx with AT, but not in STNx with BZ, STNx with LS and sham. These results suggest that the interactions against the renin-angiotensin system (RAS) either by ACE inhibitors or angiotensin AT1 receptor blockers produce considerable benefits regarding structural abnormalities in CT in this animal model of renal insufficiency beyond blood pressure control.

Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan

PubMed Central

Liu, Pang-Hsiang; Wang, Jung-Der

2008-01-01

Background Knowledge of existing prescription patterns in the treatment of newly-diagnosed hypertension can provide useful information for improving clinical practice in this field. The aims of this study are to determine the prescription patterns and time trends for antihypertensive medication in newly-diagnosed cases of uncomplicated hypertension in Taiwan and to compare these with current clinical guidelines. Methods A total of 6,536 newly-diagnosed patients with uncomplicated hypertension, aged ≥30 years, were identified from the representative 200,000-person sample in the computerized reimbursement database of the National Health Insurance in Taiwan. These patients were followed from 1998 to 2004 with all diagnoses, prescription data and medication charges being retrieved for subsequent analysis. Results Prescription patterns varied by age, gender and clinical facilities, with mono-therapies being found to be dominant in the first year, albeit declining over time. Calcium channel blockers and beta-blockers were the most frequently prescribed antihypertensive drugs, either alone or in combinations. Although least expensive, the prescription rates of diuretics were low, at 8.3% for mono-therapies and 19.9% overall. The prescription rate for angiotensin receptor blockers (ARBs) was elevated considerably over time. After controlling for other related factors by multiple logistic regression analysis, ARBs were found to be prescribed mainly by medical centers or regional hospitals. Conclusion These findings indicate the existence of a gap between current clinical practice and the desired goal of cost-effectiveness in antihypertensive treatment in Taiwan, which should be corrected. PMID:18559115

Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan.

PubMed

Liu, Pang-Hsiang; Wang, Jung-Der

2008-06-18

Knowledge of existing prescription patterns in the treatment of newly-diagnosed hypertension can provide useful information for improving clinical practice in this field. The aims of this study are to determine the prescription patterns and time trends for antihypertensive medication in newly-diagnosed cases of uncomplicated hypertension in Taiwan and to compare these with current clinical guidelines. A total of 6,536 newly-diagnosed patients with uncomplicated hypertension, aged >/=30 years, were identified from the representative 200,000-person sample in the computerized reimbursement database of the National Health Insurance in Taiwan. These patients were followed from 1998 to 2004 with all diagnoses, prescription data and medication charges being retrieved for subsequent analysis. Prescription patterns varied by age, gender and clinical facilities, with mono-therapies being found to be dominant in the first year, albeit declining over time. Calcium channel blockers and beta-blockers were the most frequently prescribed antihypertensive drugs, either alone or in combinations. Although least expensive, the prescription rates of diuretics were low, at 8.3% for mono-therapies and 19.9% overall. The prescription rate for angiotensin receptor blockers (ARBs) was elevated considerably over time. After controlling for other related factors by multiple logistic regression analysis, ARBs were found to be prescribed mainly by medical centers or regional hospitals. These findings indicate the existence of a gap between current clinical practice and the desired goal of cost-effectiveness in antihypertensive treatment in Taiwan, which should be corrected.

Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response

PubMed Central

Shahin, Mohamed H; Johnson, Julie A

2016-01-01

Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. PMID:26874237

Effects of autogenic training and antihypertensive agents on circadian and circaseptan variation of blood pressure.

PubMed

Watanabe, Yoshihiko; Cornélissen, Germaine; Watanabe, Misako; Watanabe, Fumihiko; Otsuka, Kuniaki; Ohkawa, Shi-ichiro; Kikuchi, Takenori; Halberg, Franz

2003-10-01

Even when the daily blood pressure mean is acceptable, too large a circadian amplitude of blood pressure largely increases cardiovascular disease risk. Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering an excessive blood pressure variability, may be well-suited for MESOR-normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT). Not all anti-hypertensive drugs affect blood pressure variability. Accordingly, long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline-estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT. Prospective outcome studies are needed to assess whether the relative merits of these treatments are in keeping with their effects on blood pressure and blood pressure variability.

Effects of antihypertensive agents on blood pressure during exercise.

PubMed

Arita, M; Hashizume, T; Wanaka, Y; Handa, S; Nakamura, C; Fujiwara, S; Nishio, I

2001-11-01

The relationship between blood pressure (BP) and cardiovascular morbidity has been appreciated for many years. Casual BP may not be representative of the pressure at other times. It is recognized that BP during exercise may be a more accurate predictor than casual BP. There is, however, little information about the effects of antihypertensive drugs on the BP during exercise. This study was designed to investigate the effects of various antihypertensive agents on BP during exercise. Sixty-four patients (age, 49+/-10 years) with untreated essential hypertension (WHO I, II) were studied during a supine ergometric exercise regimen. A graded exercise test was started at a workload of 50 W, and the load was increased by 25 W every 3 min. The hemodynamic responses to exercise were evaluated by changes in systolic and diastolic BP (SBP, DBP) and heart rate (HR). Plasma norepinephrine (NE) levels were measured at rest and during submaximal exercise, and before and after 4 weeks of treatment with metoprolol (METO), doxazosin (DOXA), trichlormethiazide (TCTZ), nifedipine (NIFE), amlodipine (AMLO) and temocapril (TEMO) between left ventricular mass index (LVMI) and BP values at rest, during exercise, and during the recovery period after exercise were assessed by multiple regression analysis. The stepwise selection (forward conditional) method showed that LVMI was significantly associated with SBP during submaximal exercise and during the recovery period. All antihypertensive treatments decreased SBP and DBP (p<0.01) at rest. METO, AMLO and TEMO significantly lowered SBP (p<0.05) during exercise, whereas DOXA, TCTZ and NIFE induced no change in SBP. The exercise-induced increase of plasma NE was further enhanced by METO and NIFE but not by AMLO, DOXA, or TCTZ, and it was significantly suppressed by TEMO (p<0.01). These results suggest that BP during exercise is more highly associated with the progression of left ventricular hypertrophy (LVH) than is casual BP. Because antihypertensive agents differ in their effects on exercise hemodynamics, we recommend that hemodynamic factors during exercise be considered when selecting the optimal antihypertensive medication for highly active patients.

Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive.

PubMed

Hakkou, Zineb; Maciuk, Alexandre; Leblais, Veronique; Bouanani, Nour Elhouda; Mekhfi, Hassane; Bnouham, Mohammed; Aziz, Mohammed; Ziyyat, Abderrahime; Rauf, Abdur; Hadda, Taibi Ben; Shaheen, Usama; Patel, Seema; Fischmeister, Rodolphe; Legssyer, Abdelkhaleq

2017-09-01

Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day). Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment. In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid. The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

PubMed Central

Ishida, Akio; Ohya, Yusuke

2017-01-01

Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response. PMID:28421141

Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

PubMed

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

2015-10-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

PubMed Central

Zhang, Rongrong; Jiang, Fan; Chen, Cindy Si; Wang, Tianzhu; Feng, Jinzhou; Tao, Tao; Qin, Xinyue

2015-01-01

Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1. PMID:26113783

Angiotensin II-AT1-receptor signaling is necessary for cyclooxygenase-2-dependent postnatal nephron generation.

PubMed

Frölich, Stefanie; Slattery, Patrick; Thomas, Dominique; Goren, Itamar; Ferreiros, Nerea; Jensen, Boye L; Nüsing, Rolf M

2017-04-01

Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2-dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2 -/- mice was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Administration of the angiotensin II receptor AT1 antagonist telmisartan from day P1 to P3 did not result in cortical damage. However, telmisartan treatment from day P3 to P8, the critical time frame of renal COX-2 expression, led to hypoplastic glomeruli, a thinned subcapsular cortex and maturational arrest of superficial glomeruli quite similar to that observed in COX-2 -/- mice. In contrast, AT2 receptor antagonist PD123319 was without any effect on renal development. Inhibition of the renin angiotensin system by aliskiren and enalapril caused similar glomerular defects as telmisartan. Administration of the AT1 receptor agonist L162313 to COX-2 -/- pups improved kidney growth, ameliorated renal defects, but had no beneficial effect on reduced cortical mass. L162313 rescued impaired renal function by reducing serum urea and creatinine and mitigated pathologic albumin excretion. Moreover, glomerulosclerosis in the kidneys of COX-2 -/- mice was reduced. Thus, angiotensin II-AT1-receptor signaling is necessary for COX-2-dependent normal postnatal nephrogenesis and maturation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Primary care physicians behaviour on hypertensive patients with poor blood pressure control. The PRESCAP 2006 study].

PubMed

Alonso-Moreno, F J; Llisterri Caro, J L; Rodríguez-Roca, G C; Ferreiro Madueño, M; González-Segura Alsina, D; Divisón Garrote, J A; Banegas, J R; Barrios Alonso, V; Lou Arnal, S; Sánchez Ruiz, T; Santos Rodríguez, J A; Durá Belinchón, R

2008-09-01

There is little information available on Therapeutic Inertia in Primary Care (PC). This study aimed to know the therapeutic behavior of the physician for uncontrolled hypertensive patients. Cross-sectional, multicenter study that included hypertensive patients of both genders, under pharmacological treatment who were recruited consecutively in the PC out-patient clinic in all of Spain. Social-demographic, clinical and treatment data were recorded, as well as the motives for eventual therapeutic modification. Adequate BP control was considered when BP values were below 140/90 mmHg in general, and below 130/80 mmHg in diabetes, renal insufficiency or cardiovascular disease. A total of 10,520 patients (53.7% women) were included with average age of 64.6 (11.3 years). Of these, 44.4% the patients were receiving monotherapy and 55.6% were treated with combined therapy (two drugs 41.2%, three drugs 11.7%, and more than three 2.8%). Uncontrolled hypertension was found in 58.6% (95% CI. 57.6-59.5) of the patients. Treatment was modified by physicians in 30.4% (95% CI. 29.2-31.6) of the uncontrolled patients, combination with another drug being the most frequent behavior (46.3%), followed by dose increase (26.1%), and antihypertensive drug switch (22.8%). The perception of the physician of good BP control was the factor most associated with not modifying the treatment in uncontrolled patients. Study results showed that the PC physician modified antihypertensive treatment in only 3 out of 10 uncontrolled patients. When treatment modification was made, association of drugs was the most frequent behavior.

Diabetes Drug Prescription Pattern and Awareness Among Health Care Providers in Sub-Himalayan Region of India: A Population Based Study.

PubMed

Mokta, Jatinder; Mokta, Kiran; Ranjan, Asha; Joshi, Ivan; Garg, Mahak

2017-05-01

To determine the pattern of diabetic drug prescription and awareness about diabetes among primary health providers in the rural areas of Himachal Pradesh situated in the western Himalayas at an elevation range from 350 meters (1,148ft) to 6900 meters (22,966ft) above sea level. Study was conducted in 20 rural areas of Himachal Pradesh, located 50 to 400 Km from state capital, at 2200 to 10,000 feet altitude. Non-pregnant diabetic adults were surveyed through 31 diabetic camps. Detailed history, weight, height, waist circumference, body mass index recorded. Fasting or random blood glucose, glycated hemoglobin, lipid profile measured and blood pressure recorded. 894 diabetic patients were included in the study (59.83% male) with the mean age of 52.94±6.78 years. Two in three patients were on oral hypoglycemic agents (OHAs), and one in three on alternative approaches for diabetes control. Among OHAs, sulphonylureas (SU) were the most commonly prescribed oral agents in 76.09% of patients followed by metformin in 23.87%. Glibenclamide was the most commonly prescribed SU in 44.60%. Amlodipine and atenolol was the commonest anti-hypertensive drug prescribed in 77.85% either in combination or as individual drug. Only 10.59% were on lipid lowering therapy. For primary care providers glycemic target was the mainstay of diabetes treatment with little emphasis on blood pressure control and no emphasis on lipid reduction. Sulphonylureas were the commonest anti-diabetic drug prescribed by the primary care providers followed by metformin. Insulin was prescribed to 2.23% only. Combination of amlodipine and atenolol was the commonest anti-hypertensive drugs prescribed and only 10% of patients were prescribed statin.

Deliberate drug poisonings admitted to an emergency department in Paris area - a descriptive study and assessment of risk factors for intensive care admission.

PubMed

Beaune, S; Juvin, P; Beauchet, A; Casalino, E; Megarbane, B

2016-01-01

Each year, approximately 165,000 poisonings are managed in the emergency departments (ED) in France. We performed a descriptive analysis of self-poisoned patients admitted to a university hospital ED in the Paris metropolitan area (France) aimed at investigating their outcome and the risk factors for transfer to the intensive care unit (ICU). We retrospectively reviewed patients' records and performed multivariate logistic regression analysis to identify risk factors for ICU admission. During 4 years, 882 self-poisoned patients (median age, 38 years [IQR, 26-47]; sex-ratio, 1M/3F) were admitted to the ED, representing 0.7% of all referred patients. Poisonings mainly resulted from multidrug exposures (53%), including benzodiazepines (78%), serotonin reuptake inhibitors (17%), acetaminophen (13%), antipsychotics (9.5%), imidazopyridines (9.5%), antihypertensive drugs (3%), and polycyclic antidepressants (1.3%). Ethanol was involved in 20% of the exposures. Patients were briefly (<24h) monitored in the ED (55%), transferred to the psychiatric department (30%), medical ward (2%) or ICU (6%), and took an irregular discharge (7%). Among the patients transferred to the ICU, 25% were mechanically ventilated and only one died. Risk factors for ICU admission included antihypertensive (Odds ratio (OR), 40.6; 95%-confidence interval (CI), 7.5-221.9) or antipsychotic drug ingestion (OR, 5.3; CI, 2.0-14.4), male gender (OR, 3.3; CI, 1.30-8.8), and consciousness impairment (OR, 2.1; CI, 1.8-2.5 per point lost in Glasgow coma score). Deliberate drug exposure represents a frequent cause of ED admission. Psychotropic drugs are most commonly involved. Transfer to the ICU is rare and predicted by male gender, drug class, and coma depth.

TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Hong-Bao; Li, Xiang; Huo, Chan-Juan

Previous findings from our laboratory and others indicate that the main therapeutic effect of angiotensin II type 1 receptor (AT1-R) antagonists is to decrease blood pressure and exert anti-inflammatory effects in the cardiovascular system. In this study, we determined whether AT1-R antagonist telmisartan within the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and hypothalamic inflammation via both the TLR4/MyD88/NF-κB signaling pathway and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the PVN in hypertensive rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated for 4 weeks through bilateral PVN infusion with the AT1-R antagonist telmisartan (TEL, 10 μg/h), or losartanmore » (LOS, 20 μg/h), or the PPAR-γ antagonist GW9662 (GW, 100 μg/h), or vehicle via osmotic minipump. Mean arterial pressure (MAP) was recorded by a tail-cuff occlusion method. PVN tissue and blood were collected for the measurement of AT1-R, PPAR-γ, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), inducible nitric oxide synthase (iNOS), TLR4, MyD88, nuclear factor-kappa B (NF-κB) activity and plasma norepinephrine (NE), respectively. Hypertensive rats exhibited significantly higher level of AT1-R and lower level of PPAR-γ in the PVN. PVN treatment with TEL attenuated MAP, improved cardiac hypertrophy, reduced TNF-α, IL-1β, IL-6, iNOS levels, and plasma NE in SHR but not in WKY rats. These results were associated with reduced TLR4, MyD88 and NF-κB levels and increased PPAR-γ level in the PVN of hypertensive rats. Our findings suggest that TLR4/MyD88/NF-κB signaling and PPAR-γ within the PVN are involved in the beneficial effects of telmisartan in hypertension. - Highlights: • PVN infusion of TEL in spontaneously hypertensive rats is reported. • PVN infusion of TEL attenuates hypertension and proinflammatory cytokines in PVN. • PVN blockade of AT1-R attenuates sympathoexcitation and cardiac hypertrophy. • TLR4/MyD88/NF-κB signaling and PPAR-γ in PVN are involved in the effects of TEL.« less

Can we predict the blood pressure response to renal denervation?

PubMed Central

Fink, Gregory D.; Phelps, Jeremiah T.

2016-01-01

Renal denervation (RDN) is a new therapy used to treat drug-resistant hypertension in the clinical setting. Published human trials show substantial inter-individual variability in the blood pressure (BP) response to RDN, even when technical aspects of the treatment are standardized as much as possible between patients. Widespread acceptance of RDN for treating hypertension will require accurate identification of patients likely to respond to RDN with a fall in BP that is clinically significant in magnitude, well-maintained over time and does not cause adverse consequences. In this paper we review and evaluate clinical studies that address possible predictors of the BP response to RDN. We conclude that only one generally reliable predictor has been identified to date, namely pre-RDN BP level, although there is some evidence for a few other factors. Experimental interventions in laboratory animals provide the opportunity to explore potential predictors that are difficult to investigate in human patients. Therefore we also describe results (from our lab and others) with RDN in spontaneously hypertensive rats. Since virtually all patients receiving RDN are taking three or more antihypertensive drugs, a particular focus of our work was on how ongoing antihypertensive drug treatment might alter the BP response to RDN. We conclude that patient age (or duration of hypertension) and concomitant treatment with certain drugs can affect the blood pressure response to RDN and that this information could help predict a favorable clinical response. PMID:27530600

Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

PubMed

Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

2017-05-01

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs.

PubMed

Borba, Paola Aline Amarante; Pinotti, Marihá; de Campos, Carlos Eduardo Maduro; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2016-02-10

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis(®), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis(®) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of ibuprofen vs acetaminophen on postpartum hypertension in preeclampsia with severe features: a double-masked, randomized controlled trial.

PubMed

Blue, Nathan R; Murray-Krezan, Cristina; Drake-Lavelle, Shana; Weinberg, Daniel; Holbrook, Bradley D; Katukuri, Vivek R; Leeman, Lawrence; Mozurkewich, Ellen L

2018-06-01

Nonsteroidal antiinflammatory drug use has been shown to increase blood pressure in nonpregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. Our goal was to test the hypothesis that nonsteroidal antiinflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features. At delivery, we randomized women with preeclampsia with severe features to receive around-the-clock oral dosing with either 600 mg of ibuprofen or 650 mg of acetaminophen every 6 hours. Dosing began within 6 hours after delivery and continued until discharge, with opioid analgesics available as needed for breakthrough pain. Study drugs were encapsulated in identical capsules such that patients, nurses, and physicians were masked to study allocation. Exclusion criteria were serum aspartate aminotransferase or alanine aminotransferase >200 mg/dL, serum creatinine >1.0 mg/dL, infectious hepatitis, gastroesophageal reflux disease, age <18 years, or current incarceration. Our primary outcome was the duration of severe-range hypertension, defined as the time (in hours) from delivery to the last blood pressure ≥160/110 mm Hg. Secondary outcomes were time from delivery to last blood pressure ≥150/100 mm Hg, mean arterial pressure, need for antihypertensive medication at discharge, prolongation of hospital stay for blood pressure control, postpartum use of short-acting antihypertensives for acute blood pressure control, and opioid use for breakthrough pain. We analyzed all outcome data according to intention-to-treat principles. We assessed 154 women for eligibility, of whom 100 met entry criteria, agreed to participate, and were randomized to receive postpartum ibuprofen or acetaminophen for first-line pain control. Seven patients crossed over or did not receive their allocated study drug, and 93 completed the study protocol in their assigned groups. We found no differences in baseline characteristics between groups, including mode of delivery, body mass index, parity, race, chronic hypertension, and maximum blood pressure prior to delivery. We did not find a difference in the duration of severe-range hypertension in the ibuprofen vs acetaminophen groups (35.3 vs 38.0 hours, P = .30). There were no differences between groups in the secondary outcome measures of time from delivery to last blood pressure ≥150/100 mm Hg, postpartum mean arterial pressure, maximum postpartum systolic or diastolic blood pressures, any postpartum blood pressure ≥160/110 mm Hg, short-acting antihypertensive use for acute blood pressure control, length of postpartum stay, need to extend postpartum stay for blood pressure control, antihypertensive use at discharge, or opioid use for inadequate pain control. In a subgroup analysis of patients who experienced severe-range hypertension, the mean time to blood pressure control in the acetaminophen group was 68.4 hours and ibuprofen group was 56.7 hours (P = .26). At 6 weeks postpartum, there were no differences between groups in the rates of obstetric triage visits, hospital readmissions, continued opioid use, or continued antihypertensive use. The first-line use of ibuprofen rather than acetaminophen for postpartum pain did not lengthen the duration of severe-range hypertension in women with preeclampsia with severe features. Copyright © 2018 Elsevier Inc. All rights reserved.

Rational Prescribing in Primary Care (RaPP): Economic Evaluation of an Intervention to Improve Professional Practice

PubMed Central

Fretheim, Atle; Aaserud, Morten; Oxman, Andrew D

2006-01-01

Background Interventions designed to narrow the gap between research findings and clinical practice may be effective, but also costly. Economic evaluations are necessary to judge whether such interventions are worth the effort. We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs. The tailored intervention was evaluated in a randomized trial, and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication, but had little or no impact on other outcomes. The increased use of thiazides was not expected to have an impact on health outcomes. Methods and Findings We performed cost-minimization and cost-effectiveness analyses on data from a randomized trial involving 146 general practices from two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Only patients that were being started on antihypertensive medication were included in the analyses. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders. Pharmacists conducted the visits. A cost-minimization framework was adopted, where the costs of intervention were set against the reduced treatment costs (principally due to increased use of thiazides rather than more expensive medication). The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides. The net annual cost (cost minimization) in our study population was US$53,395, corresponding to US$763 per practice. The cost per additional patient started on thiazides (cost-effectiveness) was US$454. The net annual savings in a national program was modeled to be US$761,998, or US$540 per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted, and the cost-effectiveness was estimated to be US$183. Conclusions We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial. A major reason to promote the use of thiazides is their lower price compared to other drugs. The cost of the intervention was more than twice the savings within the time frame of our study. However, we predict modest savings over a 2-y period. PMID:16737349

Effect of Antihypertensive Medications on the Severity of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

PubMed Central

Khurshid, Kiran; Yabes, Jonathan; Weiss, Patricia M.; Dharia, Sushma; Brown, Lee; Unruh, Mark; Jhamb, Manisha

2016-01-01

Study Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HTN). Increasing evidence from animal and human studies suggests that HTN exacerbates OSA. We performed a systematic review and meta-analysis of studies evaluating the effect of anti-hypertensive medications on the severity of OSA. Methods: A literature search of PubMed and Embase was done using search concepts of OSA, HTN, and drug classes used to treat HTN. Studies that reported changes in the severity of OSA objectively by using apnea-hypopnea index (AHI) or respiratory disturbance index (RDI) were included. Pooled mean difference estimates were calculated. Tests for heterogeneity, publication bias, and subgroup sensitivity analysis were conducted. Results: Of 27,376 studies screened, only 11 met inclusion criteria, including 5 randomized controlled trials and 6 single-arm prospective trials. The pooled mean difference estimate (95% confidence interval [CI]), based on a random-effects model, was −5.69 (95% CI −10.74 to −0.65), consistent with an overall decrease in AHI or RDI attributable to antihypertensive medications. The effect size was even more pronounced, −14.52 (95% CI −25.65 to −3.39), when only studies using diuretics were analyzed. There was no significant heterogeneity or publication bias among the studies. Meta-regression indicated neither age, baseline AHI, nor change in systolic/diastolic blood pressure influenced the results. Conclusions: Collectively, findings from these relatively small, short-term studies tend to support the contention that treatment with antihypertensive agents confers a statistically significant, albeit small, reduction in the severity of OSA, which may be more pronounced with the use of diuretics. Citation: Khurshid K, Yabes J, Weiss PM, Dharia S, Brown L, Unruh M, Jhamb M. Effect of antihypertensive medications on the severity of obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2016;12(8):1143–1151. PMID:27397663

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study

PubMed Central

Wu, Chunyuan; Coker, Laura H.; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E.; Rossouw, Jacques E.; Wassertheil-Smoller, Sylvia

2016-01-01

BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 PMID:26137952

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study.

PubMed

Haring, Bernhard; Wu, Chunyuan; Coker, Laura H; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E; Rossouw, Jacques E; Wassertheil-Smoller, Sylvia

2016-02-01

To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Advances in the pharmacological study of Morus alba L].

PubMed

Yang, Shuang; Wang, Bao-Lian; Li, Yan

2014-06-01

Morus alba L. (mulberry) is a well-known deciduous tree, belonging to the genus of Morus of Moraceae famlily. Its leaves, twigs, roots (bark) and fruits are widely used in the traditional Chinese medicine. The active constituents of mulberry contained flavonoids, alkaloids, steroids, coumarins, with the significant hypoglycemic, hypolipidemic, antihypertension, anti-oxidation, anti-inflammatory, anti-bacterial, anti-tumor and immunomodulatory activities. This review summarized the research progress of the major pharmacological activity, pharmacokinetics and drug-drug interaction based on CYPs and transporters of mulberry and its active constituents.

Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

PubMed

Shahin, Mohamed H; Johnson, Julie A

2016-04-01

Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

Obstructive sleep apnea syndrome and sleep quality in hypertensive patients.

PubMed

Bacci, Marcelo Rodrigues; Emboz, Jonathan Naim Mora; Alves, Beatriz da Costa Aguiar; Veiga, Glaucia Luciano da; Murad, Neif; Meneghini, Adriano; Chagas, Antonio Carlos P; Fonseca, Fernando Luiz Affonso

2017-12-01

Obstructive sleep apnea and hypopnea syndrome (OSAHS) is one of the developmental factors of high blood pressure (HBP), a relevant global public health problem. OSAHS is characterized by the reduction or complete cessation of respiratory airflow due to intermittent airway collapse. Additionally, significant changes in sleep rhythm and pattern are observed in these patients. To evaluate the association between OSAHS and sleep quality in essential and resistant hypertensives. A cross-sectional, observational study evaluated 43 hypertensive patients treated at the outpatient clinics of the Faculdade de Medicina do ABC (FMABC) who were medicated with two or more antihypertensive drugs and divided into nonresistant or resistant to treatment. Group I (using up to two antihypertensive agents - 60.47% of the sample) presented mean systolic blood pressure (SBP) of 127.5±6.4 mmHg, mean diastolic blood pressure (DBP) of 79.6±5.2 mmHg, mean body mass index (BMI) of 27.2±5.3 kg/m2 and mean age of 51.2±15.1 years. Group II (using more than two antihypertensive drugs - 37.2% of the sample) presented mean SBP of 132.1±9.3 mmHg, mean DBP of 84.5±5.8 mmHg, mean BMI of 27.2±7.2 kg/m2 and mean age of 55.5±13.4 years. The patients presented low quality of sleep/sleep disorder evaluated by the Pittsburgh Sleep Quality Index (PSQI), which represents a preponderant factor for OSAHS. Patients at high risk for OSAHS had poor sleep quality and high levels of DBP, suggesting a causal relation between these parameters. However, they did not present a higher prevalence of resistant high blood pressure (RHBP).

Choice of antihypertensive treatment in subjects with pre-diabetes. Is there a dream after the navigator.

PubMed

Eleftheriadou, Ioanna; Tsioufis, Costas; Tsiachris, Dimitrios; Tentolouris, Nicholas; Stefanadis, Christodoulos

2011-11-01

The majority of individuals with pre-diabetic states eventually appear to develop diabetes mellitus. During the pre-diabetic state, that may last many years, the risk of cardiovascular disease is modestly increased, with impaired glucose tolerance being slightly stronger predictor for future cardiovascular disease than impaired fasting glucose. The role of different antihypertensive drugs in the acceleration or the delay of diabetes onset is controversial. Agents that interrupt the renin-angiotensin system, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers are likely to be beneficial in the prevention of diabetes, while calcium channel blockers are thought to act metabolically neutral. In contrast, diuretics or β-blockers, and especially their combination, are thought to increase the incidence of diabetes. Carvedilol, a non-selective β-blocker with α(1)-blocking properties, and nebivolol, a third-generation highly selective β(1)- blocker with additional endothelial nitric oxide (NO)-mediated vasodilator activity have been shown to have a favorable effect on glucose metabolism compared with others β-blockers. Nevertheless, the key goal still remains to reduce blood pressure, which may require combination of different antihypertensive drug classes. Changes from diuretics and β- blockers to renin-angiotensin system inhibitors certainly have cost implications. However, treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers may be cheaper in the long run, due to less risk of new-onset diabetes and other metabolic disturbances. Thus, for patients with pre-diabetes it is wise to choose medications with the least diabetogenic potential and until more data are available, it seems prudent to restrict use of diuretics and classic β- blockers.

Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yoon Jung; Lee, Jue Yeon; Research Center, Nano Intelligent Biomedical Engineering Corporation

Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinicallymore » used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and according to our data doxazosin might be useful for application in the field of bone metabolism.« less

Adherence to Pharmacotherapy and Medication-Related Beliefs in Patients with Hypertension in Lima, Peru

PubMed Central

Miranda, J. Jaime; Diez-Canseco, Francisco; Malaga, German

2014-01-01

Objective To characterize adherence to pharmacological medication and beliefs towards medication in a group of patients with hypertension in a large national hospital. Materials and Methods Cross-sectional survey among patients with hypertension attending the outpatient clinic of a large national hospital. Exposure of interest was the patient's beliefs towards general medication and antihypertensive drugs, i.e. beliefs of harm, overuse, necessity and concern, measured using the Beliefs about Medication questionnaire. Main outcome was adherence measured using the Morisky Medication Adherence Scale-8. Multivariate analysis was conducted using Poisson distribution logistic regression, prevalence ratios and 95% confidence intervals were calculated. Results Data from 115 participants, 67% females and mean age 62.7 years were analyzed. Low adherence was found in 57.4%. Highest scores were on the ideas of necessity and one of the most rated statements was “physicians would prescribe less medication if they spent more time with patients”. Beliefs of harm about medications and concerns about antihypertensive drugs were higher in the low adherence group (p<0.01). Those who scored higher on ideas of harm were 52% less likely of being high adherents (PR 0.48; 95% CI 0.25–0.93) and those with higher scores on concerns were 41% less likely of being high adherents (PR 0.59; 95% CI 0.39–0.91). Patients whose ideas of necessity outweighed their concerns were more likely to be adherent (PR 2.65; 95% CI 1.21–5.81). Conclusions Low adherence to antihypertensive medication is common. High scores on ideas of harm, concern and a high necessity-concern differential were predictors of medication adherence. PMID:25470372

[Prevalence of hypertension in elderly long-term care residents in Spain. The Geriatric HTA study].

PubMed

Martín-Baranera, Montserrat; Sánchez Ferrín, Pau; Armario, Pedro

2006-11-11

This study aimed to estimate the prevalence of hypertension in elderly long-term care residents in Spain and to describe such population in terms of comorbidity and hypertension treatment and control. A countrywide cross-sectional study was conducted in May 2003 among long-term care residents aged 65 or more. Patients in palliative care units were excluded. Hypertension was defined in patients who fulfilled at least one of the following criteria: diagnosis of hypertension on the medical record, antihypertensive medication and/or highest blood pressure values during the previous year > or = 140/90 mmHg. Overall, 13,272 subjects - mean age (standard deviation) 82.9 (7.5) years (range: 65-106 years) - were included from 223 centres; 70.6% were women. Almost 2 thirds of patients met at least one hypertension criterion (8,242 patients, 62.1%; 95% confidence interval, 61.3-62.9%). In those patients, other frequent cardiovascular risk factors were obesity (26.3%), diabetes (25.7%) and dislipemia (23.8%). A concomitant diagnosis of dementia, peripheral vascular disease, stroke or congestive heart failure was present in 37.1%, 28.3%, 26.0% and 25.1%, respectively. The proportion of hypertensive patients receiving at least one antihypertensive drug was 69.7%. Diuretics were the most commonly used agents (46.3%), followed by angiotensine converting enzyme inhibitors (34.6%). The latest blood pressure measurement was < 140/90 mmHg in 60.4% of the hypertensive patients. Elderly long-term care residents in Spain showed a high prevalence of hypertension and other cardiovascular risk factors, and a substantial degree of associated clinical conditions. The proportion of antihypertensive drug therapy was comparable to those reported in similar studies.

All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions--an observational study.

PubMed

Wetzels, Gwenn E C; Nelemans, Patricia J; Schouten, Jan S A G; van Wijk, Boris L G; Prins, Martin H

2006-02-10

Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance.

Combination therapy in hypertension: an Asia-Pacific consensus viewpoint.

PubMed

Abdul Rahman, Abdul Rashid; Reyes, Eugenio B; Sritara, Piyamitr; Pancholia, Arvind; Van Phuoc, Dang; Tomlinson, Brian

2015-05-01

Hypertension incurs a significant healthcare burden in Asia-Pacific countries, which have suboptimal rates of blood pressure (BP) treatment and control. A consensus meeting of hypertension experts from the Asia-Pacific region convened in Hanoi, Vietnam, in April 2013. The principal objectives were to discuss the growing problem of hypertension in the Asia-Pacific region, and to develop consensus recommendations to promote standards of care across the region. A particular focus was recommendations for combination therapy, since it is known that most patients with hypertension will require two or more antihypertensive drugs to achieve BP control, and also that combinations of drugs with complementary mechanisms of action achieve BP targets more effectively than monotherapy. The expert panel reviewed guidelines for hypertension management from the USA and Europe, as well as individual Asia-Pacific countries, and devised a treatment matrix/guide, in which they propose the preferred combination therapy regimens for patients with hypertension, both with and without compelling indications. This report summarizes key recommendations from the group, including recommended antihypertensive combinations for specific patient populations. These strategies generally entail initiating therapy with free drug combinations, starting with the lowest available dosage, followed by treatment with single-pill combinations once the BP target has been achieved. A single reference for the whole Asia-Pacific region may contribute to increased consistency of treatment and greater proportions of patients achieving BP control, and hence reducing hypertension-related morbidity and mortality.

[Clinical utility of home blood pressure monitoring in patients under treatment].

PubMed

Bauk, L; Costa, H A; Caligiuri, S I

2015-01-01

A low number of patients who are treated with antihypertensive drugs achieve therapeutic goals. Home blood pressure monitoring is an excellent tool for studying this population. To determine the prevalence of patients with controlled and uncontrolled hypertension, as well as white-coat-effect and masked hypertension, and to evaluate the relationship with target organ damage in different groups. Blood pressure readings were performed simultaneously in the clinic and in the home using the same validated oscillometric equipment on 83 hypertensive patients on treatment with 2 or more antihypertensive drugs. They were then classified into 4 groups according to the cut-off values of the clinic and home blood pressure measurements. Left ventricular mass index, carotid intima media thickness, and microalbuminuria as markers of target organ damage, were also evaluated. Controlled blood pressure was present in 32.5%, 30.2% had sustained hypertension. The white coat effect was seen in 26.5%, while 10.8% were masked uncontrolled hypertension. Left ventricular mass index was higher in patients with no ambulatory control compared to controlled patients, and carotid IMT was also higher too in uncontrolled and white coat effect groups than controlled patients. More than one third of our patients who were treated with 2 or more drugs were not properly controlled, and they had significantly greater target organ damage than controlled patients. Copyright © 2014 SEHLELHA. Published by Elsevier Espana. All rights reserved.

The antihypertensive effectiveness and safety of dual RAAS blockade with aliskiren and valsartan.

PubMed

Chrysant, Steven G

2010-03-01

The renin-angiotensin-aldosterone system (RAAS) is a major factor for the development and maintenance of hypertension and a major cause for cardiovascular remodeling and cardiovascular complications through its active peptide angiotensin (Ang) II. Blockade of RAAS with ACE inhibitors (ACEIs) results in suppression of Ang II levels, which eventually return to baseline levels after prolonged ACEI administration. This leads to an escape phenomenon through generation of Ang II from enzymes other than ACE and led to the hypothesis that dual blockade of RAAS with an ACEI/Ang receptor blocker (ARB) combination could lead to total blockade of RAAS, since ARBs block the action of Ang II at the AT1 receptor level, irrespective of the mechanism of Ang II generation and will have an additive blood pressure (BP)-lowering effect. However, this hypothesis has not materialized clinically, as the ACEI/ARB combination produces modest BP reductions that are not significantly greater than monotherapy with the component drugs, and is frequently associated with higher incidence of side effects. A new dual RAAS blockade with the direct renin inhibitor aliskiren and the ARB valsartan produces greater BP reductions than monotherapy with the component drugs and is safe and well tolerated. The combination of aliskiren with valsartan, and with other antihypertensive drugs is discussed. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Best antihypertensive strategies to improve blood pressure control in Latin America: position of the Latin American Society of Hypertension.

PubMed

Coca, Antonio; López-Jaramillo, Patricio; Thomopoulos, Costas; Zanchetti, Alberto

2018-02-01

: Evidence from randomized trials has shown that effective treatment with blood pressure (BP)-lowering medications reduces the risk of cardiovascular morbidity and mortality in patients with hypertension. Therefore, hypertension control and prevention of subsequent morbidity and mortality should be achievable for all patients worldwide. However, many people in Latin America remain undiagnosed, untreated or have inadequately controlled BP, even where this is access to health systems. Barriers to hypertension control in low-income countries include difficulties in transportation to health services; inappropriate opening hours; difficulties in making clinic appointments; inaccessible healthcare facilities, lack of insurance and high treatment costs. After a review of the best recent available evidence on the efficacy and tolerability of antihypertensive drugs and strategies, the Latin American Society of Hypertension experts conclude that all major classes of BP-lowering drugs be available to hypertensive patients, because all have been shown to reduce major cardiovascular outcomes compared with placebo, and have shown to be associated with a comparable risk of major cardiovascular events and mortality when compared between classes. Within each class, no evidence whatsoever is available to show that one compound is more effective than another in outcome prevention. Therefore, the selection of individual drugs may be based mainly on the capacity of Latin American governments to obtain the lowest prices of the different molecules manufactured by companies with high production quality standards.

Sociodemographic factors are associated with utilisation of statins after ischaemic stroke/TIA.

PubMed

Geary, Lukas; Aronius, Jonas; Wettermark, Björn; Hasselström, Jan; Sjöborg, Bengt; von Euler, Mia

2017-03-01

To analyse if there are sociodemographic differences in the utilisation of statins 9-12 months after ischaemic stroke or transitory ischaemic attack. Anonymised linkage of registry data on all patients >18 years discharged from the hospitals in Stockholm, Sweden 2006-2010 with diagnosis of ischaemic stroke (ICD-10: I63.0-9) or TIA (ICD-10: G45.9) was performed. Data on hospitalisations and diagnoses were collected from the Stockholm County Council administrative databases on healthcare consumption. Dispensed prescriptions with statins and, for comparative purposes, antihypertensive agents 9-12 months after discharge were acquired from the National Swedish Prescribed Drug Register. Data about socioeconomic factors were obtained from Statistics Sweden. The dispensing of statins and antihypertensive agents, relative to sociodemographic variables were analysed. Using logistic regression odds ratios, crude, and adjusted with education, income, origin of birth, age, and sex as predictors where calculated. Of 24 312 patients with ischaemic stroke/TIA, 19 335 were alive 12 months after discharge. Statins were dispensed to 44% of all patients in the cohort, more frequently to men of all age groups, to patients with higher education, and to those with higher income. Antihypertensive agents were dispensed to 68% of all patients and there were no differences related to sex and income whilst patients with lower education were dispensed with antihypertensives more frequently. We find a low utilisation of statins one year after ischaemic stroke/TIA. Patients with low education, low income, and female sex were dispensed fewer prescriptions of statins indicating a need for improvement. © 2017 John Wiley & Sons Ltd.

Antihypertensive treatment and stroke prevention: are angiotensin receptor blockers superior to other antihypertensive agents?

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-06-01

Stroke remains a common vascular event with high mortality and morbidity. After heart disease, stroke is the second leading cause of death worldwide in adult persons. Silent or subclinical stroke is likely to occur with even greater frequency than clinical stroke and increases the risk of subsequent cerebrovascular events. Hypertension is by far the single most important controllable risk factor for stroke. The relationship between blood pressure (BP) and stroke mortality is strong, linear, and continuous in subjects with levels of BP higher than 115/75 mm Hg. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary). Although meta-analyses suggest that BP reduction, per se, is the most important determinant for stroke risk reduction, the question is if specific classes of antihypertensive drugs offer special protection against stroke is still controversial. Some studies have suggested that angiotensin receptors blockers (ARBs) appear to offer additional protection against stroke. This has been hypothesized in studies in hypertensives, such as LIFE and SCOPE, and especially in the only comparative trial focused on secondary stroke prevention. In the MOSES trial, the comparison of eprosartan versus nitrendipine in patients with a previous stroke resulted, despite a similar BP reduction, in a significant reduction in the primary composite endpoint of total mortality plus cardiovascular and cerebrovascular events, including recurrent events. These results may suggest a blood pressure-independent effect of ARBs, which can be mediated through several mechanisms, including their ability to counteract other markers of target organ damage, but also through a direct neuroprotective effect.

A retrospective study of the effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in diabetic nephropathy.

PubMed

Pathak, Jahnavi V; Dass, Ervilla E

2015-01-01

Till date, several studies have compared angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in terms of delaying the progression of diabetic nephropathy. But the superiority of one drug class over the other remains unsettled. This study has retrospectively compared the effects of ACE inhibitors and ARBs in diabetic nephropathy. The study aims to compare ACE inhibitors and ARBs in terms of delaying or preventing the progression of diabetic nephropathy, association between blood pressure (B.P) and urinary albumin and also B.P and serum creatinine with ACE inhibitor and ARB, know the percentage of hyperkalemia in patients of diabetic nephropathy receiving ACE inhibitor or ARB. A total of 134 patients diagnosed with diabetic nephropathy during the years 2001-2010 and having a complete follow-up were studied, out of which 99 were on ARB (63 patients of Losartan and 36 of Telmisartan) and 35 on ACE inhibitor (Ramipril). There was at least 1-month of interval between each observation made and also between the date of treatment started and the first reading that is, the observation of the 1(st) month. In total, three readings were taken that is, of the 1(st), 2(nd) and 3(rd) month after the treatment started. Comparison of the 1(st) and 3(rd) month after the treatment started was done. Mean ± standard deviation, Paired t-test, and Chi-square were used for the analysis of the data. The results reflect that ARBs (Losartan and Telmisartan) when compared to ACE inhibitor (Ramipril) are more effective in terms of delaying the progression of diabetic nephropathy and also in providing renoprotection. Also, ARBs have the property of simultaneously decreasing the systolic B.P and albuminuria when compared to ACE inhibitor (Ramipril). Angiotensin receptor blockers are more renoprotective than ACE inhibitors and also provide better cardioprotection.

Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

PubMed

Volpe, Massimo; Danser, A H Jan; Menard, Joël; Waeber, Bernard; Mueller, Dominik N; Maggioni, Aldo P; Ruilope, Luis M

2012-04-01

Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

[Control of hypertension in nursing homes].

PubMed

Thomas, J M; Alvarez, W; Mulaj, M; De Breucker, S; Leeman, M; Pepersack, T

2006-09-01

In a cross sectional study we determined prevalence of hypertension among institutionalized old subjects. Prevalence of hypertension was 69%. Among detected hypertensive patients, 76% received an antihypertensive drug treatment. 61% of the declared hypertensive patients and 80% of the treated hypertensive patients had their blood pressure controlled. The general practitioners should better detect and treat this common geriatric problem associated with a high comorbidity.

Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3-Mediated Calcium Handling in the Vasculature From Hypertensive Rats.

PubMed

Wang, Bin; Xiong, Shiqiang; Lin, Shaoyang; Xia, Weijie; Li, Qiang; Zhao, Zhigang; Wei, Xing; Lu, Zongshi; Wei, Xiao; Gao, Peng; Liu, Daoyan; Zhu, Zhiming

2017-07-15

Mitochondrial Ca 2+ homeostasis is fundamental to the regulation of mitochondrial reactive oxygen species (ROS) generation and adenosine triphosphate production. Recently, transient receptor potential channel, canonical type 3 (TRPC3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. Inhibition of TRPC3 attenuates vascular calcium influx in spontaneously hypertensive rats (SHRs). However, it remains elusive whether mitochondrial TRPC3 participates in hypertension by increasing mitochondrial calcium handling and ROS production. In this study we demonstrated increased TRPC3 expression in purified mitochondria in the vasculature from SHRs, which facilitates enhanced mitochondrial calcium uptake and ROS generation compared with Wistar-Kyoto rats. Furthermore, inhibition of TRPC3 by its specific inhibitor, Pyr3, significantly decreased the vascular mitochondrial ROS production and H 2 O 2 synthesis and increased adenosine triphosphate content. Administration of telmisartan can improve these abnormalities. This beneficial effect was associated with improvement of the mitochondrial respiratory function through recovering the activity of pyruvate dehydrogenase in the vasculature of SHRs. In vivo, chronic administration of telmisartan suppressed TRPC3-mediated excessive mitochondrial ROS generation and vasoconstriction in the vasculature of SHRs. More importantly, TRPC3 knockout mice exhibited significantly ameliorated hypertension through reduction of angiotensin II-induced mitochondrial ROS generation. Together, we give experimental evidence for a potential mechanism by which enhanced TRPC3 activity at the cytoplasmic and mitochondrial levels contributes to redox signaling and calcium dysregulation in the vasculature from SHRs. Angiotensin II or telmisartan can regulate [Ca 2+ ] mito , ROS production, and mitochondrial energy metabolism through targeting TRPC3. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Assessment and Management of Hypertension in Transplant Patients

PubMed Central

Burgess, Ellen D.; Cooper, James E.; Fenves, Andrew Z.; Goldsmith, David; McKay, Dianne; Mehrotra, Anita; Mitsnefes, Mark M.; Sica, Domenic A.; Taler, Sandra J.

2015-01-01

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients. PMID:25653099

Revisiting RAAS blockade in CKD with newer potassium-binding drugs.

PubMed

Georgianos, Panagiotis I; Agarwal, Rajiv

2018-02-01

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials. Published by Elsevier Inc.

Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits: Antihypertensive, Antioxidant, and Antidiabetic Properties.

PubMed

Admassu, Habtamu; Gasmalla, Mohammed Abdalbasit A; Yang, Ruijin; Zhao, Wei

2018-01-01

Cardiovascular diseases and diabetes are the biggest causes of death globally. Therefore, prevention of these diseases is a focus of pharmaceuticals and functional food manufacturers. This review summarizes recent research trends and scientific knowledge in seaweed protein-derived peptides with particular emphasis on production, isolation and potential health impacts in prevention of hypertension, diabetes and oxidative stress. The current status and future prospects of bioactive peptides are also discussed. Bioactive peptides have strong potential for use in therapeutic drug and functional food formulation in health management strategy, especially cardiovascular disease and diabetes. Seaweeds can be used as sustainable protein sources in the production of these peptide-based drugs and functional foods for preventing such diseases. Many studies have reported that peptides showing angiotensin converting enzyme inhibition, antihypertensive, antioxidative and antidiabetics activities, have been successfully isolated from seaweed. However, further research is needed in large-scale production of these peptides, efficient isolation methods, interactions with functional foods and other pharmaceuticals, and their ease to digestion in in vivo studies and safety to validate the health benefits of these peptides. © 2017 Institute of Food Technologists®.

Drug use and accidental falls in an intermediate care facility.

PubMed

Sobel, K G; McCart, G M

1983-01-01

The relationship between nonenvironment-caused falls and drug use was evaluated in an intermediate care facility over a 14-month period. The medical problems and selected drug use of 45 patients who had fallen were retrospectively compared with those of a matched control population of 30 patients who had not fallen during this same period. Antihypertensives, diuretics, tranquilizers, sedative/hypnotics, antidepressants, and antianginal agents were reviewed for all patients. The use of diuretics, specifically furosemide, and sedative/hypnotics was significantly greater in the population who had fallen. Observations of dizziness, confusion, insomnia, and ataxia were recorded more frequently in that group, as well. Closer monitoring of medications, especially in specific drug classes, may help prevent accidental falls in this type of institution.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

The benefit of angiotensin AT1 receptor blockers for early treatment of hypertensive patients.

PubMed

Trimarco, Bruno; Santoro, Ciro; Pepe, Marco; Galderisi, Maurizio

2017-12-01

ESC guidelines for management of arterial hypertension allow one to choose among five classes of antihypertensive drugs indiscriminately. They are based on the principle that in the management of hypertensive patients, it is fundamental to reduce blood pressure (BP), independently of the utilized drug. However, it has been demonstrated that the renin-angiotensin system (RAS) plays a relevant role in the hypertensive-derived development and progression of organ damage. Thus, antihypertensive drugs interfering with the RAS should be preferred in preventing and reducing target organ damage. The availability of two classes of drugs, ACE-inhibitors and angiotensin AT1 receptor blockers (ARBs), both interfering with the RAS, makes the choice between them difficult. Both pharmacological strategies offer an effective BP control, and a substantial improvement of prognosis in different associated pathologies. Regarding cardiovascular prevention, ACE-inhibitors have an extensive scientific literature regarding utility in high-risk patients. Nevertheless, there is evidence to support the concept that in the early phases of organ tissue damage, the RAS is activated, but the ACE pathway producing angiotensin II is not always employed. Accordingly, ACE-inhibitors appear to be less effective, whereas ARBs have a greater beneficial action in the initial stages of atherosclerotic disease. Moreover, patients undergoing ARBs therapy show a substantially lower risk of therapy discontinuation when compared to those treated with ACE-inhibitors, because of a better tolerability. In conclusion, ACE-inhibitors should be used in patients who have already developed organ damage, but tolerate this drug well, while ARBs should be the first choice in naïve hypertensive patients without organ damage or at the initial stages of disease.

Quantitative model for the blood pressure-lowering interaction of valsartan and amlodipine.

PubMed

Heo, Young-A; Holford, Nick; Kim, Yukyung; Son, Mijeong; Park, Kyungsoo

2016-12-01

The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. A two-compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D 1  + D 2 ) +ALPHA×(D 1 × D 2 ). D 1 and D 2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were -0.171 (95% CI: -0.218, -0.143) for SBP and -0.0312 (95% CI: -0.07739, -0.00283) for DBP. These infra-additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra-additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. © 2016 The British Pharmacological Society.

Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine

PubMed Central

Heo, Young‐A; Holford, Nick; Kim, Yukyung; Son, Mijeong

2016-01-01

Aims The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. Methods PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. Results A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. Conclusion PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. PMID:27504853

Medication Days' Supply, Adherence, Wastage, and Cost Among Chronic Patients in Medicaid

PubMed Central

Taitel, Michael; Fensterheim, Leonard; Kirkham, Heather; Sekula, Ryan; Duncan, Ian

2012-01-01

Background In an attempt to contain Medicaid pharmacy costs, nearly all states impose dispensing limits on medication days' supply. Although longer days' supply appears to increase the potential for medication wastage, previous studies suggest that it may also decrease pharmacy expenditures by reducing dispensing fees and drug ingredient costs. This study was conducted to determine whether 90-day refills at community pharmacies could improve adherence, minimize wastage, and control costs. Methods This retrospective observational study used California Medicaid claims, from the Walgreens pharmacy chain dated January 2010, to identify 52,898 patients prescribed statin, antihypertensive, selective serotonin reuptake inhibitor (SSRI), or oral hypoglycemic medications. Adherence was measured by medication possession ratio (MPR) and persistency with a 30-day gap. Medication wastage was defined as a switch of drug or drug strength within the same therapeutic class that occurred before the expected refill date. Results Adherence was 20% higher and persistency was 23% higher for the 90-day group than the 30-day group. This amounted to an average increase of 0.14 MPR and 44 days of continuous therapy. The two groups had comparable proportions of patients with wastage. After subtracting an average wastage cost of $7.34 per person per year (PPPY), all therapeutic classes had PPPY savings: statins ($7.70), antihypertensives ($10.80), SSRIs ($18.52), and oral hypoglycemics ($26.86). Conclusion Across four drug categories and compared to 30-day refills, patients with 90-day refills had greater medication adherence, greater persistency, nominal wastage, and greater savings. PMID:24800150

Effects of antihypertensive drugs on central blood pressure in humans: a preliminary observation.

PubMed

Agnoletti, Davide; Zhang, Yi; Borghi, Claudio; Blacher, Jacques; Safar, Michel E

2013-08-01

Central blood pressure (BP) is considered a better predictor of cardiovascular events than brachial BP. Modifications of central, beyond brachial BP, can be assessed by pressure amplification, a potential new cardiovascular risk factor. Comparison between drugs' effect on central hemodynamics has been poorly studied. Our aim was to assess the hemodynamic effect of a 12-week treatment with amlodipine 5mg, or candesartan 8mg, or indapamide sustained-release 1.5mg, in comparison with placebo. We analyzed 145 out-patients with essential hypertension in primary prevention enrolled in the Natrilix SR Versus Candesartan and Amlodipine in the Reduction of Systolic Blood Pressure in Hypertensive Patients (X-CELLENT) study, a multicenter, randomized, double-blinded, placebo-controlled trial. Arterial stiffness, central BP, pressure amplification, and wave reflection were measured by applanation tonometry. Baseline characteristics of patients were homogeneous between groups. After treatment, we found that active drugs produced similar reduction of both central and peripheral BPs, with no significant interdrug differences (all P < 0.05; excluded peripheral pulse pressure, compared with placebo). Second, amlodipine (1.9% ± 15.3%), candesartan (3.0% ± 14.6%) and indapamide (4.1% ± 14.4%) all increased pulse pressure amplification, but only indapamide was statistically different from placebo (P = 0.02). Finally, no significant changes were observed on pulse wave velocity, heart rate, and augmentation index. The 3 antihypertensive drugs similarly reduced peripheral and central BP, as compared with placebo, but a significant increase in pulse pressure amplification was obtained only with indapamide, independently of arterial stiffness modifications. 3283161 by BIOPHARMA.

Machine learning of big data in gaining insight into successful treatment of hypertension.

PubMed

Koren, Gideon; Nordon, Galia; Radinsky, Kira; Shalev, Varda

2018-06-01

Despite effective medications, rates of uncontrolled hypertension remain high. Treatment protocols are largely based on randomized trials and meta-analyses of these studies. The objective of this study was to test the utility of machine learning of big data in gaining insight into the treatment of hypertension. We applied machine learning techniques such as decision trees and neural networks, to identify determinants that contribute to the success of hypertension drug treatment on a large set of patients. We also identified concomitant drugs not considered to have antihypertensive activity, which may contribute to lowering blood pressure (BP) control. Higher initial BP predicts lower success rates. Among the medication options and their combinations, treatment with beta blockers appears to be more commonly effective, which is not reflected in contemporary guidelines. Among numerous concomitant drugs taken by hypertensive patients, proton pump inhibitors (PPIs), and HMG CO-A reductase inhibitors (statins) significantly improved the success rate of hypertension. In conclusions, machine learning of big data is a novel method to identify effective antihypertensive therapy and for repurposing medications already on the market for new indications. Our results related to beta blockers, stemming from machine learning of a large and diverse set of big data, in contrast to the much narrower criteria for randomized clinic trials (RCTs), should be corroborated and affirmed by other methods, as they hold potential promise for an old class of drugs which may be presently underutilized. These previously unrecognized effects of PPIs and statins have been very recently identified as effective in lowering BP in preliminary clinical observations, lending credibility to our big data results.

Diuretics and diabetes incidence--an appeal against the reluctance to prescribe a medication that is safe and proven.

PubMed

Siebenhofer, A; Jeitler, K; Rakovac, I; Horvath, K

2010-02-01

The publication of the scientific report of the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany on the 'Comparative evaluation of the benefits and harms of different antihypertensive drug classes [diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers and angiotensin II (AT-II) blockers] as first-choice therapy for patients with essential hypertension' raised an enormous public debate, particularly as diabetes incidence was not judged to be a patient-relevant outcome. In this assessment, the overall view of the patient-relevant results was that diuretics can be used as first-line antihypertensive treatment. Diabetes incidence is highest with diuretics, but minimal differences in fasting plasma glucose of approximately 0.28 mmol/l are magnified by the transformation of continuous blood glucose values into categorical data: with the establishment of thresholds, the diagnosis of diabetes depends on being above a certain blood glucose value. The protective cardiovascular effects of diuretics do not seem to be reduced in hypertensive patients who develop new-onset diabetes during treatment. Since blood pressure control is often worse, detection, treatment and control should be urgently improved. The debate on antihypertensive agents is mainly of scientific interest and has only minor clinical relevance for everyday patient care.

Azilsartan and chlorthalidone -new powerful fixed dose antihypertensive combination.

PubMed

Katsi, Vasiliki; Athanasiadi, Eleni; Tsioufis, Costas; Tousoulis, Dimitris

2018-04-20

Arterial hypertension is a disease that still affects a major part of the population worldwide, and leads to fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. From the CDC statistical analysis, as regarding to United States, 1 of every 3 adults has high blood pressure, and οnly about half (54%) of them have it under control. Furthermore, all that leads to a nation cost about $46 billion each year. Efforts to find new ways to regulate arterial hypertension are therefore imperative. In our days, a lot of reference has been made to the use of a new therapeutic combination, that of azilsartan - an innovative ARB, in combination with chlorthalidone. Ιn fact, it is a combination now prescribed in a number of countries. A significant number of trials shows both azilsartan vs popular antihypertensive drugs, as well as chlorthalidone vs chlorothiazide, to present a better antihypertensive effect. This effect is even greater when the two substances are combined. In this article we will try to present the latest findings concerning the efficacy, safety and clinical utility of this combination, as well as its adverse events, in comparison with other widely used therapeutic options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Targeting hypertension in patients with cardiorenal metabolic syndrome.

PubMed

Rojas, Edward; Velasco, Manuel; Bermúdez, Valmore; Israili, Zafar; Bolli, Peter

2012-10-01

Diabetes mellitus coexisting with hypertension is greater than chance alone would predict. Hypertensive patients have been shown to have altered composition of skeletal muscle tissue, decreased blood flow to skeletal muscle and post-receptor signaling alterations in the IRS insulin pathway, all inducing insulin resistance states, which partially explains why blood pressure goals in DM patients are lower than in normoglycemic patients. Although optimal first-step antihypertensive drug therapy in type 2 DM or impaired fasting glucose levels (IFG) should be individualized for each patient, converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been demonstrated in some but not all studies to decrease the rate of development of proteinuria and diabetic renal disease. According to the ACCF/AHA 2011 Expert Consensus, elderly persons with diabetes, hypertension, and nephropathy should be initially treated with ACEIs or ARBs, although the choice of a specific antihypertensive may also depend on other associated comorbidities.

Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs.

PubMed

Adigun, A Q; Ishola, D A; Akintomide, A O; Ajayi, A A L

2003-04-01

The current prescription patterns for essential hypertension and the efficacy, safety, tolerability and cost-effectiveness of the newer antihypertensive drugs were evaluated in Nigerian patients. The findings were compared with that of a previous study conducted in the same tertiary hospital 10 years earlier. A cross-sectional evaluation of blood pressure (BP) control in a hypertension clinic was undertaken among 150 Nigerian patients aged 61 +/- 12 years (55% females), with a duration of treatment on a particular drug class or combination of 9 +/- 3 months. The initial blood pressure was 176 +/- 20/108 +/- 11 mmHg and 22% of the patient had concurrent diabetes mellitus. Thiazide diuretics (D) alone or in combination remained the most commonly prescribed drugs in 56% of all patients. There were significant increases in the prescriptions of calcium channel blockers (CCBs) (51%), P < 0.0001, and ACE-inhibitors (ACEIs) (24%), P < 0.0001, but a slight reduction in the use of methyldopa, and fixed drug combinations (P < 0.01) compared to the previous study. The fall in systolic blood pressure on D (r = 0.65, P < 0.001) or CCB (r = 0.48, P < 0.02) was significantly correlated with the initial systolic blood pressure, but not age. More patients achieved normotension BP < 140/90 mmHg on CCB monotherapy (71%), than D monotherapy (56%). Combination therapy with ACEIs + D or methyldopa+thiazides normalized BP in 63 and 68%, respectively. Pulse pressure, a surrogate marker for cardiovascular complications and mortality in essential hypertension, was significantly reduced (P < 0.01) equally by all treatments, with 95% confidence intervals ranging from -28 to -1 mmHg. However, hypertensive-diabetic (HT-DM) patients (n = 33) exhibited no significant change in pulse pressure in response to treatment. Adverse drug reactions that occurred in 11% were impotence or postural dizziness with D, headache and pitting oedema with CCB, and dry cough with ACEI. Pharmaco-economic comparison of the drug classes revealed that for every US dollar (dollar) spent per month, the percentage of treated patients attaining normotension was 18.6 for D, 4.73 for CCB, 3.5 for ACEI + D and 13.6 for methyldopa + thiazides. A combination of ACEI + CCB or D was the preferred treatment for hypertensive-diabetic Nigerians, but only 24% attained a BP < 130/85 mmHg. These results demonstrate a shift in trend to a more rational and efficacious treatment of hypertension over a 10 year period. This may be associated, at least in part, with the intensive and continuous education of the prescribers in rational drug use and the introduction of a hospital formulary. Methyldopa is still a highly efficacious and cost-effective drug in this population. Black HT-DM Africans still constitute a subgroup who not only require more and costlier antihypertensive drugs, but whose BP control is suboptimal, and exhibit a poor therapeutic response to other risk factors (pulse pressure) that constitute a continuing risk for cardiovascular mortality.

Investigation of physicochemical factors affecting the stability of a pH-modulated solid dispersion and a tablet during storage.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun-Bom; Min, Dong Hun; Choi, Han-Gon; Han, Hyo-Kyung; Rhee, Yun-Seok; Lee, Beom-Jin

2011-07-29

The stability of solid dispersions (SD) during storage is of concern. We prepared the pH-modulated SD (pSD) and compressed tablets consisting of polyethylene glycol (PEG) 6000 as a carrier, drug and MgO (alkalizer). Telmisartan (TEL), an ionizable poorly water-soluble drug, was chosen as a model drug. The changes in physicochemical factors such as the dissolution rate, drug crystallinity, microenvironmental pH (pH(M)) and intermolecular interactions of the pSD and the tablets were investigated over 3 months under different temperature and relative humidity (RH) conditions: refrigerator (5-8 °C), 25 °C/32% RH, 25 °C/55% RH, 25 °C/75% RH, 40°C/32% RH, 40 °C/55% RH, and 40 °C/75% RH. Differential scanning calorimetry (DSC) analysis of all samples revealed no distinct changes in the drug melting point. In contrast, powder X-ray diffraction (PXRD) diffractograms revealed that samples stored at 40 °C/75% RH for 1 month, 25 °C/75% RH for 3 months and 40 °C at all humidity conditions for 3 months showed gradual recrystallization of the drug. Fourier transform infrared (FTIR) spectra indicated a reduced intensity of intermolecular interactions between TEL and MgO in the pSD and tablet. The pH(M) also gradually decreased. These altered physicochemical factors under the stressed conditions resulted in decreased dissolution profiles in intestinal fluid (pH 6.8). In contrast, the dissolution rate in gastric fluid (pH 1.2) was almost unchanged because of the high intrinsic solubility of TEL at this pH. Copyright © 2011 Elsevier B.V. All rights reserved.

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Current status of achieving blood pressure target and its clinical correlates in Japanese type 2 diabetes.

PubMed

Yokoyama, Hiroki; Araki, Shin-Ichi; Kawai, Koichi; Hirao, Koichi; Kurihara, Yoshio; Seino, Hiroaki; Takamura, Hiroshi; Sugimoto, Hidekatsu; Okada, Akira; Maegawa, Hiroshi

2017-07-21

To investigate the current status of achieved blood pressure levels in association with the number of antihypertensive drug classes as of 2013, and to explore the clinical correlates with achievement of target blood pressure in a large-scale cohort of Japanese subjects with type 2 diabetes. A nationwide survey was conducted including 12,811 subjects with type 2 diabetes. Subjects were divided by achieved blood pressure, <130/80 or 140/90 mmHg, and the number of drug classes taken. The percentages achieving a blood pressure of <130/80 or 140/90 mmHg were 52.0% and 86.1%, respectively. The prevalence of hypertension, if defined as ≥130/80 mmHg or treated, became 67.9%. Among subjects taking antihypertensive drugs, a blood pressure of <130/80 or <140/90 mmHg was 46.7% and 83.2%, respectively. The percentages of <130/80 mmHg were 55.9% without drugs, 47.1% on 1, 42.5% on 2, 47.2% on 3, and 56.8% on ≥4 drugs, respectively. The most prescribed drugs were renin-angiotensin system inhibitors, followed by calcium channel blockers, diuretics, and β-blockers. The multiple logistic regression analysis indicated that a blood pressure <130/80 mmHg was associated with lower values in age, body mass index, albuminuria, and glomerular filtration rate, higher proportions on targets for HbA 1C and lipids, and less retinopathy. In type 2 diabetes, hypertension is common and only 52% achieved <130/80 mmHg, indicating a difficulty in blood pressure lowering. This was correlated with difficulties in glycemic and lipid management, obesity, and vascular complications, implying these clustering to be a serious problem. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pathophysiology and Medical Treatment of Carotid Artery Stenosis

PubMed Central

Prasad, Kailash

2015-01-01

Stroke is the third leading cause of mortality. Approximately 80 to 85% strokes are ischemic due to carotid artery stenosis (CAS). The prevalence of significant CAS is 7% in women and 9% in men. Severe asymptomatic CAS varies from 0 to 3.1%. Prevalence of symptomatic CAS is high in patients with peripheral arterial disease. CAS is due to atherosclerosis, the major risk factors for which include dyslipidemia, hypertension, diabetes, obesity, cigarette smoking, advanced glycation end products (AGEs) and its receptors (RAGE, soluble RAGE [sRAGE]), lack of exercise and C-reactive protein (CRP). This article discusses the basic mechanism of atherosclerosis and the mechanisms by which these risk factors induce atherosclerosis. The role of AGEs and its receptors in the development and progression of CAS has been discussed in detail. Lifestyle changes and medical treatment of CAS such as lifestyle changes, lipid-lowering agents, antihypertensive agents, antidiabetic drugs, anti-AGE therapy, measures to elevate soluble receptors of AGE (sRAGE, esRAGE). CRP-lowering agents have been discussed in detail. The drugs especially lipid-lowering agents, and antihypertensive and antidiabetic drugs suppress, regress, and slow the progression of CAS. The possible role of lowering the levels of AGEs and raising the levels of sRAGE in the treatment of CAS has been proposed. Lifestyle changes besides medical treatment have been stressed. Lifestyle changes and medical treatment not only would slow the progression of CAS but would also regress the CAS. PMID:26417183

The international generalisability of evidence for health policy: A cross country comparison of medication adherence following policy change.

PubMed

Sinnott, Sarah-Jo; Whelton, Helen; Franklin, Jessica Myers; Polinski, Jennifer Milan

2017-01-01

Copayments for prescriptions may increase morbidity and mortality via reductions in adherence to medications. Relevant data can inform policy to minimise such unintended effects. We explored the generalisability of evidence for copayments by comparing two international copayment polices, one in Massachusetts and one in Ireland, to assess whether effects on medication adherence were comparable. We used national prescription data for public health insurance programmes in Ireland and Medicaid data in the U.S. New users of oral anti-hypertensive, anti-hyperlipidaemic and diabetic drugs were included (total n=14,259 in U.S. and n=43,843 in Ireland). We examined changes in adherence in intervention and comparator groups in each setting using segmented linear regression with generalised estimating equations. In Massachusetts, a gradual decrease in adherence to anti-hypertensive medications of -1% per month following the policy occurred. In contrast, the response in Ireland was confined to a -2.9% decrease in adherence immediately following the policy, with no further decrease over the 8 month follow-up. Reductions in adherence to oral diabetes drugs were larger in the U.S. group in comparison to the Irish group. No difference in adherence changes between the two settings for anti-hyperlipidaemic drugs occurred. Evidence on cost-sharing for prescription medicines is not 'one size fits all'. Time since policy implementation and structural differences between health systems may influence the differential impact of copayment policies in international settings. Copyright © 2016. Published by Elsevier Ireland Ltd.

Angiotensin Mediated Oxidative Stress and Neuroprotective Potential of Antioxidants and AT1 Receptor Blockers.

PubMed

Prusty, Shakti Ketan; Sahu, Pratap Kumar; Subudhi, Bharat Bhusan

2017-01-01

Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central renin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration. Although it has shown promise, clinical efficacy is limited to few drugs including telmisartan mainly due to the poor brain availability of others. In this review we aim to analyze the potential of antioxidants to reduce oxidative stress in brain. We have given critical analysis of the approaches for re-purposing of AT1 blockers against oxidative stress induced neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history.

PubMed

Zeng, Wenjie; Gustafsson, Lars L; Bennie, Marion; Finlayson, Alexander E; Godman, Brian

2015-02-01

Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. Considerable opportunities to improve prescribing efficiency in China.

[Pharmacogenetic approaches to predicting the efficiency and safety of amlodipine in patients with arterial hypertension].

PubMed

Sychev, D A; Shih, N V; Kalle, E G; Ryzhikova, K A; Morozova, T E

2017-10-01

An open, non-comparative, prospective clinical study was conducted to evaluate the antihypertensive efficacy and tolerability of amlodipine, a calcium antagonist, in patients with arterial hypertension (AH) I-II stages, depending on the genotype for the polymorphic marker C3435T of the ABCB1 gene. The study included 100 patients with AH I-II stages, aged from 45 to 58 years. The initial dose of amlodipine was 5 mg, duration of treatment was 12 weeks. General clinical examination methods, office measurement and daily blood pressure monitoring, tolerance evaluation, and genotyping using the ABCB1 polymorphic marker C3435T by the PCR-RFLP method (polymerase chain reaction and restriction fragment length polymorphism) were used. The statistical analysis of results was carried out using the Mann-Whitney U test for quantitative variables, Kruskal-Wallis one-way analysis of variance (ANOVA) for three independent groups of quantitative data. Excellent antihypertensive efficacy with the CC genotype was found in 11.8% patients, with CT - 33.9%, with TT - 43.3%; good - 35.3%, 32.1%, and 33.3% respectively, satisfactory - 52.9%, 34,0% and 23.4% respectively. Six patients with the CT genotype and nine patients with the CC genotype required the increase in the dose to 10 mg. The number of patients with Adverse drug reactions (ADR) were found in 35.3% of patients with the CC genotype, 6.7% with the TT genotype and 11.3% with the CT genotype. The Kruskal-Wallis test revealed significant differences between CC and TT genotypes in the degree of decrease in SBP (p=0.02), antihypertensive efficacy parameter (p=0.02), an increase in dose requirements (p = 0.04) and the incidence of ADR(p=0.05). In AH patients (I-II stage) with the TT genotype of the C3435T gene polymorphism one can expect higher rates of antihypertensive efficacy of amlodipine in combination with a good safety profile and the lowest ADR percentage, while patients with the CC genotype more likely to develop ADR and lower antihypertensive responsiveness.

Safety, Tolerability, and Antihypertensive Effect of SER100, an Opiate Receptor-Like 1 (ORL-1) Partial Agonist, in Patients With Isolated Systolic Hypertension.

PubMed

Kantola, Ilkka; Scheinin, Mika; Gulbrandsen, Trygve; Meland, Nils; Smerud, Knut T

2017-11-01

The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours. Seventeen patients completed treatment. There were no serious or severe adverse events. Relative to placebo SER100 induced an average reduction of SBP during the 2 treatment days of 7.0 mm Hg (P = 0.0032), whereas the average reduction of diastolic blood pressure (DBP) over the same period was 3.8 mm Hg (P = 0.0011). For patients with ISH, this short-term cross-over study of SC SER100 demonstrated an acceptable safety profile and consistent, significant lowering of SBP and DBP. As initial clinical proof of concept for a new class of drugs, a nociceptin agonist peptide, the results were encouraging and warrant further research. © 2016, The American College of Clinical Pharmacology.

Antiproteinuric effects of renin-angiotensin inhibitors in lung cancer patients receiving bevacizumab.

PubMed

Nihei, Satoru; Sato, Junya; Harada, Toshiyuki; Kuyama, Shoichi; Suzuki, Toshiro; Waga, Nobutsugu; Saito, Yoshitaka; Kisara, Shigeki; Yokota, Atsuko; Okada, Kouji; Tsuchiya, Masami; Terui, Kazufumi; Tadokoro, Yumiko; Chiba, Takeshi; Kudo, Kenzo; Oizumi, Satoshi; Inoue, Akira; Morikawa, Naoto

2018-06-01

The objective of this study was to investigate the effect of renin-angiotensin system inhibitors (RASIs) on bevacizumab (BV)-induced proteinuria in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the medical records of NSCLC patients receiving BV between 2008 and 2014 at 11 hospitals. The patients were categorized into three groups according to their antihypertensive drug use: RASI user, non-RASI user, and non-user groups. The primary outcome was a proteinuria event of any grade during the first 6 cycles of BV treatment. A total of 211 patients were included, 89 of whom received antihypertensive drugs. Of these 89 patients, 49 were in the RASI user group, and 40 were in the non-RASI user group. The non-user group comprised 122 patients. The occurrence of proteinuria in the RASI user group was significantly lower than that in the non-RASI user group (P = 0.037) but was not significantly lower than that in the non-user group (P = 0.287). Patients using RASIs had a lower rate of proteinuria than those who did not use RASIs according to multivariate analysis (odds ratio 0.32; 95% confidence interval 0.12-0.86; P = 0.024). Our study suggests that RASI administration reduces the risk of proteinuria in patients receiving BV.

Salivary flow rate and pH in patients with oral pathologies.

PubMed

Foglio-Bonda, P L; Brilli, K; Pattarino, F; Foglio-Bonda, A

2017-01-01

Determine salivary pH and flow rate (FR) in a sample of 164 patients who came to Oral Pathology ambulatory, 84 suffering from oral lesions and 80 without oral lesions. Another aim was to evaluate factors that influence salivary flow rate. Subjects underwent clinical examination and completed an anamnestic questionnaire in order to obtain useful information that was used to classify participants in different groups. Unstimulated whole saliva (UWS) was collected using the spitting method at 11:00 am. The FR was evaluated with the weighing technique and a portable pHmeter, equipped with a microelectrode, was used to measure pH. Both univariate and classification (single and Random Forest) analyses were performed. The data analysis showed that FR and pH showed significant differences (p < 0.001) between patients with oral lesions (FR = 0.336 mL/min, pH = 6.69) and the ones without oral lesions (FR = 0.492 mL/min, pH = 6.96). By Random Forest, oral lesions and antihypertensive drugs were ranked in the top two among the evaluated variables to discretize subjects with FR = 0.16 mL/min. Our study shows that there is a relationship between oral lesions, antihypertensive drugs and alteration of pH and FR.

Evaluation and management of the patient with difficult-to-control or resistant hypertension.

PubMed

Viera, Anthony J; Hinderliter, Alan L

2009-05-15

High blood pressure is often difficult to control. Resistant hypertension is blood pressure above goal despite adherence to a combination of at least three antihypertensive medications of different classes, optimally dosed and usually including a diuretic. The approach to blood pressure that is apparently difficult to control begins with an assessment of the patient's adherence to the management plan, including lifestyle modifications and medications. White-coat hypertension may need to be ruled out. Suboptimal therapy is the most common reason for failure to reach the blood pressure goal. Once-daily fixed-dose combination pills may improve control through the synergism of antihypertensive agents from different classes and improved adherence. Truly drug-resistant hypertension is commonly caused by chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed. Other strategies include adding an alpha blocker, alpha-beta blocker, clonidine, or an aldosterone antagonist (e.g., spironolactone). Particularly in patients with diabetes or renal disease, combining a long-acting nondihydropyridine with a dihydropyridine calcium channel . blocker can also be considered. Obesity, heavy alcohol intake, high levels of dietary sodium, and interfering substances (especially nonsteroidal anti-inflammatory drugs) contribute to hypertension that is resistant or difficult to control.

Identification of Tengfu Jiangya Tablet Target Biomarkers with Quantitative Proteomic Technique

PubMed Central

Xu, Jingwen; Zhang, Shijun; Jiang, Haiqiang; Wang, Nan; Lin, Haiqing

2017-01-01

Tengfu Jiangya Tablet (TJT) is a well accepted antihypertension drug in China and its major active components were Uncaria total alkaloids and Semen Raphani soluble alkaloid. To further explore treatment effects mechanism of TJT on essential hypertension, a serum proteomic study was performed. Potential biomarkers were quantified in serum of hypertension individuals before and after taking TJT with isobaric tags for relative and absolute quantitation (iTRAQ) coupled two-dimensional liquid chromatography followed electrospray ionization-tandem mass spectrometry (2D LC-MS/MS) proteomics technique. Among 391 identified proteins with high confidence, 70 proteins were differentially expressed (fold variation criteria, >1.2 or <0.83) between two groups (39 upregulated and 31 downregulated). Combining with Gene Ontology annotation, KEGG pathway analysis, and literature retrieval, 5 proteins were chosen as key target biomarkers during TJT therapeutic process. And the alteration profiles of these 5 proteins were verified by ELISA and Western Blot. Proteins Kininogen 1 and Keratin 1 are members of Kallikrein system, while Myeloperoxidase, Serum Amyloid protein A, and Retinol binding protein 4 had been reported closely related to vascular endothelial injury. Our study discovered 5 target biomarkers of the compound Chinese medicine TJT. Secondly, this research initially revealed the antihypertension therapeutic mechanism of this drug from a brand-new aspect. PMID:28408942

Effect assessment of "film coating and packaging" on the photo-stability of highly photo-labile antihypertensive products.

PubMed

Mukharya, Amit; Patel, Paresh U; Chaudhary, Shivang

2013-04-01

Lacidipine (LCDP) is chemically a "1, 4-dihydropyridine derivative" Ca+(2) channel blocker used as an antihypertensive. Type and extent of packaging have a strong influence on the photo-stability of the 1,4-dihydropyridine derivatives. In standard, light protection of drug substance/drug product can be obtained either by use of an opaque additive in the formulation that competitively absorbs or reflects light reaching the sample and/or by blocking the access of light to the drug through external protection by packaging. External protection by covering tablets with an opaque film coating involving a light-reflecting inorganic pigment such as titanium dioxide and/or by using an opaque impermeable packaging material was an appropriate suitable option for establishing photo-stability. Thus, the main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets. The main objective (% level of film coating) was optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film-coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative analysis at the end of light exposure testing. The other objective (extent of drug product packaging) was established successfully by assessing whether or not an acceptable change has occurred at the end of the light exposure testing of the LCDP film-coated tablets in a direct exposure study or a primary immediate pack and/or secondary marketing pack.

Vascular Smooth Muscle Cells From Hypertensive Patient-Derived Induced Pluripotent Stem Cells to Advance Hypertension Pharmacogenomics.

PubMed

Biel, Nikolett M; Santostefano, Katherine E; DiVita, Bayli B; El Rouby, Nihal; Carrasquilla, Santiago D; Simmons, Chelsey; Nakanishi, Mahito; Cooper-DeHoff, Rhonda M; Johnson, Julie A; Terada, Naohiro

2015-12-01

Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug responses, a biological interface is needed. Patient-derived induced pluripotent stem cells (iPSCs) provide a potential source for studying otherwise inaccessible tissues that may be important to antihypertensive drug response. The present study established multiple iPSC lines from an HTN pharmacogenomics cohort. We demonstrated that established HTN iPSCs can robustly and reproducibly differentiate into functional vascular smooth muscle cells (VSMCs), a cell type most relevant to vasculature tone control. Moreover, a sensitive traction force microscopy assay demonstrated that iPSC-derived VSMCs show a quantitative contractile response on physiological stimulus of endothelin-1. Furthermore, the inflammatory chemokine tumor necrosis factor α induced a typical VSMC response in iPSC-derived VSMCs. These studies pave the way for a large research initiative to decode biological significance of identified SNPs in hypertension pharmacogenomics. Treatment of hypertension remains suboptimal, and a pharmacogenomics approach seeks to identify genetic biomarkers that could be used to guide treatment decisions; however, it is important to understand the biological underpinnings of genetic associations. Mouse models do not accurately recapitulate individual patient responses based on their genetics, and hypertension-relevant cells are difficult to obtain from patients. Induced pluripotent stem cell (iPSC) technology provides a great interface to bring patient cells with their genomic data into the laboratory and to study hypertensive responses. As an initial step, the present study established an iPSC bank from patients with primary hypertension and demonstrated an effective and reproducible method of generating functional vascular smooth muscle cells. ©AlphaMed Press.

Effect assessment of “film coating and packaging” on the photo-stability of highly photo-labile antihypertensive products

PubMed Central

Mukharya, Amit; Patel, Paresh U; Chaudhary, Shivang

2013-01-01

Introduction: Lacidipine (LCDP) is chemically a “1, 4-dihydropyridine derivative” Ca+2 channel blocker used as an antihypertensive. Type and extent of packaging have a strong influence on the photo-stability of the 1,4-dihydropyridine derivatives. In standard, light protection of drug substance/drug product can be obtained either by use of an opaque additive in the formulation that competitively absorbs or reflects light reaching the sample and/or by blocking the access of light to the drug through external protection by packaging. Materials and Methods: External protection by covering tablets with an opaque film coating involving a light-reflecting inorganic pigment such as titanium dioxide and/or by using an opaque impermeable packaging material was an appropriate suitable option for establishing photo-stability. Thus, the main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets. Results and Conclusion: The main objective (% level of film coating) was optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film-coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative analysis at the end of light exposure testing. The other objective (extent of drug product packaging) was established successfully by assessing whether or not an acceptable change has occurred at the end of the light exposure testing of the LCDP film-coated tablets in a direct exposure study or a primary immediate pack and/or secondary marketing pack. PMID:24015379

Antihypertensive drugs: a perspective on pharmaceutical price erosion and its impact on cost-effectiveness.

PubMed

Refoios Camejo, Rodrigo; McGrath, Clare; Herings, Ron; Meerding, Willem-Jan; Rutten, Frans

2012-01-01

When comparators' prices decrease due to market competition and loss of exclusivity, the incremental clinical effectiveness required for a new technology to be cost-effective is expected to increase; and/or the minimum price at which it will be funded will tend to decrease. This may be, however, either unattainable physiologically or financially unviable for drug development. The objective of this study is to provide an empirical basis for this discussion by estimating the potential for price decreases to impact on the cost-effectiveness of new therapies in hypertension. Cost-effectiveness at launch was estimated for all antihypertensive drugs launched between 1998 and 2008 in the United Kingdom using hypothetical degrees of incremental clinical effectiveness within the methodologic framework applied by the UK National Institute for Health and Clinical Excellence. Incremental cost-effectiveness ratios were computed and compared with funding thresholds. In addition, the levels of incremental clinical effectiveness required to achieve specific cost-effectiveness thresholds at given prices were estimated. Significant price decreases were observed for existing drugs. This was shown to markedly affect cost-effectiveness of technologies entering the market. The required incremental clinical effectiveness was in many cases greater than physiologically possible so, as a consequence, a number of products might not be available today if current methods of economic appraisal had been applied. We conclude that the definition of cost-effectiveness thresholds is fundamental in promoting efficient innovation. Our findings demonstrate that comparator price attrition has the potential to put pressure in the pharmaceutical research model and presents a challenge to new therapies being accepted for funding. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

PubMed Central

Mfuh, Adelphe M.; Larionov, Oleg V.

2016-01-01

Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

[New drugs for small animals in 2014].

PubMed

Emmerich, I U

2015-01-01

In 2014, six active pharmaceutical ingredients were released on the German market for small animals. Those are the ektoparasiticide of the isoxazoline group afoxolaner (NexGard®) and fluralaner (Bravecto®) and the neonicotinoid dinotefuran (Vectra 3D, Vectra Felis), the antidiabetic protamine zinc insulin of human origin (ProZinc®), the antifungal agent ketoconazole (Fugazid®) as well as the cytostatic drug oclacitinib (Apoquel®). Two substances were authorized for an additional species. The antiparasiticide eprinomectin and the antibiotic clindamycin were also authorized for use in cats. In addition, two active pharmaceutical ingredients, which were approved 2014 for use in human medicine and are of potential interest to veterinary medicine, are discussed. These are the antihypertensive drug riociguat and the urological substance mirabegron.

PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis.

PubMed

Zou, Rong; Xu, Gang; Liu, Xiao-cheng; Han, Min; Jiang, Jing-jing; Huang, Qian; He, Yong; Yao, Ying

2010-01-01

To study the probable mechanisms of the anti-glomerulosclerosis effects induced by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists in rat intraglomerular mesangial cells (MCs). Cells were transfected with the pTAL-PPRE-tk-Luc(+) plasmid and then treated with different concentrations of PPARgamma agonist, either troglitazone or telmisartan, for the indicated times. Promega luciferase assays were subsequently used for the detection of PPARgamma activation. Protein expression levels were assessed by Western blot, and PepTag assays were used for the non-radioactive detection of protein kinase A (PKA) activity. The deposition of alpha-smooth muscle actin (alpha-SMA) and p-cyclic AMP responsive element binding protein (pCREB) were analyzed by confocal laser scanning. Both troglitazone and telmisartan remarkably inhibit the PKA activation and pCREB expression that is stimulated by TGF-beta. The PPARgamma agonists also inhibited alpha-SMA and collagen IV protein expression by blocking PKA activation. PPARgamma ligands effectively suppress the activation of MCs and the accumulation of collagen IV stimulated by TGF-beta in vitro. The renal protection provided by PPARgamma agonists is partly mediated via their blockade of TGF-beta/PKA signaling.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines.

PubMed

Boboia, Anamaria; Grigorescu, Marius Rareş; Turcu-Ştiolică, Adina

2017-01-01

The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans.

In vivo Antihypertensive and Antihyperlipidemic Effects of the Crude Extracts and Fractions of Moringa stenopetala (Baker f.) Cufod. Leaves in Rats

PubMed Central

Geleta, Bekesho; Makonnen, Eyasu; Debella, Asfaw; Tadele, Ashenif

2016-01-01

Background: Moringa stenopetala (Baker f.) Cufod. is a medicinal plant that has been used in Ethiopian traditional medicine as a remedy for treatment of hypertension and diabetes. The aim of this study was to evaluate antihypertensive and antihyperlipidemic effect in fructose induced hypertensive rats. Methods: Rats were randomly divided into control and treatment groups (n = 6). Treatment groups were given daily extracts (250, 500, and 1000 mg/kg) orally with fructose. Whereas, positive, negative and normal control groups were received captopril (20 mg/kg/day with fructose), only fructose (66% w/v ad libitum) and distilled water ad libitum for 15 days, respectively. The blood pressure was measured every 5th day using tail cuff blood pressure analyzer, and on the 16th day the blood was sampled to evaluate antihyperlipidemic effect using clinical chemistry analyzer. Results: The study showed that aqueous and 70% ethanol extracts significantly prevented blood pressure increment in a dose dependent manner comparable to that of the standard drug. Similarly, the extracts suppressed increment in lipid profile (cholesterol, glucose, and triglycerides) compared with negative control. The biochemical test revealed that extracts produced a rise in liver but no effect on kidney function indicators compared with normal control. Conclusion: These findings revealed that both crude extracts of M. stenopetala (Baker f.) Cufod. possess antihypertensive and antihyperlipidemic effect. PMID:27148056

Valsartan combination therapy in the management of hypertension – patient perspectives and clinical utility

PubMed Central

Nash, David T; McNamara, Michael S

2009-01-01

The morbidity and mortality benefits of lowering blood pressure (BP) in hypertensive patients are well established, with most individuals requiring multiple agents to achieve BP control. Considering the important role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of hypertension, a key component of combination therapy should include a RAAS inhibitor. Angiotensin receptor blockers (ARBs) lower BP, reduce cardiovascular risk, provide organ protection, and are among the best tolerated class of antihypertensive therapy. In this article, we discuss two ARB combinations (valsartan/hydrochlorothiazide [HCTZ] and amlodipine/valsartan), both of which are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy and as initial therapy in patients likely to need multiple drugs to achieve BP goals. Randomized, double-blind studies that have assessed the antihypertensive efficacy and safety of these combinations in the first-line treatment of hypertensive patients are reviewed. Both valsartan/HCTZ and amlodipine/valsartan effectively lower BP and are well tolerated in a broad range of patients with hypertension, including difficult-to-treat populations such as those with severe BP elevations, prediabetes and diabetes, patients with the cardiometabolic syndrome, and individuals who are obese, elderly, or black. Also discussed herein are patient-focused perspectives related to the use of valsartan/HCTZ and amlodipine/valsartan, and the rationale for use of single-pill combinations as one approach to enhance patient compliance with antihypertensive therapy. PMID:21949614

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics.

PubMed

Rosenbaum, David; Mattina, Alessandro; Koch, Edouard; Rossant, Florence; Gallo, Antonio; Kachenoura, Nadjia; Paques, Michel; Redheuil, Alban; Girerd, Xavier

2016-06-01

In humans, adaptive optics camera enables precise large-scale noninvasive retinal microcirculation evaluation to assess ageing, blood pressure and antihypertensive treatments respective roles on retinal arterioles anatomy. We used adaptive optics camera rtx1 (Imagine-Eyes, Orsay, France) to measure wall thickness, internal diameter and to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. This assessment was repeated within a short period in two subgroups of hypertensive individuals without or with a drug-induced blood pressure drop. In 1000 individuals, mean wall thickness, lumen diameter and WLR were 23.2 ± 3.9, 78.0 ± 10.9 and 0.300 ± 0.054 μm, respectively. Blood pressure and age both independently increased WLR by thickening arterial wall. In opposite, hypertension narrowed lumen in younger as compared to older individuals (73.2 ± 9.0 vs. 81.7 ± 10.2 μm; P < 0.001), whereas age exerted no influence on lumen diameter. Short-term blood pressure drop (-29.3 ± 17.3/-14.4 ± 10.0 mmHg) induced a WLR decrease (-6.0 ± 8.0%) because of lumen dilatation (+4.4 ± 5.9%) without wall thickness changes. By contrast, no modifications were observed in individuals with stable blood pressure. In treated and controlled hypertensives under monotherapy WLR normalization was observed because of combined wall decrease and lumen dilatation independently of antihypertensive pharmacological classes. In multivariate analysis, hypertension drug regimen was not an independent predictor of any retinal anatomical indices. Retinal arteriolar remodeling comprised blood pressure and age-driven wall thickening as well as blood pressure-triggered lumen narrowing in younger individuals. Remodeling reversal observed in controlled hypertensives seems to include short-term functional and long-term structural changes.

Impact of Clinical Factors on the Achievement of Target Blood Pressure in Hypertensive Patients from Ivanovo Region of Russia: Data of 2015.

PubMed

Kiselev, A R; Posnenkova, O M; Belova, O A; Romanchuk, S V; Popova, Y V; Prokhorov, M D; Gridnev, V I

2017-12-01

In Russia, blood pressure (BP) control is below the optimal. The little is known about regional features and barriers to adequate BP control in Russian primary care. To evaluate the impact of clinical factors on achieving the target BP in hypertensive patients in one region of Russia. Retrospective medical data of 2015 on 11,129 patients (31.4% male) with hypertension (Htn) from Ivanovo region of Russia were examined. Achievement of target BP was assessed in all patients. We study association between BP control and clinical factors. 45.9% of studied patients with Htn had controlled BP. The frequency of achieving the target BP in subsets of hypertensive patients was 37.8% in patients with diabetes, 39.5% in patients with coronary artery disease, and 29.9% in patients with chronic heart failure. The main clinical factors associated with achieving the target BP in studied hypertensive patients were the advice on alcohol consumption, advice on smoking cessation, and advice on weight reduction. Therapy with main antihypertensive drugs (in particular, beta-blockers and thiazide diuretics) were also factors of optimal BP control in these patients. Comorbidities (chronic heart failure and cardiovascular diseases requiring the prescription of aspirin and statins) and family history of coronary artery disease were associated with inadequate BP control. A negative effect of some antihypertensive drugs (potassium sparing diuretics, ARBs, ACE-Is, and dihydropyridine CCBs) on BP control that was found out in our study requires further investigation. Other studied factors had no influence on BP control in patients with Htn from Ivanovo region. We identified regional factors of BP control in hypertensive patients from Ivanovo region of Russia. It is shown that individual medical education (in particular, medical advices) is the most important factor of optimal BP control. The intervention with antihypertensive therapy (beta-blockers and thiazide diuretics) facilitates the achievement of target BP. Comorbidity and age reduce the frequency of achieving the target BP.

Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

PubMed

Kent, Shia T; Shimbo, Daichi; Huang, Lei; Diaz, Keith M; Kilgore, Meredith L; Oparil, Suzanne; Muntner, Paul

2014-01-01

After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).

Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis.

PubMed

Bai, Feng; Pang, Xue-Fen; Zhang, Li-Hui; Wang, Ning-Ping; McKallip, Robert J; Garner, Ronald E; Zhao, Zhi-Qing

2016-05-15

This study tested the hypothesis that angiotensin II (Ang II) AT1 receptor is involved in development of hypertension and cardiac fibrosis via modifying ACE2 activity, eNOS expression and CD44-hyaluronan interaction. Male Sprague-Dawley rats were subjected to Ang II infusion (500ng/kg/min) using osmotic minipumps up to 4weeks and the AT1 receptor blocker, telmisartan was administered by gastric gavage (10mg/kg/day) during Ang II infusion. Our results indicated that Ang II enhances AT1 receptor, downregulates AT2 receptor, ACE2 activity and eNOS expression, and increases CD44 expression and hyaluronidase activity, an enzyme for hyaluronan degradation. Further analyses revealed that Ang II increases blood pressure and augments vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with telmisartan significantly increased ACE2 activity and eNOS expression in the intracardiac vessels and intermyocardium. These changes occurred in coincidence with decreased blood pressure. Furthermore, the locally-expressed AT1 receptor was downregulated, as evidenced by an increased ratio of the AT2 over AT1 receptor (1.4±0.4% vs. 0.4±0.1% in Ang II group, P<0.05). Along with these modulations, telmisartan inhibited membrane CD44 expression and hyaluronidase activity, decreased populations of macrophages and myofibroblasts, and reduced expression of TGFβ1 and Smads. Collagen I synthesis and tissue fibrosis were attenuated as demonstrated by the less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in development of hypertension and cardiac fibrosis. Selective activating ACE2/eNOS and inhibiting CD44/HA interaction might be considered as the therapeutic targets for attenuating Ang II induced deleterious cardiovascular effects. Copyright © 2016 Elsevier Inc. All rights reserved.

[Regression of left ventricular hypertophy in the ECG during antihypertensive treatment: preliminary observations (author's transl)].

PubMed

Manegold, C; Patzschke, U

1979-06-08

Typical signs of left ventricular hypertrophy (LVH) were present in the ECG of 36 (10 women, 26 men) of 127 persons with essential hypertension (46 women, 81 men). After a two-year course of combined drug treatment (chlortalidone, reserpine, methyl-dopa, hydralazine) with effective blood-pressure reduction LVH was still present in the ECG of 29, after a four-year course of only 15 among 36, i. e. a reduction in the presence of LVH of nearly 60%. Since the patients' body-weight remained unchanged during this period, the regression in ECG changes is ascribed to the effectiveness of the drug treatment.

Micropropagation and in vitro flowering of Rauvolfia tetraphylla; a potent source of anti-hypertension drugs.

PubMed

Sarma, D; Sarma, S; Baruah, A

1999-04-01

A simple protocol for in vitro mass multiplication of Rauvolfia tetraphylla (Apocynaceae) has been developed. The endophytic microflora was controlled by adopting integrated measures. Multiple shoot development was achieved on MS + Kin (0.1-0.2 mg/l) + BAP (0.4-0.5 mg/l) media. Rooting from in vitro shoots occurred on NAA containing media. In vitro flowering was induced in shoot multiplication media.

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

PubMed Central

Agrawal, A.; Agarwal, S. K.; Kaleekal, T.; Gupta, Y. K.

2016-01-01

Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP) was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP <140/90 mmHg. Serial amlodipine levels were estimated in 16 patients; metoprolol and prazosin in four patients each. Drug levels declined by >50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001). Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46%) patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation. PMID:27795624

Pharmaceuticals and illicit drugs - A new threat to the application of sewage sludge in agriculture.

PubMed

Ivanová, Lucia; Mackuľak, Tomáš; Grabic, Roman; Golovko, Oksana; Koba, Olga; Staňová, Andrea Vojs; Szabová, Petra; Grenčíková, Anna; Bodík, Igor

2018-04-07

The occurrence of 93 pharmaceuticals, illicit drugs and their metabolites has been investigated in stabilized sewage sludge from five municipal wastewater treatment plants (WWTPs) in the Slovak Republic. The total population connected to the tested WWTPs was approximately 600,000 p.e. which represents >20% of the Slovak population connected to public sewer systems. The sludge production from the five tested plants was >8100tons in 2016, which is approximately 15% of the total Slovak sewage sludge production in 2016. The highest total concentration of all pharmaceuticals was found in WWTP Bratislava Devínska Nová Ves (DNV) and Senec - 11,800 and 11,300ng/g dry matter (DM), respectively. Among individual pharmaceuticals, the highest concentrations were recorded for fexofenadine (mean 2340ng/g DM, maximum 5600ng/g DM in Bratislava DNV) and telmisartan (mean 1170ng/g DM, with a maximum of 3370ng/g DM in Senec). A principal component analysis revealed differences between pharmaceutical patterns in aerobically and anaerobically stabilized sludge. The worst-case scenario based on no further degradation of pharmaceuticals between sludge production and field application was used to predict pharmaceutical mass loads in agriculture. For the result, we estimated an annual load to soil in the Slovak Republic of up to several hundred kilograms of pharmaceuticals and drugs, with the maximum for fexofenadine (120kg/year) and verapamil (29kg/year). Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

PubMed

Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

2012-04-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

PubMed Central

Gill, Katherine L.; Houston, J. Brian

2012-01-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CLint, UGT on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CLint, UGT in different tissues. Although BSA increased CLint, UGT in all tissues, the extent was tissue- and drug-dependent. Scaled CLint, UGT in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min−1 · g tissue−1 in liver, kidney, and intestinal microsomes. Renal CLint, UGT (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CLint, UGT for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CLint, UGT (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CLint, UGT is particularly important for UGT1A9 substrates. PMID:22275465

The impact of South Korea's new drug-pricing policy on market competition among off-patent drugs.

PubMed

Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R

2015-01-01

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

PubMed Central

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p<0.05) and ejection fraction (82%±3% vs 60%±5%, p<0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure. PMID:29081650

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.

PubMed

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p <0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p <0.05) and ejection fraction (82%±3% vs 60%±5%, p <0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure.

Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced impairment of memory via HPA axis deactivation and up-regulation of brain-derived neurotrophic factor gene expression.

PubMed

Wincewicz, D; Juchniewicz, A; Waszkiewicz, N; Braszko, J J

2016-09-01

Physical and psychological aspects of chronic stress continue to be a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. By the results of our previous work it has been demonstrated that telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates stress-induced cognitive decline. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the consequences of central AT1 blockade and PPARγ activation. Therefore, a critical need exists for progress in the characterization of this target for pro-cognitive drug discovery. An unusual ability of novel ARBs to exert various PPARγ binding activities is commonly being viewed as predominant over angiotensin blockade in terms of neuroprotection. Here we aimed to verify this hypothesis using an animal model of chronic psychological stress (Wistar rats restrained 2.5h daily for 21days) with simultaneous oral administration of TLM (1mg/kg), GW9662 - PPARγ receptor antagonist (0.5mg/kg), or both in combination, followed by a battery of behavioral tests (open field, elevated plus maze, inhibitory avoidance - IA, object recognition - OR), quantitative determination of serum corticosterone (CORT) and evaluation of brain-derived neurotrophic factor (BDNF) gene expression in the medial prefrontal cortex (mPFC) and hippocampus (HIP). Stressed animals displayed decreased recall of the IA behavior (p<0.001), decreased OR (p<0.001), substantial CORT increase (p<0.001) and significantly downregulated expression of BDNF in the mPFC (p<0.001), which were attenuated in rats receiving TLM and TLM+GW9662. These data indicate that procognitive effect of ARBs in stressed subjects do not result from PPAR-γ activation, but AT1 blockade and subsequent hypothalamus-pituitary-adrenal axis deactivation associated with changes in primarily cortical gene expression. This study confirms the dual activities of TLM that controls hypertension and cognition through AT1 blockade. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood pressure control status and associated factors among adult hypertensive patients on outpatient follow-up at University of Gondar Referral Hospital, northwest Ethiopia: a retrospective follow-up study

PubMed Central

Animut, Yaregal; Assefa, Alemu Takele; Lemma, Dereseh Gezie

2018-01-01

Background Large segments of the hypertensive population in the world are either untreated or inadequately treated. The incidence of heart failure and mortality from cardiovascular complications of hypertension is high among patients with uncontrolled blood pressure (BP). But BP control status of hypertensive patients has not been investigated in the study area. The study aimed to assess BP control status and determinant factors among adult hypertensive patients on antihypertensive medication attending outpatient follow-up at University of Gondar Referral Hospital, northwest Ethiopia. Methods An institution-based retrospective follow-up study was conducted from September 2015 to April 2016. Data were collected using a structured and pretested questionnaire adopted from the World Health Organization STEPwise approach. BP records of 6 months were used, and patients were classified as having controlled BP if their BP readings were <140/90 mmHg for all adults ≥18 years of age and <150/90 mmHg for adults aged ≥60 years. A generalized estimating equation was fitted, and the odds ratio with a 95% confidence level was used to determine the effect of covariates on BP control status. Results Among 395 participants, 50.4% (95% CI: 45–55) of them controlled their BP in the last 6 months of the survey. Physical activity (adjusted odds ratio [AOR]=1.95, 95% CI: 1.41–2.68), duration on antihypertensive drugs of 2–4 years (AOR=1.70, 95% CI: 1.13–2.56) and 5 years or more (AOR=1.96, 95% CI: 1.32–2.92), and high adherence (AOR=2.18, 95% CI: 1.14–4.15) to antihypertensive drugs were positively associated with BP control, while salt intake (AOR=0.67, 95% CI: 0.49–0.93), overweight (AOR=0.50, 95% CI: 0.36–0.68), and obesity (AOR=0.56, 95% CI: 0.36–0.87) were inversely associated with BP control. Conclusion In this study, only half of the hypertensive patients controlled their BP. Thus, health care providers need to be made aware about the importance of counseling hypertensive patients on drug adherence, moderate physical activity, and salt restriction to improve BP control. PMID:29720880

HYPERTENSION’S 3 DILEMMAS & 3 SOLUTIONS Pharmacology of the Kidney in Hypertension

PubMed Central

Pettinger, William

2017-01-01

SUMMARY The Hypertension Community has three conflicting dilemmas, a goal systolic pressure of 120 mmHg or less (The SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mmHg and our most potent antihypertensive drug minoxidil sits on the side-lines, imprisoned in the FDA’s Black Box Designation. My solutions to these dilemmas are: #1. Review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, #2. Treatment focus on the fundamental cause of High Blood Pressure, excess dietary sodium and, #3. Prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy. My focus at U.T. Southwestern in Dallas was on extremely severely hypertensive patients with a quantifiable, measurable complication of high blood pressure, progression of nephrosclerotic damage to kidneys. This model had the greatest likelihood of exposing fundamental dis-regulatory mechanisms in hypertensive patients (which it did) and the potential for study of the most relevant antihypertensive drug interactions to achieve optimal blood pressure control (which it did). By maintaining diastolic pressures at 80 mmHg or less in the first NIH supported, long term randomized clinical trial to save the kidneys, the bases for a fundamental blood pressure support mechanism (arteriolar hypertrophy) was illuminated but not fully described until now. This fundamental hypertensinogenic mechanism results from HBP but with time and severity, becomes its own raison d’être. I am now 84 years of age. As a result of a stroke 20 years ago which caused permanent double vision and because of poor blood pressure control with triple therapy I started using minoxidil 5 mg/day along with atenolol and occasional furosemide. Now, along with some dietary salt restriction, my resting blood pressure is 110/65–125/75 and, in spite of > 30 year history of HBP, I have no retinal arteriolar hypertrophy nor arcus senilis (Dr. Schwartz-U. of Miami) which is almost universally present at this age. YES, prevention of, or reversal of, arteriolar hypertrophy should be a central focus of HBP treatment. I simply wish to share a bit of accumulated wisdom that might be of use to others. PMID:28267687

Gender differences in hypertension awareness, antihypertensive use and blood pressure control in Bangladeshi adults: findings from a national cross-sectional survey.

PubMed

Rahman, Muntasirur; Williams, Gail; Al Mamun, Abdullah

2017-05-25

Bangladesh is facing an epidemiological transition with a growing burden of non-communicable diseases. Traditionally, hypertension and associated complications in women receive less recognition, and there is a dearth of related publications. The study aims to explore gender differences in high blood pressure awareness and antihypertensive use in Bangladeshi adults at the community level. Another objective is to identify factors associated with uncontrolled hypertension among antihypertensive users. Data from the Bangladesh Demographic and Health Survey (BDHS 2011) was analysed. From a nationally representative sample of 3870 males and 3955 females, aged ≥35 years, blood pressure and related information were collected following WHO guidelines. Logistic regression models were used to estimate adjusted odds ratio (AOR) for factors affecting blood pressure awareness, antihypertensive use and uncontrolled hypertension among males and females taking antihypertensive medications. All analyses were weighted according to the complex survey design. Women were more likely to have their blood pressure measured (76% vs. males 71%, p < 0.001) and to be 'aware' about their own high BP (55% vs. males 43%, p < 0.001). No gender difference was observed in antihypertensive medication use among those who were aware of their own high BP (females 67%, males 65%, p = 0.39). Non-working females were less likely to use antihypertensive (67% vs. non-working males 77%, p < 0.05). Poor women were worse off compared with poor males in antihypertensive medication use. One-in-three antihypertensive medication users had stage 2 hypertension (SBP ≥160/DBP ≥100 mmHg). Female sex, older age, increased wealth, higher BMI and certain geographical regions were associated with poor blood pressure control among antihypertensive medication users. BP check-ups and hypertension awareness were higher among women than men but did not translate into better antihypertensive medication practice. Gender disadvantage and inequity were observed in antihypertensive medication use. Our findings reiterate the importance of sex-disaggregated analysis and reporting. Policy makers should explore the uncontrolled hypertension burden and geographical variations in Bangladesh.

OTC analgesics and drug interactions: clinical implications

PubMed Central

Fendrick, A Mark; Pan, Deborah E; Johnson, Grace E

2008-01-01

The risk of drug interactions with concurrent use of multiple medications is a clinically relevant issue. Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. Of particular significance is the increased risk of upper abdominal gastrointestinal adverse events in patients who take traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is dose dependent and further increased in patients who take more than one NSAID or use NSAIDs in combination with certain other medications. Some NSAIDs may also mitigate the antiplatelet benefits of aspirin and may increase blood pressure in patients with hypertension. Clinicians should be aware of potential drug interactions with OTC analgesics when prescribing new medications. Additionally, patients should be properly counseled on the appropriate and safe use of OTC analgesics. PMID:18257920

[A case of loxoprofen-induced pulmonary eosinophilia].

PubMed

Ii, T; Doutsu, Y; Ashitani, J; Taniguchi, H; Mizuta, M; Toshimori, H; Matsukura, S

1992-05-01

A 65-year-old female suffering from lumbago, headache, and hypertension had been treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. On June 13, 1990, 2 weeks after the commencement of loxoprofen administration, she developed cough and low grade fever. She was treated with antibiotics and NSAIDs without improvement. Laboratory data showed marked eosinophilia (2200/mm3), elevation of IgE (3090 IU/ml), and liver dysfunction. Her chest X-ray revealed no active lesion, but the percentage of eosinophils in BALF was elevated (38%). Because drug-induced eosinophilic pneumonia was suspected, all drugs were discontinued. Her symptoms improved and the abnormalities of laboratory data normalized. The lymphocyte stimulation test was weakly positive with three NSAIDs (loxoprofen, pranoprofen, and alminoprofen). The challenge test by loxoprofen reproduced eosinophilia and liver dysfunction, suggesting that she had loxoprofen-induced eosinophilic pneumonia. To our knowledge, this is the first reported case of loxoprofen-induced lung injury.

Symmetrical drug-related intertriginous and flexural exanthema.

PubMed

Tan, Sze-Chin; Tan, Justina W-L

2011-08-01

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is a benign and self-limiting type IV hypersensitivity reaction characterized by symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. It may also occur in the absence of previous drug exposure. Antibiotics, in particular beta-lactams, comprise the majority of causes of SDRIFE. Other drugs which have been implicated include antihypertensives, radiocontrast media, chemotherapeutic agents, and biologics. Histology of lesional skin is variable with predominance of superficial perivascular inflammatory cell infiltrates. Outcomes of allergy tests are variable with positive delayed intradermal tests reported for penicillin V, allopurinol; positive patch tests for erythromycin, mitomycin, nystatin, pseudoephdrine; positive lymphocyte transformation tests for erythromycin; and positive drug provocation tests for clindamycin, cimetidine, corticosteroids, terbinafine, and valacyclovir. Diagnosis of SDRIFE is dependent upon recognition of the clinical morphology and distribution of the rash, and its temporal relationship to the use of the suspected drug. Outcomes of in-vivo and in-vitro tests have been inconsistent, and thus may not be useful in the identification of the putative drug.

Effectiveness of the selective aldosterone blocker, eplerenone, in patients with resistant hypertension.

PubMed

Calhoun, David A; White, William B

2008-01-01

Resistant hypertension is defined as uncontrolled hypertension despite intensive treatment with at least three antihypertensive agents, one of which ideally should be a diuretic. To determine the efficacy and safety of the selective aldosterone antagonist eplerenone in this population, we studied patients with resistant hypertension (clinic blood pressure [BP] >140 mm Hg systolic or >90 mm Hg diastolic on maximal doses of more than three antihypertensive agents, including a loop or thiazide diuretic). At baseline and after 12 weeks of eplerenone therapy (50 to 100 mg daily titrated to effect), patients underwent clinic and 24-hour BP measurements, serum potassium, plasma renin activity, and serum aldosterone measurements. Patients (n = 52) completing the trial averaged 62 +/- 10 years of age, were overweight (mean body mass index, 32.1 +/- 5.5 kg/m(2)), and had variable renal function (glomerular filtration rate, 106 +/- 38 mL/minute); 70% were men and 74% were non-Black. The mean number of antihypertensive agents at baseline was 3.7 +/- 0.8 (range, three to seven drugs) to achieve a clinic BP of 150.5/84.1 mm Hg. The mean serum aldosterone was 12.9 +/- 7.6 ng/mL and plasma renin activity was 2.3 +/- 2.7 ng/mL/hour. After eplerenone, the change from baseline in the clinic BP was -17.6/-7.9 mm Hg (P < .0001 for both systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and in 24-hour BP was -12.2/-6.0 mm Hg (P < .0001 for both). The number of antihypertensive drugs decreased to 3.3 +/- 0.9 (range, one to seven agents). Plasma potassium increased by 0.30 +/- 0.45 mEq/L (P < .001), but there were only three instances in two patients of mild hyperkalemia (potassium >5.5 mEq/L, but <6.0 mEq/L), despite all patients being on a background therapy that included an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Reductions in clinic and ambulatory BP were related to baseline clinic and ambulatory BP values (r(2) > 0.3 for both SBP and DBP, P < .0001), weakly related to baseline serum aldosterone (r = -0.30; P = .05), and unrelated to plasma renin activity, age, gender, or race. In conclusion, eplerenone demonstrated substantial efficacy in treatment-resistant hypertension and was well-tolerated with modest changes in plasma potassium. Serum aldosterone and plasma renin activity did not predict BP responses to eplerenone in this population.

Prescription patterns and adequacy of blood pressure control among adult hypertensive patients in Kenya; findings and implications.

PubMed

Mbui, Jennifer M; Oluka, Margaret N; Guantai, Eric M; Sinei, Kipruto A; Achieng, Loice; Baker, Amanj; Jande, Mary; Massele, Amos; Godman, Brian

2017-11-01

Hypertension is a major cause of global morbidity and mortality, with high prevalence rates in Africa including Kenya. Consequently, it is imperative to understand current treatment approaches and their effectiveness in practice. Currently, there is paucity of such data in Kenya, which is a concern. The aim is to describe prescribing patterns and adequacy of blood pressure (BP) control in adult hypertensive patients to guide future practice. Retrospective study of patients attending a sub-county outpatient clinic combined with qualitative interviews. 247 hypertensive patients, predominantly female, mean age 55.8 years on antihypertensive therapy for 1-5 years, were analyzed. ACEIs and thiazide diuretics were the most commonly prescribed drugs, mainly as combination therapy. Treatment typically complied with guidelines, mainly for stage 2 hypertension (75%). BP control was observed in 46% of patients, with a significant reduction in mean systolic (155 to 144 mmHg) and diastolic (91 to 83 mmHg) BP (P < 0.001). Patients on ≥2 antihypertensive drugs were more likely to have uncontrolled BP (OR:1.9, p = 0.021). Encouragingly good adherence to guidelines was helped by training. Poor blood pressure control in the majority needs to be addressed. Additional training of prescribers and follow-up of measures to improve BP control will be introduced and followed up.

Impact of aortic root size on left ventricular afterload and stroke volume.

PubMed

Sahlén, Anders; Hamid, Nadira; Amanullah, Mohammed Rizwan; Fam, Jiang Ming; Yeo, Khung Keong; Lau, Yee How; Lam, Carolyn S P; Ding, Zee Pin

2016-07-01

The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. We studied a large group of patients (n = 1250; 61 ± 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy.

Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition.

PubMed

Bhullar, Khushwant S; Lassalle-Claux, Grégoire; Touaibia, Mohamed; Rupasinghe, H P Vasantha

2014-05-05

Hypertension is a crucial risk factor for cardiovascular diseases and contributes to one third of global mortality. In addition to conventional antihypertensive drugs such as captopril, naturally occurring phytochemicals and their analogs are used for reducing the risk and occurrence of hypertension. Herein, we demonstrate the possible use of caffeic acid and its derivatives in the treatment of hypertension through multi-target modulation of renin-angiotensin-aldosterone system (RAAS). Caffeic acid along with its nineteen novel derivatives, chlorogenic acid, quercetin and captopril were all investigated for the inhibition of renin and angiotensin converting enzyme (ACE) activities and production of aldosterone. Compound 22 with CH2CH(Ph)2 moiety exhibited the strongest renin inhibition (IC50=229µM) among all compounds tested (P≤0.05). Caffeic acid was the weakest renin inhibitor (IC50=5704µM) among all the compounds assayed. Similar to renin inhibition, compound 22 (IC50=9.1µM) also exhibited about 47 times stronger ACE inhibition compared to the parent compound. Analysis of aldosterone revealed that compound 8 with n-Pr moiety was the strongest modulator of aldosterone production among all the derivatives (P≤0.05). Toxicity analysis using human fibroblasts (WI-38 cells) confirmed the non-toxic manifestations of caffeic acid and its derivatives in comparison to clinically used drug captopril. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial.

PubMed

Neri, Isabella; Jasonni, Valerio M; Gori, Gian Franco; Blasi, Immacolata; Facchinetti, Fabio

2006-05-01

To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p < 0.005; diastolic values F = 3.36; p < 0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p < 0.005) and diastolic (F = 2.20, p < 0.005) blood pressure values. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.

[C-reactive protein changes with antihypertensive and statin treatment].

PubMed

Rodilla, Enrique; Gómez-Belda, Ana; Costa, José A; Aragó, Miriam; Miralles, Amparo; González, Carmen; Pascual, José M

2005-10-29

The aim of this study was to evaluate the modifications of high sensitivity C-reactive protein (CRP) with antihypertensive and statin treatment in a hypertensive population with a wide range of coronary risks (CR). Retrospective follow-up study in 665 hypertensive patients: 556 (52% male) without dyslipidemia and CR (Framingham at 10 years) of 8.3 (7.6) as a control group (C) and 109 (61% male) with dyslipidemia and CR of 13.1 (8.8) who were treated with statins (T). Statins treatment was established according to NCEP-ATP-III. In both groups, the antihypertensive treatment was optimized in order to achieve blood pressure (BP) control (< 140/90 mmHg). A lipid profile and high sensitivity CRP (analyzed by nephelometry) was performed at the beginning and at the end of follow up [14.3 (3.6) months]. CRP levels were reduced in the T group -0.17 (0.2) mg/L vs. 0.14 (0.09) mg/L (p = 0.003, Mann-Whitney) in C. The lessening of CRP was not related to the reduction of lipids levels: total cholesterol (r = 0.06; p = 0.49), LDL-C (r = 0.11; p = 0.24), triglycerides (r = -0.02; p = 0.81) (Spearman), or to the reduction of systolic BP (r = -0.07; p = 0.44) and diastolic BP (r = -0.121; p = 0.21). The T group was treated with more antihypertensive drugs than C (2.2 [2.3] vs. 2.5 [1.2]; p = 0.02). Patients treated with ECA inhibitors or angiotensin II antagonist showed a tendency to decreasing the CRP levels more (p = 0.08). In hypertensive populations, statins induce a reduction of CRP levels. The reduction is not related to the lowering of lipids levels or BP values. The effect of statins on the reduction of CRP in hypertensive patients is not related to the lowering of lipids or BP.

The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

PubMed

Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

2015-01-01

Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n = 1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study groups showed distinct decreases in office BP at 4 week (p < 0.001) and the antihypertensive effects were sustained to 12 week (p < 0.001). The percentage of patients achieving BP < 140/90 mmHg was ∼70% in either group. Proteinuria and estimated glomerular filtration rate (eGFR) were significantly improved in hypertensive patients with baseline eGFR <60 ml/min/1.73 m(2). Serum uric acid was reduced either by adding AML or IRB, and the reductions were prominent in patients with serum uric acid >7 mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.

Association Between Academic Medical Center Pharmaceutical Detailing Policies and Physician Prescribing.

PubMed

Larkin, Ian; Ang, Desmond; Steinhart, Jonathan; Chao, Matthew; Patterson, Mark; Sah, Sunita; Wu, Tina; Schoenbaum, Michael; Hutchins, David; Brennan, Troyen; Loewenstein, George

2017-05-02

In an effort to regulate physician conflicts of interest, some US academic medical centers (AMCs) enacted policies restricting pharmaceutical representative sales visits to physicians (known as detailing) between 2006 and 2012. Little is known about the effect of these policies on physician prescribing. To analyze the association between detailing policies enacted at AMCs and physician prescribing of actively detailed and not detailed drugs. The study used a difference-in-differences multivariable regression analysis to compare changes in prescribing by physicians before and after implementation of detailing policies at AMCs in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) that made up the intervention group with changes in prescribing by a matched control group of similar physicians not subject to a detailing policy. Academic medical center implementation of policies regulating pharmaceutical salesperson visits to attending physicians. The monthly within-drug class market share of prescriptions written by an individual physician for detailed and nondetailed drugs in 8 drug classes (lipid-lowering drugs, gastroesophageal reflux disease drugs, diabetes drugs, antihypertensive drugs, hypnotic drugs approved for the treatment of insomnia [sleep aids], attention-deficit/hyperactivity disorder drugs, antidepressant drugs, and antipsychotic drugs) comparing the 10- to 36-month period before implementation of the detailing policies with the 12- to 36-month period after implementation, depending on data availability. The analysis included 16 121 483 prescriptions written between January 2006 and June 2012 by 2126 attending physicians at the 19 intervention group AMCs and by 24 593 matched control group physicians. The sample mean market share at the physician-drug-month level for detailed and nondetailed drugs prior to enactment of policies was 19.3% and 14.2%, respectively. Exposure to an AMC detailing policy was associated with a decrease in the market share of detailed drugs of 1.67 percentage points (95% CI, -2.18 to -1.18 percentage points; P < .001) and an increase in the market share of nondetailed drugs of 0.84 percentage points (95% CI, 0.54 to 1.14 percentage points; P < .001). Associations were statistically significant for 6 of 8 study drug classes for detailed drugs (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressant drugs) and for 9 of the 19 AMCs that implemented policies. Eleven of the 19 AMCs regulated salesperson gifts to physicians, restricted salesperson access to facilities, and incorporated explicit enforcement mechanisms. For 8 of these 11 AMCs, there was a significant change in prescribing. In contrast, there was a significant change at only 1 of 8 AMCs that did not enact policies in all 3 areas. Implementation of policies at AMCs that restricted pharmaceutical detailing between 2006 and 2012 was associated with modest but significant reductions in prescribing of detailed drugs across 6 of 8 major drug classes; however, changes were not seen in all of the AMCs that enacted policies.

Marketing research on the angiotensin-converting enzyme inhibitors antihypertensive medicines

PubMed Central

BOBOIA, ANAMARIA; GRIGORESCU, MARIUS RAREŞ; TURCU - ŞTIOLICĂ, ADINA

2017-01-01

Background and aims The research aimed at investigating sales trends of angiotensin-converting enzyme inhibitors antihypertensive medicines, both in terms of quantity and value, in ten community pharmacies, for a period of three years. The research on the antihypertensive medicines consumption is important for highlighting the ever increasing impact of hypertension among the population. Methods The methods used in this research were the following: marketing research, method of sampling, descriptive methods, retrospective analysis, method of comparison. Results The results showed that the drugs containing the active substances of the angiotensin converting enzyme inhibitors class had had significant increases in quantitative and value sales, bringing substantial revenues to pharmacies. From the quantitative perspective, the best-selling products were those containing Enalaprilum, while in terms of value, the best-selling medicines were those containing Perindoprilum. We evidenced that spectacular sales were also achieved for products that have Lisinoprilum, respectively Captoprilum, as active substances. The largest quantities were marketed for the Captopril Terapia® product and the highest earnings were recorded for the Prestarium® medicine. Conclusion This paper approaches an interesting and topical issue, which can be helpful to professionals (pharmacists, doctors) and other categories, such as economists, statisticians, representatives of companies manufacturing medicines, as well as to hypertensive patients, as it could be used to warn population regarding the incidence of cardiovascular diseases, and, at the same time, trace sales trends in order to accomplish profitable business plans. PMID:28246502

Status of lifestyle modifications in hypertension.

PubMed

Chhabra, M K; Lal, A; Sharma, K K

2001-09-01

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.

Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension.

PubMed

Boshra, Vivian; El Wakeel, Gehan Abdel Hamid; Nader, Manar A

2011-02-01

Certain nonsteroidal anti-inflammatory drugs have been reported to elevate blood pressure in some hypertensive patients, who are either untreated or treated with antihypertensive agents. This study was undertaken to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the antihypertensive effects of the angiotensin II type 1 receptor (AT1) antagonist, losartan potassium. We studied the effect of oral treatment with losartan (30 mg/kg), celecoxib (3 mg/kg), and their combination on the mean arterial blood pressure (MAP), plasma renin activity (PRA), and plasma prostaglandin E2 (PGE2) in male Sprague-Dawley rats with renovascular hypertension (RVH) induced by partial subdiaphragmatic aortic constriction. Treatment was continued for 7 days after aortic coarctation. Aortic coarctation led to significant increases in the MAP, PRA, and plasma PGE2. In RVH rats, losartan treatment caused a significant decrease of MAP with a significant increase in both plasma PGE2 and PRA. Celecoxib caused a nonsignificant change in MAP with a significant decrease in the raised levels of plasma PGE2 and PRA. Concomitant administration of celecoxib and losartan did not significantly affect the lowering effect of losartan on MAP with a subsequent significant decrease in the plasma PGE2 and PRA in RVH rats. Therefore, celecoxib could be used in renin-dependent hypertensive patients who receive losartan, without fear of a rise in their blood pressure.

[Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome].

PubMed

Machado, Hussen; Pinheiro, Helady Sanders; Terra, Marcella Martins; Guerra, Martha de Oliveira; de Paula, Rogerio Baumgratz; Peters, Vera Maria

2012-01-01

The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

Nitroglycerin hypotensive effect and application in a combined surgery for reconstruction after ipsilateral maxillectomy and orbit evisceration.

PubMed

Sun, Yuhang; Dong, Xiaohui; Zhang, Guofeng; An, Jing; Yuan, Haojun

2017-05-01

The oral and maxillofacial region is rich in blood, and it is often difficult to stop bleeding during the operation of maxilla. Nitroglycerin is one of the most commonly used antihypertensive drugs in our hospital. We observed the effect of controlled hypotension in patients with maxillary resection. In group N, the patients had different degrees of tachycardia after using nitroglycerin only. In addition, nitroglycerin has the characteristics of rapid drug resistance. A combined reversed temporal muscle flap and random forehead flap technique was performed successfully to reconstruct the large defect after ipsilateral maxillectomy and orbit evisceration. There were 43 cases used this method during 2014-2016 without large side effects.

Hypertensive Crisis and Left Ventricular Thrombi after an Upper Respiratory Infection during the Long-term Use of Oral Contraceptives.

PubMed

Suzuki, Natsuko; Suzuki, Keisuke; Mizuno, Tomofumi; Kato, Yukari; Suga, Norihiro; Yoshino, Masabumi; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

2016-01-01

A 34-year-old woman who had been using oral contraceptives for 10 years developed hypertensive crisis with papilloedema after an upper respiratory infection. Laboratory data showed hyperreninemic hyperaldosteronism and elevated levels of fibrinogen, fibrin, and fibrinogen degradation products. Echocardiography demonstrated two masses (18 mm) in the left ventricle. On the fourth hospital day, cerebral infarction, renal infarction, and upper mesenteric artery occlusion suddenly occurred despite the blood pressure being well-controlled using anti-hypertensive drugs. Echocardiography revealed the disappearance of the left ventricular masses, which suggested left ventricular thrombi. Cessation of the contraceptives and administration of heparin, warfarin, and anti-platelets drugs improved her general condition.

Application and validation of superior spectrophotometric methods for simultaneous determination of ternary mixture used for hypertension management.

PubMed

Mohamed, Heba M; Lamie, Nesrine T

2016-02-15

Telmisartan (TL), Hydrochlorothiazide (HZ) and Amlodipine besylate (AM) are co-formulated together for hypertension management. Three smart, specific and precise spectrophotometric methods were applied and validated for simultaneous determination of the three cited drugs. Method A is the ratio isoabsorptive point and ratio difference in subtracted spectra (RIDSS) which is based on dividing the ternary mixture of the studied drugs by the spectrum of AM to get the division spectrum, from which concentration of AM can be obtained by measuring the amplitude values in the plateau region at 360nm. Then the amplitude value of the plateau region was subtracted from the division spectrum and HZ concentration was obtained by measuring the difference in amplitude values at 278.5 and 306nm (corresponding to zero difference of TL) while the total concentration of HZ and TL in the mixture was measured at their isoabsorptive point in the division spectrum at 278.5nm (Aiso). TL concentration is then obtained by subtraction. Method B; double divisor ratio spectra derivative spectrophotometry (RS-DS) and method C; mean centering of ratio spectra (MCR) spectrophotometric methods. The proposed methods did not require any initial separation steps prior the analysis of the three drugs. A comparative study was done between the three methods regarding their; simplicity, sensitivity and limitations. Specificity was investigated by analyzing the synthetic mixtures containing different ratios of the three studied drugs and their tablets dosage form. Statistical comparison of the obtained results with those found by the official methods was done, differences were non-significant in regard to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for TL, HZ and AM. Copyright © 2015 Elsevier B.V. All rights reserved.

Application and validation of superior spectrophotometric methods for simultaneous determination of ternary mixture used for hypertension management

NASA Astrophysics Data System (ADS)

Mohamed, Heba M.; Lamie, Nesrine T.

2016-02-01

Telmisartan (TL), Hydrochlorothiazide (HZ) and Amlodipine besylate (AM) are co-formulated together for hypertension management. Three smart, specific and precise spectrophotometric methods were applied and validated for simultaneous determination of the three cited drugs. Method A is the ratio isoabsorptive point and ratio difference in subtracted spectra (RIDSS) which is based on dividing the ternary mixture of the studied drugs by the spectrum of AM to get the division spectrum, from which concentration of AM can be obtained by measuring the amplitude values in the plateau region at 360 nm. Then the amplitude value of the plateau region was subtracted from the division spectrum and HZ concentration was obtained by measuring the difference in amplitude values at 278.5 and 306 nm (corresponding to zero difference of TL) while the total concentration of HZ and TL in the mixture was measured at their isoabsorptive point in the division spectrum at 278.5 nm (Aiso). TL concentration is then obtained by subtraction. Method B; double divisor ratio spectra derivative spectrophotometry (RS-DS) and method C; mean centering of ratio spectra (MCR) spectrophotometric methods. The proposed methods did not require any initial separation steps prior the analysis of the three drugs. A comparative study was done between the three methods regarding their; simplicity, sensitivity and limitations. Specificity was investigated by analyzing the synthetic mixtures containing different ratios of the three studied drugs and their tablets dosage form. Statistical comparison of the obtained results with those found by the official methods was done, differences were non-significant in regard to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for TL, HZ and AM.

Controlled release of therapeutics using interpenetrating polymeric networks.

PubMed

Aminabhavi, Tejraj M; Nadagouda, Mallikarjuna N; More, Uttam A; Joshi, Shrinivas D; Kulkarni, Venkatrao H; Noolvi, Malleshappa N; Kulkarni, Padmakar V

2015-04-01

The ever-increasing developments in pharmaceutical formulations have led to the widespread use of biodegradable polymers in various forms and configurations. In particular, interpenetrating network (IPN) and semi-IPN polymer structures that are capable of releasing drugs in a controlled manner have gained much wider importance in recent years. Recently, IPNs and semi-IPNs have emerged as innovative materials of choice in controlled release (CR) of drugs as the release from these systems depends on pH of the media and temperature in addition to the nature of the system. These networks can be prepared as smart hydrogels following chemical or physical crosslinking methods to show remarkable drug release patterns compared to single polymer systems. A large number of IPNs and semi-IPNs have been reported in the literature. The present review is focused on the preparation methods and their CR properties with reference to anticancer, anti-asthmatic, antibiotic, anti-inflammatory, anti-tuberculosis and antihypertensive drugs, as majority of these drugs have been reported to be the ideal choices for using IPNs and semi-IPNs.

Control of Drug Dissolution Rate from Film Dosage Forms Containing Valsartan.

PubMed

Murata, Yoshifumi; Kofuji, Kyoko; Maida, Chieko

2016-01-01

Film dosage forms (FDs) containing valsartan (VST), a popular antihypertensive drug, were prepared using a casting method with sodium alginate and other polysaccharides as the film base. Drug dissolution profiles of the FDs were investigated in limited medium. The FDs were 170-200 μm thick and were easy to handle. All FDs immediately swelled and disintegrated in the medium. About 23% of the VST incorporated into the FD prepared with 1.5% sodium alginate dissolved at 5 min. The initial dissolution rate of VST increased upon the addition of chitosan to the film base; this effect was not observed in the case of chitin. On the other hand, the rate apparently decreased upon modification with alginic acid. In addition, the solubility of VST in the dissolution medium was changed by the addition of chitosan or alginic acid. FDs prepared with polysaccharides are useful for simplifying the administration of drugs to patients, and the drug dissolution rate from FDs can be controlled by modification.

Characteristics and Factors Associated With Antihypertensive Medication Use in Patients Attending Peruvian Health Facilities

PubMed Central

Mejia, Christian R; Failoc-Rojas, Virgilio E; Cervantes, Carmen; Aspajo, Antonio J; Leandro, Jesus Galileo; Cordova-De La Cruz, Jhomar; Charri, Julio C; García-Auqui, Kevin E; Coronel-Chucos, Lelis Gabriela; Justo-Pinto, Luz Delia; Mamani-Apaza, Marisol Stefanie; Paz-Campos, Neil Arón; Correa, Ricardo

2017-01-01

Introduction  Hypertension is a very common disease worldwide, and medication is needed to prevent its short-term and long-term complications. Our objective was to determine the characteristics and factors associated with antihypertensive medication use in patients attending Peruvian health facilities. Materials & Methods We performed a multicenter, cross-sectional study with secondary data. We obtained self-reported antihypertensive medication from patients attending health facilities in 10 departments of Peru. We looked for associations of the antihypertensive treatment according to sociopathological factors and obtained p values using generalized linear models. Results Of the 894 patients with hypertension, 61% (547) were women and 60% (503) were on antihypertensive treatment, of which 82% (389) had monotherapy and 52% (258) had recently taken their medication. Antihypertensive treatment was positively correlated with the patient's age (adjusted prevalence ratio [aPR]: 1.01; 95% confidence interval [CI]: 1.007 to 1.017; p value < 0.001), diabetes (aPR: 1.31; 95% CI: 1.11 to 1.55; p value = 0.001) and cardiovascular disease (aPR: 1.38; 95% CI: 1.26 to 1.51; p value < 0.001). Conversely, the frequency of antihypertensive treatment decreases with physical activity (aPR: 0.80; 95% CI: 0.70 to 0.92; p value = 0.001). Conclusion Patients who have comorbidities and advanced age are more likely to be on antihypertensive treatment. In contrast, patients with increased physical activity have a lower frequency of antihypertensive treatment. It is important to consider these factors for future preventive programs and to improve therapeutic compliance. PMID:28331773

Use of antihypertensive medications and diagnostic tests among privately insured adolescents and young adults with primary versus secondary hypertension.

PubMed

Yoon, Esther Y; Cohn, Lisa; Freed, Gary; Rocchini, Albert; Kershaw, David; Ascione, Frank; Clark, Sarah

2014-07-01

To compare the use of antihypertensive medications and diagnostic tests among adolescents and young adults with primary versus secondary hypertension. We conducted retrospective cohort analysis of claims data for adolescents and young adults (12-21 years of age) with ≥3 years of insurance coverage (≥11 months/year) in a large private managed care plan during 2003-2009 with diagnosis of primary hypertension or secondary hypertension. We examined their use of antihypertensive medications and identified demographic characteristics and the presence of obesity-related comorbidities. For the subset receiving antihypertensive medications, we examined their diagnostic test use (echocardiograms, renal ultrasounds, and electrocardiograms). The study sample included 1,232 adolescents and young adults; 84% had primary hypertension and 16% had secondary hypertension. The overall prevalence rate of hypertension was 2.6%. One quarter (28%) with primary hypertension had one or more antihypertensive medications, whereas 65% with secondary hypertension had one or more antihypertensive medications. Leading prescribers of antihypertensives for subjects with primary hypertension were primary care physicians (80%), whereas antihypertensive medications were equally prescribed by primary care physicians (43%) and sub-specialists (37%) for subjects with secondary hypertension. The predominant hypertension diagnosis among adolescents and young adults is primary hypertension. Antihypertensive medication use was higher among those with secondary hypertension compared with those with primary hypertension. Further study is needed to determine treatment effectiveness and patient outcomes associated with differential treatment patterns used for adolescents and young adults with primary versus secondary hypertension. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Characteristics and Factors Associated With Antihypertensive Medication Use in Patients Attending Peruvian Health Facilities.

PubMed

Mejia, Christian R; Failoc-Rojas, Virgilio E; So, Edison; Cervantes, Carmen; Aspajo, Antonio J; Leandro, Jesus Galileo; Cordova-De La Cruz, Jhomar; Charri, Julio C; García-Auqui, Kevin E; Coronel-Chucos, Lelis Gabriela; Justo-Pinto, Luz Delia; Mamani-Apaza, Marisol Stefanie; Paz-Campos, Neil Arón; Correa, Ricardo

2017-02-03

Hypertension is a very common disease worldwide, and medication is needed to prevent its short-term and long-term complications. Our objective was to determine the characteristics and factors associated with antihypertensive medication use in patients attending Peruvian health facilities. We performed a multicenter, cross-sectional study with secondary data. We obtained self-reported antihypertensive medication from patients attending health facilities in 10 departments of Peru. We looked for associations of the antihypertensive treatment according to sociopathological factors and obtained p values using generalized linear models. Of the 894 patients with hypertension, 61% (547) were women and 60% (503) were on antihypertensive treatment, of which 82% (389) had monotherapy and 52% (258) had recently taken their medication. Antihypertensive treatment was positively correlated with the patient's age (adjusted prevalence ratio [aPR]: 1.01; 95% confidence interval [CI]: 1.007 to 1.017; p value < 0.001), diabetes (aPR: 1.31; 95% CI: 1.11 to 1.55; p value = 0.001) and cardiovascular disease (aPR: 1.38; 95% CI: 1.26 to 1.51; p value < 0.001). Conversely, the frequency of antihypertensive treatment decreases with physical activity (aPR: 0.80; 95% CI: 0.70 to 0.92; p value = 0.001). Patients who have comorbidities and advanced age are more likely to be on antihypertensive treatment. In contrast, patients with increased physical activity have a lower frequency of antihypertensive treatment. It is important to consider these factors for future preventive programs and to improve therapeutic compliance.

Drug-nutrient interaction counseling programs in upper midwestern hospitals: 1986 survey results.

PubMed

Jones, C M; Reddick, J E

1989-02-01

A mail survey was conducted to determine the characteristics of drug-nutrient counseling programs provided to hospitalized patients. The survey population included general medical-surgical type hospitals with 175 or more bed capacity in five upper Midwestern states: Illinois, Iowa, Michigan, Minnesota, and Wisconsin. The average return from 289 surveys was 75%. A mean of 64% of responding hospitals provide patient counseling on drug-nutrient interactions. All statistical analysis was by chi-square. Calculations revealed that less than 50% of hospitals require a physician's order to provide drug-nutrient interaction counseling. More than 50% involve a registered dietitian in providing such counseling. The monoamine oxidase inhibitor drugs were cited most frequently as the group of drugs for which counseling was needed. Other drug groups for which patient counseling is needed include: diuretics, anticoagulants, tetracyclines, oral hypoglycemics, insulin, antihypertensives and/or cardiac drugs, antibiotics, and corticosteroids. Having the dietitian or other dietary personnel scan the patient chart was cited most often as the preferred method for detection of patients taking the drugs. A final statistical calculation revealed that there is no difference between teaching and nonteaching hospitals in the number providing a drug-nutrient counseling program.

Inpatient falls in older adults: a cohort study of antihypertensive prescribing pre- and post-fall.

PubMed

Omer, H M R B; Hodson, J; Pontefract, S K; Martin, U

2018-02-23

Falls are common during hospital admissions and may occur more frequently in patients who are taking antihypertensive medications, particularly in the context of normal to low blood pressure. The review and adjustment of these medications is an essential aspect of the post-fall assessment and should take place as soon as possible after the fall. Our aim was to investigate whether appropriate post-fall adjustments of antihypertensive medications are routinely made in a large National Health Service (NHS) Trust. Inpatient records over an eight-month period were captured from an electronic prescribing system to identify older adults (≥80 years old) with normal/low blood pressures (< 140 mmHg systolic) who had a documented inpatient fall as these patients were considered to be at high risk of further falls. Prescribed antihypertensive medication on admission was then compared with the post-fall (within 24 h after the fall) and discharge prescriptions. A total of 146 patients were included in the analysis. Of those, 120 patients (82%) were taking the same number of antihypertensive medications in the 24 h after the fall as they were before; only 19 patients (13%) had a reduction in the number of medications and seven patients (5%) had an increase in medications during that period. Only 9% of the antihypertensive classes assessed were either stopped or reduced in dose immediately post-fall. In addition, 11 new antihypertensives were prescribed at this time. At discharge, half of the patients (n = 73) remained on the same number of antihypertensive medication as on admission, 51 patients (35%) were on fewer antihypertensives and 22 (15%) were on more. Additionally, no changes were made to individual antihypertensives in 49% of prescriptions; 34% were stopped or reduced in dose but 38 new agents were started by the time of discharge. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (ACEi/ARB) were the class of medications most commonly stopped or reduced (51%). Antihypertensive prescriptions are frequently unchanged after an inpatient fall. Routine medication review needs to be part of post-fall assessments in hospital to reduce the risk of further falls.

Combined effect of polarity and pH on the chromatographic behavior of some angiotensin II receptor antagonists and optimization of their determination in pharmaceutical dosage forms.

PubMed

Demiralay, Ebru Cubuk; Cubuk, Burcu; Ozkan, Sibel A; Alsancak, Guleren

2010-11-02

In the present study, the combined effect of mobile phase polarity and pH on retention behavior of some ARA-IIs (irbesartan, losartan, valsartan and telmisartan) is investigated. The linear relationships established between retention factors of the species and the polarity parameter of the mobile phase has proved to predict accurately retention in LC as a function of the acetonitrile content (50%, 55%, 60%, v/v). The suggested model uses the pH value in the acetonitrile-water mixture as mobile phase instead of pH value in water and takes into account the effect of activity coefficients. Moreover, correlation between retention and the mobile phase pH can be established allowing prediction of the retention behavior as a function of the mobile phase pH. The model can be used to estimate the pKa in an acetonitrile percentage between 50% and 60%, at 30 degrees C. The developed method was successfully applied to both the simultaneous separation of these drug-active compounds and individual determination in their commercial pharmaceutical dosage forms.