Diuretics: a review.

PubMed

Wile, David

2012-09-01

Diuretics, in one form or another, have been around for centuries and this review sets out to chart their development and clinical use. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. The different classes of diuretics are characterized, along with their mode of action. The clinical use of diuretics in conditions like congestive cardiac failure and hypertension, as well as some rarer, but clinically important, conditions is then examined. An account is given of the adverse effects of diuretics and how they come about. Common adverse effects like hypokalaemia and hyponatraemia are examined in some detail, and other electrolyte disturbances like hypomagnesaemia also gain a mention. Diuretic use in chronic kidney disease is examined and new guidelines that have been introduced are presented. A section on diuretic abuse is included as this is becoming an all too common clinical scenario, and the sometimes tragic consequences of this abuse are emphasized. Diuretics also find a role in the diagnosis of forms of renal tubular acidosis and this role is explored. Finally, a selection of some of the newer approaches to diuretic therapy are presented, often the consequence of the increasing development of molecular biology, and some of the novel compounds - which may be in drug formularies of the future - are revealed.

Outcome of renal transplantation with and without intra-operative diuretics.

PubMed

Hanif, F; Macrae, A N; Littlejohn, M G; Clancy, M J; Murio, E

2011-01-01

This paper presents an e-survey of current clinical practice of use of intra-operative diuretics during renal transplantation in the United Kingdom and a study to compare outcome of renal transplants carried out with or without intra-operative diuretics in our centre. An e-mail questionnaire to renal transplant surgeons exploring their practice of renal transplantation with or without intra-operative diuretics, the type of a diuretic/s if used and the relevant doses. An observational study comparing the outcome of renal transplant recipients, group no-diuretics (GND, n = 80) carried out from 2004 to 2008 versus group diuretics (GD n = 69) renal transplant recipients who received intra-operative diuretics over a one year period is presented. Outcome measures were incidence of delayed graft function and a comparison of graft survival in both groups. Forty surgeons answered from 18 transplant centres with a response rate of 67%. 13 surgeons do not use diuretics. Mannitol is used by 10/40, Furosemide 6/40 and 11 surgeons use a combination of both. In comparative study there was no significant overall difference in one year graft survival of GD versus GND (N = 65/69, 94% and 75/80, 94% respectively, p = 0.08) and the incidence of delayed graft function was also comparable (16/69, 23% and 21/80, 26% respectively, p = 0.07). The donor characteristics in both groups were comparable. The study showed variation in clinical practice on the use of intra-operative diuretics in renal transplantation and it did not demonstrate that the use of diuretics can improve renal graft survival. Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Diuretic exposure in premature infants from 1997–2011

PubMed Central

Laughon, Matthew M.; Chantala, Kim; Aliaga, Sofia; Herring, Amy H.; Hornik, Christoph P.; Hughes, Rachel; Clark, Reese H.; Smith, P. Brian

2014-01-01

Objective Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia (BPD). We examined their use and safety in this group. Study Design Retrospective cohort study of infants <32 weeks gestation and <1500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997–2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and FiO2 on the first day of each course of diuretic use were identified. Results Thirty-seven percent (39,357/107,542) of infants were exposed to at least 1 diuretic; furosemide was the most commonly used (93% with ≥1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. Seventy-four percent were exposed to 1 diuretic at a time, 19% to 2 diuretics simultaneously, and 6% to 3 diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1000 infant-days for any diuretic and 35 per 1000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia. Conclusion Despite no FDA indication and little safety data, over one third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support. PMID:24801161

Effectiveness of patiromer in the treatment of hyperkalemia in chronic kidney disease patients with hypertension on diuretics

PubMed Central

Weir, Matthew R.; Mayo, Martha R.; Garza, Dahlia; Arthur, Susan A.; Berman, Lance; Bushinsky, David; Wilson, Daniel J.; Epstein, Murray

2017-01-01

Objective: Recurrent hyperkalemia frequently limits use of renin–angiotensin–aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD) patients with hypertension, diabetes, and/or heart failure. Patiromer is a sodium-free, nonabsorbed potassium (K+)-binding polymer approved by the US Food and Drug Administration for the treatment of hyperkalemia. This post-hoc analysis of OPAL-HK examined the effectiveness and safety of patiromer in reducing serum K+ in hyperkalemic CKD patients on RAASi, with hypertension, receiving diuretic therapy versus those not on diuretics. Methods: Depending on the degree of hyperkalemia at baseline, CKD patients with serum K+ from 5.1 to less than 6.5 mmol/l on RAASi (n = 243) were assigned to a patiromer of total dose 8.4 or 16.8 g, divided twice daily. Changes in serum K+, and tolerability and safety were assessed over 4 weeks in patients on and not on diuretics. Results: At baseline, 132 patients used diuretics and 111 were not on diuretics, mean age was 64.3 and 64.0 years, respectively, and 63 and 51% were men. Similar reductions in serum K+ were seen over 4 weeks in both subgroups. At week 4, serum K+ fell by −0.95 ± 0.04 mmol/l with any diuretic and −1.04 ± 0.05 mmol/l with no diuretic. Patiromer was well tolerated, with mild-to-moderate constipation reported as the most common adverse event (7.6 and 14.4% of patients on any diuretic or no diuretic, respectively). Hypokalemia (s-K+ <3.5 mEq/l) was reported in 2.3% of patients on any diuretic and in 3.7% not on diuretics. Conclusion: The serum K+-lowering efficacy and safety profile of patiromer in hyperkalemia patients with CKD was not compromised by diuretic therapy. PMID:28129247

Effectiveness of patiromer in the treatment of hyperkalemia in chronic kidney disease patients with hypertension on diuretics.

PubMed

Weir, Matthew R; Mayo, Martha R; Garza, Dahlia; Arthur, Susan A; Berman, Lance; Bushinsky, David; Wilson, Daniel J; Epstein, Murray

2017-05-01

Recurrent hyperkalemia frequently limits use of renin-angiotensin-aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD) patients with hypertension, diabetes, and/or heart failure. Patiromer is a sodium-free, nonabsorbed potassium (K)-binding polymer approved by the US Food and Drug Administration for the treatment of hyperkalemia. This post-hoc analysis of OPAL-HK examined the effectiveness and safety of patiromer in reducing serum K in hyperkalemic CKD patients on RAASi, with hypertension, receiving diuretic therapy versus those not on diuretics. Depending on the degree of hyperkalemia at baseline, CKD patients with serum K from 5.1 to less than 6.5 mmol/l on RAASi (n = 243) were assigned to a patiromer of total dose 8.4 or 16.8 g, divided twice daily. Changes in serum K, and tolerability and safety were assessed over 4 weeks in patients on and not on diuretics. At baseline, 132 patients used diuretics and 111 were not on diuretics, mean age was 64.3 and 64.0 years, respectively, and 63 and 51% were men. Similar reductions in serum K were seen over 4 weeks in both subgroups. At week 4, serum K fell by -0.95 ± 0.04 mmol/l with any diuretic and -1.04 ± 0.05 mmol/l with no diuretic. Patiromer was well tolerated, with mild-to-moderate constipation reported as the most common adverse event (7.6 and 14.4% of patients on any diuretic or no diuretic, respectively). Hypokalemia (s-K <3.5 mEq/l) was reported in 2.3% of patients on any diuretic and in 3.7% not on diuretics. The serum K-lowering efficacy and safety profile of patiromer in hyperkalemia patients with CKD was not compromised by diuretic therapy.

Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics.

PubMed

Lim, Lee Moay; Tsai, Ni-Chin; Lin, Ming-Yen; Hwang, Daw-Yang; Lin, Hugo You-Hsien; Lee, Jia-Jung; Hwang, Shang-Jyh; Hung, Chi-Chih; Chen, Hung-Chun

2016-11-14

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13-1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics.

Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics

PubMed Central

Lim, Lee Moay; Tsai, Ni-Chin; Lin, Ming-Yen; Hwang, Daw-Yang; Lin, Hugo You-Hsien; Lee, Jia-Jung; Hwang, Shang-Jyh; Hung, Chi-Chih; Chen, Hung-Chun

2016-01-01

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13–1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics. PMID:27841359

Loop Diuretics in the Treatment of Hypertension.

PubMed

Malha, Line; Mann, Samuel J

2016-04-01

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

Diuretic use, RAAS blockade and morbidity in elderly patients presenting to the Emergency Department with non-specific complaints.

PubMed

Ruedinger, Juliane M; Nickel, Christian H; Maile, Silke; Bodmer, Michael; Kressig, Reto W; Bingisser, Roland

2012-05-09

Up to 20% of elderly patients present to the emergency department (ED) with non-specific complaints (NSC), such as "generalised weakness", the majority suffering from serious conditions requiring timely intervention. Little is known about the use and influence of diuretics and renin-angiotensin-aldosterone (RAAS) blockade on morbidity in those patients. The hypothesis was tested that the use of diuretics and RAAS blockade could be associated with an increased incidence of serious conditions in those patients. During a 23-month period, all adult non-trauma patients with an Emergency Severity Index (ESI) of 2 or 3 were prospectively enrolled. Serious conditions were defined as potentially life-threatening conditions or conditions requiring early intervention to prevent further morbidity and mortality. Study population consisted of 633 patients with median age 82 years, median Charlson comorbidity index 2. 59% of all subjects suffered from a serious condition. 299 subjects (47.2%) used diuretics, of which 65.6% suffered from a serious condition. Combination therapy of RAAS blockade and diuretics was found in 158 subjects (24.9%), 70.3% of which suffered from a serious condition. The intake of two or more diuretics, loop diuretics and a combination therapy with diuretics and RAAS blockade were associated with an increased risk for serious condition (p = 0.036; p = 0.021; p = 0.004). Treatment with two or more diuretics, loop diuretics, or a combination therapy with RAAS blockade and diuretics are independently associated with serious condition and therefore should be recognized as "red flags" in elderly patients presenting to the ED with NSC.

Use of diuretics during pregnancy

PubMed Central

Al-Balas, Mosa’b; Bozzo, Pina; Einarson, Adrienne

2009-01-01

ABSTRACT QUESTION Several of my pregnant patients use diuretics for hypertension. I have heard that diuretics cannot be used in pregnancy because of the reduction of plasma volume and the potential for decreasing placental perfusion, as well as a possible diabetogenic effect. ANSWER Many studies—including a meta-analysis of almost 7000 neonates exposed to diuretics during pregnancy—did not find an increased risk of adverse effects, such as birth defects, fetal growth restriction, thrombocytopenia, or diabetes, among neonates exposed to diuretics in utero. PMID:19155365

Diuretics in heart failure: practical considerations.

PubMed

Basraon, Jagroop; Deedwani, Prakash C

2012-09-01

This review discusses the role of diuretics in heart failure by focusing on different classifications and mechanisms of action. Pharmacodynamic and pharmacokinetic properties of diuretics are elucidated. The predominant discussion highlights the use of loop diuretics, which are the most commonly used drugs in heart failure. Different methods of using this therapy in different settings along with a comprehensive review of the side-effect profile are highlighted. Special situations necessitating adjustment and the phenomenon of diuretic resistance are explained. Copyright © 2012. Published by Elsevier Inc.

[Diuretics in acute kidney failure: useful or harmful?].

PubMed

Tataw, J; Saudan, P

2011-03-02

Loop diuretics are commonly prescribed within different clinical settings to prevent and or to treat acute renal failure. In most cases they facilitate fluid management following an increased urine output. Experimental models in animals revealed protective effects of loop diuretics in acute renal failure. Several clinical trials have failed to outline better outcomes associated with the use of diuretics in acute renal failure as there was no recovery in renal function nor a reduction in the number of dialysis sessions required. Glomerular filtration rate did not improve with the administration of loop diuretics after continuous renal replacement therapy. The administration of loop diuretics in the management of acute renal failure should be mainly restricted to patients with hypervolemia.

Diuretic downsides--but in low doses they still seem among the best authenticated antihypertensives.

PubMed

Opie, L H

2000-08-01

Diuretics in low doses have the greatest support among current available antihypertensives in that they have been shown to reduce total mortality, coronary mortality, stroke, and congestive heart failure in an important meta-analysis by Psaty. Recently, Messerli has linked longterm diuretic use to renal cell carcinoma in women. In some patients, diuretic use leads to increasing blood cholesterol and blood sugar levels. Impotence is a recognized side effect, with rates rising about twofold with low-dose chlorthalidone and fourfold with a higher dose. Certain population groups such as younger (<60 years) white males often do not respond to low-dose diuretic therapy with an adequate blood pressure fall. In females of a similar age group, Messerli calculates that prolonged diuretic therapy will prevent only one stroke and no coronary events nor any deaths for every renal cell carcinoma that is provoked. Despite these evident problems, the outcome data on hard endpoints in trials with initial low-dose diuretic therapy remain valid and convincing. Thus, it is argued, low- but not high-dose diuretics retain their primacy in the ranking of antihypertensive therapy.

Study of Acute Kidney Injury on 309 Hypertensive Inpatients with ACEI/ARB - Diuretic Treatment.

PubMed

Chen, Qiaochao; Zhu, Shaofang; Liao, Jianjun; He, Wen

2018-06-01

The present study investigated risk factors for acute kidney injury (AKI) in patients found to be hypertensive during hospitalization who were prescribed angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists (ARB) + diuretic combinations, in order to determine which type of diuretic or combination of diuretics used in ACE/ARB-treated patients leads to a higher risk of acute kidney injury. Data on basic information, medical history, diagnostic information and medications prescribed were obtained from the patients' medical records. Retrospective analysis of potential risk factors and ACEI/ARB + diuretic use with AKI was performed. Multivariate analysis showed initial risk factors for AKI to be chronic kidney disease and poor cardiac function. In univariate analysis, patients whose baseline serum creatinine was between 115 and 265 μmol/L also had a higher risk of AKI. The combination of furosemide and spironolactone produced only approximately a third of the risk of AKI as the combination of hydrochlorothiazide and spironolactone. Chronic kidney disease and poor cardiac function are major risk factors for AKI in hypertensive inpatients using ACEI/ARB + diuretic therapy. The combination of thiazide diuretic and aldosterone antagonist had a higher risk of AKI than other single diuretics or diuretic combinations. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Prescription patterns of diuretics in Dutch community-dwelling elderly patients

PubMed Central

Van Kraaij, Dave J W; Jansen, René W M M; De Gier, Johan J; Gribnau, Frank W J; Hoefnagels, Willibrord H L

1998-01-01

Aims To describe age-and gender-related prescription patterns of diuretics in community-dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications. Methods Cross-sectional study of patient-specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of proportional prescription rates and prescribed daily dose (PDD) of diuretics, cardiac glycosides, nitrates, angiotensin converting enzyme (ACE) inhibitors, β-adrenoceptor blockers, and calcium channel blockers in all 5326 patients aged 65 years or older dispensed CV medications between August 1st, 1995 and February 1st, 1996. Results Diuretics were prescribed to 2677 of 5326 patients (50.3%), 1325 patients (24.9%) using thiazides and 1198 patients (22.5%) using loop diuretics. Prescription rates of loop diuretics increased from 15.1% in patients aged 65–74 years to 37.2% in patients aged 85 years or older. Rates also increased for digoxin and nitrates. Rates for thiazide diuretics remained unchanged with age; rates for β-adrenoceptor blockers, ACE inhibitors and calcium channel blockers declined with age. Thiazides were prescribed to 30.1% of women compared with 16% of men (P<0.001). Average PDD was 135±117% of defined daily dose (DDD) for loop diuretics, and highest for bumetanide (245±2.01% of DDD, equivalent to 2.5±2.0 mg). Average PDD was 74±40% of DDD for thiazides, and highest for chlorthalidone (100±49% of DDD, equivalent to 25±12 mg). Conclusions Important characteristics of diuretic usage patterns in this elderly population were a steep increase in loop diuretic use in the oldest old, a large gender difference for thiazide use, and high prescribed doses for thiazides. PMID:9803990

Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure.

PubMed

Trullàs, Joan Carles; Morales-Rull, José Luís; Casado, Jesús; Freitas Ramírez, Adriana; Manzano, Luís; Formiga, Francesc

2016-07-01

Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance. CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed. CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

PubMed

Pellicori, Pierpaolo; Cleland, John G F; Zhang, Jufen; Kallvikbacka-Bennett, Anna; Urbinati, Alessia; Shah, Parin; Kazmi, Syed; Clark, Andrew L

2016-12-01

Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

Diuretics and salt transport along the nephron.

PubMed

Bernstein, Paul L; Ellison, David H

2011-11-01

The clinical use of diuretics almost uniformly predated the localization of their site of action. The consequence of diuretic specificity predicts clinical application and side effect, and the proximity of the sodium transporters, one to the next, often dictates potency or diuretic efficiency. All diuretics function by inhibiting the normal transport of sodium from the filtrate into the renal tubular cells. This movement of sodium into the renal epithelial cells on the apical side is facilitated by a series of transporters whose function is, in turn, dependent on the adenosine triphosphate (ATP)-dependent Na-K cotransporter on the basolateral side of the cell. Our growing understanding of the physiology of sodium transport has spawned new possibilities for diuretic development. Copyright © 2011 Elsevier Inc. All rights reserved.

[Diuretics in heart failure and Karl Popper's turkey].

PubMed

Cice, Gennaro

2015-12-01

Heart failure and renal failure often coexist in the same patient. This condition is commonly referred to as cardiorenal syndrome. When this occurs, patient survival worsens significantly with increasing degree of renal dysfunction. Management of this complex patient poses treatment challenges because of unstable hemodynamics (the problem is to reduce congestion without affecting organ perfusion) and very high mid-term in-hospital mortality. Congestion is a typical feature of this syndrome, and use of diuretics is mandatory. Loop diuretics should be administered first. However, poor attention to pharmacodynamic and pharmacokinetic properties of loop diuretics may contribute to the development of diuretic resistance leading to iatrogenic hyponatremia. Accordingly, emphasis is given to the importance of sequential nephron blockade to reduce the number of non-responder patients to diuretics and to recognize a possible role for acquaretics.

Diuretics and disorders of calcium homeostasis.

PubMed

Grieff, Marvin; Bushinsky, David A

2011-11-01

Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Diuretics for heart failure.

PubMed

Faris, Rajaa F; Flather, Marcus; Purcell, Henry; Poole-Wilson, Philip A; Coats, Andrew J S

2012-02-15

Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. To assess the harms and benefits of diuretics for chronic heart failure Updated searches were run in the Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL Issue 1 of 4, 2011), MEDLINE (1966 to 22 February 2011), EMBASE (1980 to 2011 Week 07) and HERDIN database (1990 to February 2011). We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. No language restrictions were applied. Double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure. Two authors independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. This update has not identified any new studies for inclusion. The review includes 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.

Diuretics: a review and update.

PubMed

Roush, George C; Kaur, Ramdeep; Ernst, Michael E

2014-01-01

Diuretics have been recommended as first-line treatment of hypertension and are also valuable in the management of hypervolemia and electrolyte disorders. This review summarizes the key features of the most commonly used diuretics. We then provide an update of clinical trials for diuretics during the past 5 years. Compared to other classes of medications, thiazide diuretics are at least as effective in reducing cardiovascular events (CVEs) in patients with hypertension and are more effective than β-blockers and angiotensin-converting enzyme inhibitors in reducing stroke. Observational cohort data and a network analysis have shown that CVEs are lowered by one-fifth from chlorthalidone when compared to the commonly used thiazide, hydrochlorothiazide. Relative to placebo, chlorthalidone increases life expectancy. In those aged 80 years and older, the diuretic, indapamide, lowers CVEs relative to placebo. The aldosterone antagonist, eplerenone, lowers total mortality in early congestive heart failure. The benefit of eplerenone following acute myocardial infarction (MI) is limited to administration within 3 to 6 days post-MI. Aldosterone antagonists have been shown to lower the incidence of sudden cardiac death and to reduce proteinuria. In the setting of heart failure, long acting loop diuretics azosemide and torasemide are more effective in improving heart failure outcomes than the far more commonly used short acting furosemide. Evening dosing of diuretics appears to lower CVEs relative to morning dosing. In conclusion, diuretics are a diverse class of drugs that remain extremely important in the management of hypertension and hypervolemic states.

Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study.

PubMed

Blaisdell, Carol J; Troendle, James; Zajicek, Anne

2018-06-01

To determine if daily respiratory status improved more in extremely low gestational age (GA) premature infants after diuretic exposure compared with those not exposed in modern neonatal intensive care units. The Prematurity and Respiratory Outcomes Program (PROP) was a multicenter observational cohort study of 835 extremely premature infants, GAs of 23 0/7 -28 6/7 weeks, enrolled in the first week of life from 13 US tertiary neonatal intensive care units. We analyzed the PROP study daily medication and respiratory support records of infants ≤34 weeks postmenstrual age. We determined whether there was a temporal association between the administration of diuretics and an acute change in respiratory status in premature infants in the neonatal intensive care unit, using an ordered categorical ranking of respiratory status. Infants in the diuretic exposed group of PROP were of lower mean GA and lower mean birth weight (P < .0001). Compared with infants unexposed to diuretics, the probability (adjusted for infant characteristics including GA, birth weight, sex, and respiratory status before receiving diuretics) that the exposed infants were on a higher level of respiratory support was significantly greater (OR, >1) for each day after the initial day of diuretic exposure. Our analysis did not support the ability of diuretics to substantially improve the extremely premature infant's respiratory status. Further study of both safety and efficacy of diuretics in this setting are warranted. Clinicaltrials.gov: NCT01435187. Published by Elsevier Inc.

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.

[Mechanism of the diuretic effect of eufillin].

PubMed

Kantariia, V A; Lebedev, A A

1975-01-01

In acute experiments on rats the xanthine diuretic euphylline did not block the short-circuited current in the proximal tubule, nor did it lower the transtubular potential and the transepithelial resistance of the nephron wall. The diuretic speeded up significantly the passage of the tubular fluid along the proximal region of the nephron and Henle's loop. The dihydroergotoxin and inderal blocking of adrenoreceptors did not produce any influence on the renal effects of the xanthine agent. Reserpine totally blocked the diuretic and saluretic effects of euphylline, whereas other sympatholytics, such as alpha-methyl-dofa, anthabus and hemedin, did not modify the action of the diuretic.

Decongestion: Diuretics and other therapies for hospitalized heart failure

PubMed Central

Vazir, Ali; Cowie, Martin R.

2016-01-01

Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Often the syndrome is characterized by congestion, and is associated with long hospital admissions and high risk of readmission and further healthcare expenditure. Despite a limited evidence-base, diuretics remain the first-line treatment for congestion. Loop diuretics are typically the first-line diuretic strategy with some evidence that initial treatment with continuous infusion or boluses of high-dose loop diuretic is superior to an initial lower dose strategy. In patients who have impaired responsiveness to diuretics, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. The use of intravenous low-dose dopamine is no longer supported in heart failure patients with preserved systolic blood pressure and its use to assist diuresis in patients with low systolic blood pressures requires further study. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence-base is not robust, and its place in clinical practice is yet to be established. Several novel pharmacological agents remain under investigation. PMID:27056656

The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis

PubMed Central

Cadwallader, Amy B; de la Torre, Xavier; Tieri, Alessandra; Botrè, Francesco

2010-01-01

Diuretics are drugs that increase the rate of urine flow and sodium excretion to adjust the volume and composition of body fluids. There are several major categories of this drug class and the compounds vary greatly in structure, physicochemical properties, effects on urinary composition and renal haemodynamics, and site and mechanism of action. Diuretics are often abused by athletes to excrete water for rapid weight loss and to mask the presence of other banned substances. Because of their abuse by athletes, diuretics have been included on The World Anti-Doping Agency's (WADA) list of prohibited substances; the use of diuretics is banned both in competition and out of competition and diuretics are routinely screened for by anti-doping laboratories. This review provides an overview of the pharmacology and toxicology of diuretics and discusses their application in sports. The most common analytical strategies currently followed by the anti-doping laboratories accredited by the WADA are discussed along with the challenges laboratories face for the analysis of this diverse class of drugs. PMID:20718736

[The use of diuretics in kidney disease].

PubMed

Heramb, Lene; Hallan, Stein; Aasarød, Knut

2014-04-29

Diuretics are an important part of the therapy for a number of medical conditions such as heart, liver and kidney failure and hypertension. This article presents updated knowledge on the use of diuretics in kidney disease. The article is based on a literature search in PubMed, information obtained from textbooks on neurophysiology and kidney disease and on the authors' clinical experience. Kidney disease affects the pharmacokinetics and pharmacodynamics of diuretics, and this must be taken into account when selecting a drug and determining the dosage. This applies particularly to nephrotic syndrome and severe chronic renal disease (GFR < 30 ml/min/1.73 m²). Knowledge of the pharmacology of diuretics is crucial to the rational use of diuretics in renal disease. Dose titration under close clinical monitoring and an optimal dosage interval make it possible to find the lowest possible effective dose and reduce the occurrence of side effects.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Improving blood pressure control: increase the dose of diuretic or switch to a fixed-dose angiotensin receptor blocker/diuretic? the valsartan hydrochlorothiazide diuretic for initial control and titration to achieve optimal therapeutic effect (Val-DICTATE) trial.

PubMed

White, William B; Calhoun, David A; Samuel, Rita; Taylor, Addison A; Zappe, Dion H; Purkayastha, Das

2008-06-01

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.

Unexpected Extra-renal Effects of Loop Diuretics in the Preterm Neonate

PubMed Central

Cotton, Robert; Suarez, Sandra; Reese, Jeff

2012-01-01

The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, due to its actions on the ubiquitous NKCC1 co-transporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus, and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through the inhibitory neurotransmitter, GABA. Conclusion The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents since the range of their effects may be broader than the single action sought by the prescribing physician. PMID:22536874

Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

PubMed

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2016-01-01

Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

Acute Pharmacodynamic Effects of Empagliflozin With and Without Diuretic Agents in Patients With Type 2 Diabetes Mellitus.

PubMed

Heise, Tim; Jordan, Jens; Wanner, Christoph; Heer, Martina; Macha, Sreeraj; Mattheus, Michaela; Lund, Søren S; Woerle, Hans J; Broedl, Uli C

2016-10-01

The goal of this study was to investigate the pharmacodynamic effects of co-administration of empagliflozin, a sodium glucose cotransporter 2 inhibitor, with diuretic agents. In a randomized, open-label cross-over study, 22 patients with type 2 diabetes mellitus received empagliflozin 25 mg for 5 days and either hydrochlorothiazide 25 mg for 4 days followed by hydrochlorothiazide 25 mg plus empagliflozin 25 mg for 5 days, or torasemide 5 mg for 4 days followed by torasemide 5 mg plus empagliflozin 25 mg for 5 days; 20 completed treatment. Food, fluid, and sodium intake were standardized for 3 days before and during treatment. At baseline, the median age of the treated patients was 56 years (range, 40-65 years), body mass index was 26.8 kg/m 2 (range, 20.1-34.4 kg/m 2 ), fasting plasma glucose was 8.6 mmol/L (range, 6.0-12.9 mmol/L), and glycosylated hemoglobin level was 7.6% (range, 7%-10%). Empagliflozin significantly increased 24-hour urinary glucose excretion and reduced fasting serum glucose levels. These effects were maintained after co-administration with either diuretic. Urinary sodium excretion did not significantly change with empagliflozin or diuretic administration alone, but seemed to increase compared with either diuretic alone when empagliflozin was co-administered with either diuretic. Plasma renin and serum aldosterone levels were unaltered with empagliflozin or torasemide alone, but tended to increase with hydrochlorothiazide alone, and tended to increase when empagliflozin was co-administered with a diuretic compared with either diuretic alone. Urinary volume did not increase with empagliflozin or diuretics alone, but increased when empagliflozin was co-administered with either diuretic. Empagliflozin alone for 5 days increased urinary glucose excretion but did not seem to have a relevant impact on urine volume or electrolytes. When empagliflozin was co-administered with a diuretic agent, urinary glucose excretion remained increased, and the renin-angiotensin system was activated. Clinicaltrials.gov identifier: NCT01276288. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

PubMed Central

Olesen, Charlotte; de Vries, Corinne S; Thrane, Nana; MacDonald, Tom M; Larsen, Helle; Sørensen, Henrik Toft

2001-01-01

Aims The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. Results Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. Conclusions Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings. PMID:11259987

In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure: Insights From the EVEREST Trial.

PubMed

Mecklai, Alicia; Subačius, Haris; Konstam, Marvin A; Gheorghiade, Mihai; Butler, Javed; Ambrosy, Andrew P; Katz, Stuart D

2016-07-01

The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. In univariate analysis, subjects exposed to high-dose diuretic agents (≥160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Are diuretics harmful in the management of acute kidney injury?

PubMed

Ejaz, A Ahsan; Mohandas, Rajesh

2014-03-01

To assess the role of diuretics in acute kidney injury (AKI) and their effectiveness in preventing AKI, achieving fluid balance, and decreasing progression to chronic kidney disease (CKD). Diuretics are associated with increased risk for AKI. The theoretical advantage of diuretic-induced preservation of renal medullary oxygenation to prevent AKI has not been proven. A higher cumulative diuretic dose during the dialysis period can cause hypotension and increase mortality in a dose-dependent manner. Data on the use of forced euvolemic diuresis to prevent AKI remains controversial. Positive fluid balance has emerged as an independent predictor of adverse outcomes. Post-AKI furosemide dose had a favorable effect on mortality due in part to the reduction of positive fluid balance. There are exciting experimental data suggesting that spironolactone may prevent AKI once an ischemic insult has occurred and thus prevent the progression to CKD. Diuretics are ineffective and even detrimental in the prevention and treatment of AKI, and neither shorten the duration of AKI, nor reduce the need for renal replacement therapy. Diuretics have an important role in volume management in AKI, but they are not recommended for the prevention of AKI. There is increased emphasis on the prevention of progression of AKI to CKD.

Herbal diuretics in medieval Persian and Arabic medicine.

PubMed

Shoja, Mohammadali M; Tubbs, R Shane; Bosmia, Anand N; Fakhree, Mohammad A A; Jouyban, Abolghasem; Balch, Margaret Wood; Loukas, Marios; Khodadoust, Kazem; Khalili, Majid; Eknoyan, Garabed

2015-06-01

In accord with the notions of humoralism that prevailed in medieval medicine, therapeutic interventions, including diuretics, were used to restore the disturbed balance among the four humors of the human body: blood, phlegm, yellow bile, and black bile. Most diuretics were derived from plants. The primary textual reference on herbal diuretics was Dioscorides's De Materia Medica, which was written during the first century CE. The authors reviewed the medieval medical texts written in Persian and Arabic and compiled a list of 135 herbal diuretics used by the medieval medical authorities for treating various ailments. Between the 8th and 11th centuries CE, Middle Eastern physicians systematically reviewed extant books on medicine and pharmacotherapy and compiled new and expanded lists of herbal medicines, diuretics in particular. Furthermore, they introduced new chemical methods of extraction, distillation, and compounding in the use of herbal medicines. Several herbal remedies now are considered as potentially safe and affordable alternatives to chemical pharmaceuticals. Thus, research on medieval herbal therapies may prove to be relevant to the practice of current cardiovascular and renal pharmacotherapy. The authors propose that modern research methods can be employed to determine which of these agents actually are effective as diuretics.

Decongestion: Diuretics and other therapies for hospitalized heart failure.

PubMed

Vazir, Ali; Cowie, Martin R

2016-04-01

Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Often the syndrome is characterized by congestion, and is associated with long hospital admissions and high risk of readmission and further healthcare expenditure. Despite a limited evidence-base, diuretics remain the first-line treatment for congestion. Loop diuretics are typically the first-line diuretic strategy with some evidence that initial treatment with continuous infusion or boluses of high-dose loop diuretic is superior to an initial lower dose strategy. In patients who have impaired responsiveness to diuretics, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. The use of intravenous low-dose dopamine is no longer supported in heart failure patients with preserved systolic blood pressure and its use to assist diuresis in patients with low systolic blood pressures requires further study. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence-base is not robust, and its place in clinical practice is yet to be established. Several novel pharmacological agents remain under investigation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study.

PubMed

McAdams-DeMarco, Mara A; Maynard, Janet W; Baer, Alan N; Kao, Linda W; Kottgen, Anna; Coresh, Josef

2013-05-01

To test for a urate gene-by-diuretic interaction on incident gout. The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

Comparison of thiazide-like diuretics versus thiazide-type diuretics: a meta-analysis.

PubMed

Liang, Wenjing; Ma, Hui; Cao, Luxi; Yan, Wenjiang; Yang, Jingjing

2017-11-01

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide-type diuretics hydrochlorothiazide and thiazide-like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta-analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta-analysis of blood pressure reduction, thiazide-like diuretics seemed to further reduce systolic BP ([95% CI]; -5.59 [-5.69, -5.49]; P < 0.001) and diastolic BP ([95% CI]; -1.98 [-3.29, -0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; -0.14 [-0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [-0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [-0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide-like diuretics is superior to thiazide-type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Efficacy and safety assessment of isolated ultrafiltration compared to intravenous diuretics for acutely decompensated heart failure: a systematic review with meta-analysis.

PubMed

De Vecchis, R; Esposito, C; Ariano, C

2014-04-01

Intravenous diuretics at relatively high doses are currently used for treating acute decompensated heart failure (ADHF). However, the existence of harmful side effects diuretic-related, such as electrolyte abnormalities, symptomatic hypotension and marked neuro-hormonal activation have led researchers to implement alternative therapeutic tools such as isolated ultrafiltration (IUF). Our study aimed to compare intravenous diuretics vs. IUF as regards their respective efficacy and safety in ADHF patients through systematic review and meta-analysis of data derived from relevant randomized controlled trials. 6 studies grouping a total of 477 patients were included in the systematic review. By contrast, data from only three studies were pooled for the meta-analysis, because of different adopted outcomes or marked dissimilarities in the data presentation . Weight loss at 48 h was greater in IUF group compared to the diuretics group [weighted mean difference (WMD)=1.77 kg; 95%CI: 1.18-2.36 kg; P<0.001)]. Similarly, greater fluid loss at 48 h was found in IUF group in comparison with diuretics group (WMD=1.2 liters; 95%CI: 0.73-1.67 liters; P< 0.001). In contrast, the probability of exhibiting worsening renal function (WRF), i.e., increase in serum creatinine > 0.3 mg/dl at 48 hours, was similar to the one found in the diuretics group (OR=1.33; 95% CI: 0.81-2.16 P=0.26). On the basis of this meta-analysis, IUF induced greater weight loss and larger fluid removal compared to iv diuretics in ADHF patients, whereas the probability of developing WRF was not significantly different in the comparison between iv diuretics and IUF.

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study

PubMed Central

McAdams-DeMarco, Mara A; Maynard, Janet W; Baer, Alan N; Kao, Linda W; Kottgen, Anna; Coresh, Josef

2015-01-01

Objective To test for a urate gene-by-diuretic interaction on incident gout. Methods The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987–1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use. PMID:22753387

Thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus.

PubMed

Singh, Prince; Knoedler, John J; Krambeck, Amy E; Lieske, John C; Bergstralh, Eric J; Rule, Andrew D

2014-12-01

Thiazide diuretics used to treat hypertension are associated with a modest risk of diabetes mellitus. It is unknown if there is a similar risk with kidney stone prevention. We identified and validated incident stone formers in Olmsted County, Minnesota from 1984 to 2011 with manual review of medical records using the Rochester Epidemiology Project. The risk of diabetes mellitus after thiazide therapy was evaluated with and without multivariate adjustment for hypertension, age, gender, race, family history of stones, body mass index and number of stone events. Among 2,350 incident stone formers with a median followup of 10 years, 332 (14%) were treated with thiazide diuretics at some point after the first stone event and 84 (3.6%) received the thiazide diuretic only for kidney stone prevention. Stone formers who received thiazide diuretics were more likely to be older, have hypertension, have higher body mass index and have more stone events. The incidence of diabetes mellitus at 10 years after the first stone event was 9.2% in the group that received thiazide diuretics vs 4.2% in those who did not (HR 2.91; 95% CI 2.02, 4.20). After multivariate adjustment the risk of diabetes mellitus was attenuated (HR 1.20; 95% CI 0.78, 1.83). The risk of diabetes mellitus among those receiving thiazide diuretics solely for kidney stones was further attenuated (multivariate adjusted HR 0.80; 95% CI 0.28, 2.23). Thiazide diuretic use for kidney stone prophylaxis was not associated with a high risk of diabetes mellitus. Larger studies are needed to determine if there is a modest risk of diabetes mellitus with thiazide diuretics. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials.

PubMed

Kiernan, Michael S; Stevens, Susanna R; Tang, W H Wilson; Butler, Javed; Anstrom, Kevin J; Birati, Edo Y; Grodin, Justin L; Gupta, Divya; Margulies, Kenneth B; LaRue, Shane; Dávila-Román, Victor G; Hernandez, Adrian F; de Las Fuentes, Lisa

2018-03-01

Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240-11775) with median furosemide dose of 320 mg (220-480) compared with 8030 ml (6300-9915) and 840 mg (600-1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24-0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Diuretics on Urinary Excretion of Cephalothin in Humans

PubMed Central

Tice, Alan D.; Barza, Michael; Bergeron, Michel G.; Brusch, John L.; Weinstein, Louis

1975-01-01

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide. PMID:1137368

Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

PubMed Central

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2016-01-01

Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Results Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. Conclusions The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient. PMID:27442587

Use of Diuretics in the Treatment of Heart Failure in Older Adults.

PubMed

Sica, Domenic A; Gehr, Todd W B; Frishman, William H

2017-07-01

Diuretics are the most commonly prescribed class of drugs in patients with heart failure, and in the short term they remain the most effective treatment for relief from fluid congestion. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow and sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly. In addition, the article reviews the common side effects related to diuretics. Copyright © 2017 Elsevier Inc. All rights reserved.

[All diuretics used in the treatment of hypertension are not the same].

PubMed

Asil, Serkan; Atalar, Enver

2017-01-01

Diuretics have been used for years to treat hypertension as both a monotherapy and in combination. Hydrochlorothiazide, indapamide, and chlorthalidone have frequently been considered in the same category as thiazide diuretics, but there is no evidence that their activities are similar. Studies have shown that chlorthalidone and indapamide reduce cardiovascular morbidity and mortality; however, there is no study indicating that hydrochlorothiazide has beneficial effects on cardiovascular outcomes such as myocardial infarction, renal failure, stroke, or death. Hydrochlorothiazide has less effect on blood pressure, a high risk of metabolic side effects, and may not have pleiotropic effects. As a result, it is not accurate to evaluate chlorthalidone and indapamide as similar to thiazide diuretics. Indapamide or chlorthalidone is a better choice of diuretic for use in the treatment of hypertension.

Unexpected extra-renal effects of loop diuretics in the preterm neonate.

PubMed

Cotton, Robert; Suarez, Sandra; Reese, Jeff

2012-08-01

The loop diuretics furosemide and bumetanide are commonly used in neonatal intensive care units (NICUs). Furosemide, because of its actions on the ubiquitous Na(+) -K(+) -2Cl(-) isoform cotransporter and its promotion of prostanoid production and release, also has non-diuretic effects on vascular smooth muscle, airways, the ductus arteriosus and theoretically the gastrointestinal tract. Loop diuretics also affect the central nervous system through modulation of the GABA-A chloride channel.   The loop diuretics have a variety of biological effects that are potentially harmful as well as beneficial. Care should be taken with the use of these agents because the range of their effects may be broader than the single action sought by the prescribing physician. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Effects of diuretics on urinary proteins.

PubMed

Li, Xundou

2015-01-01

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. The human orthologs of most of these 14 proteins affected are stable in the healthy human urinary proteome, and 10 of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

Effect of combined treatment with diuretics and gabapentin on convulsive threshold in mice.

PubMed

Łukawski, Krzysztof; Swiderska, Grajyna; Czuczwar, Stanisław J

2013-01-01

Research data show that diuretics can have anticonvulsant properties. This study examined effects of ethacrynic acid, a loop diuretic, and hydrochlorothiazide, a thiazide-type diuretic, on the anticonvulsant activity of gabapentin, a newer antiepileptic drug, in the maximal electroshock seizure threshold test in mice. Diuretics were administered intraperitoneally (ip.) both acutely (single dose) and chronically (once daily for seven days). Electroconvulsions were produced by an alternating current (50 Hz, 500 V, 0.2 s stimulus duration) delivered via ear-clip electrodes by a generator. Additionally, the influence of combined treatment with the diuretics and gabapentin on motor performance in the chimney test has been assessed. In the current study, ethacrynic acid at the chronic dose of 12.5 mg/kg and the single dose of 100 mg/kg did not affect the anticonvulsant activity of gabapentin. Similarly, hydrochlorothiazide (100 mg/kg), both in acute and chronic experiments, had no effect on the gabapentin action. On the other hand, in the chimney test, the combined treatment with ethacrynic acid (100 mg/kg) and gabapentin (50 mg/kg) significantly impaired motor performance in mice. Based on the current preclinical findings, it can be suggested that the diuretics should not affect the anticonvulsant action of gabapentin in epileptic patients. However, the combination of ethacrynic acid with gabapentin may cause neurotoxicity.

Plasma potassium, diuretic use and risk of developing chronic kidney disease in a predominantly White population

PubMed Central

Eisenga, Michele F.; Joosten, Michel M.; de Boer, Rudolf A.; Gansevoort, Ron T.; Kootstra-Ros, Jenny E.; Navis, Gerjan; Bakker, Stephan J. L.

2017-01-01

Objective Both hypokalemia and hyperkalemia are associated with disease progression in patients with chronic kidney disease (CKD). It is unclear whether similar associations are present in the general population. Our aim was to examine the association of plasma potassium with risk of developing CKD and the role of diuretics in this association in a population-based cohort. Research design and methods We studied 5,130 subjects free of CKD at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women aged 28–75 years. Hypokalemia was defined as plasma potassium <3.5 mmol/L, and hyperkalemia as plasma potassium ≥5.0 mmol/L. Risk of CKD was defined as de novo development of eGFR <60 ml/min/1.73m2 and/or albuminuria >30 mg/24h. Results Mean baseline plasma potassium was 4.4±0.3 mmol/L. The prevalences of hypokalemia and hyperkalemia were 0.5% and 3.8%, respectively; 3.0% of the subjects used diuretics. During a median follow-up of 10.3 years (interquartile range: 6.3–11.4 years), 753 subjects developed CKD. The potassium-CKD association was modified by diuretic use (Pinteraction = 0.02). Both hypokalemia without (HR, 7.74, 95% CI, 3.43–17.48) or with diuretic use (HR, 4.32, 95% CI, 1.77–10.51) were associated with an increased CKD risk as compared to plasma potassium 4.0–4.4 mmol/L without diuretic use. Plasma potassium concentrations ≥3.5 mmol/L were associated with an increased CKD risk among subjects using diuretics (Ptrend = 0.01) but not among subjects not using diuretics (Ptrend = 0.74). Conclusion In this population-based cohort, hypokalemia was associated with an increased CKD risk, regardless of diuretic use. In the absence of hypokalemia, plasma potassium was not associated with an increased CKD risk, except among subjects using diuretics. PMID:28346526

Diuretics, calciuria and secondary hyperparathyroidism in the Chronic Renal Insufficiency Cohort.

PubMed

Isakova, Tamara; Anderson, Cheryl A M; Leonard, Mary B; Xie, Dawei; Gutiérrez, Orlando M; Rosen, Leigh K; Theurer, Jacquie; Bellovich, Keith; Steigerwalt, Susan P; Tang, Ignatius; Anderson, Amanda Hyre; Townsend, Raymond R; He, Jiang; Feldman, Harold I; Wolf, Myles

2011-04-01

Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD) that is associated with bone disease, cardiovascular disease and death. Pathophysiological factors that maintain secondary hyperparathyroidism in advanced CKD are well-known, but early mechanisms of the disease that can be targeted for its primary prevention are poorly understood. Diuretics are widely used to control volume status and blood pressure in CKD patients but are also known to have important effects on renal calcium handling, which we hypothesized could alter the risk of secondary hyperparathyroidism. We examined the relationship of diuretic treatment with urinary calcium excretion, parathyroid hormone (PTH) levels and prevalence of secondary hyperparathyroidism (PTH ≥ 65 pg/mL) in a cross-sectional study of 3616 CKD patients in the Chronic Renal Insufficiency Cohort. Compared with no diuretics, treatment with loop diuretics was independently associated with higher adjusted urinary calcium (55.0 versus 39.6 mg/day; P < 0.001), higher adjusted PTH [67.9, 95% confidence interval (CI) 65.2-70.7 pg/mL, versus 52.8, 95% CI 51.1-54.6 pg/mL, P < 0.001] and greater odds of secondary hyperparathyroidism (odds ratio 2.1; 95% CI 1.7-2.6). Thiazide monotherapy was associated with lower calciuria (25.5 versus 39.6 mg/day; P < 0.001) but only modestly lower PTH levels (50.0, 95% CI 47.8-52.3, versus 520.8, 95% CI 51.1-54.6 pg/mL, P = 0.04) compared with no diuretics. However, coadministration of thiazide and loop diuretics was associated with blunted urinary calcium (30.3 versus 55.0 mg/day; P <0.001) and odds of hyperparathyroidism (odds ratio 1.3 versus 2.1; P for interaction = 0.05) compared with loop diuretics alone. Loop diuretic use was associated with greater calciuria, PTH levels and odds of secondary hyperparathyroidism compared to no treatment. These associations were attenuated in patients who were coadministered thiazides. Diuretic choice is a potentially modifiable determinant of secondary hyperparathyroidism in CKD.

Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study.

PubMed

Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

2015-01-01

Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients.

Diuretics, calciuria and secondary hyperparathyroidism in the Chronic Renal Insufficiency Cohort

PubMed Central

Isakova, Tamara; Anderson, Cheryl A. M.; Leonard, Mary B.; Xie, Dawei; Gutiérrez, Orlando M.; Rosen, Leigh K.; Theurer, Jacquie; Bellovich, Keith; Steigerwalt, Susan P.; Tang, Ignatius; Anderson, Amanda Hyre; Townsend, Raymond R.; He, Jiang; Feldman, Harold I.; Wolf, Myles

2011-01-01

Background. Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD) that is associated with bone disease, cardiovascular disease and death. Pathophysiological factors that maintain secondary hyperparathyroidism in advanced CKD are well-known, but early mechanisms of the disease that can be targeted for its primary prevention are poorly understood. Diuretics are widely used to control volume status and blood pressure in CKD patients but are also known to have important effects on renal calcium handling, which we hypothesized could alter the risk of secondary hyperparathyroidism. Methods. We examined the relationship of diuretic treatment with urinary calcium excretion, parathyroid hormone (PTH) levels and prevalence of secondary hyperparathyroidism (PTH ≥ 65 pg/mL) in a cross-sectional study of 3616 CKD patients in the Chronic Renal Insufficiency Cohort. Results. Compared with no diuretics, treatment with loop diuretics was independently associated with higher adjusted urinary calcium (55.0 versus 39.6 mg/day; P < 0.001), higher adjusted PTH [67.9, 95% confidence interval (CI) 65.2–70.7 pg/mL, versus 52.8, 95% CI 51.1–54.6 pg/mL, P < 0.001] and greater odds of secondary hyperparathyroidism (odds ratio 2.1; 95% CI 1.7–2.6). Thiazide monotherapy was associated with lower calciuria (25.5 versus 39.6 mg/day; P < 0.001) but only modestly lower PTH levels (50.0, 95% CI 47.8–52.3, versus 520.8, 95% CI 51.1–54.6 pg/mL, P = 0.04) compared with no diuretics. However, coadministration of thiazide and loop diuretics was associated with blunted urinary calcium (30.3 versus 55.0 mg/day; P <0.001) and odds of hyperparathyroidism (odds ratio 1.3 versus 2.1; P for interaction = 0.05) compared with loop diuretics alone. Conclusions. Loop diuretic use was associated with greater calciuria, PTH levels and odds of secondary hyperparathyroidism compared to no treatment. These associations were attenuated in patients who were coadministered thiazides. Diuretic choice is a potentially modifiable determinant of secondary hyperparathyroidism in CKD. PMID:21382989

Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study

PubMed Central

Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

2015-01-01

Background and Objectives Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. Design, Setting, Participants, and Measurements This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. Results There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Conclusions Prescription of diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients. PMID:26146836

Diuretics, first-line antihypertensive agents: are they always safe in the elderly?

PubMed

Diaconu, Camelia C; Balaceanu, Alice; Bartos, Daniela

2014-01-01

Diuretics are frequently recommended as antihypertensive agents. Some of the main side effects of diuretic therapy are hypokalaemia and hyponatremia. The objective of the study was to describe the frequency of hyponatremia in a group of elderly hypertensive patients treated with diuretics. The study included 202 elderly hypertensive patients (over 65 years old), treated with diuretics at least 4 weeks before hospitalization, consecutivly admitted in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest during a period of 4 months. The distribution by sex: 103 (52.28%) men and 94 (47.71%) women. The mean age of the patients was 72 ± 8 years. Incidence of hyponatremia was 24.87% (49 patients) in the whole group. From the 49 hyponatremic patients, 31 (63.26%) were women and 18 (36.73%) men. The distribution by age of hypertensive hyponatremic female patients was: between 65-70 years old--4 patients (12.90%), between 70-75 years old--7 patients (22.58%), over 75 years old--20 patients (64.51%). The distribution by age of hypertensive hyponatremic male patients was: between 65-70 years old--3 patients (16.66%), between 70-75 years old--2 patients(11.11%), over 75 years old--13 patients (72.22%). Most of the patients affected (73.46%) used a thiazide-type diuretic, the other 26.54% being on loop diuretics. Elderly hypertensive patients were more likely to develop hyponatremia after age 75. Female patients had a higher frequency of hyponatremia than male patients. The main cause of hyponatremia in patients treated with diuretics was thiazide.

Serum potassium level and dietary potassium intake as risk factors for stroke.

PubMed

Green, D M; Ropper, A H; Kronmal, R A; Psaty, B M; Burke, G L

2002-08-13

Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

PubMed

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-05-01

Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

PubMed Central

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-01-01

Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.

PubMed

Mizuochi, Tatsuki; Suda, Kenji; Seki, Yoshitaka; Yanagi, Tadahiro; Yoshimoto, Hironaga; Kudo, Yoshiyuki; Iemura, Motofumi; Tanikawa, Ken; Matsuishi, Toyojiro

2015-04-01

There are few reports on successful high-dose spironolactone treatment of refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first-line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome. © 2015 Japan Pediatric Society.

Diuretic Activity of Ethanolic Root Extract of Mimosa Pudica in Albino Rats

PubMed Central

SL, Shruthi; PS, Vaibhavi; VH, Pushpa; AM, Satish; Sibgatullah, Mohammad

2015-01-01

Introducation Diuretics are the drugs which increase the urine output. This property is useful in various pathological conditions of fluid overload. The presently available diuretics have lot of adverse effects. Our study has evaluated the diuretic activity of ethanolic root extract of Mimosa pudica as an alternative/new drug which may induce diuresis. Aim To evaluate the diuretic activity of ethanolic root extract of Mimosa pudicaa in albino rats. Materials and Methods Ethanolic root extract of Mimosa pudica (EEMP) was prepared using soxhlet’s apparatus. Albino rats were divided into 5 groups of 6 rats each. Group-I (Control) received distilled water 25ml/kg orally. Group-II (Standard) received Furosemide 20mg/kg orally. Group-III received EEMP 100 mg/kg, Group-IV received EEMP 200 mg/kg and Group-V received EEMP 400 mg/kg. The urine samples were collected for all the groups upto 5 hours after dosing and urine volume was measured. Urine was analysed for electrolytes (Na+, K+ and Cl-). ANOVA, Dunnet’s test and p-values were measured and data was analysed. Results EEMP exhibited significant diuretic activity by increasing urine volume and also by enhancing elimination of Sodium (Na+), Potassium (K+) and Chloride (Cl-) at doses of 100 and 200mg/kg. Conclusion EEMP possesses significant diuretic activity and has a beneficial role in volume overload conditions. PMID:26870704

Effects of Three Commonly-used Diuretics on the Urinary Proteome

PubMed Central

Li, Xundou; Zhao, Mindi; Li, Menglin; Jia, Lulu; Gao, Youhe

2014-01-01

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F; hydrochlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography–tandem mass spectrometry (LC–MS/MS). Based on the criteria of P ⩽ 0.05, a fold change ⩾2, a spectral count ⩾5, and false positive rate (FDR) ⩽1%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC–MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics. PMID:24508280

Fluid removal in acute heart failure: diuretics versus devices.

PubMed

Krishnamoorthy, Arun; Felker, G Michael

2014-10-01

Fluid removal and relief of congestion are central to treatment of acute heart failure. Diuretics have been the decongestive mainstay but their known limitations have led to the exploration of alternative strategies. This review compares diuretics with ultrafiltration and examines the recent evidence evaluating their use. Relevant recent studies are the Diuretic Optimization Strategies Evaluation trial (of diuretics) and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (of ultrafiltration). The Diuretic Optimization Strategies Evaluation study evaluated strategies of loop diuretic use during acute heart failure (continuous infusion versus intermittent bolus and high dose versus low dose). After 72  h, there was no significant difference with either comparison for the coprimary end points. Patients treated with a high-dose strategy tended to have greater diuresis and more decongestion compared with low-dose therapy, at the cost of transient changes in renal function. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure study showed that in acute heart failure patients with persistent congestion and worsening renal function, ultrafiltration, as compared with a medical therapy, was associated with similar weight loss but greater increase in serum creatinine and more adverse events. Decongestion remains a major challenge in acute heart failure. Although recent studies provide useful data to guide practice, the relatively poor outcomes point to the continued need to identify better strategies for safe and effective decongestion.

[Diuretics].

PubMed

Filipowicz, Ewa; Staszków, Monika

2013-01-01

Diuretics are an important class of medicine used to treat a wide variety of acute and chronic conditions, like: heart failure, hypertension and renal diseases. They act by increasing urinary excretion of water, sodium, and some others electrolytes, at different sites in the nephron. In this paper the mechanisms of action, use, dosing and adverse effects of the commonly used diuretics are reviewed.

[Prescribing diuretics: what a practitioner needs to know].

PubMed

Richard, C; Saudan, P; Ernandez, T

2015-02-25

Diuretics are among the most frequently prescribed drugs. Most of them act by inhibiting sodium reabsorption in various nephron segments. By understanding their pharmacological characteristics, it is possible to adapt the type of diuretic to different clinical situations. Practical aspects of their use, including in heart failure, cirrhosis, the nephrotic syndrome and renal failure, are discussed.

Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine

PubMed Central

Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Parola, Maurizio

2016-01-01

Background In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites. Aim To compare clonidine (aspecific α2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites. Methods and Results Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6). Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance). In comparison with G4, the addition of clonidine (G5) or guanfacine (G6) to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels. Conclusions α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time. PMID:27384184

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

PubMed

Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

2015-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Effect of diuretics on renal tubular transport of calcium and magnesium.

PubMed

Alexander, R Todd; Dimke, Henrik

2017-06-01

Calcium (Ca 2+ ) and Magnesium (Mg 2+ ) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca 2+ and Mg 2+ reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca 2+ and Mg 2+ transport. Alterations in these molecular constituents can have profound effects on tubular Ca 2+ and Mg 2+ handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na + ) transport, but also indirectly affect renal Ca 2+ and Mg 2+ handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca 2+ and Mg 2+ handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca 2+ and Mg 2+ transport. Acetazolamide, osmotic diuretics, Na + /H + exchanger (NHE3) inhibitors, and antidiabetic Na + /glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca 2+ transport predominates. Loop diuretics and renal outer medullary K + (ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca 2+ and Mg 2+ transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na + transport at distal sites, can also affect divalent cation transport. Copyright © 2017 the American Physiological Society.

Diuretics for Hypertension: A Review and Update.

PubMed

Roush, George C; Sica, Domenic A

2016-10-01

This review and update focuses on the clinical features of hydrochlorothiazide (HCTZ), the thiazide-like agents chlorthalidone (CTDN) and indapamide (INDAP), potassium-sparing ENaC inhibitors and aldosterone receptor antagonists, and loop diuretics. Diuretics are the second most commonly prescribed class of antihypertensive medication, and thiazide-related diuretics have increased at a rate greater than that of antihypertensive medications as a whole. The latest hypertension guidelines have underscored the importance of diuretics for all patients, but particularly for those with salt-sensitive and resistant hypertension. HCTZ is 4.2-6.2 systolic mm Hg less potent than CTDN, angiotensin-converting enzyme inhibitors, beta blockers, and calcium channel blockers by 24-hour measurements and 5.1mm Hg systolic less potent than INDAP by office measurements. For reducing cardiovascular events (CVEs), HCTZ is less effective than enalapril and amlodipine in randomized trials, and, in network analysis of trials, it is less effective than CTDN and HCTZ-amiloride. Combined with thiazide-type diuretics, potassium-sparing agents decrease ventricular ectopy and reduce the risk for sudden cardiac death relative to thiazide-type diuretics used alone. A recent synthesis of 44 trials has shown that the relative potencies in milligrams among spironolactone (SPIR), amiloride, and eplerenone (EPLER) are approximately from 25 to 10 to 100, respectively, which may be important when SPIR is poorly tolerated. SPIR reduces proteinuria beyond that provided by other renin angiotensin aldosterone inhibitors. EPLER also reduces proteinuria and has beneficial effects on endothelial function. While guidelines often do not differentiate among specific diuretics, this review demonstrates that these distinctions are important for managing hypertension. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Position of diuretics in the treatment of heart failure in light of current guidelines].

PubMed

Bury, Krzysztof; Nessler, Jadwiga

Diuretics are the longest-used drugs in heart failure after digoxin. This is due to their effect on the retention of sodium and an increase in the volume of fluid in the extracellular space secondary to neurohormonal and hemodynamic disorders occurs in heart failure, and their effectiveness in the treatment of symptomatic heart failure. Discontinuation of treatment with diuretics or use them in too small doses is one of the causes of exacerbation or acute heart failure.The effectiveness of most of diuretics does not confirm in the clinical trials, and the indications for their use are often based only on expert opinion. The effect of these drugs on morbidity and mortality in patients with HF was not examined. Diuretics reduce shortness of breath and swelling. For this reasons it is recom-mended to use them in patients with signs and symptoms of fluid retention regardless of the left ventricular ejection fraction.

Diuretics in acute kidney injury.

PubMed

Nigwekar, Sagar U; Waikar, Sushrut S

2011-11-01

Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the outcomes associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field. Copyright © 2011 Elsevier Inc. All rights reserved.

Evidence-based diuretics: focus on chlorthalidone and indapamide.

PubMed

DiNicolantonio, James J; Bhutani, Jaikrit; Lavie, Carl J; O'Keefe, James H

2015-03-01

Thiazide and thiazide-like diuretics are cornerstone treatments for hypertension. However, unlike chlorthalidone (CTD) and indapamide (IDP), hydrochlorothiazide (HCTZ) lacks evidence for reducing morbidity and mortality as monotherapy compared with placebo or control. Despite this fact, HCTZ is prescribed much more frequently than CTD or IDP. We believe that all hypertension guidelines should follow the National Institute for Health and Excellence (NICE) and make IDP and CTD first choice 'thiazide-like diuretics.' This article will focus on the available evidence pertaining to HCTZ versus CTD and IDP. We will review the pharmacological differences between these three diuretics, as well as the clinical trial data and important side effects.

[Diuretic activity of the infusion of flowers from Lavandula officinalis].

PubMed

Elhajili, M; Baddouri, K; Elkabbaj, S; Meiouat, F; Settaf, A

2001-01-01

The diuretic activity of an infusion of Lavandula officinalis was studied in the Wistar rat. Thus, the kinetics of hydroelectrolytic elimination in response to the oral administration of an infusion of pharmaceutical lavender flowers were measured in the rats. Experiments were completed under similar conditions using a synthetic pharmacological diuretic, Diamox. The aqueous extract of this aromatic plant accelerated the elimination of the water overload. At the peak of the diuretic response, urinary osmolarity was significantly less than that of controls (111+/-14 vs. 195+/-11 mosmol x kg(-1)). Sodium excretion was moderate following administration of the infusion when compared to the synthetic diuretic. The stability of the aldosterone concentrations in the plasma and the absence of correlation with plasma sodium concentrations, coupled with the observed clearance of the free water (0.055+/-0.007 vs. 0.045+/-0.012 mL x min(-1)) show that the increase in diuresis and the moderate increase in sodium excretion are of tubular origin. The result of the phytochemical analysis of hexane extracts in the infusion and in urine indicated that four or five chemical factors may be involved in the diuretic effect of lavender.

Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.

PubMed

Schroeder, Emily B; Chonchol, Michel; Shetterly, Susan M; Powers, J David; Adams, John L; Schmittdiel, Julie A; Nichols, Gregory A; O'Connor, Patrick J; Steiner, John F

2018-05-07

In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of significant kidney events is unknown. We used an observational, multicenter cohort of 21,897 individuals with diabetes to compare individuals who added β -blockers, dihydropyridine calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We examined the hazard of significant kidney events, cardiovascular events, and death using Cox proportional hazard models with propensity score weighting. The composite significant kidney event end point was defined as the first occurrence of a ≥30% decline in eGFR to an eGFR<60 ml/min per 1.73 m 2 , initiation of dialysis, or kidney transplant. The composite cardiovascular event end point was defined as the first occurrence of hospitalization for acute myocardial infarction, acute coronary syndrome, stroke, or congestive heart failure; coronary artery bypass grafting; or percutaneous coronary intervention, and it was only examined in those free of cardiovascular disease at baseline. Over a maximum of 5 years, there were 4707 significant kidney events, 1498 deaths, and 818 cardiovascular events. Compared with thiazide diuretics, hazard ratios for significant kidney events for β -blockers, calcium channel blockers, and loop diuretics were 0.81 (95% confidence interval, 0.74 to 0.89), 0.67 (95% confidence interval, 0.58 to 0.78), and 1.19 (95% confidence interval, 1.00 to 1.41), respectively. Compared with thiazide diuretics, hazard ratios of mortality for β -blockers, calcium channel blockers, and loop diuretics were 1.19 (95% confidence interval, 0.97 to 1.44), 0.73 (95% confidence interval, 0.52 to 1.03), and 1.67 (95% confidence interval, 1.31 to 2.13), respectively. Compared with thiazide diuretics, hazard ratios of cardiovascular events for β -blockers, calcium channel blockers, and loop diuretics compared with thiazide diuretics were 1.65 (95% confidence interval, 1.39 to 1.96), 1.05 (95% confidence interval, 0.80 to 1.39), and 1.55 (95% confidence interval, 1.05 to 2.27), respectively. Compared with thiazide diuretics, calcium channel blockers were associated with a lower risk of significant kidney events and a similar risk of cardiovascular events. Copyright © 2018 by the American Society of Nephrology.

Effects of three commonly-used diuretics on the urinary proteome.

PubMed

Li, Xundou; Zhao, Mindi; Li, Menglin; Jia, Lulu; Gao, Youhe

2014-06-01

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F; hydrochlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on the criteria of P≤0.05, a fold change ≥2, a spectral count ≥5, and false positive rate (FDR) ≤1%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics. Copyright © 2014. Production and hosting by Elsevier Ltd.

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

PubMed

Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

2016-05-25

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

What differentiates primary care physicians who predominantly prescribe diuretics for treating mild to moderate hypertension from those who do not? A comparative qualitative study.

PubMed

Rochefort, Christian M; Morlec, Julia; Tamblyn, Robyn M

2012-02-29

Thiazide diuretics are cost-effective for the treatment of mild to moderate hypertension, but physicians often opt for more expensive treatment options such as angiotensin II receptor blockers or angiotensin converting enzyme inhibitors. With escalating health care costs, there is a need to elucidate the factors influencing physicians' treatment choices for this highly prevalent chronic condition. The purpose of this study was to describe the characteristics of physicians' decision-making process regarding hypertension treatment choices. A comparative qualitative study was conducted in 2009 in the Canadian province of Quebec. Overall, 29 primary care physicians--who are also participating in an electronic health record research program--participated in a semi-structured interview about their prescribing decisions. Physicians were categorized into two groups based on their patterns of prescribing antihypertensive drugs: physicians who predominantly prescribe diuretics, and physicians who predominantly prescribe drug classes other than diuretics. Cases of hypertension that were newly started on antihypertensive therapy were purposely selected from each physician's electronic health record database. Chart stimulated recall interview, a technique utilizing patient charts to probe recall and provide context to physician decision-making during clinical encounters, was used to elucidate reasons for treatment choices. Interview transcripts were synthesized using content analysis techniques, and factors influencing physicians' decision making were inductively generated from the data. We identified three themes that differentiated physicians who predominantly prescribe diuretics from those who predominantly prescribe other drug classes for the initial treatment of mild to moderate hypertension: a) perceptions about the efficacy of diuretics, b) preferred approach to hypertension management and, c) perceptions about hypertension guidelines. Specifically, physicians had differences in beliefs about the efficacy, safety and tolerability of diuretics, the most effective approach for managing mild to moderate hypertension, and in aggressiveness to achieve treatment targets. Marketing strategies employed by the pharmaceutical industry and practice experience appear to contribute to these differences in management approach. Physicians preferring more expensive treatment options appear to have several misperceptions about the efficacy, safety and tolerability of diuretics. Efforts to increase physicians' prescribing of diuretics may need to be directed at overcoming these misperceptions.

Study on the diuretic activity of Euphorbia fusiformis Buch.-Ham. in albino rats.

PubMed

Ashok, B K; Bhat, Savitha D; Shukla, V J; Ravishankar, B

2011-07-01

The present study was undertaken to evaluate diuretic activity of Euphorbia fusiformis root powder in Wistar strain albino rats. Randomly selected animals were divided into three groups of six animals each. The root powder was suspended in distilled water and administered orally at a dose of 90 mg/kg therapeutically equivalent dose (TED) and 180 mg/kg (TED × 02) to overnight fasted rats. The diuretic activity was evaluated by determination of urine volume and urinary electrolyte concentrations. Test drug showed significant increase in urine volume and urinary electrolyte excretion in a dose-dependant manner. Thus, from this study, it can be concluded that roots of E. fusiformis possess diuretic activity.

Validity of Retrospective Reports of Eating Behavior from the Eating Disorder Examination

DTIC Science & Technology

1999-01-01

counts of self- induced vomiting. misuse of laxatives or diuretics, fasting, and excessive exercise . To date, only three semi-structured assessment...of weight control (self- induced vomiting, laxative misuse. diuretic misuse. and intense exercising ) are assessed. Some of the individual items are...gain, such as self- induced vomiting; misuse of laxatives, diuretics, enemas, or other medications; fasting; or excessive exercise . C. The binge eating

Urea transporter proteins as targets for small-molecule diuretics.

PubMed

Esteva-Font, Cristina; Anderson, Marc O; Verkman, Alan S

2015-02-01

Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.

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.

[Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats].

PubMed

Alviz, Antistio Aníbal; Salas, Rubén Darío; Franco, Luis Alberto

2013-01-01

Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

Diuretics Combined With Compression in Resistant Limb Edema of Advanced Disease-A Case Series Report.

PubMed

Gradalski, Tomasz

2018-04-01

The extremity edema of advanced disease is a common, multifactorial feature, which impairs patients' activities and quality of life. The most frequently chosen management is based on combined decongestive physiotherapy or pharmacotherapy (with diuretics or steroids). Subcutaneous lymphatic drainage in refractory edema may decrease the swelling, prevent spontaneous lymphorrhea, but also increase the risk of infection. Safe and effective conservative management in diuretics-resistant edemas is lacking. The objective of this prospective, observational study was to assess the effectiveness and tolerability of combined physiotherapeutic and diuretic therapy in edemas refractory to parenteral diuretics. A group of 19 patients with advanced disease and severe bilateral leg edema resistant to parenteral diuretic therapy were treated for three days with a combination of multilayer short-stretch compression bandaging and furosemide in hypersaline intravenous infusion. A clinically meaningful decrease in mean limb volume (of 1.52 L; 20.6%; P < 0.0001)-strongly correlating with patients' weight loss (ρ = 0.71; P = 0.0001), with a lowering of the intensity of complaints-was achieved. The treatment was well tolerated, without decreasing the performance status in any patient. Stable levels of blood pressure, laboratory kidney profile (potassium, sodium, creatinine clearance), and serum albumin were observed. Maintenance of the achieved results with a good compliance was seen during an informal follow-up at the hospice. The combination of compression therapy with hypersaline diuretics could be considered as a valuable option for refractory cases of limb edema in advanced disease. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Fonarow, Gregg C; Jaski, Brian E; Bart, Bradley A; Heywood, J Thomas; Nabut, Jose L; Schollmeyer, Michael P

2015-09-01

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure. Copyright © 2015. Published by Elsevier Inc.

Can Shear-Wave Elastography be Used to Discriminate Obstructive Hydronephrosis from Nonobstructive Hydronephrosis in Children?

PubMed

Dillman, Jonathan R; Smith, Ethan A; Davenport, Matthew S; DiPietro, Michael A; Sanchez, Ramon; Kraft, Kate H; Brown, Richard K J; Rubin, Jonathan M

2015-10-01

To determine if ultrasonographic (US) renal shear-wave speed (SWS) measurements obtained either before or after intravenous diuretic administration can be used to discriminate obstructive hydronephrosis from unobstructive hydronephrosis in children, with diuretic renal scintigraphy as the reference standard. Institutional review board approval and parental informed consent were obtained for this HIPAA-compliant prospective cross-sectional blind comparison with a reference standard. Between November 2012 and September 2014, 37 children (mean age, 4.1 years; age range, 1 month to 17 years) underwent shear-wave elastography of the kidneys immediately before and immediately after diuretic renal scintigraphy (reference standard for presence of urinary tract obstruction). Median SWS measurements (in meters per second), as well as change in median SWS (median SWS after diuretic administration minus median SWS before diuretic administration) were correlated with the amount of time required for kidney radiotracer activity to fall by 50% after intravenous administration of the diuretic (T1/2). Median SWS measurements were compared with degree of obstruction and degree of hydronephrosis with analysis of variance. Receiver operating characteristic (ROC) curves were created. Radiotracer T1/2 values after diuretic administration did not correlate with median SWS measurements obtained before (r = -0.08, P = .53) or after (r = -0.0004, P >.99) diuretic administration, nor did they correlate with intraindividual change in median SWS (r = 0.07, P = .56). There was no significant difference in pre- or postdiuretic median SWS measurements between kidneys with scintigraphic evidence of no, equivocal, or definite urinary tract obstruction (P > .5) or for median SWS measurements between kidneys with increasing degree of hydronephrosis (P > .5). ROC curves showed poor diagnostic performance of median SWS in discerning no, equivocal, or definite urinary tract obstruction (area under the ROC curve ranged from 0.50 to 0.62). US SWS measurements did not enable discrimination of obstructive hydronephrosis from unobstructive hydronephrosis in children. (©) RSNA, 2015 Online supplemental material is available for this article.

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.

What differentiates primary care physicians who predominantly prescribe diuretics for treating mild to moderate hypertension from those who do not? A comparative qualitative study

PubMed Central

2012-01-01

Background Thiazide diuretics are cost-effective for the treatment of mild to moderate hypertension, but physicians often opt for more expensive treatment options such as angiotensin II receptor blockers or angiotensin converting enzyme inhibitors. With escalating health care costs, there is a need to elucidate the factors influencing physicians' treatment choices for this highly prevalent chronic condition. The purpose of this study was to describe the characteristics of physicians' decision-making process regarding hypertension treatment choices. Methods A comparative qualitative study was conducted in 2009 in the Canadian province of Quebec. Overall, 29 primary care physicians--who are also participating in an electronic health record research program--participated in a semi-structured interview about their prescribing decisions. Physicians were categorized into two groups based on their patterns of prescribing antihypertensive drugs: physicians who predominantly prescribe diuretics, and physicians who predominantly prescribe drug classes other than diuretics. Cases of hypertension that were newly started on antihypertensive therapy were purposely selected from each physician's electronic health record database. Chart stimulated recall interview, a technique utilizing patient charts to probe recall and provide context to physician decision-making during clinical encounters, was used to elucidate reasons for treatment choices. Interview transcripts were synthesized using content analysis techniques, and factors influencing physicians' decision making were inductively generated from the data. Results We identified three themes that differentiated physicians who predominantly prescribe diuretics from those who predominantly prescribe other drug classes for the initial treatment of mild to moderate hypertension: a) perceptions about the efficacy of diuretics, b) preferred approach to hypertension management and, c) perceptions about hypertension guidelines. Specifically, physicians had differences in beliefs about the efficacy, safety and tolerability of diuretics, the most effective approach for managing mild to moderate hypertension, and in aggressiveness to achieve treatment targets. Marketing strategies employed by the pharmaceutical industry and practice experience appear to contribute to these differences in management approach. Conclusions Physicians preferring more expensive treatment options appear to have several misperceptions about the efficacy, safety and tolerability of diuretics. Efforts to increase physicians' prescribing of diuretics may need to be directed at overcoming these misperceptions. PMID:22375684

Diuretic effect of extracts, fractions and two compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone from Rubus rosaefolius Sm. (Rosaceae) leaves in rats.

PubMed

de Souza, Priscila; Boeing, Thaise; Somensi, Lincon Bordignon; Cechinel-Zanchett, Camile Cecconi; Bastos, Jairo Kenupp; Petreanu, Marcel; Niero, Rivaldo; Cechinel-Filho, Valdir; da Silva, Luisa Mota; de Andrade, Sérgio Faloni

2017-04-01

Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of Rubus rosaefolius Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na + and K + excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E 2 levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from R. rosaefolius leaves in rats.

Reduction of diuretics and analysis of water and muscle volumes to prevent falls and fall-related fractures in older adults.

PubMed

Okada, Kosuke; Okada, Masahiro; Kamada, Nanao; Yamaguchi, Yumiko; Kakehashi, Masayuki; Sasaki, Hidemi; Katoh, Shigeko; Morita, Katsuya

2017-02-01

In an attempt to decrease the incidence of falls and fall-related fractures at a special geriatric nursing home, we endeavored to reduce diuretic doses, and examined the relationship between the effectiveness of this approach with the body compositions and activities of daily living of the study cohort. We enrolled 93 participants living in the community, 60 residents of an intermediate geriatric nursing home and 50 residents of the 100-bed Kandayama Yasuragien special geriatric nursing home. We recorded body composition using a multifrequency bioelectrical impedance analyzer. Daily loop diuretic and other diuretic regimens of those in the special geriatric nursing home were reduced or replaced with "NY-mode" diuretic therapy, namely, spironolactone 12.5 mg orally once on alternate days. The incidence of falls fell from 53 in 2011 to 29 in 2012, and there were no fall-related proximal femoral fractures for 3 years after the introduction of NY-mode diuretic therapy. We also found statistically significant differences in muscle and intracellular water volumes in our elderly participants: those with higher care requirements or lower levels of independence had lower muscle or water volumes. We found that reducing or replacing daily diuretics with NY-mode therapy appeared to reduce the incidence of falls and fall-related proximal femoral fracture, likely by preserving intracellular and extracellular body water volumes. Low-dose spironolactone (12.5 mg on alternate days) appears to be an effective means of treating elderly individuals with chronic heart failure or other edematous states, while preventing falls and fall-related fractures. Geriatr Gerontol Int 2017; 17: 262-269. © 2016 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

PubMed

García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

2017-12-01

The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Diuretic and natriuretic activity of two mistletoe species in rats

PubMed Central

Jadhav, Namita; Patil, C. R.; Chaudhari, K. B.; Wagh, J. P.; Surana, S. J.; Jadhav, R. B.

2010-01-01

In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects. PMID:21808540

Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study

PubMed Central

Jensen, A Ø; Thomsen, H F; Engebjerg, M C; Olesen, A B; Sørensen, H T; Karagas, M R

2008-01-01

Diuretics have photosensitising properties. However, little is known about how these diuretics affect the risk of skin cancers. In North Jutland County, Denmark, we investigated whether the use of photosensitising diuretics was associated with an increased risk for developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer registry, we identified primary cases of BCC, SCC and MM during the period of 1989–2003. We selected four population controls for each case from the Danish Civil Registration System, matched on age and gender. Prescriptions for photosensitising diuretics before cancer diagnosis were ascertained in the county's Prescription Database. We used conditional logistic regression to compute incidence rate ratio (IRR), controlling for the chronic medical conditions and for the previous use of oral glucocorticoids. We found an increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45–2.21)) and MM (IRR of 1.43 (95% CI: 1.09–1.88)) among users of combined amiloride and hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34–8.10)) was found among users of indapamide. We found little associations with risk of BCC. Our findings provide evidence that the use of some photosensitising diuretics is associated with an increased risk for SCC and MM. PMID:18813314

Proton-pump inhibitor use is associated with low serum magnesium concentrations

PubMed Central

Danziger, John; William, Jeffrey H.; Scott, Daniel J.; Lee, Joon; Lehman, Li-wei; Mark, Roger G.; Howell, Michael D.; Celi, Leo A.; Mukamal, Kenneth J.

2017-01-01

Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (< 1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of neither among 11,490 consecutive adult admissions to an intensive care unit of a tertiary medical center. Of these, 2632 patients reported PPI use prior to admission, while 657 patients were using a histamine-2 receptor antagonist. PPI use was associated with 0.012 mg/dl lower adjusted serum magnesium concentration compared to users of no acid-suppressive medications, but this effect was restricted to those patients taking diuretics. Among the 3286 patients concurrently on diuretics, PPI use was associated with a significant increase of hypomagnesemia (odds ratio 1.54) and 0.028 mg/dl lower serum magnesium concentration. Among those not using diuretics, PPI use was not associated with serum magnesium levels. Histamine-2 receptor antagonist use was not significantly associated with magnesium concentration without or with diuretic use. The use of PPI was not associated with serum phosphate concentration regardless of diuretic use. Thus, we verify case reports of the association between PPI use and hypomagnesemia in those concurrently taking diuretics. Hence, serum magnesium concentrations should be followed in susceptible individuals on chronic PPI therapy. PMID:23325090

Amiloride

MedlinePlus

Amiloride is usually used in combination with other diuretics ('water pills') to treat high blood pressure and ... Amiloride is in a class of medications called diuretics. It works by causing the kidneys to get ...

Potassium

MedlinePlus

... disease with vomiting and diarrhea) and drugs, especially diuretics ('water pills'), remove potassium from the body. Potassium ... captopril (Capoten), enalapril (Vasotec),and lisinopril (Prinivil, Zestril); diuretics ('water pills'); and vitamins. Do not take potassium ...

Medications

MedlinePlus

... also slows down some fast heart rhythms. Diuretics (water pills) decrease fluid in the body and are very effective in treating high blood pressure. New research suggests that diuretics also can help to prevent ...

Diuretic renography in evaluating dilated upper urinary tract in children

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

Ireton, R.C.; Parker, R.M.; Hayden, P.

1987-02-01

The diuretic renogram provides a previously unavailable noninvasive method for assessing and following urinary tract dilation of diverse cause, and defining true obstruction in children. Technetium-99m-DTPA (diethylenetriaminepentaacetic acid) is injected intravenously and a posteriorly placed gamma scintillation camera used to image the kidneys, ureters, and bladder. Furosemide is subsequently injected to stimulate a diuresis, and the washout pattern of isotope is monitored (time-activity histogram). Nonobstructive, obstructive, and poor renal function patterns were seen. Forty patients with varying degrees of hydroureteronephrosis were evaluated. Tracings were performed serially and compared with the clinical course in time, as well as with pressure flowmore » studies and operative findings. All patients with a nonobstructed diuretic renogram did well, except for 1 boy in whom ureteropelvic obstruction developed later. Difficulty in evaluating the obstructive renogram pattern occurred only in some children with severe (grade V) hydronephrosis. Further standardization of the diuretic renogram with regard to time of diuretic injection, state of patient hydration, and regions of imaging may improve diagnostic accuracy.« less

Orthostatic Hypotension

MedlinePlus

... the body), resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or ... the body), resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or ...

[DIURETIC ACTIVITY OF 4-O-CARBOXYPHENYL-D-GLUCOPYRANOSIDE SODIUM SALT ADMINISTERED VIA DIFFERENT ROUTES].

PubMed

Smirnov, I V; Murashko, T O; Ivanov, A A; Nemtsev, A O; Postnikov, P S; Bondarev, A A; Udut, V V

2016-01-01

It was compared the diuretic activity of the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid for enteral (intragastric) and parenteral ways of administration. The test substance was administered enterally and parenterally (subcutaneously in the region of the withers) in a daily dose of 18 µmol/kg for the first seven days and in a dose of 54 mmol/kg for the next seven days. Diuretic activity of the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid was evaluated in terms of urine volume. Urine was analyzed for creatinine and the concentration of sodium, potassium and chloride ions. Experiments showed that the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid produced a diuretic effect only for the enteral administration route.

Sodium blood test

MedlinePlus

... Lithium Nonsteroidal anti-inflammatory drugs (NSAIDs) Water pills (diuretics) DO NOT stop taking any medicine before talking ... salt or fluid Receive intravenous (IV) fluids Take diuretics (water pills) or certain other medicines, including the ...

Low potassium level

MedlinePlus

... of low potassium level include: Medicines, such as diuretics (water pills), certain antibiotics Diarrhea or vomiting Using ... potassium through a vein (IV). If you need diuretics, your provider may: Switch you to a form ...

Urinating more at night

MedlinePlus

... blood calcium level Certain medicines, including water pills (diuretics) Diabetes insipidus Waking often during the night to ... cause. If excessive nighttime urination is due to diuretic medicines, you may be told to take your ...

Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease.

PubMed

Hoshino, Taro; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Mori, Honami; Yoshida, Izumi; Tabei, Kaoru

2015-04-01

Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m(2) who were suffering from severe edema even with loop diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month, D-BP: at 12 months, p < 0.05 vs. 0 month, proteinuria: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month). The annual decline in eGFR was not significantly different before and after HCTZ therapy (-7.7 ± 8.5 and -8.4 ± 4.8 mL/min/1.73 m(2)/year, respectively). Our findings suggest that the combination of HCTZ and loop diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

PubMed

Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria

2016-06-01

A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

Heart failure - fluids and diuretics

MedlinePlus

... are often called "water pills." There are many brands of diuretics. Some are taken 1 time a ... failure: a scientific statement from the American Heart Association. Circulation . 2009;120(12):1141-1163. PMID: 19720935 ...

Can Diuretics Decrease Your Potassium Level?

MedlinePlus

... of low potassium? Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, ... your urine. This can lead to low potassium levels in your blood (hypokalemia). Signs and symptoms of ...

Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica.

PubMed

Somova, L I; Shode, F O; Moodley, K; Govender, Y

2001-10-01

The extractives, crude and pure, of Alepidea amatymbica (AA) and Xylopia aethiopica (XA) were subjected to bioassay-directed phytochemical examination for potential cardiovascular and diuretic activity. All extractives and derivatives (XA/O, AA/1, xylopic acid, AA/3, AA/4, AA/5, AA/6, XA/1, XA/2, XA/3) displayed low toxicity, with LC(50) 0.5-5.0 ng/ml. For the first time, diterpene kaurenoids were reported to have significant systemic hypotensive and coronary vasodilatory effect accompanied with bradycardia. These effects were attributed to calcium antagonistic mechanism. The diuretic and natriuretic effects found were similar to the effects of chlorothiazide, suggesting inhibition of Na+ and K+ reabsorption in the early portion of the distal tubule. Further experiments are needed to elaborate the exact mechanisms of the hypotensive and diuretic effects of diterpene kaurenoids.

Is adherence to weight monitoring or weight-based diuretic self-adjustment associated with fewer heart failure-related emergency department visits or hospitalizations?

PubMed

Jones, Christine D; Holmes, George M; Dewalt, Darren A; Erman, Brian; Broucksou, Kimberly; Hawk, Victoria; Cene, Crystal W; Wu, Jia-Rong; Pignone, Michael

2012-07-01

Heart failure (HF) self-care interventions can improve outcomes, but less than optimal adherence may limit their effectiveness. We evaluated if adherence to weight monitoring and diuretic self-adjustment was associated with HF-related emergency department (ED) visits or hospitalizations. We performed a case-control analysis nested in a HF self-care randomized trial. Participants received HF self-care training, including weight monitoring and diuretic self-adjustment, which they were to record in a diary. We defined case time periods as HF-related ED visits or hospitalizations in the 7 preceding days; control time periods were defined as 7-day periods free of ED visits and hospitalizations. We used logistic regression to compare weight monitoring and diuretic self-adjustment adherence in case and control time periods, adjusted for demographic and clinical covariates. Among 303 participants, we identified 81 HF-related ED visits or hospitalizations (cases) in 54 patients over 1 year of follow-up. Weight monitoring adherence (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.23-0.76) and diuretic self-adjustment adherence (OR 0.44, 95% CI 0.19-0.98) were both associated with lower adjusted odds of HF-related ED visits or hospitalizations. Adherence to weight monitoring and diuretic self-adjustment was associated with lower odds of HF-related ED visits or hospitalizations. Adherence to these activities may reduce HF-related morbidity. Copyright © 2012 Elsevier Inc. All rights reserved.

Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

PubMed

Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

2013-06-01

To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

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

Beaumont, K.; Vaughn, D.A.; Fanestil, D.D.

Thiazides and related diuretics inhibit NaCl reabsorption in the distal tubule through an unknown mechanism. The authors report here that ({sup 3}H)metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter. ({sup 3}H)Metolazone bound with high affinity to a site with a density of 0.717 pmol/mg of protein in kidney membranes. The binding site was localized to the renal cortex, with little or not binding in other kidney regions and 11 other tissues. The affinities of thiazide-type diuretics for this binding site were significantly correlated withmore » their clinical potency. Halide anions specifically inhibited high-affinity binding of ({sup 3}H)metolazone to this site. ({sup 3})Metolazone also bound with lower affinity to sites present in kidney as well as in liver, testis, lung, brain, heart, and other tissues. Calcium antagonists and certain smooth muscle relaxants had K{sub i} values of 0.6-10 {mu}M for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested. Properties of the high-affinity ({sup 3}H)metolazone binding site are consistent with its identity as the receptor for thiazide-type diuretics.« less

Real-Life Use of Neurohormonal Antagonists and Loop Diuretics in Chronic Heart Failure: Analysis of Serial Biomarker Measurements and Clinical Outcome.

PubMed

Brankovic, Milos; Akkerhuis, K Martijn; van Boven, Nick; Manintveld, Olivier; Germans, Tjeerd; Brugts, Jasper; Caliskan, Kadir; Umans, Victor; Constantinescu, Alina; Kardys, Isabella

2017-11-06

We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Continuous infusion or bolus injection of loop diuretics for congestive heart failure?

PubMed

Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

2016-04-22

Loop diuretics are widely used in acute heart failure. However, there is controversy about the superiority of continuous infusion over bolus administration. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 pertinent randomized controlled trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded continuous administration of loop diuretics probably reduces mortality and length of stay compared to intermittent administration in patients with acute heart failure.

Ethnopharmacological investigation of the diuretic and hemodynamic properties of native species of the Brazilian biodiversity.

PubMed

Lima Prando, Thiago Buno; Barboza, Lorena Neris; Gasparotto, Francielly Mourão; Araújo, Valdinei de Oliveira; Slgnor Tirloni, Cleide Adriane; de Souza, Lauro Mera; Lourenço, Emerson Luiz Botelho; Gasparotto Junior, Arquimedes

2015-11-04

Although Echinodorus grandiflorus, Cuphea carthagenensis, and Phyllanthus tenellus infusions are used in Brazilian folk medicine due to their possible diuretic effect, none of these species was critically investigated as a diuretic drug. So, the aim of this study was to evaluate the possible acute diuretic activity of ethanol soluble fractions (ES) obtained from these species and assess the relationship between renal cortical blood flow and their antioxidant and hypotensive activity using normotensive Wistar rats. The preparation obtained from E. grandiflorus (ES-EG), C. carthagenensis (ES-CC), and P. tenellus (ES-PT) infusions was orally administered in a single dose to rats. Urine excretion rate, pH, density, conductivity and Na(+), K(+), Cl(-) and HCO3(-) contents were measured in the urine of saline-loaded animals. Concentration of electrolytes, total protein, urea, creatinine, and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The involvement of the renal cortical blood flow and antioxidative activity in the hypotensive and diuretic effects was also determined. Water and Na(+), Cl(-) and Na(+) excretion rates were significantly increased by ES-EG, while urinary bicarbonate excretion was reduced. Moreover, ES obtained from E. grandiflorus was able to significantly increase renal blood flow and reduce mean arterial pressure and oxidative stress in "in vitro" and "in vivo" models. All other parameters evaluated were not affected by any treatment. The results presented here shown that the ES-EG obtained from E. grandiflorus leaves shown a significant diuretic and hypotensive activity and suggest that these effects could be related with an important renal and systemic vasodilator effect. In addition, it was shown for the first time that the pharmacological effects of ES obtained from P. tenellus and C. carthagenensis do not support its popular use as a diuretic agent. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[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.

Use of diuretics and the risk of gouty arthritis: a systematic review.

PubMed

Hueskes, Berdine A A; Roovers, Elisabeth A; Mantel-Teeuwisse, Aukje K; Janssens, Hein J E M; van de Lisdonk, Eloy H; Janssen, Matthijs

2012-06-01

To systematically review the literature investigating the relationship between use of diuretics and the risk of gouty arthritis. PubMed (1950-October 2009), Embase (1974-October 2009), and the Cochrane Library (up to October 2009) were searched using keywords and MeSH terms diuretics, adverse effects, and gout. For this review, the technique of "best evidence synthesis" was used. Studies reporting frequency, absolute or relative risks, odds ratio, or rate ratio of gouty arthritis in diuretic users compared with nonusers were selected and evaluated. Studies had to be published in English. Checklists from the Dutch Cochrane Centre were used to assess the quality of randomized controlled trials (RCTs), cohort, and case-control studies. Two RCTs, 6 cohort studies, and 5 case-control studies met the inclusion criteria. The overall quality of the studies was moderate. In a RCT the rate ratio of gout for use of bendrofluazide vs placebo was 11.8 (95% CI 5.2-27.0). The other RCT found a rate ratio of 6.3 (95% CI 0.8-51) for use of hydrochlorothiazide plus triamterene vs placebo. Three cohort studies and 4 case-control studies found higher risks of gouty arthritis in users compared with nonusers of diuretics. There is a trend toward a higher risk for acute gouty arthritis attacks in patients on loop and thiazide diuretics, but the magnitude and independence is not consistent. Therefore, stopping these useful drugs in patients who develop gouty arthritis is not supported by the results of this review. Copyright © 2012 Elsevier Inc. All rights reserved.

Diuretics with carbonic anhydrase inhibitory action: a patent and literature review (2005 - 2013).

PubMed

Carta, Fabrizio; Supuran, Claudiu T

2013-01-01

The benzothiadiazines and high ceiling diuretics (hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide) contain primary sulfamoyl moieties acting as zinc-binding groups in the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). These drugs are widely used clinically and were recently shown to weakly inhibit isoforms CA I and II, but to possess stronger activity against isoforms involved in other important pathologies, for example, obesity, cancer, epilepsy and hypertension. The class of clinically used diuretics, with CA inhibitory properties, is the main topic of the review. A patent literature review covering the period from 2005 to 2013 is presented. This section presents an overview of the patent literature in the sulfonamide diuretic field. Most of the patents deal with the combination of diuretic sulfonamide CA inhibitors with other agents useful in the management of cardiovascular diseases and obesity. Such combinations exert a better therapeutic activity compared to similar diuretics that do not inhibit CAs, raising the question of the polypharmacological and drug repositioning effects of these old drugs. These effects seem to be due to the potent inhibition of such drugs against CA isoforms present in kidneys and blood vessels, which explain both the blood pressure lowering effects as well as organ-protective activity of the drugs. An explanation of these data is provided by the fact that inhibition of the renal CAs leads to a large increase of the nitrite excretion in urine, suggesting that renal CAs are involved in nitrite reabsorption in humans. Important lessons for the drug design of sulfonamide CA inhibitors (CAIs) can be drawn from these data.

Pharmacological characterization of the diuretic effect of Hibiscus sabdariffa Linn (Malvaceae) extract.

PubMed

Alarcón-Alonso, Javier; Zamilpa, Alejandro; Aguilar, Francisco Alarcón; Herrera-Ruiz, Maribel; Tortoriello, Jaime; Jimenez-Ferrer, Enrique

2012-02-15

Hibiscus sabdariffa L. (Malvaceae) populary known in Mexico as "Jamaica", "flor de Jamaica", has widely used in Mexican Traditional Medicine as antihypertensive and diuretic, although the latter activity has been reported the present work show evidence about the diuretic, natriuretic and potassium-sparing effects. To evaluate the diuretic activity of Hibiscus sabdariffa aqueous extract on in vivo and in situ models. The Hibiscus sabdariffa aqueous extract was administrated in increasing doses and evaluated the diuresis produced and disposal of electrolytes. Moreover, in isolated kidney was determined the renal filtration rate with plant extract, furosemide and amiloride. The yield of Hibiscus sabdariffa aqueous extraction was 28.3% and the chemical standardization from 1 g of extract was: 56.5 mg delphinidin-3-O-sambubioside, 20.8 mg/g cyanidin-3-O-sambubioside, 3.2 mg/g quercetin, 2.1 mg/g rutin and 2.7 mg/g chlorogenic acid. The diuretic and natriuretic effect of Hibiscus sabdariffa aqueous extract showed a dose-dependent behavior. The pharmacological constants of natriuretic effect was ED50=86 mg/kg and Emax=0.9 mEq/100 g/5 h. In the model of kidney in situ was observed that renal filtration increased 48% with the aqueous extract of Hibiscus sabdariffa and an additive effect when was perfuse with furosemide. The compound presents in Hibiscus sabdariffa as quercetin had effect on the vascular endothelium causing oxide nitric release, increasing renal vasorelaxation by increasing kidney filtration. Therefore, the diuretic effect of Hibiscus sabdariffa may be mediated by nitric oxide release. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Structure-Activity Relationships for in vitro Diuretic Activity of CAP2b in the Housefly

DTIC Science & Technology

2007-01-01

p e p t i d e s 2 8 ( 2 0 0 7 ) 5 7 – 6 1Structure-activity relationships for in vitro diuretic activity of CAP2b in the housefly Ronald J. Nachman a...the peptide Manse-CAP2b (pELYAFPRV-NH2) were assayed for diuretic activity on Malpighian tubules of the housefly Musca domestica (M. domestica). The C...required the C-terminal heptapeptide, which was equipotent with the most active of the native housefly CAP2b peptides. Replacement of Arg7 and Val8 with

Chemical composition and diuretic, natriuretic and kaliuretic effects of extracts of Mimosa bimucronata (DC.) Kuntze leaves and its majority constituent methyl gallate in rats.

PubMed

Schlickmann, Fabile; de Souza, Priscila; Boeing, Thaise; Mariano, Luisa N B; Steimbach, Viviane M B; Krueger, Clarissa de M A; da Silva, Luísa M; de Andrade, Sérgio F; Cechinel-Filho, Valdir

2017-11-01

Some species of the genus Mimosa showed promising results in previous investigations, which include diuretic effect; however, no chemical analyses or animal model has been conducted so far to evaluate the biological properties of M. bimucronata. Male Wistar rats received the oral treatment with vehicle; hydrochlorothiazide; methanolic extract from M. bimucronata (MEMB), dichloromethane (DCM) and ethyl acetate (EA) fractions or methyl gallate (MG). The cumulative urine volume, electrolytes excretion, pH and osmolality were determined at the end of the experiment. The chemical studies demonstrated that the phenolic compounds are the majorities in the plant, with the MG being the main substance identified. We showed that MEMB and EA fraction, but not DCM, exhibited diuretic and saluretic effects. Similarly, the MG also revealed diuretic, natriuretic and kaliuretic properties to both normotensive and spontaneously hypertensive rats. Atropine, a muscarinic receptor antagonist, fully prevented MG-induced diuresis and saluresis. In addition, MG did not alter the viability of A7r5 and L929 cell lines and neither stimulated nitric oxide generation. These findings suggest that M. bimucronata extracts and its majority compound MG present diuretic, natriuretic and kaliuretic properties, which was dependent on the activation of muscarinic acetylcholine receptor. © 2017 Royal Pharmaceutical Society.

Co-administration of furosemide with albumin for overcoming diuretic resistance in patients with hypoalbuminemia: a meta-analysis.

PubMed

Kitsios, Georgios D; Mascari, Paolo; Ettunsi, Riad; Gray, Anthony W

2014-04-01

To systematically review clinical studies of co-administration of albumin and loop diuretics in hypoalbuminemic patients as a strategy to overcome diuretic resistance. Systematic search of electronic databases up to October 2012. We included randomized clinical trials of adults with hypoalbuminemia, comparing co-administration of loop diuretics and albumin versus loop diuretics alone. Quantitative data were synthesized with meta-analytic techniques for clinical, surrogate (urinary volume and urinary sodium excretion) and intermediate (pharmacokinetic and hemodynamic parameters) outcomes. Ten studies were included, of which 8 trials with crossover design were synthesized with meta-analysis. A statistically significant increase in the amount of urine volume (increment of 231 mL [95% confidence interval 135.5-326.5]) and sodium excreted (15.9 mEq [4.9-26.8]) at 8 hours were found in favor of co-administration of albumin and furosemide. These differences were no longer statistically significant at 24 hours. Meta-analyses for intermediate outcomes (ie, furosemide excretion, distribution volume etc.) did not reveal statistically significant differences. Synthesis of a heterogeneous body of evidence shows transient effects of modest clinical significance for co-administration of albumin with furosemide in hypoalbuminemic patients. Pragmatic, large-scale randomized studies are needed to delineate the role of this strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

[Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics].

PubMed

Kann, P H; Hadji, P; Bergmann, R S

2014-05-01

[corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.

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.

Impact of late fluid balance on clinical outcomes in the critically ill surgical and trauma population.

PubMed

Elofson, Kathryn A; Eiferman, Daniel S; Porter, Kyle; Murphy, Claire V

2015-12-01

Management of fluid status in critically ill patients poses a significant challenge due to limited literature. This study aimed to determine the impact of late fluid balance management after initial adequate fluid resuscitation on in-hospital mortality for critically ill surgical and trauma patients. This single-center retrospective cohort study included 197 patients who underwent surgical procedure within 24 hours of surgical intensive care unit admission. Patients with high fluid balance on postoperative day 7 (>5 L) were compared with those with a low fluid balance (≤5 L) with a primary end point of in-hospital mortality. Subgroup analyses were performed based on diuretic administration, diuretic response, and type of surgery. High fluid balance was associated with significantly higher in-hospital mortality (30.2 vs 3%, P<.001) compared with low fluid balance; this relationship remained after multivariable regression analysis. High fluid balance was associated with increased mortality, independent of diuretic administration, diuretic response, and type of surgery. Consistent with previous literature, high fluid balance on postoperative day 7 was associated with increased in-hospital mortality. Patients who received and responded to diuretic therapy did not demonstrate improved clinical outcomes, which questions their use in the postoperative period. Copyright © 2015 Elsevier Inc. All rights reserved.

[Alternatives to conventional diuretic therapy in heart failure].

PubMed

Morales-Rull, José Luis; Trullàs, Joan Carles; Formiga, Francesc

2014-03-01

Although treatment of acute heart failure is based primarily on the administration of intravenous loop diuretics, evidence supporting this practice is still scarce and there is uncertainty about the optimal dose. The existence of a considerable percentage of patients refractory to diuretic therapy and worsening of renal failure associated with the use of these drugs, with possible implications for medium-term mortality, have prompted the search for more effective and safer alternatives. Extracorporeal purification techniques, such as ultrafiltration, have demonstrated efficacy, although their superiority is unclear, due to the possible adverse effects associated with the procedure. The use of low-dose dopamine is not superior to conventional diuretic therapy after the first few hours of treatment. Moreover, combination with furosemide and hypertonic saline could be a valid alternative for patients with refractory congestion and depressed ejection fraction and serum creatinine ≤ 2.5mg/dL, but further studies are needed before its widespread use. The use of tolvaptan may be an effective alternative in the short-term but its use may be limited by its price. There is still controversy about whether treatment with loop diuretics is associated with higher mortality in all groups of patients with HF exacerbations. These controversies should be clarified by future clinical trials. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Diuretic use is associated with better learning and memory in older adults in the Ginkgo Evaluation of Memory Study.

PubMed

Yasar, Sevil; Lin, Fu-Mei; Fried, Linda P; Kawas, Claudia H; Sink, Kaycee M; DeKosky, Steven T; Carlson, Michelle C

2012-05-01

To investigate the association between diuretics, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB), and cognitive function. This post hoc analysis of the randomized controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented community-dwelling participants aged >75 years. At baseline visit, detailed information about medication use was collected and five cognitive domains were assessed. Multivariate linear regression analyses were used to assess cross-sectional associations between medication use and cognitive function. In all, 36% of participants reported history of hypertension and 53% reported antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2% AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better verbal learning and memory measured by California Verbal Learning Test as compared with no antihypertensive medication users (β = 0.068, P = .01; β = 0.094, P < .001) and other antihypertensive medication users (β = 0.080, P = .03; β = 0.153, P < .001). Use of ACE-I or AT2RB was not associated with better cognitive function. Results warrant further investigation into possible protective effects of potassium-sparing diuretics and the role of potassium in mitigating cognitive decline. Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Shoshin beriberi induced by long-term administration of diuretics: a case report.

PubMed

Misumida, Naoki; Umeda, Hisashi; Iwase, Mitsunori

2014-01-01

Previous studies have suggested that diuretic therapy for heart failure may lead to thiamine deficiency due to the increased urinary thiamine excretion. Herein, we present the case of a 61-year-old man with shoshin beriberi, a fulminant form of wet beriberi, induced by long-term diuretic therapy. The patient had a history of heart failure with preserved ejection fraction and was receiving furosemide and trichlormethiazide therapy. He presented with worsening exertional dyspnea and was admitted for heart failure exacerbation. His condition failed to improve even after intensive treatment. A hemodynamic evaluation with the Swan-Ganz catheter revealed high-output heart failure with low peripheral vascular resistance. Thiamine was administered for suspected shoshin beriberi; his hemodynamic status improved dramatically within the next six hours. The serum thiamine level was below the normal range; the patient was therefore diagnosed with shoshin beriberi. The common causes of thiamine deficiency were not identified. Long-term diuretic therapy with furosemide and thiazide was thought to have played a major role in the development of thiamine deficiency. This case illustrates the importance of considering wet beriberi as a possible cause of heart failure exacerbation in patients taking diuretics, even when the common thiamine deficiency causes are not identified with history-taking.

Diuretics.

ERIC Educational Resources Information Center

Plummer, Nancy; Michael, Nancy, Ed.

This module on diuretics is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then provided.…

Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome.

PubMed

Rahman, Asadur; Kittikulsuth, Wararat; Fujisawa, Yoshihide; Sufiun, Abu; Rafiq, Kazi; Hitomi, Hirofumi; Nakano, Daisuke; Sohara, Eisei; Uchida, Shinichi; Nishiyama, Akira

2016-05-01

Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp). Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively. Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P < 0.01), which were associated with a significant increase in urinary excretion of sodium. Addition of diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp. These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.

Diuretics prescribing in chronic kidney disease patients: physician assessment versus bioimpedence spectroscopy.

PubMed

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2017-06-01

The relationship between hypertension and fluid overload in pre-dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS). A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS. A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m 2 were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics. BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

PubMed

Fukunami, Masatake; Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru

2011-12-01

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

[Effect of early postoperative use of ACEI/ARB or diuretics on the incidence of acute kidney injury after cardiac surgery in elderly patients].

PubMed

Hu, Peng-hua; Chen, Yuan-han; Liang, Xin-ling; Li, Rui-zhao; Li, Zhi-lian; Jiang, Fen; Shi, Wei

2013-07-01

To explore the influence of early postoperative use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) or diuretics on acute kidney injury (AKI) after cardiac surgery in elderly patients. Data from elderly patients (age≥60 years old) who underwent cardiac surgery with extracorporeal circulation in Guangdong General Hospital between January 2007 and December 2010 were analyzed in this retrospective research. The primary endpoint was AKI as diagnosed according to the serum creatinine criteria of RIFLE (risk, injury, failure, loss, end stage renal disease). The baseline serum creatinine was defined as the latest serum creatinine level before cardiac surgery. Multivariate analysis by logistic regression was used to obtain the independent risk factors for AKI. Among 618 elderly patients, 76 (12.3%) patients received ACEI/ARB during early postoperative period, 491 (79.4%) patients were given diuretics during early postoperative period, and postoperative AKI occurred in 394 (63.8%) patients. The incidence of AKI was 46.1% in patients who received early postoperative ACEI/ARB, and 66.2% in patients who did not (P<0.001). Patients who received diuretics postoperatively were less likely to suffer from AKI compared with patients who did not (57.0% vs. 89.8%, P<0.001). After adjustment of other potential factors of postoperative AKI, logistic regression analysis showed that early postoperative use of ACEI/ARB [odds ratio (OR)=0.131, 95% confidence interval (95%CI) 0.033-0.517, P=0.004], and early postoperative use of diuretics (OR=0.149, 95%CI 0.076-0.291, P<0.001) independently predicted the occurrence of AKI. Early postoperative use of ACEI/ARB or diuretics is associated with a lower incidence of AKI after cardiac surgery with extracorporeal circulation in elderly patients.

Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis.

PubMed

Kendrick, Jessica B; Zelnick, Leila; Chonchol, Michel B; Siscovick, David; Hoofnagle, Andrew N; Ix, Joachim H; Sarnak, Mark; Shlipak, Michael G; Kestenbaum, Bryan; de Boer, Ian H

2017-01-01

Low serum bicarbonate concentrations are associated with mortality and kidney disease progression. Data regarding associations between bicarbonate and cardiovascular disease (CVD) are scarce. We performed a cohort study of 6,229 adult participants from the Multi-Ethnic Study of Atherosclerosis, a community-based cohort free of CVD at baseline. Serum bicarbonate was measured at baseline. Cardiovascular outcomes were defined as: (1) subclinical CVD (left ventricular mass [LVM] and aortic pulse pressure [PP] measured at baseline), (2) incident atherosclerotic cardiovascular events (CVE; composite of myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death, and stroke death), and (3) incident heart failure. During a median (interquartile range) follow-up of 8.5 (7.7-8.6) years, 331 (5.3%) participants had an incident CVE and 174 (2.8%) developed incident heart failure. We stratified analyses by use of diuretics because we observed a significant interaction between diuretic use and bicarbonate with study outcomes. Among diuretic nonusers, with adjustment, bicarbonate ≥25 mEq/L was associated with an estimated 3.0 g greater LVM (95% CI 0.5-5.0) and 1.0 mm Hg higher aortic PP (95% CI 0.4-2.0) compared to bicarbonate 23-24 mEq/L. Each 1 mEq/L of bicarbonate increase was associated with a 13% higher risk of incident heart failure (hazards ratio 1.13, 95% CI 1.01-2.11). Among diuretic users, higher bicarbonate was not associated with CVD. Bicarbonate was not associated with incident atherosclerotic CVE irrespective of diuretic use. Among nonusers of diuretics in a large community-based study, higher serum bicarbonate concentrations are associated with subclinical CVD and new heart failure. © 2016 S. Karger AG, Basel.

Serum Bicarbonate is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Kendrick, Jessica; Zelnick, Leila; Chonchol, Michel; Siscovick, David; Hoofnagle, Andrew N.; Ix, Joachim H.; Sarnak, Mark; Shlipak, Michael; Kestenbaum, Bryan; de Boer, Ian H.

2016-01-01

Background Low serum bicarbonate concentrations are associated with mortality and kidney disease progression. Data regarding associations between bicarbonate and cardiovascular disease (CVD) are scarce. Methods We performed a cohort study of 6229 adult participants from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort free of CVD at baseline. Serum bicarbonate was measured at baseline. Cardiovascular outcomes were defined as: 1) subclinical CVD (left ventricular mass (LVM) and aortic pulse pressure (PP) measured at baseline), 2) incident atherosclerotic cardiovascular events (CVE) (composite of myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death and stroke death), and 3) incident heart failure. Results During a median (IQR) follow-up of 8.5 (7.7–8.6) years, 331 (5.3%) participants had an incident CVE and 174 (2.8%) developed incident heart failure. We stratified analyses by use of diuretics because we observed a significant interaction between diuretic use and bicarbonate with study outcomes. Among diuretic nonusers, with adjustment, bicarbonate ≥25 mEq/L was associated with an estimated 3.0 gram greater LVM (95% CI 0.5 to 5.0) and 1.0 mmHg higher aortic PP (95% CI 0.4 to 2.0) compared to bicarbonate 23–24 mEq/L. Each 1mEq/L higher bicarbonate was associated with a 13% higher risk of incident heart failure (HR 1.13, 95% CI 1.01 to 2.11). Among diuretic users, higher bicarbonate was not associated with CVD. Bicarbonate was not associated with incident atherosclerotic CVE irrespective of diuretic use. Conclusion Among nonusers of diuretics in a large community-based study, higher serum bicarbonate concentrations are associated with subclinical CVD and new heart failure. PMID:27941322

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae).

PubMed

Leme, Thiago dos Santos Vilhena; Prando, Thiago Bruno Lima; Gasparotto, Francielly Mourão; de Souza, Priscila; Crestani, Sandra; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Lourenço, Emerson Luiz Botelho; Gasparotto, Arquimedes

2013-10-28

Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats. The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H2O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO3(-) were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined. Water and Na(+) excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2',5'-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment. The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway. © 2013 Elsevier Ireland Ltd. All rights reserved.

Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study.

PubMed

Yasar, Sevil; Xia, Jin; Yao, Wenliang; Furberg, Curt D; Xue, Qian-Li; Mercado, Carla I; Fitzpatrick, Annette L; Fried, Linda P; Kawas, Claudia H; Sink, Kaycee M; Williamson, Jeff D; DeKosky, Steven T; Carlson, Michelle C

2013-09-03

The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20-0.73). Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

Value of routine investigations to predict loop diuretic down-titration success in stable heart failure.

PubMed

Martens, Pieter; Verbrugge, Frederik H; Boonen, Levinia; Nijst, Petra; Dupont, Matthias; Mullens, Wilfried

2018-01-01

Guidelines advocate down-titration of loop diuretics in chronic heart failure (CHF) when patients have no signs of volume overload. Limited data are available on the expected success rate of this practice or how routine diagnostic tests might help steering this process. Fifty ambulatory CHF-patients on stable neurohumoral blocker/diuretic therapy for at least 3months without any clinical sign of volume overload were prospectively included to undergo loop diuretic down-titration. All patients underwent a similar pre-down-titration evaluation consisting of a dyspnea scoring, physical examination, transthoracic echocardiography (diastolic function, right ventricular function, cardiac filling pressures and valvular disease), blood sample (serum creatinine, plasma NT-pro-BNP and neurohormones). Loop diuretic maintenance dose was subsequently reduced by 50% or stopped if dose was ≤40mg furosemide equivalents. Successful down-titration was defined as a persistent dose reduction after 30days without weight increase >1.5kg or new-onset symptoms of worsening heart failure. At 30-day follow-up, down-titration was successful in 62% (n=31). In 12/19 patients exhibiting down-titration failure, this occurred within the first week. Physical examination, transthoracic echocardiography and laboratory analysis had limited predictive capability to detect patients with down-titration success/failure (positive likelihood-ratios below 1.5, or area under the curve [AUC] non-statically different from AUC=0.5). Loop diuretic down-titration is feasible in a majority of stable CHF patients in which the treating clinician felt continuation of loops was unnecessary to sustain euvolemia. Importantly, routine diagnostics which suggest euvolemia, have limited diagnostic impact on the post-test probability. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of hypotensive, diuretic and renal effects between cladodes of Opuntia ficus-indica and furosemide.

PubMed

Bakour, Meryem; Al-Waili, Noori; El-Haskoury, Redouan; El-Menyiy, Nawal; Al-Waili, Thia; Al-Waili, Ali; Lyoussi, Badiaa

2017-09-01

To investigate the diuretic, hypotensive and renal effect of Opuntia ficus-indica in two different species in oral and intravenous administration. Diuretic activity was evaluated in rats with the plant cladode gel and aqueous extract administrated orally, and was evaluated in rabbits with plant extract administered intravenously. Single and repeated doses of cladode gel or aqueous extract of cladode were tested. Urine volume and blood and urine creatinine, sodium and potassium were measured, and creatinine clearance was calculated. The hypotensive effect of lyophilized extract of cladode was evaluated in rabbits. Two polyethylene PE50 catheters were used: one in the jugular vein for the infusion of the plant extract and the other in the carotid for the evaluation of the arterial pressure. The cladode gel or aqueous extract increased urine volume, creatinine clearance and urinary excretion of sodium and potassium without significant effect on serum creatinine or blood urea. Furosemide, gel and aqueous extract of cladode insignificantly lowered plasma potassium in rats. Intravenous administration of the lyophilized extract caused a significant decrease in mean arterial pressure in rabbits with a significant increase in urine volume and urine sodium and potassium; the effect was dose dependent. Intravenous administration of lyophilized extract did not affect plasma sodium or potassium. Gel and aqueous extract of Opuntia ficus-indica cladode have a significant diuretic effect on rats, and the lyophilized extract has a diuretic and hypotensive effect on normotensive rabbits without deterioration in renal function test. Additional studies on active ingredients are essential to pave the way for clinical studies on diuretic and hypotensive effect of the plant. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Acute kidney injury secondary to a combination of renin-angiotensin system inhibitors, diuretics and NSAIDS: "The Triple Whammy".

PubMed

Camin, Rosa Maria Garcia; Cols, Montse; Chevarria, Julio Leonel; Osuna, Rosa García; Carreras, Marc; Lisbona, Josep Maria; Coderch, Jordi

2015-01-01

Renin-angiotensin system inhibitors (ACEI/ARB-II), diuretics and NSAIDs, a combination known as "Triple Whammy", can result in decreased glomerular filtration rate (GFR) and acute kidney injury (AKI). Objectives: To describe the incidence of AKI for each drug type and their combinations. To define the profile of patients admitted for drug-related AKI secondary to Triple Whammy drugs (AKITW), with an assessment of costs and mortality. A retrospective observational 15-month study developed in three stages: - First: a cross-sectional stage to identify and describe hospitalizations due to AKITW. - Second: a follow-up stage of an outpatient cohort consuming these drugs (15,307 subjects). - Third: a cohort stage to assess costs and mortality, which compared 62 hospitalized patients with AKITW and 62 without AKI, paired by medical specialty, sex, age and comorbidity according to their Clinical Risk Groups. There were 85 hospitalization episodes due to AKITW, and 78% of patients were over the age of 70. The incidence of AKITW in the population was 3.40 cases/1000 users/year (95% CI: 2.59-4.45). By categories, these were: NSAIDs + diuretics 8.99 (95% CI: 3.16-25.3); Triple Whammy 8.82 (95% CI: 4.4-17.3); ACEI/ARB-II + diuretics 6.87 (95% CI: 4.81-9.82); and monotherapy with diuretics 3.31 (95% CI: 1.39-7.85). Mean hospital stay was 7.6 days (SD 6.4), and mean avoidable costs were estimated at €214,604/100,000 inhabitants/year. Mortality during hospitalization and at 12 months was 11.3% and 38.7% respectively, and there were no significant differences when compared with the control group. Treatment with ACEI, ARB-II, diuretics and/or NSAIDs shows a high incidence of hospitalization episodes due to AKI; diuretics as monotherapy or dual and triple combination therapy cause the highest incidence. AKITW involves high health care costs and avoidable mortality. Copyright © 2015. Published by Elsevier España, S.L.U.

Misperceptions About β-Blockers and Diuretics

PubMed Central

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-01-01

BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that β-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and β-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of β-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines. PMID:14687255

Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians.

PubMed

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-12-01

Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P <.001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P <.001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines.

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.

7B.10: THIAZIDE DIURETICS AND FRACTURE-RISK AMONG HYPERTENSIVE PATIENTS. RESULTS FROM THE SWEDISH PRIMARY CARE CARDIOVASCULAR DATABASE (SPCCD).

PubMed

Bokrantz, T; Ljungman, C; Kahan, T; Schioler, L; Hjerpe, P; Hasselstrom, J; Wettermark, B; Bostrom, K; Manhem, K

2015-06-01

To investigate whether treatment with thiazide diuretics reduces the risk of osteoporotic fractures in hypertensive patients in primary health care. Further we aimed to examine the impact of duration of thiazide use, the consequences of discontinuation of use and effect-modifications by gender. This retrospective cohort study includes 60 893 individuals, diagnosed with hypertension during 2001-2008 included in the Swedish Primary Care Cardiovascular Database. All patients were followed from a fixed baseline (1 Jan 2006, or the date the patient received their first diagnosis of hypertension if that date came later) until they had an incident osteoporotic fracture, died, or reached the end of the study at 31 Dec 2012, whichever came first. Patients exposed to thiazide diuretics (dispensed drugs recorded through the Prescribed Drug Register) were compared with hypertensive patients never exposed to thiazides. During follow up 2421 osteoporotic fractures occurred. Current use of thiazide diuretics was found to be associated with significantly reduced risk of osteoporotic fractures (adjusted hazard ratios 0.88; 95% CI 0.81-0.97) independent of blood pressure level. In addition, risk appeared to decline with longer duration of use. In contrast, discontinuation of dispensed prescriptions of thiazides was associated with increased risk of osteoporotic fractures (HR 1.17; 95% CI 1.04-1.31).However, a trend towards attenuation of the increased risk with longer duration past treatment period was seen. When analyzing men and women separately similar results were seen, for both genders, although only statistically significant for men. In this large retrospective cohort study of hypertensive men and women from Sweden, we could identity a protective effect on osteoporotic fractures among current users of thiazide diuretic drugs independent of blood pressure level. However, the risk of fracture was found to be increased in patients shortly after discontinuation of treatment compared to patients never prescribed thiazide diuretic drugs. The reason for an augmented outcome on osteoporotic fractures among patients with former thiazide diuretic therapy needs to be further elucidated.

Evaluation of diuretic activity of different extracts of Mimosa pudica Linn.

PubMed

Baghel, A; Rathore, D S; Gupta, V

2013-10-15

In that study, Mimosa pudica linn was tested for diuretic activity using the lipschitz test. The ethanolic and aqoues extract of Mimosa pudica Linn. was studied at two dose level 100 and 200 mg kg(-1) b.wt. Furosemide (20 mg kg(-1) b.wt.) was used as standard drug in a 0.9% saline solution. Urine volumes were measured for all the groups up to 5 h. The ethanolic extract of Mimosa pudica linn was exhibited significant diuretic activity at doses of 100 and 200 mg kg(-1) b.wt. by increasing total urine volume and ion concentration of Na+ k+ and Cl-.

Renal Function and Diuretic Therapy in Infants and Children. Part i

ERIC Educational Resources Information Center

Loggie, Jennifer M. H.; And Others

1975-01-01

Included in the review are a description of the anatomic and functional development of the human kidney, a comparison of the renal physiology of the infant and adult, and a discussion of the pediatric clinical pharmacology of the most commonly used diuretic agents. (DB)

Lack of Gene-Diuretic Interactions on the Risk of Incident Gout: the Nurses’ Health Study and Health Professionals Follow-Up Study

PubMed Central

Bao, Ying; Curhan, Gary; Merriman, Tony; Plenge, Robert; Kraft, Peter; Choi, Hyon K.

2015-01-01

Background Diuretic-induced gout might occur only among those with a genetic predisposition to hyperuricemia, as suggested by a recent study with 108 self-reported gout cases. Methods We examined the role of urate genes on the risk of diuretic-induced incident gout in 6850 women from the Nurses’ Health Study (NHS) and in 4,223 men from the Health Professionals Follow-up Study (HPFS). Two published genetic risk scores (GRS) were calculated using urate-associated SNPs for eight genes (GRS8) and for 29 genes (GRS29). Results Our analyses included 727 and 354 confirmed incident gout cases in the HPFS and NHS, respectively. The multivariate RR for diuretic use was 2.20 and 1.69 among those with a GRS8 < and ≥ the median (p for interaction=0.27). The corresponding RRs using GRS29 were 2.19 and 1.88 (p for interaction=0.40). The lack of interaction persisted in the NHS (all p values >0.20) and in our analyses limited to those with hypertension in both cohorts. SLC22A11 (OAT4) showed a significant interaction only among women but in the opposite direction to the recent study. Conclusion In these large prospective studies, individuals with a genetic predisposition for hyperuricemia are not at a higher risk of developing diuretic-induced gout than those without. PMID:25667207

Simultaneous analysis of 17 diuretics in dietary supplements by HPLC and LC-MS/MS.

PubMed

Woo, H; Kim, J W; Han, K M; Lee, J H; Hwang, I S; Lee, J H; Kim, J; Kweon, S J; Cho, S; Chae, K R; Han, S Y; Kim, J

2013-01-01

In order to test health foods for illegally added diuretics for weight loss, we developed simple, rapid, selective, and sensitive methods using HPLC and LC-MS/MS for the simultaneous analysis of 17 diuretics in dietary supplements. HPLC conditions were set with a Capcell-pak C18, using a mobile phase consisting of gradient conditions, UV detection at 254 nm and validated for linearity (r(2)> 0.999), precision (CV ≤ 3%), recoveries (90.4-102.8%) and reproducibility. Identification and quantification of 17 diuretics were accomplished by ion-spray LC-MS/MS using multiple reaction monitoring (MRM). The chromatographic separation was carried out under the reversed-phase mechanism on an HSS-T3 column. The LC-MS/MS method was validated for linearity (r(2)> 0.99) and precision (CV < 13%). Sixteen dietary supplements were tested with the developed methods. Diuretics were not detected in all samples. Extraction recovery was also investigated and the extraction recoveries in different formulations were from 88% to 110% and from 81% to 116% using HPLC and LC-MS/MS, respectively. There was no significant difference in recoveries in the type of dietary supplements. Based on this result, the developed methods to monitor illegal drug adulterations in dietary supplements using HPLC and LC-MS/MS are simple, fast and reliable. Therefore, it is applicable to routine drug-adulteration screening.

[Ultrafiltration versus intravenous diuretics in decompensated heart failure: a meta-analysis of randomized controlled trials].

PubMed

Zhao, Yu-liang; Zhang, Ling; Yang, Ying-ying; Tang, Yi; Liu, Fang; Fu, Ping

2013-08-13

To explore whether ultrafiltration is superior to intravenous diuretics in ameliorating fluid overload and preserving renal functions in decompensated heart failure patients. By searching in Pubmed, Cochrane Library, Embase, Springer, WanFang, CQVIP, CNKI and CBM database as well as related Chinese journals, qualified randomized controlled trials (RCTs) were included for meta-analysis by Revman 5.0 and STATA 10.0. Six RCTs were included with 241 patients in ultrafiltration group and 240 patients in intravenous diuretics group. Pooled analyses demonstrated ultrafiltration was superior to intravenous diuretics in the aspects of weight loss (WMD = 1.44 kg, 95%CI:0.33-2.55 kg, P = 0.01) and fluid removal (WMD = 1.23 kg, 95%CI:0.63-1.82 kg, P < 0.01) while no significant difference was observed in serum creatinine level (WMD = -5.70 µmol/L, 95%CI: -35.02-23.61 µmol/L, P = 0.70), serum creatinine change from baseline (WMD = 4.74 µmol/L, 95%CI:-13.72-23.20 µmol/L, P = 0.61), mortality (RR = 1.09, 95%CI: 0.69-1.70, P = 0.72) or rehospitalization (RR = 0.92, 95%CI:0.53-1.61, P = 0.78). For decompensated heart failure patients, ultrafiltration is superior to intravenous diuretics in mitigating fluid overload. No intergroup difference was observed in renal function preservation, mortality or rehospitalization.

Changes in brain natriuretic peptide in chronic heart failure patients treated with long-acting versus short-acting loop diuretics: J-MELODIC subanalysis.

PubMed

Fukui, Miho; Tsujino, Takeshi; Hirotani, Shinichi; Ito, Hiroshi; Yamamoto, Kazuhiro; Akasaka, Takashi; Hirano, Yutaka; Ohte, Nobuyuki; Daimon, Takashi; Nakatani, Satoshi; Kawabata, Masaaki; Masuyama, Tohru

2017-07-01

We have previously reported that a long-acting loop diuretic, azosemide, reduces cardiovascular risks in patients with chronic heart failure (CHF) as compared with a short-acting one, furosemide, in Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure (J-MELODIC). However, the mechanisms of the difference have not been elucidated. This study aimed to examine whether there is a difference in the reduction in plasma brain natriuretic peptide (BNP) level and in left ventricular (LV) functional recovery between the CHF patients treated with the long-acting diuretic (the azosemide group) and the short-acting diuretic (the furosemide group). We reviewed changes in plasma BNP level and echo-assessed LV functional parameters from baseline to a year after the entry in 288 CHF patients with New York Heart Association class II or III symptoms that joined J-MELODIC. The decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group (p < 0.01). The changes in echocardiographic parameters were not more favorable in the azosemide group than in the furosemide group. In conclusion, the decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group. These findings may account for the better prognosis in CHF patients treated with azosemide than those with furosemide in J-MELODIC.

Loop diuretics are associated with greater risk of sarcopenia in patients with non-dialysis-dependent chronic kidney disease.

PubMed

Ishikawa, Seiko; Naito, Shotaro; Iimori, Soichiro; Takahashi, Daiei; Zeniya, Moko; Sato, Hidehiko; Nomura, Naohiro; Sohara, Eisei; Okado, Tomokazu; Uchida, Shinichi; Rai, Tatemitsu

2018-01-01

Sarcopenia, the age-related loss of muscle mass and function, frequently accompanies chronic kidney disease. The aim of this study was to clarify the prevalence and the risk factors for sarcopenia among patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), focusing on the use of drugs. We conducted a cross-sectional analysis on a cohort of 260 patients with NDD-CKD in a university hospital, recruited between June 2016 and March 2017. We extracted data on patient gender, age, cause of chronic kidney disease, use of drugs, and comorbidities that could potentially affect the prevalence of sarcopenia. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia. Logistic regression analysis was performed to analyze the association of each factor on the prevalence of sarcopenia. 25.0% of our study subjects had sarcopenia. Multivariable analysis revealed that an increased risk of sarcopenia was significantly associated with age, male gender, body mass index, diabetes mellitus, and loop diuretic use (odds ratio, 4.59: 95% confidence interval, 1.81-11.61: P-value 0.001). In our cohort, the prevalence of sarcopenia in patients with NDD-CKD was high, and diuretics use, particularly loop diuretic use, was suggested to be a risk factor of sarcopenia. Although loop diuretics are commonly used in patients with CKD, careful consideration of the risk of sarcopenia may be necessary.

Loop diuretics inhibit cholinergic and noncholinergic nerves in guinea pig airways.

PubMed

Elwood, W; Lötvall, J O; Barnes, P J; Chung, K F

1991-06-01

Furosemide, a loop diuretic, is known to inhibit the response to a variety of indirect bronchial challenges in humans but does not inhibit bronchoconstriction induced by inhaled methacholine or histamine. We have investigated the effects of the two loop diuretics, furosemide (10(-6) to 10(-3) M) and bumetanide (10(-7) to 10(-4) M), on airway smooth muscle contraction in vitro induced by electrical field stimulation (EFS), or exogenously applied acetylcholine (ACh) or substance P (SP) in guinea pig tracheal and bronchial smooth muscle strips pretreated with indomethacin (10(-5) M) and propranolol (10(-6) M). Both furosemide and bumetanide caused a concentration-dependent inhibition of cholinergically mediated neural contraction in the trachea. The effect of furosemide was not influenced by the presence of airway epithelium. Furthermore, both furosemide and bumetanide inhibited in a concentration-dependent fashion nonadrenergic, noncholinergic (NANC) contraction induced by electrical field stimulation of bronchi pretreated with atropine (10(-5) M). Neither drug at the highest concentration inhibited the responses to exogenous acetylcholine (10(-8) to 10(-2) M) or substance P (10(-9) to 10(-5) M). Thus loop diuretics inhibit the neurally induced contraction of guinea pig airways without a direct effect on airway smooth muscle. We conclude that loop diuretics inhibit both cholinergic and excitatory NANC neurotransmission in guinea pig airways and that this effect may be related to their inhibitory effects on the sodium-potassium-chloride cotransporter.

Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

PubMed

Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

2015-01-01

Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury

PubMed Central

Estrella, Michelle M.; Coresh, Josef; Brower, Roy G.; Liu, Kathleen D.

2011-01-01

Summary Background and objectives Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients. Design, setting, participants, & measurements Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria. Results 306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased. Conclusions A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance. PMID:21393482

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters

PubMed Central

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M.

2014-01-01

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na+, K+, or Cl− levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

PubMed

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

2014-12-15

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. Copyright © 2014 the American Physiological Society.

Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study.

PubMed

Chuang, Yi-Fang; Breitner, John C S; Chiu, Yen-Ling; Khachaturian, Ara; Hayden, Kathleen; Corcoran, Chris; Tschanz, JoAnn; Norton, Maria; Munger, Ron; Welsh-Bohmer, Kathleen; Zandi, Peter P

2014-11-01

Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer's disease (AD), it remains unclear which class provides the most benefit. The Cache County Study of Memory Health and Aging is a prospective longitudinal cohort study of dementing illnesses among the elderly population of Cache County, Utah. Using waves I to IV data of the Cache County Study, 3417 participants had a mean of 7.1 years of follow-up. Time-varying use of antihypertensive medications including different class of diuretics, angiotensin converting enzyme inhibitors, β-blockers, and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses. During follow-up, 325 AD cases were ascertained with a total of 23,590 person-years. Use of any antihypertensive medication was associated with lower incidence of AD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.61-0.97). Among different classes of antihypertensive medications, thiazide (aHR, 0.7; 95% CI, 0.53-0.93), and potassium-sparing diuretics (aHR, 0.69; 95% CI, 0.48-0.99) were associated with the greatest reduction of AD risk. Thiazide and potassium-sparing diuretics were associated with decreased risk of AD. The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort, now with longer follow-up, and merits further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Loop diuretics are associated with greater risk of sarcopenia in patients with non-dialysis-dependent chronic kidney disease

PubMed Central

Ishikawa, Seiko; Iimori, Soichiro; Takahashi, Daiei; Zeniya, Moko; Sato, Hidehiko; Nomura, Naohiro; Sohara, Eisei; Okado, Tomokazu; Uchida, Shinichi; Rai, Tatemitsu

2018-01-01

Introduction Sarcopenia, the age-related loss of muscle mass and function, frequently accompanies chronic kidney disease. The aim of this study was to clarify the prevalence and the risk factors for sarcopenia among patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), focusing on the use of drugs. Methods We conducted a cross-sectional analysis on a cohort of 260 patients with NDD-CKD in a university hospital, recruited between June 2016 and March 2017. We extracted data on patient gender, age, cause of chronic kidney disease, use of drugs, and comorbidities that could potentially affect the prevalence of sarcopenia. Sarcopenia was diagnosed using the criteria of the Asian Working Group for Sarcopenia. Logistic regression analysis was performed to analyze the association of each factor on the prevalence of sarcopenia. Results 25.0% of our study subjects had sarcopenia. Multivariable analysis revealed that an increased risk of sarcopenia was significantly associated with age, male gender, body mass index, diabetes mellitus, and loop diuretic use (odds ratio, 4.59: 95% confidence interval, 1.81–11.61: P-value 0.001). Conclusions In our cohort, the prevalence of sarcopenia in patients with NDD-CKD was high, and diuretics use, particularly loop diuretic use, was suggested to be a risk factor of sarcopenia. Although loop diuretics are commonly used in patients with CKD, careful consideration of the risk of sarcopenia may be necessary. PMID:29447254

Use of diuretics is associated with reduced risk of Alzheimer’s disease: the Cache County Study

PubMed Central

Chuang, Yi-Fang; Breitner, John C.S.; Chiu, Yen-Ling; Khachaturian, Ara; Hayden, Kathleen; Corcoran, Chris; Tschanz, JoAnn; Norton, Maria; Munger, Ron; Welsh-Bohmer, Kathleen; Zandi, Peter P.

2015-01-01

Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer’s disease (AD), it remains unclear which class provides the most benefit. The Cache County Study of Memory Health and Aging is a prospective longitudinal cohort study of dementing illnesses among the elderly population of Cache County, Utah. Using waves I to IV data of the Cache County Study, 3417 participants had a mean of 7.1 years of follow-up. Time-varying use of antihypertensive medications including different class of diuretics, angiotensin converting enzyme inhibitors, β-blockers, and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses. During follow-up, 325 AD cases were ascertained with a total of 23,590 person-years. Use of any anti-hypertensive medication was associated with lower incidence of AD (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.61–0.97). Among different classes of antihypertensive medications, thiazide (aHR, 0.7; 95% CI, 0.53–0.93), and potassium-sparing diuretics (aHR, 0.69; 95% CI, 0.48–0.99) were associated with the greatest reduction of AD risk. Thiazide and potassium-sparing diuretics were associated with decreased risk of AD. The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort, now with longer follow-up, and merits further investigation. PMID:24910391

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure.

PubMed

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-05-01

Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): -2.65 to -0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = -0.25 mg/dL; 95% CI: -0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64-1.56; p = 0.993). Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

PubMed

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

2013-12-09

To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

PubMed Central

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-01-01

Introduction Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed. PMID:25626761

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

PubMed

Radulović, Marija; Pucar, Dragan; Jauković, Ljiljana; Sisić, Marija; Krstić, Zoran; Ajdinović, Boris

2015-12-01

The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

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.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

PubMed Central

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John JV; Califf, Robert M

2013-01-01

Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. Trial registration ClinicalTrials.gov NCT00097786. PMID:24322398

Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients.

PubMed

Slagman, Maartje C J; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D

2012-03-01

Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients. In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P < 0.001 versus LS), in random order. As controls, 27 healthy volunteers were studied. NT-proBNP was elevated in patients during placebo + RS [90 (60-137) versus 35 (27-45) pg/mL in healthy controls, P = 0.001]. NT-proBNP was lowered by LS, ARB and diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen. Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.

Diuretic effect of compounds from Hibiscus sabdariffa by modulation of the aldosterone activity.

PubMed

Jiménez-Ferrer, Enrique; Alarcón-Alonso, Javier; Aguilar-Rojas, Arturo; Zamilpa, Alejandro; Jiménez-Ferrer C, Itzia; Tortoriello, Jaime; Herrera-Ruiz, Maribel

2012-12-01

Recent studies of Hibiscus sabdariffa Linn. have demonstrated that it presents diuretic, natriuretic, and potassium sparing effects. However, the mechanism that induces these effects has not yet been elucidated. The aim of this study was to explore the possible mechanism of action for the diuretic effect of Hibiscus sabdariffa extract and its fractions.The aqueous extract from this plant and the fractions obtained with solvents of different polarities were administered to adrenalectomized rats, and the diuretic effect was measured in the presence of deoxycorticosterone acetate (aldosterone analog).The effect on renal filtration was also evaluated in an in situ kidney model, and finally, the effect of diuretic active extracts on gene expression of the alpha subunit from the transporter (αENaC) of renal epithelial cell was quantified. The subsequent results were obtained: The aqueous extract of Hibiscus sabdariffa presented the following chemical composition, 32.4 mg/g delphinidin-3-O-sambubioside, 11.5 mg/g cyanidin-3-O-sambubioside, 11.5 mg/g quercetin, and chlorogenic acid 2.7 mg/g. The concentration of anthocyanins was diminished until disappearance due to decrease of the polarity of the solvents used in the extraction process, in contrast to the flavonoids and chlorogenic acid, which had their concentration increased. The diuretic effect caused by adrenalectomy in rats was reversed by deoxycorticosterone acetate activity. However, the effect of deoxycorticosterone acetate was antagonized by spironolactone, the aqueous extract of Hibiscus sabdariffa, and the acetonitrile : methanol 5 : 5 mixture extract, administered orally. A similar effect was observed on renal filtration obtained from the isolated kidney model.When the gene expression levels of αENaC was measured in adrenalectomized rats, it was observed that spironolactone, the aqueous extract of Hibiscus sabdariffa, the acetonitrile : methanol 5 : 5 mixture, as well as the acetonitrile extract significantly decreased the expression of this protein.The conclusion of this work is that the diuretic, natriuretic, and potassium sparing effects of Hibiscus sabdariffa are due in part to the modulation of aldosterone activity by the presence in the extract of this plant of compounds potentially responsible for this modulation, as anthocyanins, flavonoids, and chlorogenic acid. Georg Thieme Verlag KG Stuttgart · New York.

Improving Emotional Face Perception in Autism with Diuretic Bumetanide: A Proof-of-Concept Behavioral and Functional Brain Imaging Pilot Study

ERIC Educational Resources Information Center

Hadjikhani, Nouchine; Zürcher, Nicole R; Rogier, Ophelie; Ruest, Torsten; Hippolyte, Loyse; Ben-Ari, Yehezkel; Lemonnier, Eric

2015-01-01

Clinical observations have shown that GABA-acting benzodiazepines exert paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)[subscript i] and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer antagonist bumetanide, that decreases…

The Effects on Knowledge of the Systematic Education of Patients with Joint Diseases Treated with NSAIDs and Diuretics.

ERIC Educational Resources Information Center

Linne, Agneta Bjorck; Liedholm, Hans; Jacobsson, Lennart

2001-01-01

In a randomized, controlled trial, patients with joint diseases and concomitant treatment with NSAIDs and diuretics received systematic education. The intervention group was given information focusing on awareness of drug interactions and encouragement of self-adjustment of treatment. Results reveal that the intervention group achieved greater…

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.

Lack of gene-diuretic interactions on the risk of incident gout: the Nurses' Health Study and Health Professionals Follow-up Study.

PubMed

Bao, Ying; Curhan, Gary; Merriman, Tony; Plenge, Robert; Kraft, Peter; Choi, Hyon K

2015-07-01

Diuretic-induced gout might occur only among those with a genetic predisposition to hyperuricaemia, as suggested by a recent study with 108 self-reported gout cases. We examined the role of urate genes on the risk of diuretic-induced incident gout in 6850 women from the Nurses' Health Study (NHS) and in 4223 men from the Health Professionals Follow-up Study (HPFS). Two published genetic risk scores (GRSs) were calculated using urate-associated single-nucleotide polymorphisms for 8 (GRS8) and 29 genes (GRS29). Our analyses included 727 and 354 confirmed incident gout cases in HPFS and NHS, respectively. The multivariate relative risk (RR) for diuretic use was 2.20 and 1.69 among those with GRS8 < and ≥ the median (p for interaction=0.27). The corresponding RRs using GRS29 were 2.19 and 1.88 (p for interaction=0.40). The lack of interaction persisted in NHS (all p values >0.20) and in our analyses limited to those with hypertension in both cohorts. SLC22A11 (OAT4) showed a significant interaction only among women but in the opposite direction to the recent study. In these large prospective studies, individuals with a genetic predisposition for hyperuricaemia are not at a higher risk of developing diuretic-induced gout than those without. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

ROMK inhibitor actions in the nephron probed with diuretics

PubMed Central

Kharade, Sujay V.; Flores, Daniel; Lindsley, Craig W.; Satlin, Lisa M.

2015-01-01

Diuretics acting on specific nephron segments to inhibit Na+ reabsorption have been used clinically for decades; however, drug interactions, tolerance, and derangements in serum K+ complicate their use to achieve target blood pressure. ROMK is an attractive diuretic target, in part, because its inhibition is postulated to indirectly inhibit the bumetanide-sensitive Na+-K+-2Cl− cotransporter (NKCC2) and the amiloride- and benzamil-sensitive epithelial Na+ channel (ENaC). The development of small-molecule ROMK inhibitors has created opportunities for exploring the physiological responses to ROMK inhibition. The present study evaluated how inhibition of ROMK alone or in combination with NKCC2, ENaC, or the hydrochlorothiazide (HCTZ) target NCC alter fluid and electrolyte transport in the nephron. The ROMK inhibitor VU591 failed to induce diuresis when administered orally to rats. However, another ROMK inhibitor, termed compound A, induced a robust natriuretic diuresis without kaliuresis. Compound A produced additive effects on urine output and Na+ excretion when combined with HCTZ, amiloride, or benzamil, but not when coadministered with bumetanide, suggesting that the major diuretic target site is the thick ascending limb (TAL). Interestingly, compound A inhibited the kaliuretic response induced by bumetanide and HCTZ, an effect we attribute to inhibition of ROMK-mediated K+ secretion in the TAL and CD. Compound A had no effect on heterologously expressed flow-sensitive large-conductance Ca2+-activated K+ channels (Slo1/β1). In conclusion, compound A represents an important new pharmacological tool for investigating the renal consequences of ROMK inhibition and therapeutic potential of ROMK as a diuretic target. PMID:26661652

Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

PubMed

Jokinen, Viljami; Lilius, Tuomas; Laitila, Jouko; Niemi, Mikko; Kambur, Oleg; Kalso, Eija; Rauhala, Pekka

2017-01-01

Spironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co-administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)- and morphine (3 mg/kg, s.c.)-induced antinociception using tail-flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Treatment of Severe Edema in Children with Nephrotic Syndrome with Diuretics Alone — A Prospective Study

PubMed Central

Kapur, Gaurav; Valentini, Rudolph P.; Imam, Abubakr A.; Mattoo, Tej K.

2009-01-01

Background and objective: Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. Design, setting, participants, & measurements: Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2% identified VC in 20 phase 2 patients. Results: All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment. Conclusions: FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective. PMID:19406963

ROMK inhibitor actions in the nephron probed with diuretics.

PubMed

Kharade, Sujay V; Flores, Daniel; Lindsley, Craig W; Satlin, Lisa M; Denton, Jerod S

2016-04-15

Diuretics acting on specific nephron segments to inhibit Na + reabsorption have been used clinically for decades; however, drug interactions, tolerance, and derangements in serum K + complicate their use to achieve target blood pressure. ROMK is an attractive diuretic target, in part, because its inhibition is postulated to indirectly inhibit the bumetanide-sensitive Na + -K + -2Cl - cotransporter (NKCC2) and the amiloride- and benzamil-sensitive epithelial Na + channel (ENaC). The development of small-molecule ROMK inhibitors has created opportunities for exploring the physiological responses to ROMK inhibition. The present study evaluated how inhibition of ROMK alone or in combination with NKCC2, ENaC, or the hydrochlorothiazide (HCTZ) target NCC alter fluid and electrolyte transport in the nephron. The ROMK inhibitor VU591 failed to induce diuresis when administered orally to rats. However, another ROMK inhibitor, termed compound A, induced a robust natriuretic diuresis without kaliuresis. Compound A produced additive effects on urine output and Na + excretion when combined with HCTZ, amiloride, or benzamil, but not when coadministered with bumetanide, suggesting that the major diuretic target site is the thick ascending limb (TAL). Interestingly, compound A inhibited the kaliuretic response induced by bumetanide and HCTZ, an effect we attribute to inhibition of ROMK-mediated K + secretion in the TAL and CD. Compound A had no effect on heterologously expressed flow-sensitive large-conductance Ca 2+ -activated K + channels (Slo1/β1). In conclusion, compound A represents an important new pharmacological tool for investigating the renal consequences of ROMK inhibition and therapeutic potential of ROMK as a diuretic target. Copyright © 2016 the American Physiological Society.

Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

PubMed

van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

2000-12-01

Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

The diuretic effect of urea analog dimethylthiourea in female Wistar rats.

PubMed

Cil, O; Ertunc, M; Onur, R

2012-10-01

Urea plays an important role in the urinary concentrating mechanism in the kidney by contributing greatly in the generation of hyperosmolar medulla due to the presence of urea transporters, which mediate facilitated transport of urea. In this study, we investigated the possible diuretic effect of urea analog and urea transporter inhibitor, dimethylthiourea (DMTU), in rats. Female Wistar rats were divided into two groups, group 1 (control group, n = 7) rats were injected with saline intraperitoneally (i.p.), while group 2 (DMTU group, n = 7) rats were injected with 500 mg/kg DMTU (i.p.) and an additional dose of 125 mg/kg DMTU after 8 h. DMTU administration induced an approximately three times increase in daily urine volume (p < 0.001) and decreased urine osmolality to approximately 35% of controls (p < 0.0001). DMTU also increased free water clearance (p < 0.0001) without a significant change in osmolar clearance. DMTU treatment caused an increase in urea clearance (p < 0.05) and fractional excretion of urea (p < 0.05) with a decrease in serum urea concentration (p < 0.001). DMTU had no effect on creatinine clearance or serum electrolytes, creatinine levels and osmolality. With these findings, we report for the first time that DMTU has a prominent diuretic effect with increased urea excretion, which may be explained by the inhibitory effect of the drug on urea transporters. Our findings suggest that DMTU may be used as a diuretic agent and also could be used as a lead compound for the development of novel diuretics.

Gallic acid, a phenolic compound isolated from Mimosa bimucronata (DC.) Kuntze leaves, induces diuresis and saluresis in rats.

PubMed

Schlickmann, Fabile; Boeing, Thaise; Mariano, Luisa Nathália Bolda; da Silva, Rita de Cássia Melo Vilhena de Andrade Fonseca; da Silva, Luisa Mota; de Andrade, Sérgio Faloni; de Souza, Priscila; Cechinel-Filho, Valdir

2018-06-01

Although present in the leaves of Mimosa bimucronata (DC.) and many other medicinal plants commonly used to augment urinary volume excretion, the effects of gallic acid as a diuretic agent remain to be studied. Wistar rats were orally treated with vehicle, hydrochlorothiazide, or gallic acid. The effects of gallic acid in the presence of hydrochlorothiazide, furosemide, amiloride, L-NAME, atropine, and indomethacin were also investigated. Diuretic index, pH, conductivity, and electrolyte excretion were evaluated at the end of the experiment (after 8 or 24 h). Gallic acid induced diuretic and saluretic (Na + and Cl - ) effects, without interfering with K + excretion, when orally given to female and male rats at a dose of 3 mg/kg. These effects were associated with increased creatinine and conductivity values while pH was unaffected by any of the treatments. Plasma Na + , K + , and Cl - levels were not affected by any of the acute treatments. The combination with hydrochlorothiazide or furosemide was unable to intensify the effects of gallic acid when compared with the response obtained with each drug alone. On the other hand, the treatment with amiloride plus gallic acid amplified both diuresis and saluresis, besides to a marked potassium-sparing effect. Its diuretic action was significantly prevented in the presence of indomethacin, a cyclooxygenase inhibitor, but not with the pretreatments with L-NAME or atropine. Although several biological activities have already been described for gallic acid, this is the first study demonstrating its potential as a diuretic agent.

Acetazolamide Therapy for Metabolic Alkalosis in Pediatric Intensive Care Patients.

PubMed

López, Carolina; Alcaraz, Andrés José; Toledo, Blanca; Cortejoso, Lucía; Gil-Ruiz, Maite Augusta

2016-12-01

Patients in PICUs frequently present hypochloremic metabolic alkalosis secondary to loop diuretic treatment, especially those undergoing cardiac surgery. This study evaluates the effectiveness of acetazolamide therapy for metabolic alkalosis in PICU patients. Retrospective, observational study. A tertiary care children's hospital PICU. Children receiving at least a 2-day course of enteral acetazolamide. None. Demographic variables, diuretic treatment and doses of acetazolamide, urine output, serum electrolytes, urea and creatinine, acid-base excess, pH, and use of mechanical ventilation during treatment were collected. Patients were studied according to their pathology (postoperative cardiac surgery, decompensated heart failure, or respiratory disease). A total of 78 episodes in 58 patients were identified: 48 were carried out in cardiac postoperative patients, 22 in decompensated heart failure, and eight in respiratory patients. All patients received loop diuretics. A decrease in pH and PCO2 in the first 72 hours, a decrease in serum HCO3 (mean, 4.65 ± 4.83; p < 0.001), and an increase in anion gap values were observed. Urine output increased in cardiac postoperative patients (4.5 ± 2.2 vs 5.1 ± 2.0; p = 0.020), whereas diuretic treatment was reduced in cardiac patients. There was no significant difference in serum electrolytes, blood urea, creatinine, nor chloride after the administration of acetazolamide from baseline. Acetazolamide treatment was well tolerated in all patients. Acetazolamide decreases serum HCO3 and PCO2 in PICU cardiac patients with metabolic alkalosis secondary to diuretic therapy. Cardiac postoperative patients present a significant increase in urine output after acetazolamide treatment.

Comparison of the anticonvulsant potency of various diuretic drugs in the maximal electroshock-induced seizure threshold test in mice.

PubMed

Załuska, Katarzyna; Kondrat-Wróbel, Maria W; Łuszczki, Jarogniew J

2018-05-01

The coexistence of seizures and arterial hypertension requires an adequate and efficacious treatment involving both protection from seizures and reduction of high arterial blood pressure. Accumulating evidence indicates that some diuretic drugs (with a well-established position in the treatment of arterial hypertension) also possess anticonvulsant properties in various experimental models of epilepsy. The aim of this study was to assess the anticonvulsant potency of 6 commonly used diuretic drugs (i.e., amiloride, ethacrynic acid, furosemide, hydrochlorothiazide, indapamide, and spironolactone) in the maximal electroshock-induced seizure threshold (MEST) test in mice. Doses of the studied diuretics and their corresponding threshold increases were linearly related, allowing for the determination of doses which increase the threshold for electroconvulsions in drug-treated animals by 20% (TID20 values) over the threshold in control animals. Amiloride, hydrochlorothiazide and indapamide administered systemically (intraperitoneally - i.p.) increased the threshold for maximal electroconvulsions in mice, and the experimentally-derived TID20 values in the maximal electroshock seizure threshold test were 30.2 mg/kg for amiloride, 68.2 mg/kg for hydrochlorothiazide and 3.9 mg/kg for indapamide. In contrast, ethacrynic acid (up to 100 mg/kg), furosemide (up to 100 mg/kg) and spironolactone (up to 50 mg/kg) administered i.p. had no significant impact on the threshold for electroconvulsions in mice. The studied diuretics can be arranged with respect to their anticonvulsant potency in the MEST test as follows: indapamide > amiloride > hydrochlorothiazide. No anticonvulsant effects were observed for ethacrynic acid, furosemide or spironolactone in the MEST test in mice.

A prospective randomised double-blind placebo-controlled trial to assess the effect of diuretics on shockwave lithotripsy of calculi.

PubMed

Sabharwal, Sagar; Jeyaseelan, L; Panda, Arabind; Gnanaraj, Lionel; Kekre, Nitin S; Devasia, Antony

2017-12-01

To assess the effect of diuretics with shockwave lithotripsy (SWL) on the treatment of renal and upper ureteric calculi. Adult patients with a solitary non-obstructive radio-opaque renal or upper ureteric calculus with normal renal function were included. They were prospectively randomised to receive either SWL with placebo or SWL with diuretics (40 mg parenteral furosemide) in a double-blind manner with a sample size of 48 patients in each arm. The primary outcomes were the SWL success and failure rates. The secondary outcomes were the number of shocks and sessions. Complete fragmentation was achieved in 89.6% of the patients in the furosemide arm as compared to 81.3% in the placebo arm. Clearance was achieved in 77.1% of the patients in the furosemide arm as compared to 70.8% in the placebo arm. The number of shocks and the number of sessions were higher in the placebo arm. These differences were not statistically significant. The use of diuretics along with SWL treatment of renal and upper ureteric calculi does not show a statistically significant improvement in fragmentation or clearance.

[Supportive care for malignant ascites in palliative phase: Place of paracentesis and diuretics].

PubMed

Gamblin, Vincent; Da Silva, Arlette; Villet, Stéphanie; El Hajbi, Farid

2015-11-01

Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

PubMed

Bakris, George; Molitch, Mark; Zhou, Qian; Sarafidis, Pantelis; Champion, Annette; Bacher, Peter; Sowers, James R

2008-01-01

Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1 receptor antagonist, in conscious dogs.

PubMed

Kobayashi, T; Mizumoto, H; Karasawa, A

1993-12-01

The diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1 receptor antagonist, were determined and compared with those of trichlormethiazide (TCM) and furosemide in saline-loaded conscious dogs. KW-3902, at doses higher than 0.1 mg/kg (p.o.), produced dose-dependent increases of urine volume and sodium excretion and these effects were statistically significant at doses of 1-100 mg/kg. The increase in potassium excretion was lower than that of sodium, and the ratio of sodium to potassium excretion (Na/K) tended to be elevated. TCM (0.3 mg/kg) and furosemide (3 mg/kg) also induced increases in urine volume and sodium excretion. The diuretic effects of KW-3902 lasted for 4 h after administration, whereas TCM and furosemide caused significant natriuresis for 2 h after administration. Thus, KW-3902 exhibited a longer lasting natriuresis than TCM and furosemide. These results indicate that adenosine A1 receptor blockade by KW-3902 causes consistent diuresis and natriuresis in dogs and suggest that adenosine A1 receptor blockade is a promising approach to diuretic therapy.

Role of EDHF in the vasodilatory effect of loop diuretics in guinea-pig mesenteric resistance arteries

PubMed Central

Pourageaud, Fabrice; Bappel-Gozalbes, Catherine; Marthan, Roger; Freslon, Jean-Louis

2000-01-01

Relaxing effect of loop diuretics, piretanide and furosemide in comparison with acetylcholine (ACh) was investigated in guinea-pig isolated mesenteric resistance arteries. Concentration-response curves to ACh (0.001–10 μM) and diuretics (0.0001–1 μM) were constructed in noradrenaline (10–30 μM)-precontracted arteries incubated either in normal physiological salt solution (PSS) or in 30 mM KCl PSS (K-PSS). In PSS, maximal relaxations (Rmax) and pD2 to ACh were 87±2% and 7.1±0.1 (n=10). L-NG-nitro-arginine methyl ester (L-NAME, 100 μM) reduced Rmax by 20% (P<0.01, n=7) and pD2 by 10% (P<0.01). In contrast, indomethacin (10 μM) increased Rmax by 19% (P<0.01, n=8) and pD2 by 10% (P<0.05). Combination of L-NAME+indomethacin reversed the effect observed with either of these inhibitors used alone. In K-PSS, Rmax was attenuated by 40% (P<0.001, n=6) compared to PSS. L-NAME reduced Rmax by 65% (P<0.01, n=5) and increased pD2 by 15 fold. L-NAME+indomethacin suppressed the resistant relaxation. In PSS+L-NAME+indomethacin, inhibitors of small (SKCa; apamin, 0.1 μM) and large (BKCa; iberiotoxin and charybdotoxin, 0.1 μM) conductance Ca2+-sensitive K−-channels used alone had little effect on the ACh-response. Combination of apamin+iberiotoxin reduced Rmax by 40% (P<0.05, n=7) while apamin+charybdotoxin fully abolished the resistant relaxation. In PSS, piretanide and furosemide induced relaxation with Rmax: 89±3% vs 84±5% and pD2: 8.5±0.1 vs 7.7±0.2 (P<0.01) for piretanide (n=11) and furosemide (n=10), respectively. Endothelial abrasion suppressed relaxation to diuretics. L-NAME and indomethacin used alone or in combination did not significantly modify the response to diuretics. In K-PSS, piretanide-induced relaxation was abolished whereas that to furosemide was reduced by 70% (P<0.001, n=9) compared to PSS and was suppressed by L-NAME+indomethacin. In PSS+L-NAME+indomethacin, apamin slightly reduced relaxation to diuretics whereas charybdotoxin or iberiotoxin abolished the response. These results indicate that ACh-evoked relaxation is mediated by both NO/PGl2-dependent and -independent mechanisms. The EDHF-dependent component relies on activation of Ca2+-activated K+ channels, is sensitive to a combination of apamin+charybdotoxin and to a smaller degree to a combination of apamin+iberiotoxin. Loop diuretic-induced relaxation is endothelium-dependent, appears to be mediated by NO, PGl2 and EDHF for furosemide and EDHF only for piretanide. For the two diuretics, opening of BKCa channels may be involved in the relaxation. PMID:11082130

Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.

PubMed

Ahmed, M; Shikha, H A; Sadhu, S K; Rahman, M T; Datta, B K

2001-08-01

Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action.

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

PubMed Central

Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer-reviewed journal. Trial registration number NCT03226457; Pre-results. PMID:29042392

Urinary composition predicts diuretic efficiency of hypertonic saline solution with furosemide therapy and heart failure prognosis.

PubMed

Ando, Tomotaka; Okuhara, Yoshitaka; Orihara, Yoshiyuki; Nishimura, Koichi; Yamamoto, Kyoko; Masuyama, Tohru; Hirotani, Shinichi

2018-03-19

Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure > 90 mmHg, and estimated glomerular filtration rate > 15 ml/min/1.73 m 2 ). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and < 2000 ml (low urine volume: LUV). The basal clinical characteristics of both groups were analyzed and the predictors of HUV after receiving the treatment were identified. There were not significant differences between two groups in baseline clinical characteristics and medication. Univariate logistic analysis revealed that blood urea nitrogen/creatinine ratio, urine urea nitrogen/creatinine ratio (UUN/UCre), fractional excretion of sodium, and tricuspid annular plane systolic excursion positively associated with HUV. Multivariate logistic regression analysis revealed that UUN/UCre at baseline was independently associated with HUV, and UUN/UCre best predicts HUV by the therapy with a cut-off value of 6.16 g/dl/g Cre (AUC 0.910, 95% CI 0.696-0.999, sensitivity 80%, specificity 87%). The Kaplan-Meier curves revealed significant difference for HF rehospitalization and death rate at 180 days between patients with UUN/UCre ≥ 6.16 g/dl/g Cre and those with UUN/UCre < 6.16 g/dl/g Cre (log-rank P = 0.0489). UUN/UCre at baseline strongly predicted of diuretic efficiency in the hypertonic saline solution with furosemide therapy, and was associated with HF prognosis.

Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

PubMed

Orth, Lucas E; O'Mara, Keliana L

2018-01-01

This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

Are Surrogate Assumptions and Use of Diuretics Associated with Diagnosis and Staging of Acute Kidney Injury after Cardiac Surgery?

PubMed Central

Hussein, Hayder K.; Prabhu, Mahesh; Kanagasundaram, N. Suren

2012-01-01

Summary Background and objectives This study measured the association between the Acute Kidney Injury Network (AKIN) diagnostic and staging criteria and surrogates for baseline serum creatinine (SCr) and body weight, compared urine output (UO) with SCr criteria, and assessed the relationships between use of diuretics and calibration between criteria and prediction of outcomes. Design, setting, participants, & measurements This was a retrospective cohort study using prospective measurements of SCr, hourly UO, body weight, and drug administration records from 5701 patients admitted, after cardiac surgery, to a cardiac intensive care unit between 1995 and 2006. Results More patients (n=2424, 42.5%) met SCr diagnostic criteria with calculated SCr assuming a baseline estimated GFR of 75 ml/min per 1.73 m2 than with known baseline SCr (n=1043, 18.3%). Fewer patients (n=484, 8.5%) met UO diagnostic criteria with assumed body weight (70 kg) than with known weight (n=624, 10.9%). Agreement between SCr and UO criteria was fair (κ=0.28; 95% confidence interval 0.25–0.31). UO diagnostic criteria were specific (0.95; 0.94–0.95) but insensitive (0.36; 0.33–0.39) compared with SCr. Intravenous diuretics were associated with higher probability of falling below the UO diagnostic threshold compared with SCr, higher 30-day mortality (relative risk, 2.27; 1.08–4.76), and the need for renal support (4.35; 1.82–10.4) compared with no diuretics. Conclusions Common surrogates for baseline estimated GFR and body weight were associated with misclassification of AKIN stage. UO criteria were insensitive compared with SCr. Intravenous diuretic use further reduced agreement and confounded association between AKIN stage and 30-day mortality or need for renal support. PMID:22246280

Comparative Effectiveness of Blood Pressure-lowering Drugs in Patients who have Already Suffered From Stroke

PubMed Central

Wang, Wei-Ting; You, Li-Kai; Chiang, Chern-En; Sung, Shih-Hsien; Chuang, Shao-Yuan; Cheng, Hao-Min; Chen, Chen-Huan

2016-01-01

Abstract Hypertension is the most important risk factor for stroke and stroke recurrence. However, the preferred blood pressure (BP)-lowering drug class for patients who have suffered from a stroke has yet to be determined. To investigate the relative effects of BP-lowering therapies [angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blockers (ARB), β blockers, calcium channel blockers (CCBs), diuretics, and combinations of these drugs] in patients with a prior stroke history, we performed a systematic review and meta-analysis using both traditional frequentist and Bayesian random-effects models and meta-regression of randomized controlled trials (RCTs) on the outcomes of recurrent stroke, coronary heart disease (CHD), and any major adverse cardiac and cerebrovascular events (MACCE). Trials were identified from searches of published hypertension guidelines, electronic databases, and previous systematic reviews. Fifteen RCTs composed of 39,329 participants with previous stroke were identified. Compared with the placebo, only ACEI along with diuretics significantly reduced recurrent stroke events [odds ratio (OR) = 0.54, 95% credibility interval (95% CI) 0.33–0.90]. On the basis of the distribution of posterior probabilities, the treatment ranking consistently identified ACEI along with diuretics as the preferred BP-lowering strategy for the reduction of recurrent stroke and CHD (31% and 35%, respectively). For preventing MACCE, diuretics appeared to be the preferred agent for stroke survivors (34%). Moreover, the meta-regression analysis failed to demonstrate a statistical significance between BP reduction and all outcomes (P = 0.1618 for total stroke, 0.4933 for CHD, and 0.2411 for MACCE). Evidence from RCTs supports the use of diuretics-based treatment, especially when combined with ACEI, for the secondary prevention of recurrent stroke and any vascular events in patients who have suffered from stroke. PMID:27082571

Development and Validation of the Suprathreshold Stochastic Resonance-Based Image Processing Method for the Detection of Abdomino-pelvic Tumor on PET/CT Scans.

PubMed

Saroha, Kartik; Pandey, Anil Kumar; Sharma, Param Dev; Behera, Abhishek; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

2017-01-01

The detection of abdomino-pelvic tumors embedded in or nearby radioactive urine containing 18F-FDG activity is a challenging task on PET/CT scan. In this study, we propose and validate the suprathreshold stochastic resonance-based image processing method for the detection of these tumors. The method consists of the addition of noise to the input image, and then thresholding it that creates one frame of intermediate image. One hundred such frames were generated and averaged to get the final image. The method was implemented using MATLAB R2013b on a personal computer. Noisy image was generated using random Poisson variates corresponding to each pixel of the input image. In order to verify the method, 30 sets of pre-diuretic and its corresponding post-diuretic PET/CT scan images (25 tumor images and 5 control images with no tumor) were included. For each sets of pre-diuretic image (input image), 26 images (at threshold values equal to mean counts multiplied by a constant factor ranging from 1.0 to 2.6 with increment step of 0.1) were created and visually inspected, and the image that most closely matched with the gold standard (corresponding post-diuretic image) was selected as the final output image. These images were further evaluated by two nuclear medicine physicians. In 22 out of 25 images, tumor was successfully detected. In five control images, no false positives were reported. Thus, the empirical probability of detection of abdomino-pelvic tumors evaluates to 0.88. The proposed method was able to detect abdomino-pelvic tumors on pre-diuretic PET/CT scan with a high probability of success and no false positives.

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

Mootrala Karma of Kusha [Imperata cylindrica Beauv.] and Darbha [Desmostachya bipinnata Stapf.] - A comparative study.

PubMed

Shah, Niti T; Pandya, Tarulata N; Sharma, Parameshwar P; Patel, Bhupesh R; Acharya, Rabinarayan

2012-07-01

Kusha (Imperata cylindrica Beauv.) and Darbha (Desmostachya bipinnata Stapf.) are enlisted among Trinapanchamoola, which is a well-known diuretic and are individually enumerated in the Mootravirechaneeya Dashemani. The article deals with the evaluation and comparison of the individual Mootrala (diuretic) action of the two drugs in healthy volunteers. In this study, 29 healthy volunteers were divided into three groups administered with Darbha Moola Churna, Kusha Moola Churna, and placebo in each group for 14 days. The volunteers were subjected to evaluation of diuretic activity by maintaining the daily total input-output charts during the course of the study. The volunteers were advised to consume a minimum 2 l of water daily. Results show that Darbha and Kusha leaded to a percentage increase in urine volume as compared to placebo group, but the result was statistically insignificant.

Thiazide Diuretics in the Management of Young Children with Central Diabetes Insipidus.

PubMed

Al Nofal, Alaa; Lteif, Aida

2015-09-01

To report our experience in treating infants and toddlers with central diabetes insipidus (DI) with thiazide diuretics. A retrospective chart review of all infants and toddlers who were treated with thiazide diuretics for central DI at the Mayo Clinic between 1996 and 2014. Our cohort consisted of 13 patients. The median age at the start of therapy was 6 months (IQR, 1-14 months). Eight patients were given chlorothiazide at a starting dose of 5-10 mg/kg/day, and 5 patients were treated with hydrochlorothiazide at a starting dose of 1-2 mg/kg/day. The median age at the cessation of thiazide therapy was 18 months (IQR, 11.5-39 months). The main reason for stopping was the lack of continued response, in addition to hypernatremia. There was no hospitalization secondary to hyponatremia and only 1 hospitalization secondary to hypernatremia while receiving thiazide therapy. Calcium was checked periodically in 7 of the 13 patients, and 2 of these 7 patients had persistent hypercalcemia. Thiazide diuretics appear to be safe and effective in treating infants with central DI. They can be continued after the introduction of solid food, and until a lack of response is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis.

PubMed

Tajiri, Kazuto; Tokimitsu, Yoshiharu; Ito, Hiroyuki; Atarashi, Yoshinari; Kawai, Kengo; Minemura, Masami; Yasumura, Satoshi; Takahara, Terumi; Shimizu, Yukihiro; Sugiyama, Toshiro

2018-05-31

The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the "Decreased" and "Not-decreased" groups, respectively. Median body weight change 1 week after tolvaptan treatment was -1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment. © 2018 S. Karger AG, Basel.

Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon?

PubMed

De Vecchis, Renato; Ciccarelli, Antonio; Pucciarelli, Armando

2010-08-01

A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.

Comparison of the diuretic renogram and the pressure perfusion study in children

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

Kass, E.J.; Majd, M.; Belman, A.B.

1985-07-01

The authors evaluated 42 hydronephrotic kidneys with diuretic renography and pressure perfusion studies to diagnose or exclude the presence of obstruction. Both studies were highly accurate but a small number of false positive and false negative studies were observed with each testing modality. The advantages, disadvantages and potential sources of inaccuracy of each study are discussed, and a protocol for the evaluation of hydronephrosis incorporating both studies is proposed.

Are diuretics effective for Ménière`s disease?

PubMed

Rosenbaum, Andrés; Winter, Matías

2018-03-28

Ménière`s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. Diuretics have been widely used for the treatment of attacks, but there is controversy about their effectiveness. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We identified three systematic reviews including nineteen studies overall, of which four were randomized trials. We concluded it is not clear whether diuretics lead to a symptomatic improvement of vertigo or an objective decrease in hearing loss in patients with Ménière`s disease, because the certainty of the evidence is very low.

[Acute renal failure due to RAAS-inhibitors combined with dehydration].

PubMed

Scherpbier, Nynke D; de Grauw, Wim J C; Wetzels, Jack F M; Vervoort, Gerald M M

2010-01-01

Two men (61 and 81 years old) with mild impaired kidney function developed acute renal failure due to dehydration combined with the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS). After rehydration, correction of hyperkalaemia and stopping RAAS-inhibition and diuretics, they recovered completely. Many patients using RAAS-inhibitors have impaired renal function. In the case of dehydration due to gastroenteritis or prolonged fever they risk developing acute renal failure. The high risk groups are elderly patients, patients with atherosclerosis or heart failure and those with co-medication of diuretics or NSAIDs. The underlying mechanism is that the normal pathways to protect kidney perfusion in case of hypovolaemia are blocked by the use of RAAS-inhibitors or NSAIDs. In the case of dehydration in patients with chronic kidney disease using RAAS-inhibitors, serum creatinine and potassium levels should be monitored. Temporary discontinuation of RAAS-inhibitors or diuretics is often necessary.

Mootrala Karma of Kusha [Imperata cylindrica Beauv.] and Darbha [Desmostachya bipinnata Stapf.] - A comparative study

PubMed Central

Shah, Niti T.; Pandya, Tarulata N.; Sharma, Parameshwar P.; Patel, Bhupesh R.; Acharya, Rabinarayan

2012-01-01

Kusha (Imperata cylindrica Beauv.) and Darbha (Desmostachya bipinnata Stapf.) are enlisted among Trinapanchamoola, which is a well-known diuretic and are individually enumerated in the Mootravirechaneeya Dashemani. The article deals with the evaluation and comparison of the individual Mootrala (diuretic) action of the two drugs in healthy volunteers. In this study, 29 healthy volunteers were divided into three groups administered with Darbha Moola Churna, Kusha Moola Churna, and placebo in each group for 14 days. The volunteers were subjected to evaluation of diuretic activity by maintaining the daily total input–output charts during the course of the study. The volunteers were advised to consume a minimum 2 l of water daily. Results show that Darbha and Kusha leaded to a percentage increase in urine volume as compared to placebo group, but the result was statistically insignificant. PMID:23723646

Poor concordance between different definitions of worsening renal function in patients with acute exacerbation of chronic heart failure: a retrospective study.

PubMed

De Vecchis, Renato; Baldi, Cesare; Di Biase, Giuseppina

2016-04-01

Approximately one-third of patients with acute decompensated heart failure (ADHF) treated with an intravenous (iv) loop diuretic at a relatively high dose (>80 mg/day of furosemide, or an equivalent dose of another loop diuretic), exhibit worsening renal function (WRF) after a single course of iv infusions or iv bolus injections maintained for several days. WRF is currently defined as an increase in serum creatinine >0.3 mg/dL (WRF-Cr) or a decrease in the estimated glomerular filtration rate of ≥20% (WRF-GFR) compared to baseline measurements. Furthermore, small increases in serum creatinine in the high-normal range of its values are indicative of significant reductions in estimated glomerular filtration rate (eGFR) due to the exponential relationship between serum creatinine and eGFR. Therefore, underestimating this relationship could lead to an erroneous quantitative estimate of new-onset renal dysfunction, diuretic-related. The relationship between baseline serum creatinine (exposure variable) and the risk of diuretic-related WRF (dichotomous outcome variable), expressed either as WRF-Cr or as WRF-GFR, was assessed by logistic regression analysis. For this purpose, medical records with a diagnosis of previous ADHF were collated, and retrospectively analyzed. The eGFR was calculated using the equation "Modification of Diet in Renal Disease" (MDRD). The WRF was inferred from measurements of serum creatinine that had been made daily during the scheduled courses of intravenous diuretic therapy. Thirty-eight patients with chronic heart failure (CHF) and history of a previous episode of ADHF were enrolled in the study. An increase higher than 0.3 mg/dL of serum creatinine (WRF-Cr) was detected in 14 of 38 patients (36.8%). In addition, a decrease of ≥20% in GFR (WRF-GFR) was detected in 14 of 38 patients (36.8%). However, a poor concordance between the two criteria was found (Cohen's Kappa =0.208, 95% CI: -0.110 to 0.526). WRF-Cr and WRF-GFR showed opposing relations with baseline serum creatinine. In fact, the risk of WRF-Cr appeared positively associated with baseline serum creatinine (odds ratio =33.56; 95% CI:2.93- 384.18 P=0.0047), while the risk of WRF-GFR was inversely associated with the same analyte (odds ratio =0.0393; 95% CI: 0.0039 to 0.3966 P=0.0061). The criterion to discontinue the iv diuretic or to reduce its dosage in the presence of WRF-Cr for patients with ADHF or resistance to oral diuretic should be joined with the useful notion that this finding indicates a significant reduction of eGFR only for values of serum creatinine in the normal or near-normal ranges.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

PubMed

Baroletti, Steven A; Gabardi, Steven; Magee, Colm C; Milford, Edgar L

2003-06-01

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.

Antiinflammatory, Diuretic and Antimicrobial Activities of Rungia pectinata Linn. and Rungia repens Nees

PubMed Central

Swain, S. R.; Sinha, B. N.; Murthy, P. N.

2008-01-01

The hydroalcoholic extracts prepared from leaves of Rungia pectinata and Rungia repens were investigated for antiinflammatory and diuretic activity in wistar rats. The results obtained were compared with that of standard drug aspirin and frusemide for their antiinflammatory and diuretic activity respectively. The acute toxicity study was also carried out using adult swiss albino mice of either sex which indicates the safety of the extracts even at a dose of 4000 mg/kg. R. pectinata showed better anti-inflammatory activity than R. repens. In the present study, it was demonstrated that hydroalcoholic extracts of both R. repens and R. pectinata produce diuretic effect by increasing the excretion of Na+, K+ and Cl−. Results showed that R. repens is most effective in increasing urinary electrolyte concentration of Na+ and K+ ions. The antimicrobial potency of the aerial parts of Rungia pectinata and Rungia repens have been studied using the petroleum ether, benzene, chloroform, acetone and ethanol extract against a wide number of bacteria and fungi by disc diffusion method. The ethanol extract at a concentration of 30 to 60 μg/disc showed significant activity against the bacteria and fungus investigated. All the extracts of R. pectinata and R. repens have got moderate action but chloroform and acetone extracts of R. repens and ethanol extract of R. pectinata have got significant activity against Trichophyton mentagrophytes. PMID:21394276

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

PubMed

Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysis.

PubMed

Roush, George C; Abdelfattah, Ramy; Song, Steven; Kostis, John B; Ernst, Michael E; Sica, Domenic A

2018-06-01

Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

PubMed

Nygård, Peder; Jansman, Frank G A; Kruik-Kollöffel, Willemien J; Barnaart, Alex F W; Brouwers, Jacobus R B J

2012-06-01

The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. One teaching hospital in the Netherlands. The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.

Physiologic Systems and Their Responses to Conditions of Heat and Cold

DTIC Science & Technology

2012-01-01

serial measures are made. Hypohydration increases heat storage by reducing sweating rate and skin blood-flow responses for a given core temperature. In...Capi’llary (3.5 L) E_xc_h~ (B%TBW) - - t Lymph Fluid Output I ) Urine Sweat ,JSF (1 1.5 L) (25% TBW) Osmotic Exchange ..._ _ ICF (30 L) (67%TBW...diuretics increase urine formation and generally result in the loss of boch solures and warer. Diuretic-induced hypohydrarion generally results in an

The Effects of Postoperative Activity on Subcuranious Tissue Oxygen Tension and Blood Flow in Orthopedic Surgical Patients

DTIC Science & Technology

1993-06-01

use of diuretics, beta blocking drugs , or steroids were also excluded. Because...1293. Zurier, R.B. & Weissman, G. (1979) Antiimmunologic and anti - inflammatory effects of steroid therapy. In D.L. Azarnoff (Ed.), Steroid Therapy...4.16 NSAID use (Y/N) 4/1 3/2 Diuretic use (Y/N) 0/5 1/4 Cardiac Med use (Y/N) 1/4 1/4 Pain Med use (Y/N) 1/4 1/4 Anaesthetic (Gen/Gen+Epi/Epi) 0/5/0

Formulation and in vitro examination of furosemide containing suppositories and preliminary experiences of their clinical use.

PubMed

Regdon, G; Fazekas, T; Regdon, G; Selmeczi, B

1996-02-01

Rectal suppositories containing furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid) and furosemide sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from the vehicle having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, crossover clinical trial including 8 patients. Both preparations have induced an increase of urine flow, which was comparable to the diuretic effect of the tablet.

Bumetanide, a new loop diuretic.

PubMed

Carrière, S; Dandavino, R

1976-10-01

The effect of bumetanide on renal function has been compared with that of furosemide and a placebo in a double-blind study of 9 healthy young men. The sequence for oral administration of the drug was subjected to a random assignation based upon the Latin-square methodology under three different conditions. (1) Normal hydration: The administration of bumetanide (2 mg) produced within the next 4 hr a diuresis comparable to that induced by 80 mg of furosemide. Urinary excretion of sodium, potassium, chloride, calcium, and uric acid also followed comparable patterns. Phosphaturia occurred only under bumetanide. The effect of bumetanide seemed longer lasting. (2) Water loading: The effects of bumetanide and furosemide were comparable with the exception of the phosphaturic effect induced by bumetanide. The action of both diuretics on the diluting segment of the nephron was well demonstrated by the marked depression of CH2O. (3) Water deprivation: The effects of the two diuretics were comparable, including depression tCH20. In none of these conditions did the placebo produce any significant effect.

More Efficient Sodium Removal by Ultrafiltration Compared to Diuretics in Acute Heart Failure; Underexplored and Overstated.

PubMed

Kazory, Amir

2016-01-01

Enhanced removal of sodium has often been cited as an advantage of ultrafiltration (UF) therapy over diuretic-based medical treatment in the management of acute decompensated heart failure. However, so far clinical studies have rarely evaluated the precise magnitude of sodium removal, and this assumption is largely based on the physiologic mechanisms and anecdotal observations that predate the contemporary management of heart failure. Recent data suggest that patients treated with UF experience substantial reduction in urinary sodium excretion possibly due to prolonged intravascular volume contraction. Consequently, the efficient sodium extraction through production of isotonic ultrafiltrate can be offset by urine hypotonicity. Based on the limited currently available data, it seems unlikely that the persistent benefits of UF could be solely explained by its greater efficiency in sodium removal. The design of the future studies should include frequent measurements of urine sodium to precisely compare the impact of UF and diuretics on sodium balance. © 2016 S. Karger AG, Basel.

Tolvaptan for the treatment of liver cirrhosis oedema.

PubMed

Sakaida, Isao

2014-07-01

No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension.

PubMed

Sawai, Toshiki; Dohi, Kaoru; Fujimoto, Naoki; Okubo, Setsuya; Isaka, Naoki; Ichikawa, Takehiko; Makino, Katsutoshi; Okamoto, Shinya; Koyabu, Sukenari; Kitamura, Tetsuya; Ogura, Toru; Yamada, Tomomi; Tamaru, Satoshi; Nishikawa, Masakatsu; Nakamura, Mashio; Ito, Masaaki

2017-10-01

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria. ©2017 Wiley Periodicals, Inc.

99mTc-DTPA diuretic renal scintigraphy in dogs with nephroureterolithiasis

PubMed Central

Hecht, Silke; Lawson, S. Meg; Lane, India F.; Sharp, Dorothy E.; Daniel, Gregory B.

2010-01-01

This study evaluated the results of diuretic renal scintigraphy in dogs with urolithiasis. Eighty-three kidneys with nephroureterolithiasis +/− renal pelvis/ureteral dilation were included in the study. Sixty-three kidneys showed a non-obstructive pattern, with a steep drop or gradual downward slope of renal time-activity curve (TAC). Excretion half-time of radiopharmaceutical (T1/2) was 3.99 (2.99 to 7.95) min. Three kidneys showed an obstructive pattern, with continuous rise of the TAC and median T1/2 of −10.71 (−5.20 to −17.56) min. Fifteen kidneys had non-diagnostic studies characterized by flat TAC. Individual kidney glomerular filtration rate was < 0.5 mL/min/kg body weight in most non-diagnostic studies. Diuretic renal scintigraphy appears to be a useful adjunct modality to rule out or confirm ureteral obstruction in dogs. Additional diagnostic procedures may be necessary to achieve a definitive diagnosis in cases of severely impaired renal function. PMID:21358928

Acute diuretic activity of aqueous Erica multiflora flowers and Cynodon dactylon rhizomes extracts in rats.

PubMed

Sadki, Chrifa; Hacht, Brahim; Souliman, Amrani; Atmani, Fouad

2010-03-24

The aim of the present study is to evaluate the diuretic potential and effect on urinary electrolytes of aqueous Erica multiflora L. (Ericaceae) flowers and Cynodon dactylon L. (Poaceae) rhizomes extracts in rats. Different concentrations of these plants extract (0.125, 0.250, and 0.500 g/kg of body weight) or the reference drug furosemide (0.015 g/kg) were administrated orally to hydrated male Wistar rats and their urine output was measured at several interval of time after a single dose administration. Furthermore, a toxicological effect of both plants was undertaken as well. The results showed that furosemide induced significant diuresis and electrolytes excretion during the first hours. Plant extracts increased significantly urinary output and electrolytes excretion at the dose of 0.250 g/kg for Erica multiflora and 0.500 g/kg for Cynodon dactylon. This diuretic effect seems to be not related to K(+) plant content. Urinary pH remained mostly unchanged during the course of the study for both plant extracts. No lethality was observed among animals when using Erica multiflora even at the dose of 10 g/kg while Cynodon dactylon, instead, caused 50% of rat death (LD50) at 4.5 g/kg. We concluded that both aqueous herb extracts administered, particularly, at the dose of 0.500 g/kg induce significant effect on urinary output of water and electrolytes and justify their use as diuretic remedy in traditional medicine. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Methanolic extract of Cola nitida elicits dose-dependent diuretic, natriuretic and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity in rats.

PubMed

Adeosun, Olukayode Isaac; Olaniyi, Kehinde S; Amusa, Oluwatobi A; Jimoh, Gbemisola Z; Oniyide, Adesola A

2017-01-01

Cola nitida (Kolanut) is conventionally used in tropical Africa for the treatment of all kinds of ailments such as migraine, morning sickness, metabolic disorders etc. However, this study was designed to investigate the diuretic, natriuretic and kaliuretic activities of methanolic extract of Cola nitida (MECN) in male Wistar rats. Adult male Wistar rats were randomly allotted into control (25 ml/kg b.w .), furosemide (20 mg/kg b.w ; standard), MECN 1 (100 mg/kg), MECN 2 (200 mg/kg), MECN 3 (300 mg/kg), MECN 4 (400 mg/kg), MECN 5 (500 mg/kg), MECN 6 (600 mg/kg) groups with n=6. The extract was prepared as previously described and the treatment lasted for 14 days. Urine volume and diuretic indices were estimated. Urine electrolytes, plasma electrolytes, plasma/renal AST/ALT, plasma creatinine and urea were assayed using flame photometry and standard colorimetric method respectively.Administration of different doses of C. nitida significantly altered body weight gain and water intake but not food intake compared with control group. There were significant increases in urine volume and urine electrolytes (Na + , K + and Cl - ), a decrease in plasma/renal ALT and AST activities, a decrease in plasma creatinine and urea concentration and no alteration in plasma electrolytes when compared with control and furosemide-treated groups. Our study suggests that MECN elicits diuretic, natriuretic, and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity. These effects are dose-dependent.

Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and Calcium Channel Blocker.

PubMed

Tsai, Min-Shan; Tang, Chao-Hsiun; Lin, Chia-Ying; Chuang, Po-Ya; Chen, Nai-Chuan; Huang, Chien-Hua; Chang, Wei-Tien; Wang, Tzung-Dau; Yu, Ping-Hsun; Chen, Wen-Jone

2017-12-01

In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004-2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051-2.307; p < 0.05) as compared with the A + B + C group. Adding a diuretic may be better than adding a beta-blocker for treating hypertensive patients with prior CVA history who have already received ACEIs/ARBs and CCBs.

Methanolic extract of Cola nitida elicits dose-dependent diuretic, natriuretic and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity in rats

PubMed Central

Adeosun, Olukayode Isaac; Olaniyi, Kehinde S; Amusa, Oluwatobi A; Jimoh, Gbemisola Z; Oniyide, Adesola A

2017-01-01

Cola nitida (Kolanut) is conventionally used in tropical Africa for the treatment of all kinds of ailments such as migraine, morning sickness, metabolic disorders etc. However, this study was designed to investigate the diuretic, natriuretic and kaliuretic activities of methanolic extract of Cola nitida (MECN) in male Wistar rats. Adult male Wistar rats were randomly allotted into control (25 ml/kg b.w.), furosemide (20 mg/kg b.w; standard), MECN1 (100 mg/kg), MECN2 (200 mg/kg), MECN3 (300 mg/kg), MECN4 (400 mg/kg), MECN5 (500 mg/kg), MECN6 (600 mg/kg) groups with n=6. The extract was prepared as previously described and the treatment lasted for 14 days. Urine volume and diuretic indices were estimated. Urine electrolytes, plasma electrolytes, plasma/renal AST/ALT, plasma creatinine and urea were assayed using flame photometry and standard colorimetric method respectively.Administration of different doses of C. nitida significantly altered body weight gain and water intake but not food intake compared with control group. There were significant increases in urine volume and urine electrolytes (Na+, K+ and Cl-), a decrease in plasma/renal ALT and AST activities, a decrease in plasma creatinine and urea concentration and no alteration in plasma electrolytes when compared with control and furosemide-treated groups. Our study suggests that MECN elicits diuretic, natriuretic, and kaliuretic activities without causing electrolyte impairment, hepatotoxicity and nephrotoxicity. These effects are dose-dependent. PMID:29348800

Effects of maleic acid and uranyl on mercurial diuresis in dogs

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

Nigrovic, V.; Koechel, D.A.; Cafruny, E.J.

1973-01-01

The effects of two nephrotoxic agents were studied in anesthetized dogs undergoing mercurial diuresis. One of the agents, uranyl, accumulates in the kidneys when administered as the acetate salt but does not readily react with sulfhydryl groups. In acute experiments uranyl acetate in doses up to 5 ..mu..mol/kg produced no change in the urinary excretion of sodium or chloride. Uranyl acetate given before the injection of mercury(II) did not reduce the diuretic response to inorganic mercury. The other compound, maleic acid, accumulates in the kidneys and also reacts readily with sulfhydryl groups. The administration of small doses of maleic acidmore » did not change the excretion of sodium but it decreased the excretion of chloride. The administration of maleic acid either before or after the administration of mercury completely abolished the diuretic response. The inhibition occurred without significant changes in urinary pH. Diuretic responses to ethacrynic acid, furosemide, hydrochlorothiazide or acetazolamide were preserved in maleate-treated dogs. Both the lack of any effect of uranyl on mercurial diuresis and the specific inhibition of mercurial diuresis by maleic acid support the presently accepted view that the renal diuretic receptor for mercury(II) has at least one sulfhydryl binding site. Although the inhibition is ascribed to competition between mercury(II) and maleate for binding on the receptor, it is conceivable that the reduction in urinary chloride excretion produced by maleate may be responsible, in part, for refractoriness to mercury(II).« less

The concomitant prescribing of ethinyl estradiol/drospirenone and potentially interacting drugs.

PubMed

McAdams, Mara; Staffa, Judy A; Dal Pan, Gerald J

2007-10-01

Ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin drospirenone with antimineralocorticoid properties that may cause potassium retention leading to hyperkalemia. We estimated the percentage of EE/DRSP users prescribed concomitant potassium-sparing drugs [nonsteroidal antiinflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors (with diuretics), angiotensin II agonists (with diuretics), and potassium chloride] between January 1, 2002, and March 31, 2005. We analyzed a population-based data set of 62,527 EE/DRSP users (Dimension Rx, Caremark). We compared the fill date and end date for each prescription (Rx) for an interacting drug to the start and end date for each EE/DRSP episode (linked Rxs). If a day of an interacting Rx overlapped with an EE/DRSP episode, concomitant prescribing was recorded. A total of 17.6% of the women concomitantly used EE/DRSP and an interacting drug. Twenty-nine percent of concomitant use occurred within a month of EE/DRSP initiation. Nonsteroidal antiinflammatory drugs and diuretics were most frequently used concomitantly with EE/DRSP. Forty percent of the women with concomitant use were 35 yearsof age or older at EE/DRSP initiation compared with 29% without concomitant use (p<.001). Obstetricians/gynecologists and family practitioners were the most common prescribers of EE/DRSP and potassium-sparing drugs, respectively. Concomitant prescribing of EE/DRSP and potassium-sparing drugs occurred frequently in our study population. As EE/DRSP becomes more widely used, physicians prescribing it should monitor patients for potassium-sparing drug use.

Assessing opioid shopping behaviour: a large cohort study from a medication dispensing database in the US.

PubMed

Cepeda, M Soledad; Fife, Daniel; Chow, Wing; Mastrogiovanni, Gregory; Henderson, Scott C

2012-04-01

: Risks of abuse, misuse and diversion of opioids are of concern. Obtaining opioid prescriptions from multiple prescribers, known as opioid shopping, is a way in which opioids may be abused and diverted. Previous studies relied on counting the number of prescribers or number of pharmacies a subject goes to in a year to define shopping behaviour, but did not distinguish successive prescribers from concomitant prescribers. : The aim of the study was to assess the frequency of opioid overlapping prescriptions from different prescribers, compare it with diuretics and benzodiazepines, and provide a definition of shopping behaviour that differentiates opioids from diuretics, avoiding the inappropriate flagging of individuals with legitimate use of opioids. : Population-based cohort study using the IMS LRx database. This database covers 65% of all retail prescriptions in the US and includes mail service and specialty pharmacy provider prescriptions independent of the method of payment. : Ambulatory. : Subjects with at least one dispensing for any type of opioid in 2008. Similar cohorts were created for subjects exposed to benzodiazepines or diuretics. Analyses were performed separately for naïve subjects and those with prior use. : Frequency of overlapping prescriptions defined as at least 1 day of overlapping dispensing of prescriptions written by two or more different prescribers at any time during an 18-month period. : A total of 25 161 024 subjects exposed to opioids were included, of whom 13.1% exhibited at least one episode of overlapping prescriptions during 18 months of follow-up. Almost 10% of subjects exposed to benzodiazepines and 13.8% of subjects exposed to diuretics exhibited a similar behaviour. Having overlapping prescriptions dispensed by three or more pharmacies differentiates opioids from the other medication classes. Using that criterion, the overall risk of shopping behaviour was 0.18% in subjects exposed to opioids, 0.10% in subjects exposed to benzodiazepines and 0.03% in subjects exposed to diuretics. For opioids, subjects aged between 25 and 64 years exhibited shopping behaviour more commonly (0.25%) than subjects 65 years or older (0.07%), and subjects with a history of prior opioid use exhibited such behaviour more commonly (0.7%) than opioid-naïve subjects (0.07%). : Overlapping of prescriptions is not unique to opioids and therefore a criterion that incorporates number of pharmacies is needed to define shopping behaviour. Having two or more overlapping prescriptions written by different prescribers and filled at three or more pharmacies differentiates opioids from diuretics and likely constitutes shopping behaviour.

The effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in patients undergoing coronary artery bypass surgery.

PubMed

Kato, Tomoko S; Nakamura, Hiroshi; Murata, Mai; Kuroda, Kishio; Suzuki, Hitoshi; Yokoyama, Yasutaka; Shimada, Akie; Matsushita, Satoshi; Yamamoto, Taira; Amano, Atsushi

2016-09-13

Adequate fluid management is an important component of patient care following cardiac surgery. Our aim in this study was to determine the benefits of tolvaptan, an oral selective vasopressin-2 receptor antagonist that causes electrolyte-free water diuresis, in postoperative fluid management. We prospectively examined the effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in cardiac surgery patients. Patients undergoing coronary artery bypass surgery were randomized to receive conventional loop diuretics (Group C, n = 30) or conventional loop diuretic therapy plus tolvaptan (Group T, n = 27). Fractional excretions of sodium (FENA), potassium (FEK) and urea nitrogen (FEUN) were measured in both groups during post-surgical hospitalization. Urine output was greater with tolvaptan (Group T) than without it (Group C), and some patients in Group C required intravenous as well as oral loop diuretics. Serum sodium concentrations decreased after surgery in Group C, but were unchanged in Group T (postoperative day [POD] 3, 139.8 ± 3.5 vs. 142.3 ± 2.6 mEq/L, p = 0.006). However, postoperative FENA values in Group C did not decrease, and the values were similar in both groups. Serum potassium levels remained lower and FEK values remained higher than the preoperative values, but only in Group C (all p < 0.05). BUN increased postoperatively in both groups, but it remained higher than its preoperative value only in Group C (all p < 0.01). Group T showed an initial increase in BUN, which peaked and then returned to its preoperative value within a week. The FEUN increased postoperatively in both groups, but the change was more pronounced in Group T (POD7, 52.7 ± 9.3 vs. 58.2 ± 6.5 %, p = 0.025). Renal excretion of sodium and potassium reflects the changes in serum concentration in patients treated with tolvaptan. Patients treated only with loop diuretics showed a continuous excretion of sodium and potassium that led to electrolyte imbalance, whereas the combination of loop diuretics and tolvaptan increased renal urea nitrogen elimination. Tolvaptan therefore appears to be an effective diuretic that minimally affects serum electrolytes while adequately promoting the elimination of urea nitrogen from the kidneys in patients undergoing coronary artery bypass surgery. The present study is registered with the UMIN Clinical Trials Registry (ID: UMIN000011039 ).

Nephrogenic diabetes insipidus: treat with caution.

PubMed

Boussemart, Thierry; Nsota, Jacqueline; Martin-Coignard, Dominique; Champion, Gérard

2009-09-01

Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

PubMed Central

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-01-01

Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

PubMed

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-08-07

Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥ 140 mm Hg and home BP ≥ 130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K(+), clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Is cardiovascular risk reduction therapy effective in South Asian, Chinese and other patients with diabetes? A population-based cohort study from Canada.

PubMed

Ke, Calvin H; Morgan, Steve; Smolina, Kate; Gasevic, Danijela; Qian, Hong; Khan, Nadia A

2017-08-31

Guidelines recommend ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics in all patients with diabetes mellitus. However, the effectiveness of these agents in South Asian and Chinese populations is unknown. We sought to determine whether ACEi, ARB, CCB and diuretics are associated with reduced mortality in South Asian, Chinese and other patients with diabetes. Population-based cohort study using administrative health databases. Province of British Columbia, Canada (2006-2013). Patients aged ≥35 years with incident diabetes. Primary outcome was all-cause mortality for each medication class compared with untreated patients within each ethnicity. Treatment effect was assessed using inverse probability of treatment weighted Cox proportional hazards models. Medication adherence effect on mortality was also evaluated. 208 870 patients (13 755 South Asian, 22 871 Chinese, 172 244 other Canadian) were included. ACEi reduced mortality in other patients (HR=0.88, 0.84-0.91), but power was insufficient to evaluate for benefit in Chinese and South Asian patients. ARB and diuretics reduced mortality in Chinese (ARB HR=0.64, 0.50-0.82; diuretics HR=0.77, 0.62-0.96) and other patients (ARB HR=0.69, 0.64-0.74; diuretics HR=0.66, 0.63-0.69) compared with untreated patients. No mortality benefit was observed among South Asians for any drug class or for CCB among all ethnicities. Higher medication adherence was associated with lower mortality for other patients only (HR=0.79, 0.72-0.86). Effectiveness of cardiovascular risk reduction therapy on mortality varies considerably by ethnicity. Further study is needed to evaluate the mortality benefit of antihypertensive agents in South Asians. Inclusion of these ethnic groups in future clinical trials is essential to examine for differential responses. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Possible Opioid Shopping and its Correlates.

PubMed

Walker, Alexander M; Weatherby, Lisa B; Cepeda, M Soledad; Bradford, Daniel; Yuan, Yingli

2017-11-01

We created an operational definition of possible opioid shopping in US commercial health insurance data and examined its correlates. The population consisted of 264,204 treatment courses in persons with a fill for an opioid or diuretic prescription in 2012 and a second within 18 months. We examined counts of prescribers and pharmacies and the numbers of fills and overlaps for ability to discriminate courses of opioids from diuretics, which were a negative control. The most discriminatory measure, indicating possible shopping behavior, was cross-tabulated against other prescriptions filled and diagnoses as found in insurance claims. The associations between claims characteristics and shopping behavior were assessed in a logistic regression. A definition that classified possible "moderate" or "extensive" shopping when a person obtained drug through at least 3 practices and at least 3 pharmacies over 18 months was highly discriminatory between opioid and diuretic treatment. Overlaps between fills and number of fills did not improve the discrimination. Data from insurance claims strongly predicted moderate-to-extensive levels of possible shopping (c=0.82). Prominent among 20 significant predictors were: state of residence; amount of opioid dispensed; self-payment; use of nonspecialist prescribers; high use of anxiolytics, hypnotics, psychostimulants, and antipsychotics; and use of both immediate release and extended-release or long-acting opioids. The use of ≥3 prescribing practices and ≥3 dispensing pharmacies over 18 months sharply discriminated courses of opioid treatment from courses of diuretics. This pattern of fills was additionally associated with the numbers of nonspecialist and self-paid fills, the total morphine milligram equivalents dispensed, and heavier use of drugs for anxiety, sleep, attention, and psychosis.

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

PubMed

Yamamura, Y; Ogawa, H; Yamashita, H; Chihara, T; Miyamoto, H; Nakamura, S; Onogawa, T; Yamashita, T; Hosokawa, T; Mori, T

1992-04-01

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist

PubMed Central

Yamamura, Yoshitaka; Ogawa, Hidenori; Yamashita, Hiroshi; Chihara, Tomihiko; Miyamoto, Hisashi; Nakamura, Shigeki; Onogawa, Toshiyuki; Yamashita, Tatsuya; Hosokawa, Tetsumi; Mori, Toyoki; Tominaga, Michiaki; Yabuuchi, Youichi

1992-01-01

1 OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2 OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 ± 0.2 × 10-6 M and 1.4 ± 0.2 × 10-8 M, respectively. 3 OPC-31260 at doses of 10 to 100 μg kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4 After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5 The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention. PMID:1387020

Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia Haw. (Cactaceae).

PubMed

Kazama, Caroline Calixto; Uchida, Denise Thiemi; Canzi, Karina Natally; de Souza, Priscila; Crestani, Sandra; Gasparotto, Arquimedes; Laverde, Antonio

2012-10-31

Pereskia grandifolia Haw. (Cactaceae), popularly known as "ora-pro-nobis" is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action. The infusions (2.5-10%) and the HEPG (3-100 mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO(3)(-) were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V(2) vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined. Water excretion rate was significantly increased by HEPG, while the urinary K(+) and Cl(-) excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment. The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

How are patients with heart failure treated in primary care?
.

PubMed

Vaillant-Roussel, Hélène; Pereira, Bruno; Gibot-Boeuf, Sylvaine; Eschalier, Romain; Dubray, Claude; Boussageon, Rémy; Vorilhon, Philippe

2018-05-24

The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. 178 patients were studied: their mean age was 73.5 years (± 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.
.

Antidiabetics and diuretics show phototoxicity in HaCaT cells

NASA Astrophysics Data System (ADS)

Selvaag, Edgar; Petersen, Anita B.; Gniadecki, Robert; Thorn, Tine; Wulf, Hans Christian

2001-10-01

The antidiabetics tolbutamide, glibenclamide, and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide, and trichlormethiazide were investigated for potential phototoxicity in the HaCaT cell line. The cells were incubated with the drugs and then exposed to UVA1 irradiation. The effects of the antioxidants L-ascorbic acid, and (alpha) -tocopherol on oxidative DNA damage were assessed. Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide, or tolbutamide induced dose-dependent phototoxicity. Cells incubated with bendroflumethiazide, tolbutamide, and glibenclamide, and irradiated with UVA1 demonstrated an increased oxidative DNA damage. Pre-treatment with L-ascorbic acid, or (alpha) -tocopherol, suppressed the UVA-induced DNA damage in cells incubated with 1 mM of bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide, and trichloromethiazide, further implying the involvement of reactive oxygen species in the phototoxic DNA damage. These results may indicate a link between phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs, as it has previously been recognized for psoralen, chlorpromazine, and fluoroquinolones. Excessive exposure to UV light may be deleterious for patients treated with these drugs.

Diuretics, Limited Ultrafiltration, and Residual Renal Function in Incident Hemodialysis Patients: A Case Series.

PubMed

Sjolund, Jessica; Garcia Anton, Desiree; Bayes, Liz Y; Hoekstra, Tiny; Dekker, Friedo W; Munoz Mendoza, Jair

2016-09-01

The effect of diuretics on residual renal function expressed as residual GFR (rGFR) and urine volume (rUV) using 24-hour urine collections has not been well examined in hemodialysis (HD) patients. We present a small (seven patient) but provocative case series describing a strikingly low rate of decline in rUV and rGFR (average of creatinine and urea clearances, 24-hour urine collections) in patients treated with increasing doses of furosemide (up to 360 mg/day) during the first 2 years after initiation of HD. Between 6 and 12 months, the mean rUV fell by 1 ml/month, whereas rGFR declined by 0.03 ml/min/1.73 m(2) /month. The mean rate of decline from 12 to 24 months for rUV (33 ml/month) and rGFR (0.02 ml/min/1.73 m(2) /month) were also low. While data are clearly limited and the observation retrospective, they are consistent with the better documented benefit of diuretics observed in end-stage renal disease patients treated with peritoneal dialysis. © 2016 Wiley Periodicals, Inc.

(99m)Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis.

PubMed

Hecht, Silke; Lawson, Sarah M; Lane, India F; Sharp, Dorothy E; Daniel, Gregory B

2010-06-01

The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T((1/2))) of 6.09 (5.08-8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T((1/2)) of -7.91 (-43.13-0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

[Physiological analysis of various types of osmotic diuresis].

PubMed

Marina, A S; Kutina, A V; Natochin, Iu V

2011-12-01

Efficacy of drugs reduced proximal reabsorption was compared in experiments with female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold, exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal values of Na+ excretion were observed during Na2SO4 and exenatide administration (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs. 7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3 micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were additive after combined administration of maximal doses of exenatide and PEG which suggests a different mechanism of action of solutes filtrated (PEG) to the proximal nephron segment and generated due to Na+/HW-exchange inhibition (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action and selectivity of ion excretion).

[Thiazide diuretics in the treatment of hypertensive patients].

PubMed

Rasmussen, Knud

2015-05-11

This Cochrane review had the objectives to determine the dose-related decrease in blood pressure due to thiazide diuretics compared with placebo control in the treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2, 6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers as shown in other Cochrane reviews, which have compared these antihypertensive drugs with placebo having used similar inclusion/exclusion criteria.

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.

Eighth Joint National Committee (JNC-8) Guidelines and the Outpatient Management of Hypertension in the African-American Population.

PubMed

Abel, Nicole; Contino, Krysta; Jain, Navjot; Grewal, Navjot; Grand, Elizabeth; Hagans, Iris; Hunter, Krystal; Roy, Satyajeet

2015-10-01

Hypertension is a common medical disease, occurring in about one third of young adults and almost two thirds of individuals over the age of 60. With the release of the Eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment (JNC-8) guidelines, there have been major changes in blood pressure management in the various subgroups. Optimal blood pressure management and markers of end-organ damage in African-American adult patients were compared between patients who were managed according to the JNC-8 hypertension management guidelines and those who were treated with other regimens. African-American patients aged 18 years or older with an established diagnosis of hypertension were included in the study who were followed up in our internal medicine clinic between January 1, 2013 and December 31, 2103; the data on their systolic and diastolic blood pressure readings, heart rate, body mass index (BMI), age, gender, comorbidities, and medications were recorded. Patients were divided into four groups based on the antihypertensive therapy as follows - Group 1: Diuretic only; Group 2: Calcium channel blocker (CCB) only; Group 3: Diuretic and CCB; Group 4: Other antihypertensive agent. Their blood pressure control, comorbidities, and associated target organ damage were analyzed. In all 323 patients, blood pressures were optimally controlled. The majority of the patients (79.6%) were treated with either a diuretic, a CCB, or both. Intergroup comparison analysis showed no statistically significant difference in the mean systolic blood pressure, mean diastolic blood pressure, associated comorbidities, or frequency of target organ damage. Although diuretics or CCBs are recommended as first-line agents in African-American patients, we found no significant difference in the optimal control of blood pressure and frequency of end-organ damage compared to management with other agents.

A Systematic Review of Diuretics in the Medical Management of Ménière's Disease.

PubMed

Crowson, Matthew G; Patki, Aniruddha; Tucci, Debara L

2016-05-01

(1) Review evidence for the use of oral diuretic medications in the management of Ménière's disease. (2) Analyze therapy-related hearing and vertigo outcomes. Literature was obtained through directed searches of MEDLINE, EMBASE, Web of Science, EBSCO Host, Cochrane Reviews, and linked citations through seminal papers. We searched independent electronic databases for articles that reported the use of diuretics in patients with Ménière's disease. All articles of level 4 evidence or higher, per the Oxford Centre for Evidence-Based Medicine, were included with no limit for number of patients, duration of therapy, or follow-up period. Two independent investigators reviewed the articles for inclusion eligibility. Outcomes were tabulated, including subjective or quantitative measures of hearing, tinnitus, vertigo episode frequency, and medication adverse effects. Nineteen articles were included from 1962 to 2012 from 11 countries. Twelve retrospective case series, 4 randomized controlled trials, 2 case-control trials, and 1 prospective case series were identified. Six studies investigated isosorbide; 5, hydrochlorothiazide; 2, acetazolamide; 2, chlorthalidone; and 1 each of betahistine, hydrochlorothiazide, chlorthalidone, acetazolamide, hydrochlorothiazide-triamterene, and nimodipine. Eight (42.1%) studies reported hearing outcomes improvement. Fifteen (79.0%) studies reported vertigo outcomes improvement. Ten (52.6%) studies reported no side effects, and 4 studies (21.1%) reported abdominal discomfort. No significant morbidity or mortality was reported in any study. Multiple low evidence-level studies report that oral diuretic therapy may be beneficial in the medical management of Ménière's disease. Improvement in vertigo episode frequency was consistently reported, with less convincing evidence for improvement in hearing outcomes. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

An investigation of the concomitant use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and diuretics.

PubMed

Bucsa, C; Moga, D C; Farcas, A; Mogosan, C; Dumitrascu, D L

2015-08-01

To determine in retrospective data the prevalence at hospital discharge of co-prescribing angiotensin-converting enzyme inhibitors (ACE-I) and non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-I/NSAIDs and diuretics and to identify factors associated with the co-prescription. Secondary, we evaluated the extent of serum creatinine and potassium monitoring in patients treated with ACE-I and these associations and determined the prevalence of values above the upper normal limit (UNL) in monitored patients. Hospitalized patients with ACE-I in their therapy at discharge were included in 3 groups as follows: ACE-I, DT (double therapy with ACE-I and NSAIDs) and TT (triple therapy with ACE-I, NSAIDs and diuretics) groups. We evaluated differences on demographic characteristics, co-morbidities, medications, laboratory monitoring and quantified the patients with serum creatinine and potassium levels above the UNL using descriptive statistics. Logistic regression analysis with backward elimination was performed to identify significant predictors of combination therapy. Of 9960 admitted patients, 1214 were prescribed ACE-I, 40 were prescribed ACE-I/NSAIDs and 22 were prescribed ACE-I/NSAIDs/diuretics (3.13% and 1.72%, respectively, of the patients prescribed with ACE-I). Serum creatinine and potassium were monitored for the great majority of patients from all groups. The highest percentage of hyperkalemia was found in the DT group (10% of the patients) and of serum creatinine above UNL in the TT group (45.45%). The logistic regression final model showed that younger patients and monitoring for potassium were significantly associated with combination therapy. The prevalence of patients receiving DT/TT was relatively low and their monitoring during hospitalization was high. Factors associated with the combinations were younger patients and patients not tested for serum potassium.

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.

Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.

PubMed

Wieshammer, S; Hetzel, M; Hetzel, J; Kochs, M; Hombach, V

1993-07-01

To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics. Randomised, double blind, placebo controlled, 16 week treatment periods. Outpatient clinic at a university hospital. 54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study. After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics. Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure. The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment. The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.

Continuous infusion or bolus injection of loop diuretics for patients admitted for severe acute heart failure: is one strategy better than the other?

PubMed

Caetano, Francisca; Mota, Paula; Almeida, Inês; Fernandes, Andreia; Botelho, Ana; Leitão Marques, António

2015-02-01

Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p<0.001). They had longer hospitalizations (p=0.014) and a higher incidence of cardiorenal syndrome (p=0.009); however, at discharge, there were no differences in renal function between the groups. In-hospital mortality was similar, and during follow-up there were no differences in mortality or readmission for acute heart failure. Continuous infusion was preferred in patients presenting with worse clinical status, in whom renal dysfunction was transiently worse. However, in-hospital mortality and creatinine at discharge were similar. Continuous infusion thus appears to counteract the initial dire prognosis of more unstable patients. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats

PubMed Central

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O.; Ertunc, Mert; Verkman, A. S.

2015-01-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics (‘urearetics’) with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10–20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2–3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 hours, and a urine concentration of 20–40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of Syndrome of Inappropriate Antidiuretic Hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition. PMID:25993324

Thiazide-induced hyponatraemia is associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporin-2.

PubMed

Frenkel, Nanne J; Vogt, Liffert; De Rooij, Sophia E; Trimpert, Christiane; Levi, Marcel M; Deen, Peter M T; van den Born, Bert-Jan H

2015-03-01

Hyponatraemia is a common, potentially life-threatening, complication of thiazide diuretics. The mechanism of thiazide-induced hyponatraemia is incompletely understood. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin (AQP)2. We examined the effects of a single re-exposure to hydrochlorothiazide (HCTZ) 50 mg on water balance, renal sodium handling and osmoregulation in 15 elderly hypertensive patients with a history of thiazide-induced hyponatraemia and 15 matched hypertensive controls using thiazide diuretics without previous hyponatraemia. Patients with thiazide-induced hyponatraemia had significantly lower body weight and lower plasma sodium and osmolality at baseline. After HCTZ administration, plasma sodium and osmolality significantly decreased and remained lower in patients compared with controls (P < 0.001). Plasma antidiuretic hormone (ADH) and urine AQP2 were low or suppressed in patients, whereas solute and electrolyte-free water clearance was significantly increased compared with controls. Ad libitum water intake was significantly higher in patients (2543 ± 925 ml) than in controls (1828 ± 624 ml, P < 0.05), whereas urinary sodium excretion did not differ. In contrast, urea excretion remained significantly lower in patients (263 ± 69 mmol per 24 h) compared with controls (333 ± 97 mmol per 24 h, P < 0.05) and predicted the decrease in plasma sodium following HCTZ administration. Thiazide diuretics are associated with markedly impaired free water excretion at low ADH and AQP2 in elderly patients. The higher water intake and lower urea excretion in patients points to an important role for polydipsia and urea-mediated water excretion in the pathogenesis of thiazide-induced hyponatraemia.

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats.

PubMed

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O; Ertunc, Mert; Verkman, Alan S

2015-08-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics ('urearetics') with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10-20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2-3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 h, and a urine concentration of 20-40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of syndrome of inappropriate antidiuretic hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition.

Decongestion Strategies and Renin-Angiotensin-Aldosterone System Activation in Acute Heart Failure

PubMed Central

Mentz, Robert J.; Stevens, Susanna R.; DeVore, Adam D.; Lala, Anuradha; Vader, Justin M.; AbouEzzeddine, Omar F.; Khazanie, Prateeti; Redfield, Margaret M.; Stevenson, Lynne W.; O'Connor, Christopher M.; Goldsmith, Steven R.; Bart, Bradley A.; Anstrom, Kevin J.; Hernandez, Adrian F.; Braunwald, Eugene; Felker, G. Michael

2014-01-01

Background High dose diuretics in patients with acute heart failure (AHF) are thought to activate the renin-angiotensin-aldosterone system (RAAS), and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation. Methods We analyzed 427 AHF patients enrolled in the DOSE-AHF and CARRESS-HF trials. We assessed the relationship between two markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72-96h and decongestion strategy; high vs. low-dose and continuous infusion vs. bolus furosemide for DOSE-AHF and UF vs. stepped pharmacologic care for CARRESS-HF. We determined the relationship between RAAS biomarkers and 60-day outcomes. Results Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium, and higher BUN. Continuous infusion furosemide and UF were associated with greater PRA increases (median +1.66 vs. +0.66 ng/mL/h with continuous vs. bolus, P=0.021; +4.05 vs. +0.56 ng/mL/h with UF vs. stepped care, P=0.014). There was no significant difference in RAAS biomarker change with high vs. low-dose diuretics (both P>0.5). Neither baseline log PRA nor log aldosterone was associated with increased death/HF hospitalization (HR for a doubling 1.05; 95% CI: 0.98-1.13, P=0.18 and HR 1.13; 95% CI: 0.99-1.28, P=0.069, respectively). The change in RAAS biomarkers from baseline to 72-96 h was not associated with outcomes (both P>0.5). Conclusions High-dose loop diuretics did not result in greater RAAS activation than low-dose diuretics. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. PMID:25543972

Continuous Positive Airway Pressure Adherence In Patients with Obstructive Sleep Apnea & Symptomatic BPH.

PubMed

Metta, Ramesh V V S; Zaka, Awais; Lee, Vincent C; Mador, M Jeffery

2017-04-01

Purpose To determine the short-term and long-term adherence rates with continuous positive airway pressure (CPAP) therapy in sleep apnea patients with benign prostatic hyperplasia (BPH) compared to matched controls. Methods A case-control retrospective analysis was performed in a veterans affairs hospital. All symptomatic patients with BPH (n = 107) ever started on CPAP therapy between 2006 and 2012 were compared with controls matched for severity of sleep apnea (AHI). Adherence measures were obtained at the third and twelfth month visits. The cases included symptomatic BPH patients on active medical therapy. Diuretic use among cases and controls, and severity of nocturia among the cases were also analyzed. Results The mean AHI among cases and controls was 35.6 ± 27.3 and 35.5 ± 31 (p = 0.96). The population was male and predominantly Caucasian. There was no statistically significant difference in percent days CPAP device use ≥4 h. between symptomatic BPH patients and controls at 3-month (51.6 ± 38 vs. 47.2 ± 36; p = 0.43) and 1-year (64 ± 40.5 vs. 64.7 ± 31.3; p = 0.90) visits. The use of diuretics in the cases and controls, and the severity of nocturia in the cases did not influence adherence with CPAP therapy. Conclusions BPH or diuretic use did not affect adherence with CPAP therapy in obstructive sleep apnea. Severity of nocturia did not have any influence on adherence among the cases. BPH, regardless of the severity of nocturia, and diuretic use does not influence CPAP adherence in patients with OSA.

[Formulation and in vitro examination of furosemide-containing suppositories and preliminary experiences of their clinical use].

PubMed

Regdon, G; Fazekas, T; Regdon, G; Selmeczi, B

1997-01-01

Rectal suppositories containing Furosemide (4-Chloro-N-furfuryl-5-sulfamoylanthranilic acid) and Furosemide Sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from among the vehicles having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, cross-over clinical trial including 8 patients. Both preparations have induced and increase of urine flow, which was comparable to the diuretic effect of the tablet. Thus the possibility of rectal use has been added to the modalities of therapeutic Furosemide administration.

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

Pruss, T.; Wolf, P.S.

Indapamide is a new indoline antihypertensive diuretic agent whose chemical structure differs substantially from those of the thiazides. The hydrophobic indoline moiety of indapamide confers a lipid solubility to the molecule that is 5 to 80 times greater than that of the thiazide diuretics. Thus indapamide accumulates in vascular smooth muscle at a concentration 10 times higher than that of protein-free perfusate. The affinity of indapamide for vascular smooth muscle manifests itself in vitro and in vivo as a decrease in reactivity following various pharmacologic interventions. Moreover, in vitro studies have demonstrated that indapamide decreases the inward calcium current andmore » the transmembrane influx of calcium. The diuretic effect of indapamide is predominantly due to inhibition of sodium reabsorption at the cortical diluting segment of the distal convoluted tubule. In animal studies, intravenous indapamide has no effect on glomerular filtration rate or renal blood flow. Indapamide is well absorbed and extensively metabolized in animals and humans, with biliary excretion being the predominant route of elimination in animals. Most important, repeat administration of indapamide to dogs with both kidneys removed produces no accumulation of intact indapamide or its metabolites. Extensive drug safety studies in animals indicate that indapamide produces no overt toxicity and exhibits a good margin of safety.« less

Diuretics Prime Plant Immunity in Arabidopsis thaliana

PubMed Central

Noutoshi, Yoshiteru; Ikeda, Mika; Shirasu, Ken

2012-01-01

Plant activators are agrochemicals that activate the plant immune system, thereby enhancing disease resistance. Due to their prophylactic and durable effects on a wide spectrum of diseases, plant activators can provide synergistic crop protection when used in combination with traditional pest controls. Although plant activators have achieved great success in wet-rice farming practices in Asia, their use is still limited. To isolate novel plant activators applicable to other crops, we screened a chemical library using a method that can selectively identify immune-priming compounds. Here, we report the isolation and characterization of three diuretics, bumetanide, bendroflumethiazide and clopamide, as immune-priming compounds. These drugs upregulate the immunity-related cell death of Arabidopsis suspension-cultured cells induced with an avirulent strain of Pseudomonas syringae pv. tomato in a concentration-dependent manner. The application of these compounds to Arabidopsis plants confers disease resistance to not only the avirulent but also a virulent strain of the pathogen. Unlike salicylic acid, an endogenous phytohormone that governs disease resistance in response to biotrophic pathogens, the three diuretic compounds analyzed here do not induce PR1 or inhibit plant growth, showing potential as lead compounds in a practical application. PMID:23144763

Diuretics as pathogenetic treatment for heart failure

PubMed Central

Guglin, Maya

2011-01-01

Increased intracardiac filling pressure or congestion causes symptoms and leads to hospital admissions in patients with heart failure, regardless of their systolic function. A history of hospital admission, in turn, predicts further hospitalizations and morbidity, and a higher number of hospitalizations determine higher mortality. Congestion is therefore the driving force of the natural history of heart failure. Congestion is the syndrome shared by heart failure with preserved and reduced systolic function. These two conditions have almost identical morbidity, mortality, and survival because the outcomes are driven by congestion. A small difference in favor of heart failure with preserved systolic function comes from decreased ejection fraction and left ventricular remodeling which is only present in heart failure with decreased systolic function. The magnitude of this difference reflects the contribution of decreased systolic function and ventricular remodeling to the progression of heart failure. The only treatment available for congestion is fluid removal via diuretics, ultrafiltration, or dialysis. It is the only treatment that works equally well for heart failure with reduced and preserved systolic function because it affects congestion, the main pathogenetic feature of the disease. Diuretics are pathogenetic therapy for heart failure. PMID:21403798

Recurrent severe abdominal pain in the pediatric patient.

PubMed

Homme, James L; Foster, Ashley A

2014-05-01

Ureteropelvic junction obstruction (UPJO) is a blockage occurring at the junction of the ureter and the renal pelvis. Pediatric patients with UPJO pose a diagnostic challenge when they present to the emergency department (ED) with severe recurrent abdominal pain if there is not a level of suspicion for this condition. Our aim was to review presentation of UPJO to the ED, methods of diagnosis, and treatment of this common but often overlooked condition. We report on 2 patients, a 9-year-old and 3-year-old, who had multiple presentations to health care providers and the ED with intermittent and recurrent abdominal pain. Subsequent testing, including ultrasound (US) and computed tomography (CT) with diuretic-recreated symptoms, revealed UPJO. Open pyeloplasty was performed, resulting in complete resolution of symptoms. UPJO is an important diagnosis to consider when patients present to the ED with recurrent abdominal pain. US can be helpful in suspecting the diagnosis, but often CT, magnetic resonance urography, or diuretic scintigraphy is required for confirmation. Diuretics can be used to aid diagnostic testing by reproducing abdominal pain at the time of imaging. Referral to a urologist for open pyeloplasty is definitive treatment for this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

The risks and benefits of patients temporarily discontinuing medications in the event of an intercurrent illness: a systematic review protocol.

PubMed

Morden, Andrew; Horwood, Jeremy; Whiting, Penny; Savovic, Jelena; Tomlinson, Laurie; Blakeman, Thomas; Tomson, Charles; Richards, Alison; Stone, Tracey; Caskey, Fergus

2015-10-24

Acute kidney injury (AKI) is common and often leads to significant morbidity and/or death. The development of AKI, or complications associated with it, may be due to use of certain medications in at-risk patients experiencing an intercurrent illness. Implicated drugs include diuretics, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/direct renin inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), metformin and sulfonylureas. Expert consensus opinion (and clinical guidelines) recommend considering discontinuation of diuretics, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/direct renin inhibitors, NSAIDs, metformin and sulfonylureas in the event of an intercurrent illness to prevent AKI onset or reduce severity or complications. However, the evidence base for these recommendations is very limited. This systematic review aims to address the available evidence for the temporary discontinuation of diuretics, ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors, non-steroidal anti-inflammatories and metformin and sulfonylureas for those at risk of AKI or with newly diagnosed AKI. Randomised controlled trials; non-randomised trials; cohort studies; case-control studies; interrupted time series studies; and before-and-after studies featuring adults aged 18 and over in any setting currently taking diuretics, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/direct renin inhibitors, NSAIDs and metformin; experiencing an intercurrent illness; or undergoing a radiological/surgical procedure (planned or unplanned) will be searched for. Relevant trial registers and systematic review databases will be searched. Systematic reviews will be assessed for methodological quality using the ROBIS tool, trials will be assessed using the Cochrane risk of bias tool, and observational studies will be assessed using the ACROBAT-NRS tool. If sufficient studies assessing similar populations, study type, settings and outcomes are found, then a formal meta-analysis will be performed to estimate summary measures of effect. If not, a narrative synthesis will be adopted. This review will synthesise evidence for the efficacy of discontinuing diuretics, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/direct renin inhibitors, NSAIDs, metformin or sulfonylureas to prevent or delay onset of AKI or associated complications. Results will provide guidance on efficacy and safety of this strategy and potentially help to develop an intervention to test the best mechanism of guiding medication discontinuation in at-risk populations. PROSPERO CRD42015023210.

Cost–Utility of Angiotensin-Converting Enzyme Inhibitor-Based Treatment Compared With Thiazide Diuretic-Based Treatment for Hypertension in Elderly Australians Considering Diabetes as Comorbidity

PubMed Central

Chowdhury, Enayet K.; Ademi, Zanfina; Moss, John R.; Wing, Lindon M.H.; Reid, Christopher M.

2015-01-01

Abstract The objective of this study was to examine the cost-effectiveness of angiotensin-converting enzyme inhibitor (ACEI)-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as an outcome along with cardiovascular outcomes from the Australian government's perspective. We used a cost–utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data on cardiovascular events and new onset of diabetes were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based (hydrochlorothiazide) versus ACEI-based (enalapril) treatment in 6083 elderly (age ≥65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into 2 groups. Group A was restricted to participants diabetes free at baseline (n = 5642); group B was restricted to participants with preexisting diabetes mellitus (type 1 or type 2) at baseline (n = 441). Data on utility scores for different events were used from available published literatures; whereas, treatment and adverse event management costs were calculated from direct health care costs available from Australian government reimbursement data. Costs and QALYs were discounted at 5% per annum. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data. After a treatment period of 5 years, for group A, the ICER was Australian dollars (AUD) 27,698 (€ 18,004; AUD 1–€ 0.65) per QALY gained comparing ACEI-based treatment with diuretic-based treatment (sensitive to the utility value for new-onset diabetes). In group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On probabilistic sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for group B; whereas for group A, the probability of being below AUD 50,000 was 85%. Although the dispensed price of diuretic-based treatment of hypertension in the elderly is lower, upon considering the potential enhanced likelihood of the development of diabetes in addition to the costs of treating cardiovascular disease, ACEI-based treatment may be a more cost-effective strategy in this population. PMID:25738481

Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease

PubMed Central

Pérez-Calvo, Juan I; Sánchez-Marteles, Marta; Ruiz-Ruiz, Francisco-José; Morales-Rull, José-Luis; Nieto-Rodríguez, José-Antonio

2010-01-01

Objectives To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. Design Prospective, observational, non-interventional study. Setting CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. Participants Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. Main outcome measures NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. Results During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44–4628.55) vs 502.70 pg/mL (95% CI 395.44–645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21–1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09–1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57–1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80–632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). Conclusions In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can contribute to the early identification of patients at risk of developing clinical ventricular dysfunction. PMID:21103136

Impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities of glucose and uric acid metabolisms.

PubMed

Zhang, Jian-Liang; Yu, Hui; Hou, Ying-Wei; Wang, Ke; Bi, Wen-Shan; Zhang, Liang; Wang, Qian; Li, Pan; Yu, Man-Li; Zhao, Xian-Xian

2018-04-01

Treatment of hypertension with thiazide diuretics may trigger hypokalemia, hyperglycemia, and hyperuricemia. Some studies suggest simultaneous potassium supplementation in hypertensive patients using thiazide diuretics. However, few clinical studies have reported the impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities in blood glucose and uric acid (UA) metabolisms. One hundred hypertensive patients meeting the inclusion criteria were equally randomized to two groups: IND group receiving indapamide (1.25-2.5 mg daily) alone, and IND/KCI group receiving IND (1.25-2.5 mg daily) plus potassium chloride (40 mmol daily), both for 24 weeks. At the end of 24-week follow-up, serum K + level in IND group decreased from 4.27 ± 0.28 to 3.98 ± 0.46 mmol/L (P < 0.001), and fasting plasma glucose (FPG) and UA increased from 5.11 ± 0.52 to 5.31 ± 0.57 mmol/L (P < 0.05), and from 0.404 ± 0.078 to 0.433 ± 0.072 mmol/L (P < 0.05), respectively. Serum K + level in IND/KCl group decreased from 4.27 ± 0.36 to 3.89 ± 0.28 mmol/L (P < 0.001), and FPB and UA increased from 5.10 ± 0.41 to 5.35 ± 0.55 mmol/L (P < 0.01), and from 0.391 ± 0.073 to 0.457 ± 0.128 mmol/L (P < 0.001), respectively. The difference value between the serum K + level and FPG before and after treatment was not statistically significant between the two groups. However, the difference value in UA in IND/KCl group was significantly higher than that in IND group (0.066 (95% confidence interval (CI): 0.041-0.090)  mmol/L vs. 0.029 (95% CI: 0.006-0.058) mmol/L, P < 0.05). The results showed that long-term routine potassium supplementation could not prevent or attenuate thiazide diuretic-induced abnormalities of glucose metabolism in hypertensive patients; rather, it may aggravate the UA metabolic abnormality.

What have we learned from the current trials?

PubMed

Abbott, Kevin C; Bakris, George L

2004-01-01

Even well-conducted randomized controlled trials can only reduce uncertainty, not eliminate it. The trials presented in this article all have gaps, and like many studies, some raise more questions than answers. A summary of the current trials, however, can be presented as follows. For patients with essential hypertension who are at high risk for cardiovascular disease, the use of diuretic therapy (excluding simultaneous use of ACE or CCB) resulted in outcomes at least equivalent to the use of either ACE or CCB without diuretics. Naturally, the dilemma for clinicians is that these drugs are most often used in combination with thiazide diuretics, as indicated by the RENAAL trial where 80% of ARB were used with diuretics in patients with type II diabetes and known nephropathy. The increased risk of heart failure observed with ACE and CCB in that trial may be relevant only to patients in whom diuretics were not also used. The study does raise important awareness, however, that ACE or CCB use without diuretic therapy is no better than diuretic therapy, and may be associated with higher risk of certain outcomes. A substantial number of patients with essential hypertension might achieve adequate blood pressure control with diuretic monotherapy. If so, that certainly has important implications for the cost of medical care in this country. For African Americans with essential hypertension, ACE may have advantages as a component of therapy in comparison with CCBs or beta-blockers, although diuretics should probably be the cornerstone of therapy for them and supported by the Seventh Joint National Committee. For patients with proteinuric renal disease, whether associated with diabetes or hypertension, it should be considered inappropriate to use DHP CCB as monotherapy in any setting, whether as part of a clinical trial or in clinical practice. These drugs should not be considered as ethical placebo arms in trials, most especially in diabetic nephropathy, nor should they be used without an ACE or ARB in patients with proteinuric renal disease in the absence of documented contraindications or intolerance to ACE, ARB, or non-DHP CCB (which are now considered second-line agents for proteinuric renal disease, and are acceptable placebo or comparison arms in clinical trials). For patients with type I diabetes, ACE remain the cornerstone of therapy. Because of recent RENAAL and IDNT trial results, the greatest benefit for slowing progression of renal disease in type II diabetic nephropathy now belongs to ARBs. In contrast, however, the HOPE trial showed that ACE, specifically ramipril, had the greatest evidence for prevention of cardiovascular outcomes in patients with renal insufficiency, regardless of diabetic status. Cardiovascular outcomes were secondary end points in the RENAAL and IDNT trials, and with the exception of heart failure for losartan, no benefits on cardiovascular outcomes were statistically significant. Progression of renal disease has only been studied in a relatively small cohort of Israeli patients comparing enalapril with nifedipine. These gaps lead to a classic dilemma in medical decision-making. Because evidence has shown that patients with elevated serum creatinine (greater than or equal to 1.4 mg/dL) are just as likely to die from cardiovascular disease as they are to reach end-stage renal disease, which outcome should be the focus for clinicians, or for researchers? Using a strictly evidence-based approach, this question can only be answered by yet another large, long, randomized, controlled trial. Given the similarity of actions between the ARB and ACE, it is likely there is considerable overlap of both benefits and side-effects between the two, although ARB may have a lower incidence of cough and hyperkalemia. The decision of which antihypertensive agents to use will have to be tailored carefully to the needs of the patient and careful consideration of both medical and economic factors. Regardless of the choice between an ACE or ARB, however, post hoc analysis of clinical trials [21,47] and observational data clearly indicate that patients with chronic kidney disease, even if considered mild (ie, serum creatinine greater than or equal to 1.4 mg/dL) are at significantly greater risk of cardiovascular morbidity and mortality compared with those with better kidney function. As stated in a recent review by the authors of the HOPE trial [50], "the frequent practice of withholding ACE [or ARB] in patients with mild renal insufficiency is unwarranted," because not only are these patients precisely those who might benefit most from their use, but safety and tolerability are generally excellent. Based on the results of the AASK trial, the authors add the same for the use of ACE inhibitors in African Americans.

Initial Therapy for Patients with Uncomplicated Hypertension

PubMed Central

Haynes, R. Brian

1985-01-01

Although commonly prescribed for hypertension, nonpharmacologic treatments have, at best, a minor adjunctive role to play. Current Canadian recommendations call for either a diuretic or beta blocker. If the diastolic blood pressure does not fall below 90 mmHg, a beta blocker or diuretic, respectively, should be added. Medications should be carefully adjusted until the BP is well controlled without adverse effects. About one-third of patients will experience side effects from a medication, but these often subside with time or can be overcome by switching medications. In the long run, antihypertensive therapy does much more good than harm for most patients. Optimizing the cost/benefit ratio for individual patients is the most important challenge. Imagesp321-a PMID:21274104

Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus).

PubMed

Doan, D D; Nguyen, N H; Doan, H K; Nguyen, T L; Phan, T S; van Dau, N; Grabe, M; Johansson, R; Lindgren, G; Stjernström, N E

1992-06-01

Herbal remedies are widely used in Vietnam alongside modern drugs. We assessed the diuretic effect of four traditional Vietnamese herbal remedies from Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus, all claimed to produce an increase of diuresis. No influence was recorded for the 12- and 24-h urine output or on the sodium excretion for any of the drugs when tested under standardized conditions in a placebo controlled double-blind crossover model. The present study indicates the need for critical review of the present recommendations regarding therapy with plant materials in countries relying on empiric traditions.

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.

Diuretic plants in the Bible: ethnobotanical aspects.

PubMed

Aliotta, Giovanni; De Santo, Natale Gaspare; Iorio, Luigi

2016-02-01

Besides its religious importance, the Bible, because of its ancient origin represents a relevant witness of the way of life of the people mentioned in it. The Holy Scripture is also the first text revealing the utility of plants for man, as natural sources of food, wood, fibers, oils and medicinal herbs. In the last 60 years, several distinguished botanists have attempted to identify the scientific names of the plants cited in the Bible. Nonetheless, these scholars have provided different lists of plants appearing in the Bible, none of which could be accepted as indisputable. The authors have combined their expertise to focus on the identification of the diuretic plants, through an historical analysis of the literature on this issue.

Continuous recording of excretory water loss from Musca domestica using a flow-through humidity meter: hormonal control of diuresis.

PubMed

Coast, Geoffrey M

2004-05-01

Water loss from adult male houseflies was continuously recorded using a flow-through humidity meter, which enabled losses to be apportioned between the sum of cuticular and respiratory transpiration, salivation and excretion. Transpiration accounted for >95% of water lost from sham-injected flies, compared with excretion (3.0%) and salivation (2.4%). In contrast, excretion accounted for 40% of water lost from flies injected with > or =3 microl of saline, whereas salivary losses were unchanged. Saline injections (1-5 microl) expanded the abdomen in the dorsal-ventral plane, and this expansion was positively correlated with the magnitude of the ensuing diuresis, suggesting the signal for diuretic hormone release originates from stretch receptors in abdominal tergal-sternal muscles. The effects of decapitation, severing the ventral nerve cord within the neck or ligaturing the neck, showed the head was needed to initiate and maintain diuresis, but was neither the source of diuretic hormone nor did it control the discharge of urine from the anus. These findings indicate the head is part of the neural-endocrine pathway between abdominal stretch receptors and sites for diuretic hormone release from the thoracic-abdominal ganglion mass. Evidence is presented for Musdo-K having a hormonal role in the control of diuresis, although other neuropeptides may also be implicated.

Renal function monitoring in heart failure – what is the optimal frequency? A narrative review

PubMed Central

Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2017-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication‐based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. PMID:28901643

Hypertension Update: Resistant Hypertension.

PubMed

Viera, Anthony J

2018-06-01

Resistant hypertension is a blood pressure (BP) level that remains above the goal level despite adherence to at least three appropriately dosed antihypertensive drugs of different classes, one of which is a diuretic. Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen. White coat hypertension should be ruled out with out-of-office BP level measurements, ideally using 24-hour ambulatory BP monitoring. Obesity, significant alcohol intake, and interfering drugs and other substances can contribute to resistant hypertension. Lifestyle modifications, including exercise and dietary sodium restriction, can be useful in management. Resistant hypertension may be due to secondary etiologies (eg, parenchymal kidney disease, obstructive sleep apnea, hyperaldosteronism). Adequate diuretic treatment is a key part of therapy. In addition to a diuretic, patients with resistant hypertension should take a dihydropyridine calcium channel blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Spironolactone is an effective fourth drug. Other drug options include a beta blocker, a long-acting nondihydropyridine calcium channel blocker, or clonidine or guanfacine. When the BP level is not controlled despite adherence to a four-drug regimen, referral to a hypertension subspecialist should be considered. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Short-term responses of the kidney to high altitude in mountain climbers

PubMed Central

Goldfarb-Rumyantzev, Alexander S.; Alper, Seth L.

2014-01-01

In high-altitude climbers, the kidneys play a crucial role in acclimatization and in mountain sickness syndromes [acute mountain sickness (AMS), high-altitude cerebral edema, high-altitude pulmonary edema] through their roles in regulating body fluids, electrolyte and acid–base homeostasis. Here, we discuss renal responses to several high-altitude-related stresses, including changes in systemic volume status, renal plasma flow and clearance, and altered acid–base and electrolyte status. Volume regulation is considered central both to high-altitude adaptation and to maladaptive development of mountain sickness. The rapid and powerful diuretic response to the hypobaric hypoxic stimulus of altitude integrates decreased circulating concentrations of antidiuretic hormone, renin and aldosterone, increased levels of natriuretic hormones, plasma and urinary epinephrine, norepinephrine, endothelin and urinary adrenomedullin, with increased insensible fluid losses and reduced fluid intake. The ventilatory and hormonal responses to hypoxia may predict susceptibility to AMS, also likely influenced by multiple genetic factors. The timing of altitude increases and adaptation also modifies the body's physiologic responses to altitude. While hypovolemia develops as part of the diuretic response to altitude, coincident vascular leak and extravascular fluid accumulation lead to syndromes of high-altitude sickness. Pharmacological interventions, such as diuretics, calcium blockers, steroids, phosphodiesterase inhibitors and β-agonists, may potentially be helpful in preventing or attenuating these syndromes. PMID:23525530

The diuretic effect in human subjects of an extract of Taraxacum officinale folium over a single day.

PubMed

Clare, Bevin A; Conroy, Richard S; Spelman, Kevin

2009-08-01

Taraxacum officinale (L.) Weber (Asteraceae) has been extensively employed as a diuretic in traditional folk medicine and in modern phytotherapy in Europe, Asia, and the Americas without prior clinical trial substantiation. In this pilot study, a high-quality fresh leaf hydroethanolic extract of the medicinal plant T. officinale (dandelion) was ingested by volunteers to investigate whether an increased urinary frequency and volume would result. Volume of urinary output and fluid intake were recorded by subjects. Baseline values for urinary frequency and excretion ratio (urination volume:fluid intake) were established 2 days prior to dandelion dosing (8 mL TID) and monitored throughout a 1-day dosing period and 24 hours postdosing. For the entire population (n = 17) there was a significant (p < 0.05) increase in the frequency of urination in the 5-hour period after the first dose. There was also a significant (p < 0.001) increase in the excretion ratio in the 5-hour period after the second dose of extract. The third dose failed to change any of the measured parameters. Based on these first human data, T. officinale ethanolic extract shows promise as a diuretic in humans. Further studies are needed to establish the value of this herb for induction of diuresis in human subjects.

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.

Relation of plasma aldosterone concentration to diuretic treatment in patients with severe heart disease.

PubMed Central

Knight, R K; Miall, P A; Hawkins, L A; Dacombe, J; Edwards, C R; Hamer, J

1979-01-01

To assess the relation of hyperaldosteronism and potassium depletion to the intensity of diuretic therapy we have measured plasma aldosterone by radioimmunoassay and total exchangeable potassium by radioisotope dilution in 24 patients when they were stable at the end of their preparation for cardiac operation. Some patients required intensive frusemide therapy to reach an optimal state for operation and many showed hyperaldosteronism. Plasma aldosterone was significantly related to daily dose of frusemide (r=0.77). Depletion of total exchangeable potassium expressed in terms of predicted weight was significantly related to plasma aldosterone (r= -0.64). The reduction in total exchangeable potassium is interpreted as chiefly related to loss of lean tissue mass from the wasting that leads to cardiac cachexia, but evidence is presented on the basis of measurements of extracellular fluid volume as sulphate space (20 patients) of entry of sodium into the cells which may indicate a true cellular potassium loss. Although plasma potassium is usually easily maintained with oral potassium supplements or aldosterone antagonists, we postulate that intensive diuretic therapy in severe heart disease may provoke hyperaldosteronism which accentuates potassium loss and may contribute to wasting and to intracellular potassium depletion in critical tissue, such as myocardium. PMID:508454

The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics

PubMed Central

Lee, Chien-Te; Ng, Hwee-Yeong; Lee, Yueh-Ting; Lai, Li-Wen

2015-01-01

Calbindin-D28k (CBD-28k) is a calcium binding protein located in the distal convoluted tubule (DCT) and plays an important role in active calcium transport in the kidney. Loop and thiazide diuretics affect renal Ca and Mg handling: both cause Mg wasting, but have opposite effects on Ca excretion as loop diuretics increase, but thiazides decrease, Ca excretion. To understand the role of CBD-28k in renal Ca and Mg handling in response to diuretics treatment, we investigated renal Ca and Mg excretion and gene expression of DCT Ca and Mg transport molecules in wild-type (WT) and CBD-28k knockout (KO) mice. Mice were treated with chlorothiazide (CTZ; 50 mg·kg−1·day−1) or furosemide (FSM; 30 mg·kg−1·day−1) for 3 days. To avoid volume depletion, salt was supplemented in the drinking water. Urine Ca excretion was reduced in WT, but not in KO mice, by CTZ. FSM induced similar hypercalciuria in both groups. DCT Ca transport molecules, including transient receptor potential vanilloid 5 (TRPV5), TRPV6, and CBD-9k, were upregulated by CTZ and FSM in WT, but not in KO mice. Urine Mg excretion was increased and transient receptor potential subfamily M, member 6 (TRPM6) was upregulated by both CTZ and FSM in WT and KO mice. In conclusion, CBD-28k plays an important role in gene expression of DCT Ca, but not Mg, transport molecules, which may be related to its being a Ca, but not a Mg, intracellular sensor. The lack of upregulation of DCT Ca transport molecules by thiazides in the KO mice indicates that the DCT Ca transport system is critical for Ca conservation by thiazides. PMID:26582761

Adding point of care ultrasound to assess volume status in heart failure patients in a nurse-led outpatient clinic. A randomised study

PubMed Central

Gundersen, Guri Holmen; Norekval, Tone M; Haug, Hilde Haugberg; Skjetne, Kyrre; Kleinau, Jens Olaf; Graven, Torbjorn; Dalen, Havard

2016-01-01

Objectives Medical history, physical examination and laboratory testing are not optimal for the assessment of volume status in heart failure (HF) patients. We aimed to study the clinical influence of focused ultrasound of the pleural cavities and inferior vena cava (IVC) performed by specialised nurses to assess volume status in HF patients at an outpatient clinic. Methods HF outpatients were prospectively included and underwent laboratory testing, history recording and clinical examination by two nurses with and without an ultrasound examination of the pleural cavities and IVC using a pocket-size imaging device, in random order. Each nurse worked in a team with a cardiologist. The influence of the different diagnostic tests on diuretic dosing was assessed descriptively and in linear regression analyses. Results Sixty-two patients were included and 119 examinations were performed. Mean±SD age was 74±12 years, EF was 34±14%, and N-terminal pro-brain natriuretic peptide (NT-proBNP) value was 3761±3072 ng/L. Dosing of diuretics differed between the teams in 31 out of 119 consultations. Weight change and volume status assessed clinically with and without ultrasound predicted dose adjustment of diuretics at follow-up (p<0.05). Change of oedema, NT-proBNP, creatinine, and symptoms did not (p≥0.10). In adjusted analyses, only volume status based on ultrasound predicted dose adjustments of diuretics at first visit and follow-up (all ultrasound p≤0.01, all other p≥0.2). Conclusions Ultrasound examinations of the pleural cavities and IVC by nurses may improve diagnostics and patient care in HF patients at an outpatient clinic, but more studies are needed to determine whether these examinations have an impact on clinical outcomes. Trial registration number NCT01794715. PMID:26438785

Adding point of care ultrasound to assess volume status in heart failure patients in a nurse-led outpatient clinic. A randomised study.

PubMed

Gundersen, Guri Holmen; Norekval, Tone M; Haug, Hilde Haugberg; Skjetne, Kyrre; Kleinau, Jens Olaf; Graven, Torbjorn; Dalen, Havard

2016-01-01

Medical history, physical examination and laboratory testing are not optimal for the assessment of volume status in heart failure (HF) patients. We aimed to study the clinical influence of focused ultrasound of the pleural cavities and inferior vena cava (IVC) performed by specialised nurses to assess volume status in HF patients at an outpatient clinic. HF outpatients were prospectively included and underwent laboratory testing, history recording and clinical examination by two nurses with and without an ultrasound examination of the pleural cavities and IVC using a pocket-size imaging device, in random order. Each nurse worked in a team with a cardiologist. The influence of the different diagnostic tests on diuretic dosing was assessed descriptively and in linear regression analyses. Sixty-two patients were included and 119 examinations were performed. Mean±SD age was 74±12 years, EF was 34±14%, and N-terminal pro-brain natriuretic peptide (NT-proBNP) value was 3761±3072 ng/L. Dosing of diuretics differed between the teams in 31 out of 119 consultations. Weight change and volume status assessed clinically with and without ultrasound predicted dose adjustment of diuretics at follow-up (p<0.05). Change of oedema, NT-proBNP, creatinine, and symptoms did not (p≥0.10). In adjusted analyses, only volume status based on ultrasound predicted dose adjustments of diuretics at first visit and follow-up (all ultrasound p≤0.01, all other p≥0.2). Ultrasound examinations of the pleural cavities and IVC by nurses may improve diagnostics and patient care in HF patients at an outpatient clinic, but more studies are needed to determine whether these examinations have an impact on clinical outcomes. NCT01794715. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication.

PubMed

Mancia, Giuseppe; Cannon, Christopher P; Tikkanen, Ilkka; Zeller, Cordula; Ley, Ludwin; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik

2016-12-01

In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: -3.89/-2.58 mm Hg; 25 mg: -3.77/-2.45 mm Hg), 1 (10 mg: -4.74/-1.97 mm Hg; 25 mg: -4.27/-1.81 mm Hg), or ≥2 (10 mg: -2.36/-0.68 mm Hg; 25 mg: -4.17/-1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. URL: https://clinicaltrials.gov. Unique identifier: NCT01370005. © 2016 American Heart Association, Inc.

Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights

PubMed Central

Hanberg, Jennifer S.; Rao, Veena; ter Maaten, Jozine M.; Laur, Olga; Brisco, Meredith A.; Wilson, F. Perry; Grodin, Justin L.; Assefa, Mahlet; Broughton, J. Samuel; Planavsky, Noah J.; Ahmad, Tariq; Bellumkonda, Lavanya; Wilson Tang, W. H.; Parikh, Chirag R.; Testani, Jeffrey M.

2016-01-01

Background Recent epidemiologic studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure (HF). Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiologic literature. Methods and Results Two HF cohorts were included: (1) Observational: Patients receiving loop diuretics at the Yale Transitional Care Center (YTCC; N=162); (2) Interventional Pilot: Stable outpatients receiving ≥80mg furosemide equivalents were studied before and after three days of 115 mmol/d supplemental lysine chloride (N=10). In YTCC, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=−0.46, p<0.001) with no incremental contribution from serum sodium (p=0.49). Hypochloremic vs. non-hypochloremic patients exhibited renal wasting of chloride (p=0.04) and of chloride relative to sodium (p=0.01), despite better renal free water excretion (urine osmolality 372±94 mOsm/kg vs. 507±118, p<0.001). Hypochloremia was associated with poor diuretic response (OR=7.3, 95% CI 3.3–16.1, p<0.001). In the interventional pilot, lysine chloride supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in NT-proBNP, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. Conclusions Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardio-renal parameters. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02031354. PMID:27507113

[Influence of non-sodium restricted diet with diuretics on plasma rennin, renal blood flow and in patients with cirrhotic ascites].

PubMed

Zhu, Yin-fang; Gu, Xi-bing; Zhu, Hong-ying; Yang, Xiao-juan; Wang, Dong; Yu, Ping

2013-02-01

To explore influence of sodium restricted diet and non-sodium restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood flow (RBF) and subside of ascites in patients with cirrhotic ascites. Eighty cases of hepatitis B with cirrhotic ascites were randomly divided into sodium restricted diet group and non-sodium restricted diet group. 39 cases were in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily; 41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg daily. Both groups received diuretics furosemide and spironolactone. Blood sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after treatment. In non-sodium restricted diet group, blood sodium and urine sodium increased 10 days after treatment compared with those before treatment, and compared with those of sodium restricted diet group 10 days after treatment, P <0. 01. RBF increased compared with that before treatment, and compared with that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal damage induced by low blood sodium after treatment was less in non-sodium restricted diet group than that in sodium restricted diet group, P <0. 05. Ascites disappearance upon discharge was more in sodium restricted diet group than that in non-sodium restricted diet group, P <0. 01. Time of ascites disappearance was shorter in non-sodium restricted diet group than that in sodium restricted diet group, P < 0. 01. Compared with sodium restricted diet, while using diuretics of both groups, non-sodium restricted diet can increase level of blood sodium, thus increasing excretion of urine sodium and diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal blood flow and prevent renal damage induced by low blood sodium and facilitate subsiding of ascites.

Diuretic or sodium-restricted diet for obstructive sleep apnea-a randomized trial.

PubMed

Fiori, Cintia Zappe; Martinez, Denis; Montanari, Carolina Caruccio; Lopez, Pedro; Camargo, Rodrigo; Sezerá, Lauren; Gonçalves, Sandro Cadaval; Fuchs, Flavio Danni

2018-04-01

Interventions that decrease leg fluid retention reduce obstructive sleep apnea (OSA) severity in nonrandomized experiments. We aimed to investigate in a randomized trial the effect of interventions that reduce fluid volume on OSA severity. Men diagnosed with severe OSA were randomized to receive daily spironolactone 100 mg + furosemide 20 mg or nutritional counseling to sodium-restricted diet plus placebo pill or placebo pill. All participants underwent home sleep apnea testing at baseline and after 1 week follow-up. The change in apnea-hypopnea index (AHI) was the primary outcome. The study included 54 participants and all were assessed at follow-up. The average baseline value of the AHI was similar among groups and from baseline to follow-up the AHI reduced 14.4 per cent (δ value -7.3 events per hour; 95% confidence interval, -13.8 to -0.9) in the diuretic group, 22.3 per cent (-10.7; 95% CI, -15.6 to -5.7) in the diet group, and 0.8 per cent (0.4; 95% CI, -2.5 to 3.2) in the placebo group (p = .001 for time × group interaction). None of the patients had their AHI returned to normal. The reduction in the total body water was 2.2 ± 2.2 L in the diuretic group (p < .001) and 1.0 ± 1.6 l in the low salt diet group (p = .002). Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively). Interventions to reduce bodily fluid content in men with severe OSA promoted a limited decrease of apnea frequency. This finding suggests that rostral fluid displacement affects only partially the OSA severity and/or that other factors prevail in determining pharyngeal collapsibility. Sodium-Restricted Diet and Diuretic in the Treatment of Severe Sleep Apnea (DESALT), https://clinicaltrials.gov/ct2/show/NCT01945801 ClinicalTrials.gov number: NCT01945801.

Demographic and clinical features of gout patients in Turkey: a multicenter study.

PubMed

Öztürk, Mehmet Akif; Kaya, Arif; Şenel, Soner; Dönmez, Salim; Balkarlı, Ayşe; Çobankara, Veli; Erhan, Çiğdem; Sayarlıoğlu, Mehmet; Ugan, Yunus; Tunç, Ş Ercan; Pehlivan, Yavuz; Kısacık, Bünyamin; Tufan, Abdurrahman; Onat, Ahmet Mesut; Tezcan, Engin; Yıldırım Çetin, Gözde; Pamuk, Omer Nuri

2013-04-01

Gout results from multifactor interactions between gender, age, genetic and environmental factors. Environmental factors underlying gout and precipitating factors triggering acute attacks might vary in different populations with different lifestyles. In this study, we aimed to collect data regarding the demographic and clinical features, comorbid factors, and precipitating factors associated with the initiation of acute attacks in gout patients in Turkey. A total of 312 patients were included in this study (mean age, 58.8 ± 13.8 years; female/male ratio, 55/257). The demographic features, alcohol intake, clinical and laboratory features, and comorbid conditions including obesity, diabetes mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in a standard questionnaire. Precipitating factors initiating acute attacks (if any) were also noted. The patients were divided into 4 groups according to the region of location as central Anatolian region, southeast Anatolian region, Aegean region, and Trakya region. Our results were compared according to the gender and the location of the patients. The mean age at the start of the symptoms was 10 years higher in women (60.4 ± 14.8 and 50.6 ± 13.5 years in women and men, respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9 %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in 17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %, alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %, diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %, and none in 14.1 %. The presence of diabetes and diuretic use was more common among women. Use of diuretics is a more common trigger for gout flares among women. On the other hand, various comorbid conditions, such as obesity and hypertension, and triggers for gout flares may differ between patients living in different geographic regions. In summary, we reported the first data regarding clinical and demographic characteristics of gout in Turkey. The majority of our patients could describe at least one "trigger" that initiated gout flare. Both comorbid conditions and triggers of attack might differ between men and women, and in different geographic areas. Better knowledge of the modifiable risk factors can be useful for the management strategy to optimize long-term patient outcomes in local clinics.

Diuretic activity and toxicity study of the aqueous extract of Cola nitida seed on markers of renal function and electrolytes in rats.

PubMed

Nnemdi Ashibuogwu, Mirian; Isaac Adeosun, Olukayode; Ojo Akomolafe, Rufus; Olaniyi Sanni, Douglas; Sesan Olukiran, Olaoluwa

2016-12-01

BackgroundCola nitida is a plant, conventionally used in Africa in the treatment of various ailments such as migraine, morning sickness and indigestion. The aim of the present study was to explore the diuretic activity of the aqueous extract of C. nitida seed (AECONS) and alteration caused by its subchronic administration on the structure and function of the kidney of male Wistar rats. MethodsThe study was divided into diuretic and subchronic studies. Twenty-five male Wistar rats weighing between 140 and 180 g were divided into five groups of five rats each. The first 24 h of this study investigated the possible diuretic activity of C. nitida seed. Group I (the control) received 25 mL/kg of normal saline. Group II (the standard) received 20 mg/kg/day of furosemide. Groups III, IV, V received 400, 600 and 800 mg/kg/day of AECONS, respectively, and orally. Urine volume, pH, specific gravity and electrolytes were estimated in the samples of urine collected after 6 h of the study. From the second day onward and up to a period of 4 weeks, the rats in each group were given normal saline, furosemide and AECONS once daily as was done on the first day. At the end of the 4-week treatment period, blood and urine samples were collected for the determination of creatinine, urea, Na+, K+ and Cl- concentrations. Results The results of the diuretic study showed that the AECONS at all doses used and furosemide produced a significant increase in urine output with respect to the control group. AECONS also induced a significant increase in the urine concentrations of Na+, K+, Cl- in the experimental and standard groups when compared with the control group, except for group III which showed no significant variation in K+ concentration. In the subchronic study, AECONS caused a significant increase in the urine levels of Na+, K+, Cl- in the experimental and standard groups when compared with the control rats. The plasma Na+ concentration of groups IV and V was significantly lower than that of the control group. Photomicrographs of the kidneys of the experimental and standard groups revealed no significant alterations in the histology of their kidney tissues. Conclusions It is concluded that AECONS induced diuresis which is associated with increased Na+, K+ and Cl- loss in rats without any significant alteration in the structure of their kidneys.

Matrix effect on the determination of synthetic corticosteroids and diuretics by liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Dikunets, M. A.; Appolonova, S. A.; Rodchenkov, G. M.

2009-04-01

This work presents a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) procedure for selective and reliable screening of corticosteroids and diuretics in human urine. Sample preparation included the extraction, evaporation of the organic extract under nitrogen, and solution of the dry residue. The extract was analyzed by HPLC combined with tandem mass spectrometry using electro-spraying ionization at atmospheric pressure with negative ion recording. The mass spectra of all compounds were recorded, and the characteristic ions, retention times, and detection limits were determined. The procedure was validated by evaluating the degree of the matrix suppression of ionization, extraction of analytes from human biological liquid, and the selectivity and specificity of determination.

Lack of efficacy of phenytoin in the syndrome of inappropriate anti-diuretic hormone secretion of neurological origin.

PubMed Central

Decaux, G.; Przedborski, S.; Soupart, A.

1989-01-01

Phenytoin has been proposed in the management of patients with the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) of neurological origin who fail to respond to water restriction. We have conducted a prospective study in order to evaluate the role of phenytoin in the management of seven consecutive patients with SIADH of neurological origin which could not be controlled by limited water intake. Only one patient was successfully treated with chronic phenytoin regimen. This patient, like one previously reported, had suffered a basal skull fracture. It seems likely that in the majority of cases of SIADH of neurological origin phenytoin is ineffective on a long-term basis. PMID:2602236

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.

The effect of empagliflozin on muscle sympathetic nerve activity in patients with type II diabetes mellitus.

PubMed

Jordan, Jens; Tank, Jens; Heusser, Karsten; Heise, Tim; Wanner, Christoph; Heer, Martina; Macha, Sreeraj; Mattheus, Michaela; Lund, Søren S; Woerle, Hans J; Broedl, Uli C

2017-09-01

Inhibition of sodium glucose cotransporter 2 with empagliflozin results in caloric loss by increasing urinary glucose excretion and has a mild diuretic effect. Diuretic effects are usually associated with reflex-mediated increases in sympathetic tone, whereas caloric loss is associated with decreased sympathetic tone. In an open-label trial, muscle sympathetic nerve activity (MSNA) (burst frequency, burst incidence, and total MSNA) was assessed using microneurography performed off-treatment and on day 4 of treatment with empagliflozin 25 mg once daily in 22 metformin-treated patients with type II diabetes (mean [range] age 54 [40-65] years). Systolic and diastolic blood pressure (BP), heart rate, urine volume, and body weight were assessed before and on day 4 (BP, heart rate), day 5 (urine volume), or day 6 (body weight) of treatment with empagliflozin. After 4 days of treatment with empagliflozin, no significant changes in MSNA were apparent despite a numerical increase in urine volume, numerical reductions in BP, and significant weight loss. There were no clinically relevant changes in heart rate. Empagliflozin is not associated with clinically relevant reflex-mediated sympathetic activation in contrast to increases observed with diuretics in other studies. Our study suggests a novel mechanism through which sodium glucose cotransporter 2 inhibition affects human autonomic cardiovascular regulation. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema.

PubMed

Sakaida, Isao; Yamashita, Satoyoshi; Kobayashi, Tomoo; Komatsu, Masafumi; Sakai, Terufumi; Komorizono, Yasuji; Okada, Mitsuru; Okita, Kiwamu

2013-06-01

To investigate the efficacy and safety of 14 days' orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days' treatment. Responders at day 7 (achieving ≥ 1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.

Tolvaptan in Patients Hospitalized With Acute Heart Failure: Rationale and Design of the TACTICS and the SECRET of CHF Trials.

PubMed

Felker, G Michael; Mentz, Robert J; Adams, Kirkwood F; Cole, Robert T; Egnaczyk, Gregory F; Patel, Chetan B; Fiuzat, Mona; Gregory, Douglas; Wedge, Patricia; O'Connor, Christopher M; Udelson, James E; Konstam, Marvin A

2015-09-01

Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials. © 2015 American Heart Association, Inc.

The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease.

PubMed

Sanjay, Srinivas; Annigeri, Rajeev A; Seshadri, Rajagopalan; Rao, Budithi Subba; Prakash, Kowdle C; Mani, Muthu Krishna

2008-06-01

To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuous versus bolus intravenous furosemide administration in patients with chronic renal insufficiency. In a prospective randomized cross-over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed. Mean age was 53.6 +/- 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 +/- 17 mL/min per 1.73 m(2). The urinary excretion of sodium in intravenous bolus and infusion was 98.1 +/- 78 and 114.4 +/- 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 +/- 627 and 1170 +/- 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 +/- 16.6) and infusion (14.3 +/- 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 +/- 16.1) than bolus administration (12.87 +/- 9) of furosemide (P = 0.016). Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.

Central nervous system considerations in the use of beta-blockers, angiotensin-converting enzyme inhibitors, and thiazide diuretics in managing essential hypertension.

PubMed

Gengo, F M; Gabos, C

1988-07-01

The most common mild side effects occurring with use of beta-blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors for blood pressure control are central nervous system symptoms, specifically lethargy, sedation, and fatigue. These symptoms affect 5% to 10% of patients taking these drugs. The mechanism by which beta-blockers may induce central nervous system effects is uncertain. Relative lipophilicity as a factor affecting penetrance of the blood-brain barrier has not proved to be a reliable predictor of whether the drug will cause such disturbances. Comparisons of atenolol (hydrophilic) and metoprolol (lipophilic) have shown no differences between these drugs with respect to side effects of the central nervous system. The incidence of central nervous system effects with angiotensin-converting enzyme inhibitors is similar to that for most beta-blockers. The precise role of the angiotensin-converting enzyme in the central nervous system is not well defined. Most thiazide diuretics are not associated with major complications of the central nervous system, although electrolyte imbalance may occasionally lead to complaints of neurologic symptoms. Because the incidence of central nervous system effects with these three classes of drugs is so low, concern for the side effects of the central nervous system is not a prime consideration in the choice of an initial antihypertensive agent.

The Diuretic Action of Weak and Strong Alcoholic Beverages in Elderly Men: A Randomized Diet-Controlled Crossover Trial.

PubMed

Polhuis, Kristel C M M; Wijnen, Annemarthe H C; Sierksma, Aafje; Calame, Wim; Tieland, Michael

2017-06-28

With ageing, there is a greater risk of dehydration. This study investigated the diuretic effect of alcoholic beverages varying in alcohol concentration in elderly men. Three alcoholic beverages (beer (AB), wine (AW), and spirits (S)) and their non-alcoholic counterparts (non-alcoholic beer (NAB), non-alcoholic wine (NAW), and water (W)) were tested in a diet-controlled randomized crossover trial. For the alcoholic beverages, alcohol intake equaled a moderate amount of 30 g. An equal volume of beverage was given for the non-alcoholic counterpart. After consumption, the urine output was collected every hour for 4 h and the total 24 h urine output was measured. AW and S resulted in a higher cumulative urine output compared to NAW and W during the first 4 h (effect size: 0.25 mL p < 0.003, effect size: 0.18 mL, p < 0.001, respectively), but not after the 24h urine collection ( p > 0.40, p > 0.10). AB and NAB did not differ at any time point (effect size: -0.02 mL p > 0.70). For urine osmolality, and the sodium and potassium concentration, the findings were in line. In conclusion, only moderate amounts of stronger alcoholic beverages, such as wine and spirits, resulted in a short and small diuretic effect in elderly men.

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Influence of Prostanoids in the Diuretic and Natriuretic Effects of Extracts and Kaempferitrin from Bauhinia forficata Link Leaves in Rats.

PubMed

de Souza, Priscila; da Silva, Luisa Mota; Boeing, Thaise; Somensi, Lincon Bordignon; Cechinel-Zanchett, Camile Cecconi; Campos, Adriana; Krueger, Clarissa de Medeiros Amorim; Bastos, Jairo Kenupp; Cechinel-Filho, Valdir; Andrade, Sérgio Faloni de

2017-10-01

Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na + and K + excretion, calcium, creatinine, prostaglandin E 2 , pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract, trichloromethane, or ethyl acetate-butanolic fractions significantly increase urinary volume and electrolytes levels when orally given to rats, without altering the pH or density parameters. Kaempferitrin induced diuretic, natriuretic, but not kaliuretic effects in both normotensive and hypertensive rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E 2 excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was unaffected by previous treatment with a nonselective inhibitor of nitric oxide synthase and neither with a nonselective muscarinic receptor antagonist. On the other hand, a cyclooxygenase inhibitor was able to decrease its effect when compared with vehicle-treated rats, suggesting that the diuretic and natriuretic properties from kaempferitrin are associated with endogenous prostanoids generation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over a Single Day

PubMed Central

Clare, Bevin A.; Conroy, Richard S.

2009-01-01

Abstract Background Taraxacum officinale (L.) Weber (Asteraceae) has been extensively employed as a diuretic in traditional folk medicine and in modern phytotherapy in Europe, Asia, and the Americas without prior clinical trial substantiation. Objectives In this pilot study, a high-quality fresh leaf hydroethanolic extract of the medicinal plant T. officinale (dandelion) was ingested by volunteers to investigate whether an increased urinary frequency and volume would result. Design Volume of urinary output and fluid intake were recorded by subjects. Baseline values for urinary frequency and excretion ratio (urination volume:fluid intake) were established 2 days prior to dandelion dosing (8 mL TID) and monitored throughout a 1-day dosing period and 24 hours postdosing. Results For the entire population (n = 17) there was a significant (p < 0.05) increase in the frequency of urination in the 5-hour period after the first dose. There was also a significant (p < 0.001) increase in the excretion ratio in the 5-hour period after the second dose of extract. The third dose failed to change any of the measured parameters. Conclusions Based on these first human data, T. officinale ethanolic extract shows promise as a diuretic in humans. Further studies are needed to establish the value of this herb for induction of diuresis in human subjects. PMID:19678785

Metolazone

MedlinePlus

... in a class of medications called diuretics ('water pills'). It causes the kidneys to reduce the amount ... of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, ...

Bumetanide

MedlinePlus

... in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get ... of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, ...

Diuretics

MedlinePlus

... 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee. Journal of the American Medical Association. 2014;311:507. ...

Frequent or urgent urination

MedlinePlus

Urgent urination; Urinary frequency or urgency; Urgency-frequency syndrome; Overactive bladder (OAB) syndrome; Urge syndrome ... Medicines such as water pills (diuretics) Overactive bladder syndrome Radiation therapy to the pelvis, which is used ...

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

Case Report: Bilateral reexpansion pulmonary edema following treatment of a unilateral hemothorax

PubMed Central

de Wolf, Steven P; Deunk, Jaap; Cornet, Alexander D; Elbers, Paul WG

2014-01-01

Bilateral re-expansion pulmonary edema (RPE) is an extremely rare entity. We report the unique case of bilateral RPE following a traumatic, unilateral hemopneumothorax in a young healthy male. Bilateral RPE occurred only one hour after drainage of a unilateral hemopneumothorax. The patient was treated with diuretics and supplemental oxygen. Diagnosis was confirmed by excluding other causes, using laboratory findings, chest radiography, pulmonary and cardiac ultrasound and high resolution computed tomography. His recovery was uneventful. The pathophysiology of bilateral RPE is not well known. Treatment is mainly supportive and consists of diuretics, mechanical ventilation, inotropes and steroids. In case of a pulmonary deterioration after the drainage of a traumatic pneumothorax, bilateral RPE should be considered after exclusion of more common causes of dyspnea. PMID:25713699

Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension.

PubMed Central

Lijnen, P; Fagard, R; Staessen, J; Amery, A

1981-01-01

1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the maximum level reached after 1 week. 3 A significant (P less than 0.01) correlation (r = 0.74) between changes in plasma angiotensin II and renin activity provoked by chronic treatment for 3 months with hydrochlorothiazide and tienilic acid was found. 4 The increase in plasma aldosterone during chronic treatment with hydrochlorothiazide and tienilic acid (1000 mg) is related (r = 0.68; P less than 0.01) to the rise in plasma angiotensin II. PMID:7028060

Fluids and diuretics for acute ureteric colic.

PubMed

Worster, Andrew S; Bhanich Supapol, Wendy

2012-02-15

Acute ureteric colic is commonly associated with severe and debilitating pain. Theoretically, increasing fluid flow through the affected kidney might expedite stone passage, thereby improving symptoms more quickly. The efficacy and safety of interventions such as high volume intravenous (IV) or oral fluids and diuretics aimed at expediting ureteric stone passage is, however, uncertain. To look at the benefits and harms of diuretics and high volume (above maintenance) IV or oral fluid therapy for treating adult patients presenting with uncomplicated acute ureteric colic. We searched the Cochrane Renal Group's specialised register (3 January 2012). Previously we searched the Cochrane Central Register of Controlled Trials (CENTRAL The Cochrane Library), MEDLINE (from 1966), EMBASE (from 1980) and handsearched reference lists of nephrology and urology textbooks, review articles, relevant studies, and abstracts from nephrology scientific meetings. All randomised controlled trials (RCTs) and quasi-RCTs (including the first period of randomised cross-over studies) looking at diuretics or high volume IV or oral fluids for treating uncomplicated acute ureteric colic in adult patients presenting to the emergency department for the first time during that episode were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model for multiple studies of the same outcomes, otherwise the fixed-effect model was used. Results were expressed as risk ratios (RR) for dichotomous outcomes or as mean differences (MD) for continuous data with 95% confidence intervals (CI). Two studies (enrolling 118 participants) examined the association between intense hydration and ureteric colic outcomes. There was no significant difference in pain at six hours (1 study, 60 participants: RR 1.06, 95% CI 0.71 to 1.57), surgical stone removal (1 study, 60 participants: RR 1.20, 95% CI 0.41 to 3.51) or manipulation by cystoscopy (1 study, 60 participants: RR 0.67, 95% CI 0.21 to 2.13) when no fluids over six hours was compared to three litres IV fluids administered over a six hour period. There was no difference in stone clearance (1 study 43 participants: RR 1.38, 95% CI 0.50 to 3.84), hourly pain score or patients' narcotic requirements (P > 0.05 for all comparisons) when forced IV hydration of two litres over four hours was compared with minimal IV hydration at 20 mL/hour.One study did not provide any details which would have allowed us to assess any of the risk of bias items (selection, detection, performance, attrition or reporting bias). The second study did not report the method of randomisation or allocation (selection bias - unclear), they reported that the patients were blinded to therapy (low risk of bias), analgesics were administered according to predetermined pain score criteria (low risk), and assessment of stone passage was unlikely to have been biased by knowledge of group assignment (low risk). However the second study also reported a high percentage of participants excluded post randomisation (26%; high risk of bias). We were unable to assess or ascertain any of the other risk of bias items. We found no reliable evidence in the literature to support the use of diuretics and high volume fluid therapy for people with acute ureteric colic. However, given the potential positive therapeutic impact of fluids and diuretics to facilitate stone passage, the capacity of these interventions warrants further investigation to determine safety and efficacy profiles.

Evaluation of the diuretic activity in two Mexican medicinal species: Selaginella nothohybrida and Selaginella lepidophylla and its effects with ciclooxigenases inhibitors.

PubMed

Aguilar, María I; Benítez, Wendy V; Colín, Arturo; Bye, Robert; Ríos-Gómez, Ramiro; Calzada, Fernando

2015-04-02

Doradilla is a plant that has a long history in the Mexican traditional system of medicine for gall and renal stones, diuresis, stomach and liver inflammation among other diseases. Major components isolated from these plants include biflavonoids as amentoflavone (1), robustaflavone (2) and (S)-2,3-dihydrorobustaflavone (3) and the carbohydrate trehalose (4). The aim of this study was to evaluate the diuretic effect of the decoction of Selaginella nothohybrida Valdespino and Selaginella lepidophylla (Hook & Grev) Spring (Selaginellaceae), and compounds 1-4. We also explored the probable mode of action comparing the effects when using nonspecific and specific COX׳s inhibitors. Three biflavonoids (1-3) were isolated from the ethyl acetate extraction of the aqueous decoction and the carbohydrate trehalose (4) from the aqueous phase. The structures of all compounds were elucidated by spectroscopic methods and comparisons were made against published data. The diuretic activity was assessed in mice by oral administration of the decoctions in doses of 1000 and 2000mg/kg and biflavonoids 1-3 and trehalose (4) in a dose range of 10mg/kg using furosemide as a standard drug. Inhibitors of COX׳s such as acetyl salicylic acid, sodium naproxen, indomethacin and Celebrex were also assayed to analyze the involvement of renal prostaglandins in diuresis. Water excretion rate, pH, density, conductivity, and contents of Na(+) and K(+) were measured in the urine of mice. Decoction of Selaginella lepidophylla showed lower effect in the urine output at doses of 1000 and 2000mg/kg, while decoction of Selaginella nothohybrida produced an increase at 2000mg/kg (P<0.05). Urinary electrolytes excretion was also affected by this last extract and pure compounds: decoction diminished urinary excretion of sodium and potassium ions, so as compounds 1 and 4; compounds 2 and 3 observed just a natriuretic effect. Pretreated mice with COX׳s inhibitors and then with test compounds 1, 2, 4 and decoction showed inhibition of diuresis in all cases exception for treatment with trehalose (4); natriuretic effect was observed in all cases except for biflavonoid robustaflavone (2) which behaved as the reference compound furosemide. Selaginella nothohybrida decoction behaved similarly to COX-2 inhibitor Celebrex (8), inhibiting diuresis. Selaginella nothohybrida presents a moderate diuretic effect, which appears to be in partly mediated by the presence of biflavonoids and trehalose. Renal prostaglandins may be involved in the mechanism of diuresis. The present results provide a quantitative basis explaining the traditional folk medicine use of Selaginella nothohybrida as a diuretic agent by Mexican population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Spironolactone and Hydrochlorothiazide

MedlinePlus

... antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine, ... is in a class of medications called diuretics (''water pills''). It works by causing the kidneys to ...

Azilsartan

MedlinePlus

... It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the ... Advil, Motrin) and naproxen (Aleve, Naprosyn) and selective COX-2 inhibitors such as celecoxib (Celebrex); diuretics ('water pills'); lithium ( ...

Calcium blood test

MedlinePlus

... may be found in nutritional supplements or antacids) Lithium Thiazide diuretics (water pills) Thyroxine Vitamin D Drinking ... like substance. Use of certain medicines such as lithium, tamoxifen, and thiazides. A lower than normal levels ...

Calcium - ionized

MedlinePlus

... diuretics Thrombocytosis (high platelet count) Tumors Vitamin A excess Vitamin D excess Lower-than-normal levels may be due to: Hypoparathyroidism Malabsorption Osteomalacia Pancreatitis Renal failure Rickets Vitamin D deficiency Alternative Names Free calcium; Ionized calcium ...

Doxercalciferol Injection

MedlinePlus

... injection is in a class of medications called vitamin D analogs. It works by helping the body to ... thiazide diuretics (''water pills''), or other forms of vitamin D. You and your caregiver should know that many ...

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

PubMed

Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-12-01

Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β 1 ), gene expression of TGF-β 1 , connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall

PubMed Central

Araos, Patricio; Mondaca, David; Jalil, Jorge E.; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-01-01

Background: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Methods: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague–Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. Results: All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β1), gene expression of TGF-β1, connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. Conclusions: In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. PMID:27587602

Benefits of Permanent His Bundle Pacing Combined With Atrioventricular Node Ablation in Atrial Fibrillation Patients With Heart Failure With Both Preserved and Reduced Left Ventricular Ejection Fraction.

PubMed

Huang, Weijian; Su, Lan; Wu, Shengjie; Xu, Lei; Xiao, Fangyi; Zhou, Xiaohong; Ellenbogen, Kenneth A

2017-04-01

Clinical benefits from His bundle pacing (HBP) in heart failure patients with preserved and reduced left ventricular ejection fraction are still inconclusive. This study evaluated clinical outcomes of permanent HBP in atrial fibrillation patients with narrow QRS who underwent atrioventricular node ablation for heart failure symptoms despite rate control by medication. The study enrolled 52 consecutive heart failure patients who underwent attempted atrioventricular node ablation and HBP for symptomatic atrial fibrillation. Echocardiographic left ventricular ejection fraction and left ventricular end-diastolic dimension, New York Heart Association classification and use of diuretics for heart failure were assessed during follow-up visits after permanent HBP. Of 52 patients, 42 patients (80.8%) received permanent HBP and atrioventricular node ablation with a median 20-month follow-up. There was no significant change between native and paced QRS duration (107.1±25.8 versus 105.3±23.9 milliseconds, P =0.07). Left ventricular end-diastolic dimension decreased from the baseline ( P <0.001), and left ventricular ejection fraction increased from baseline ( P <0.001) in patients with a greater improvement in heart failure with reduced ejection fraction patients (N=20) than in heart failure with preserved ejection fraction patients (N=22). New York Heart Association classification improved from a baseline 2.9±0.6 to 1.4±0.4 after HBP in heart failure with reduced ejection fraction patients and from a baseline 2.7±0.6 to 1.4±0.5 after HBP in heart failure with preserved ejection fraction patients. After 1 year of HBP, the numbers of patients who used diuretics for heart failure decreased significantly ( P <0.001) when compared to the baseline diuretics use. Permanent HBP post-atrioventricular node ablation significantly improved echocardiographic measurements and New York Heart Association classification and reduced diuretics use for heart failure management in atrial fibrillation patients with narrow QRS who suffered from heart failure with preserved or reduced ejection fraction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Impact of worsening renal function related to medication in heart failure.

PubMed

Brunner-La Rocca, Hans-Peter; Knackstedt, Christian; Eurlings, Luc; Rolny, Vinzent; Krause, Friedemann; Pfisterer, Matthias E; Tobler, Daniel; Rickenbacher, Peter; Maeder, Micha T

2015-02-01

Renal failure is a major challenge in treating heart failure (HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function (WRF) and the relationship to outcome. This post-hoc analysis of TIME-CHF (NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit (n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system (RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses (P = 0.0002) and more spironolactone (P = 0.02), whereas beta-blockers (P = 0.69) did not differ and lower doses of RAS-blockers were given (P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given (P = 0.001), but not with low doses (P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients (P <0.001), but most in those with WRF III (P <0.05 for interaction). RAS-blockade was associated with improved outcome (P = 0.006), irrespective of WRF III. Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Computer assisted diagnosis in renal nuclear medicine: rationale, methodology and interpretative criteria for diuretic renography

PubMed Central

Taylor, Andrew T; Garcia, Ernest V

2014-01-01

The goal of artificial intelligence, expert systems, decision support systems and computer assisted diagnosis (CAD) in imaging is the development and implementation of software to assist in the detection and evaluation of abnormalities, to alert physicians to cognitive biases, to reduce intra and inter-observer variability and to facilitate the interpretation of studies at a faster rate and with a higher level of accuracy. These developments are needed to meet the challenges resulting from a rapid increase in the volume of diagnostic imaging studies coupled with a concurrent increase in the number and complexity of images in each patient data. The convergence of an expanding knowledge base and escalating time constraints increases the likelihood of physician errors. Errors are even more likely when physicians interpret low volume studies such as 99mTc-MAG3 diuretic scans where imagers may have had limited training or experience. Decision support systems include neural networks, case-based reasoning, expert systems and statistical systems. iRENEX (renal expert) is an expert system for diuretic renography that uses a set of rules obtained from human experts to analyze a knowledge base of both clinical parameters and quantitative parameters derived from the renogram. Initial studies have shown that the interpretations provided by iRENEX are comparable to the interpretations of a panel of experts. iRENEX provides immediate patient specific feedback at the time of scan interpretation, can be queried to provide the reasons for its conclusions and can be used as an educational tool to teach trainees to better interpret renal scans. iRENEX also has the capacity to populate a structured reporting module and generate a clear and concise impression based on the elements contained in the report; adherence to the procedural and data entry components of the structured reporting module assures and documents procedural competency. Finally, although the focus is CAD applied to diuretic renography, this review offers a window into the rationale, methodology and broader applications of computer assisted diagnosis in medical imaging. PMID:24484751

Symptoms and Warning Signs

MedlinePlus

... Signs Past Issues / Spring 2008 Table of Contents Anorexia Nervosa emaciation (extremely thin from lack of nutrition) relentless ... from diuretic abuse severe dehydration from purging Binge Eating Disorder frequently eating large amounts of food (binge-eating) ...

SVC obstruction

MedlinePlus

The goal of treatment is to relieve the blockage. Diuretics (water pills) or steroids (anti-inflammtory drugs) may be used to temporarily relieve swelling . Other treatment options may include radiation or chemotherapy to shrink the tumor, or surgery to ...

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.

Sociodemographic factors and the quality of prenatal care.

PubMed Central

Hansell, M J

1991-01-01

BACKGROUND: In this study, maternal sociodemographic factors are examined in relationship to the quality of prenatal health services US women receive. METHODS: Data from the 1980 National Natality Survey and 1980 Fetal Mortality Survey were used for the analysis. Indicator variables for prenatal care quality are the percentages of prenatal visits at which blood pressure and urine were tested, the performance of hemoglobin or hematocrit tests, and the presence or absence of advice regarding salt restriction and diuretics usage during pregnancy. RESULTS: Distribution of the basic examinations in prenatal care vary according to marital status, parity, education, and residence in a metropolitan or nonmetropolitan county. The advice received concerning salt and diuretics usage was also influenced by sociodemographic variables. CONCLUSIONS: The analyses reveal that prenatal care is not of even minimally acceptable quality for many women. PMID:1953875

Successful treatment of paraneoplastic hypercalcemia in a patient with giant condyloma acuminatum: a case report.

PubMed

Linnemann, Thomas; Müller, Frauke; Löhnert, Mathias; Hirnle, Peter; Görner, Martin

2013-11-07

While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment. The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found. Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions.

A review on phytochemical and pharmacological investigations of miswak (Salvadora persica Linn)

PubMed Central

Akhtar, Jamal; Siddique, Khalid M.; Bi, Salma; Mujeeb, Mohd

2011-01-01

The miswak is a natural toothbrush made from the twigs of the Salvadora persica (Salvadoraceae). Its use predates the inception of Islam and is frequently advocated in the Hadith (the traditions relating to the life of Prophet MuhammadPBUH). In addition to strengthening the gums, it prevents tooth decay, eliminating toothaches and halt further increase in decay that has already set in. It creates a fragrance in the mouth, eliminates bad odor, improves the sense of taste, and causes the teeth to glow and shine. The other parts of the tree have therapeutic values as corrective, deobstruent, liver tonic, diuretic, analgesic, anthelmintic, astringent, lithontriptic, carminative, diuretic, aphrodisiac, and stomachic. The present review is therefore an effort to give detailed survey of the literature on phytochemistry and pharmacological activities of miswak. PMID:21430961

Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring　- The NOCTURNE Study.

PubMed

Kario, Kazuomi; Tomitani, Naoko; Kanegae, Hiroshi; Ishii, Hajime; Uchiyama, Kazuaki; Yamagiwa, Kayo; Shiraiwa, Toshihiko; Katsuya, Tomohiro; Yoshida, Tetsuro; Kanda, Kiyomi; Hasegawa, Shinji; Hoshide, Satoshi

2017-06-23

Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled. The ARB/CCB combination therapy (irbesartan 100 mg+amlodipine 5 mg) achieved a significantly greater reduction in nocturnal home systolic BP (primary endpoint) than the ARB/diuretic combination (daily irbesartan 100 mg+trichlormethiazide 1 mg) (-14.4 vs. -10.5 mmHg, P<0.0001), independently of urinary sodium excretion and/or nocturnal BP dipping status. However, the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity (diabetes, chronic kidney disease, and elderly patients). This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM. The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake, despite the similar impact of the 2 combinations in patients with higher salt sensitivity.

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

Noordewier, B.; Saari, J.T.

This study examined the effects of furosemide (Furo), a Loop diuretic, and amiloride (Am), a potassium (K)-sparing diuretic, on the excretion of sodium (Na) and K in copper-adequate (CuAdeq) and copper-deficient (CuDef) rats. Weanling male Sprague Dawley rats were fed a CuDef or CuAdeq diet ad libitum and given deionized water to drink. After 5 weeks on the diets, rats were assigned to one of four treatment regimens: Furo, Am or Furo + Am. Rats were anesthetized and electrolyte excretion was measured in 2 {times} 15 min control periods followed by 3 {times} 15 min treatment periods. Furo increased Namore » excretion in a dose dependent manner in both the CuAdeq and the CuDef rats. The response of the CuAdeq rats was slightly greater than that of the CuDef rats in each of the 3 treatment groups in which Furo was given. K excretion following Furo increased to the same extent in the CuAdeq and CuDef rats. The natriuretic response to Am alone was slightly greater in the CuDef than the CuAdeq rats. The antikaliuretic response of the CuDef rats was similar to that of the CuAdeq rats whether Am was given alone or in combination with Furo. These data show that CuDef rats respond to Furo and Am in a manner which is similar to that of CuAdeq rats, this indicates that the sensitivity of the Na reabsorption mechanisms to inhibition by diuretics is not markedly affected by copper deficiency.« less

(99m)Tc-MAG3 diuretic renography in diagnosis of obstructive nephropathy in adults: a comparison between F-15 and a new procedure F+10(sp) in seated position.

PubMed

Tartaglione, Girolamo; D'Addessi, Alessandro; De Waure, Chiara; Pagan, Marco; Raccioppi, Marco; Sacco, Emilio; Cadeddu, Chiara; Vittori, Matteo; Bassi, Pier Francesco; Ferretti, Alice; Al-Nahhas, Adil; Rubello, Domenico

2013-06-01

The objective of this study was to compare 2 diuretic renography procedures: F-15 versus F+10(sp) for diagnosis of obstructive uropathy in adults. Thirty-six patients with unilateral or bilateral hydronephrosis had 2 consecutive Tc-MAG3 diuretic renograms within 7 days, using the widely used procedure F-15 in supine position, and a new seated-position procedure whereby the patient drinks 400 to 500 mL of water at 5 minutes and receives an injection of 20 mg of furosemide at 10 minutes [F+10 (sp)]. F-15 showed nonobstructive results in 63.9% of kidneys, obstruction in 26.4%, and equivocal findings in 6.9% and was not applicable in 2.8%. F+10(sp) showed nonobstructive results in 70.9%, obstruction in 27.8%, and equivocal result in 1.4% of kidneys. Nephroptosis was observed by F+10(sp) in 22.2% of kidneys. Adverse effects reported for the F-15 were hypotension in 2 patients, renal colic in 3 patients, and interruption due to voiding in 5 patients. No adverse effects were reported for F+10(sp). This study shows that the F+10(sp) procedure reduces the equivocal findings of F-15 procedure in 36 patients. It can improve the accuracy and compliance, avoiding adverse effects and reducing bladder filling-related problems.

Metabolism of an insect diuretic hormone by Malpighian tubules studied by liquid chromatography coupled with electrospray ionization mass spectrometry

PubMed Central

Li, Hong; Wang, Houle; Schegg, Kathleen M.; Schooley, David A.

1997-01-01

The larger of two diuretic hormones of the tobacco hornworm, Manduca sexta, (Mas-DH) is a peptide of 41 residues. It is one of a family of seven currently known insect diuretic hormones that are similar to the corticotropin-releasing factor–urotensin–sauvagine family of peptides. We investigated the possible inactivation of Mas-DH by incubating it in vitro with larval Malpighian tubules (Mt), the target organ of the hormone. The medium was analyzed, and degradation products were identified, using on-line microbore reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry (RPLC-ESI-MS). This sensitive technique allows identification of metabolites of Mas-DH (present at an initial level of ≈1 μM). An accurate Mr value for a metabolite is usually sufficient for unambiguous identification. Mas-DH is cleaved by Mt proteases initially at L29–R30 and R30–A31 under our assay conditions; some Mas-DH is also oxidized, apparently at M2 and M11. The proteolysis can be inhibited by 5 mM EDTA, suggesting that divalent metals are needed for peptide cleavage. The oxidation of the hormone can be inhibited by catalase or 1 mM methionine, indicating that H2O2 or related reactive oxygen species are responsible for the oxidative degradation observed. RPLC-ESI-MS is shown here to be an elegant and efficient method for studying peptide hormone metabolism resulting from unknown proteases and pathways. PMID:9391048

Sympatho-renal axis in chronic disease.

PubMed

Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

2011-12-01

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

Pathogenesis of hypokalemia in autosomal dominant hypocalcemia type 1.

PubMed

Kamiyoshi, Naohiro; Nozu, Kandai; Urahama, Yoshimichi; Matsunoshita, Natsuki; Yamamura, Tomohiko; Minamikawa, Shogo; Ninchoji, Takeshi; Morisada, Naoya; Nakanishi, Koichi; Kaito, Hiroshi; Iijima, Kazumoto

2016-04-01

Autosomal dominant hypocalcemia type 1 (ADH1) is a relatively rare endocrine disorder characterized by hypocalcemia and inadequate parathyroid hormone secretion. ADH is caused by activating mutations in the calcium-sensing receptor (CaSR) gene, CASR. CaSR plays a crucial role in calcium and magnesium homeostasis in the kidney. ADH may be accompanied by hypokalemia and metabolic alkalosis when it is classified as type V Bartter syndrome. However, the mechanism underlying hypokalemia in this disease is unclear. We investigated a 33-year-old woman with hypocalcemia and hypoparathyroidism since childhood, whose mother also had hypocalcemia and hypoparathyroidism, but with no clinical symptoms. Blood examinations showed hypokalemia and metabolic alkalosis in the patient, but not her mother. We conducted mutation analysis and diuretic tests to clarify the patient's and her mother's diagnosis and to investigate the onset mechanism of hypokalemia in ADH1. We also determined the localization of CaSR in the kidney by immunohistochemistry. We detected a known gain-of-function mutation in CASR in both the patient and her mother. Diuretic tests revealed a response to furosemide and no reaction to thiazide in the patient, although the mother responded well to both diuretics. CaSR co-localized with the Na(+)-Cl(-) cotransporter (NCCT) on distal tubular epithelial cells. These results indicate that the NCCT in the distal convoluted tubule was secondarily affected in this patient. We conclude that the main pathogenesis of secondary hypokalemia in ADH1 in this patient was secondary NCCT dysfunction.

Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats.

PubMed

Hocher, Berthold; Heiden, Susi; von Websky, Karoline; Arafat, Ayman M; Rahnenführer, Jan; Alter, Markus; Kalk, Philipp; Ziegler, Dieter; Fischer, Yvan; Pfab, Thiemo

2011-03-10

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1) receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1) receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05), especially in those receiving furosemide (-41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1) receptor antagonists are clinically beneficial at different stages of liver cirrhosis.

Phytochemical and biological assessments on Lipidium meyenii (maca) and Epimidium sagittatum (horny goat weed).

PubMed

Qureshi, Mahmood; Mehjabeen, -; Noorjahan, -; Muhammad, Shafi; Siddiqui, Faheem Ahmed; Baig, Iftikhar; Ahmad, Mansoor

2017-01-01

The effects of Lipidium meyenii (maca, LM) and Epimidium sagittatum (horny goat weed, ES) have been investigated due to their involvement in fertilization. Both of the drugs showed good results before, during and after fertilization in male and female mice. The results revealed that the crude extract of Lipidium meyenii caused a significant decrease in the no. of writhes at 300 and 500mg/kg (p<0.05) as compare to control, Epimidium sagittatum and standard drug. The gross behavioral, open field, exploratory behaviour, forced swimming test for stress, diuretic activity, chronic toxicity with the effect on reproduction of both male and female and change in body weight were also studied. The phytochemical study showed the presence of tannin, alkaloid, carbohydrate, rich protein and absence of sterol in LM, whereas ES shows presence of sterol and less protein. LS improve in muscle activity and exploratory behaviours without any toxic effects on mice and their pups. It does not have diuretic effect for first two hour but act normally after initial phase of drug therapy. Epimidium sagittatum has dual action that is at low dose it has slight stimulation action and at high dose little depressive effect. ES also has some diuretic effect. Overall these results suggest that LM is highly effective remedy for treatment of impotency and reduces stress and depression, because of dual effect ES not only suggested as an anxiolytic medicine but also effective in female hormonal disorder.

A novel small-molecule thienoquinolin urea transporter inhibitor acts as a potential diuretic.

PubMed

Li, Fei; Lei, Tianluo; Zhu, Juanjuan; Wang, Weiling; Sun, Yi; Chen, Jihui; Dong, Zixun; Zhou, Hong; Yang, Baoxue

2013-06-01

Urea transporters (UTs) are a family of membrane channel proteins that are specifically permeable to urea and play an important role in intrarenal urea recycling and in urine concentration. Using an erythrocyte osmotic lysis assay, we screened a small-molecule library for inhibitors of UT-facilitated urea transport. A novel class of thienoquinolin UT-B inhibitors were identified, of which PU-14 had potent inhibition activity on human, rabbit, rat, and mouse UT-B. The half-maximal inhibitory concentration of PU-14 on rat UT-B-mediated urea transport was ∼0.8 μmol/l, and it did not affect urea transport in mouse erythrocytes lacking UT-B but inhibited UT-A-type urea transporters, with 36% inhibition at 4 μmol/l. PU-14 showed no significant cellular toxicity at concentrations up to its solubility limit of 80 μmol/l. Subcutaneous delivery of PU-14 (at 12.5, 50, and 100 mg/kg) to rats caused an increase of urine output and a decrease of the urine urea concentration and subsequent osmolality without electrolyte disturbances and liver or renal damages. This suggests that PU-14 has a diuretic effect by urea-selective diuresis. Thus, PU-14 or its analogs might be developed as a new diuretic to increase renal fluid clearance in diseases associated with water retention without causing electrolyte imbalance. PU-14 may establish 'chemical knockout' animal models to study the physiological functions of UTs.

Misdiagnosis of resistant hypertension: Real frequency of true resistant hypertension in patients with suspected resistance to treatment.

PubMed

Doménech, Mónica; Sastre, Enric; Camafort, Miguel; Sierra, Cristina; Coca, Antonio

2018-01-12

Resistant hypertension(RH) has been defined as failure to control office blood pressure (BP) despite the use of≥3 different antihypertensive agents at optimal doses, including, ideally, a diuretic. Apparent RH, defines patients with an incorrect diagnosis of RH due to different causes. The objective was to determine whether most patients with RH in fact have apparent but not true RH. Observational study involving 93 patients with suspected RH, being 60 patients finally included. Screening for secondary causes of hypertension was perfomed. True RH was defined as office BP>140/90mmHg despite full doses of 3 antihypertensive drugs including a diuretic. Mean age 63.7±9.8years, 68.3%were male. Office BP 154.3±14.4/84.4±13.7mmHg. Of the 60 patients, 23.3% had white coat effect, 3.3% didn't have a diuretic and 8.3% were non-adherent-to-treatment. Accordingly, 58.3% were classified as true RH. Spironolactone was added in 62.5% of patients of whom 78.4% achieved ambulatory BP control. Almost half of the patients with suspected RH were not really true RH. We provide more evidence of excess of fluid retention as an underlying cause of lack of BP control in patients with RH, reinforce the relevant paper of spironolactone for the management in those patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Interstitial Nephritis

MedlinePlus

... A reaction to a medicine, such as certain antibiotics. Too much of certain medicines. These include diuretics (water pills) or pain relievers, such as acetaminophen, aspirin, or a non-steroidal anti-inflammatory drug (NSAID). Unbalanced levels of certain nutrients in ...

Chayote (Sechium edule) causing hypokalemia in pregnancy.

PubMed

Jensen, L P; Lai, A R

1986-11-01

A case of severe hypokalemia in pregnancy is presented. Chayote, a subtropical vegetable with potent diuretic action, is implicated, as the potassium level returned to normal, without recurrence of hypokalemia, once the ingestion was stopped.

Choosing Blood Pressure Medications

MedlinePlus

... 14, 2016. Fisher NDL, et al. Renin inhibitors. Journal of Clinical Hypertension. 2011;13:662. Wong GWK, et al. Blood ... blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. Journal of Clinical Hypertension. 2011;13:644. Mann JFE. Choice of therapy ...

The Metabolism of the Volatile Amines

PubMed Central

Tobe, Barry A.; Goldman, Bernard S.

1963-01-01

The effects of certain drugs on metabolism of ammonia by the liver and kidneys in dogs were investigated by a technique in which both hepatic inflow and outflow bloods could be repeatedly sampled in unanesthetized healthy animals. Specific representatives of the classes of the drugs studied included thiopental (barbiturates), morphine (opiates and analgesics), promazine (tranquillizers), and chlorothiazide (oral diuretics). The three drugs commonly used as sedatives were all found to impair the ability of the liver to metabolize ammonia. The diuretic, by contrast, increased the amount of ammonia put into the systemic system by the kidneys. Ethanol appeared to have little or no direct effect on ammonia metabolism. The possibility exists that the occurrence of acute hepatic encephalopathy in patients with severe liver disease may be avoided in many cases if these drugs are administered with proper care. Results also indicated that current concepts of the pharmacological action of sedatives, opiates and tranquillizers may require revision. ImagesFig. 2 PMID:14069611

Use, misuse and abuse of diuretics.

PubMed

Bartoli, Ettore; Rossi, Luca; Sola, Daniele; Castello, Luigi; Sainaghi, Pier Paolo; Smirne, Carlo

2017-04-01

Resolution of edema requires a correct interpretation of body fluids-related renal function, to excrete the excess volume while restoring systemic hemodynamics and avoiding renal failure. In heart failure, the intensive diuresis should be matched by continuous fluids refeeding from interstitium to plasma, avoiding central volume depletion. The slowly reabsorbed ascites cannot refeed this contracted volume in cirrhosis: the ensuing activation of intrathoracic receptors, attended by increased adrenergic and Renin release, causes more avid sodium retention, producing a positive fluid and Na balance in the face of continuous treatment. High-dose-furosemide creates a defect in tubular Na causing diuresis adequate to excrete the daily water and electrolyte load in Chronic Renal Failure. Diuretic treatment requires care, caution and bedside "tricks" aimed at minimizing volume contraction by correctly assessing the homeostatic system of body fluids and related renal hemodynamics. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Phototoxicity to sulphonamide-derived oral antidiabetics and diuretics: comparative in-vitro and in-vivo investigations

NASA Astrophysics Data System (ADS)

Selvaag, Edgar; Anholt, Helle; Moan, Johan; Thune, Per

1997-12-01

Seven oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide, and tolbutamide), and 14 diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide, and xipamide) were investigated for potential phototoxicity in vitro using a cell culture model and in vivo in hairless mice. After exposure to broad band UVA, the majority of the substances tested in vitro yielded phototoxic action leading to loss of culture forming ability. In vivo, all tested substances induced edema or ulceration, and lead to a significant increase in skin fold thickness of the mouse skin. In all a number of substances not described to induce clinical photosensitivity nor phototoxicity in vitro or in vivo were detected in our testing. In determining potential photosensitizers, it seems important to utilize different test methods, as not all substances will exhibit action in a given assay.

Physiology of Fluid and Electrolyte Responses During Inactivity: Water Immersion and Bed Rest

NASA Technical Reports Server (NTRS)

Greenleaf, John E.

1984-01-01

This manuscript emphasizes the physiology of fluid-electrolyte-hormonal responses during the prolonged inactivity of bed rest and water immersion. An understanding of the total mechanism of adaptation (deconditioning) should provide more insight into the conditioning process. Findings that need to be confirmed during bed rest and immersion are: (1) the volume and tissues of origin of fluid shifted to the thorax and head; (2) interstitial fluid pressure changes in muscle and subcutaneous tissue, particularly during immersion; and (3) the composition of the incoming presumably interstitial fluid that contributes to the early hypervolemia. Better resolution of the time course and source of the diuretic fluid is needed. Important data will be forthcoming when hypotheses are tested involving the probable action of the emerging diuretic and natriuretic hormones, between themselves and among vasopressin and aldosterone, on diuresis and blood pressure control.

Successful treatment of paraneoplastic hypercalcemia in a patient with giant condyloma acuminatum: a case report

PubMed Central

2013-01-01

Introduction While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment. Case presentation The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found. Conclusions Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions. PMID:24200238

Mersalyl: a Diuretic with Antiviral Properties

PubMed Central

Kramer, M. J.; Cleeland, R.; Grunberg, E.

1975-01-01

Mersalyl (Salyrgan), an organic mercurial diuretic, was tested against human and animal viruses with in vivo model infections in mice and tissue culture systems. Mersalyl was active against coxsackieviruses A21 and B1 in mice if administered intraperitoneally immediately after infection. No effect was observed if intraperitoneal treatment was delayed 1 or 2 h postinfection, or if treatment was administered either subcutaneously or per os. Topical treatment with a 5% aqueous solution of mersalyl produced a statistically significant effect against herpes simplex dermatitis in mice but the substance was inactive against systemic infections in mice with herpes simplex as well as Columbia SK, influenza, Semliki Forest, and Sendai viruses. Contact inactivation of coxsackieviruses A21 and B1 and herpes simplex virus was observed, but mersalyl was inactive in tissue culture against coxackieviruses A21 and B1, herpes simplex, influenza, rhinovirus, Semliki Forest, Sendai, and vaccinia viruses. PMID:810082

A review on plant Cordia obliqua Willd. (Clammy cherry)

PubMed Central

Gupta, Richa; Gupta, Ghanshyam Das

2015-01-01

Cordia obliqua Willd. plant (Common name-Clammy Cherry) belongs to family Boraginaceae. It is a medium-sized deciduous tree and very vigorous in growth. According to traditional system, it possesses anthelmintic, purgative, diuretic, expectorant, antipyretic, hepatoprotective and analgesic action. The fruits are edible and used as pickle. The gum obtained from mucilage is used for pasting sheets of paper and as matrix forming material in tablet formulations. Phytochemical investigations show the presence of alkaloids, flavonoids, phenolics, tannins and reducing sugar. Evaluation of pharmacological activities confirmed C. obliqua plant as antimicrobial, hypotensive, respiratory stimulant, diuretic and anti-inflammatory drug. A number of traditional activities of this plant still need scientific approval which will increase its medicinal potential. This review presents the Pharmacognostic properties, phytochemical constituents, traditional uses and biological activities reported for the plant and it will be helpful to explore the knowledge about Cordia obliqua Willd. for the researchers. PMID:26392710

A review on plant Cordia obliqua Willd. (Clammy cherry).

PubMed

Gupta, Richa; Gupta, Ghanshyam Das

2015-01-01

Cordia obliqua Willd. plant (Common name-Clammy Cherry) belongs to family Boraginaceae. It is a medium-sized deciduous tree and very vigorous in growth. According to traditional system, it possesses anthelmintic, purgative, diuretic, expectorant, antipyretic, hepatoprotective and analgesic action. The fruits are edible and used as pickle. The gum obtained from mucilage is used for pasting sheets of paper and as matrix forming material in tablet formulations. Phytochemical investigations show the presence of alkaloids, flavonoids, phenolics, tannins and reducing sugar. Evaluation of pharmacological activities confirmed C. obliqua plant as antimicrobial, hypotensive, respiratory stimulant, diuretic and anti-inflammatory drug. A number of traditional activities of this plant still need scientific approval which will increase its medicinal potential. This review presents the Pharmacognostic properties, phytochemical constituents, traditional uses and biological activities reported for the plant and it will be helpful to explore the knowledge about Cordia obliqua Willd. for the researchers.

Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide.

PubMed

Kjeldsen, Sverre E; Os, Ingrid; Høieggen, Aud; Beckey, Kim; Gleim, Gilbert W; Oparil, Suzanne

2005-01-01

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/10 mm Hg above goal.

Spironolactone in cardiovascular disease: an expanding universe?

PubMed

Funder, John W

2017-01-01

Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i.e. with a preserved ejection fraction). The third currently accepted role for spironolactone is in hypertension resistant to three conventional antihypertensives including a diuretic, where it has been proven to be effective, in contra-distinction to renal artery denervation. Finally, brief consideration will be given to 'areas in waiting' - pulmonary hypertension/fibrosis, cancer - where spironolactone may play very useful roles.

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.

A pharmacokinetic/pharmacodynamic model capturing the time course of torasemide-induced diuresis in the dog.

PubMed

Paulin, A; Schneider, M; Dron, F; Woehrlé, F

2016-12-01

A pharmacokinetic/pharmacodynamic modelling approach was used to determine a dosage regimen which maximizes diuretic efficiency of torasemide in dogs. Kinetic profiles of plasma concentration, torasemide excretion rate in urine (TERU) and diuresis were investigated in 10 dogs after single oral administrations at 3 dose levels, 0.2, 0.8 and 1.6 mg/kg, and an intravenous injection of 0.2 mg/kg. Endogenous regulation was evidenced by a proteresis loop between TERU and diuresis. To describe the diuresis-time profile, TERU served as input into a turnover model with inhibition of loss of response, extended by a moderator acting on both loss and production of response. Estimated maximum inhibition of loss of response, I max , was 0.984 showing that torasemide is an efficacious diuretic able to suppress almost total water reabsorption. A TERU 50, value producing half of I max , of 1.45 μg/kg/h was estimated from the model. Pharmacokinetic and pharmacodynamic parameters were used to simulate the torasemide dose-effect relationship after oral administration. Model predictions were in good agreement with diuresis measured in a validation study conducted in 10 dogs, which were administered oral doses of 0.15, 0.4, 0.75, 1.5 and 4.5 mg/kg for 5 days. Finally, oral dose associated with the highest daily diuretic efficiency was predicted to be 0.1 mg/kg. © 2016 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

A sea urchin Na(+)K(+)2Cl(-) cotransporter is involved in the maintenance of calcification-relevant cytoplasmic cords in Strongylocentrotus droebachiensis larvae.

PubMed

Basse, Wiebke C; Gutowska, Magdalena A; Findeisen, Ulrike; Stumpp, Meike; Dupont, Sam; Jackson, Daniel J; Himmerkus, Nina; Melzner, Frank; Bleich, Markus

2015-09-01

The cellular mechanisms of calcification in sea urchin larvae are still not well understood. Primary mesenchyme cells within the larval body cavity form a syncytium to secrete CaCO3 spicules from intracellular amorphous CaCO3 (ACC) stores. We studied the role of Na(+)K(+)2Cl(-) cotransporter (NKCC) in intracellular ACC accumulation and larval spicule formation of Strongylocentrotus droebachiensis. First, we incubated growing larvae with three different loop diuretics (azosemide, bumetanide, and furosemide) and established concentration-response curves. All loop diuretics were able to inhibit calcification already at concentrations that specifically inhibit NKCC. Calcification was most effectively inhibited by azosemide (IC50=6.5 μM), while larval mortality and swimming ability were not negatively impacted by the treatment. The inhibition by bumetanide (IC50=26.4 μM) and furosemide (IC50=315.4 μM) resembled the pharmacological fingerprint of the mammalian NKCC1 isoform. We further examined the effect of azosemide on the maintenance of cytoplasmic cords and on the occurrence of calcification vesicles using fluorescent dyes (calcein, FM1-43). Fifty micromolars of azosemide inhibited the maintenance of cytoplasmic cords and resulted in increased calcein fluorescence within calcification vesicles. The expression of NKCC in S. droebachiensis was verified by PCR and Western blot with a specific NKCC antibody. In summary, the pharmacological profile of loop diuretics and their specific effects on calcification in sea urchin larvae suggest that they act by inhibition of NKCC via repression of cytoplasmic cord formation and maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

Diuretic effects of medetomidine compared with xylazine in healthy dogs.

PubMed

Talukder, Md Hasanuzzaman; Hikasa, Yoshiaki

2009-07-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 microg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine's effect is less dose-dependent than xylazine's effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation.

Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by targeting a NaCl cotransporter in bone

PubMed Central

Dvorak, Melita M; De Joussineau, Cyrille; Carter, D Howard; Pisitkun, Trairak; Knepper, Mark A; Gamba, Gerardo; Kemp, Paul J; Riccardi, Daniela

2008-01-01

Thiazide diuretics are used, worldwide, as the first-choice drug for patients with uncomplicated hypertension. In addition to their anti-hypertensive actions, they increase bone mineral density and reduce the prevalence of fractures, indicating that thiazides may have a role in the management of postmenopausal osteoporosis. Traditionally, the bone-protective effects of thiazides have been attributed to an increase in renal calcium reabsorption, secondary to the inhibition of the sodium chloride cotransporter, NCC, expressed in the kidney distal tubule. Whether thiazides exert a direct osteoanabolic effect independently of their renal action is controversial. Here we demonstrate that freshly frozen sections of human and rat bone express NCC, principally in bone-forming cells, the osteoblasts. In primary and established culture models of osteoblasts, fetal rat calvarial (FRC) and human MG63 cells, NCC protein is virtually absent in proliferating cells while its expression is dramatically increased during differentiation. Thiazides directly stimulate the production of osteoblast markers, runt-related transcription factor 2 (runx2) and osteopontin, in the absence of a proliferative effect. Using overexpression/knockdown studies in FRC cells, we show that thiazides, but not loop diuretics, increase mineralized nodule formation acting on NCC. Overall, our study demonstrates that thiazides stimulate osteoblast differentiation and bone mineral formation independently of their renal actions. In addition to their use as part of a therapeutic treatment plan for elderly, hypertensive individuals, our discovery opens up the possibility that bone-specific drug targeting by thiazides may be developed for the prevention and treatment of osteoporosis in the patient population as a whole. PMID:17656470

Quantitative Ultrasound for Measuring Obstructive Severity in Children with Hydronephrosis.

PubMed

Cerrolaza, Juan J; Peters, Craig A; Martin, Aaron D; Myers, Emmarie; Safdar, Nabile; Linguraru, Marius George

2016-04-01

We define sonographic biomarkers for hydronephrotic renal units that can predict the necessity of diuretic nuclear renography. We selected a cohort of 50 consecutive patients with hydronephrosis of varying severity in whom 2-dimensional sonography and diuretic mercaptoacetyltriglycine renography had been performed. A total of 131 morphological parameters were computed using quantitative image analysis algorithms. Machine learning techniques were then applied to identify ultrasound based safety thresholds that agreed with the t½ for washout. A best fit model was then derived for each threshold level of t½ that would be clinically relevant at 20, 30 and 40 minutes. Receiver operating characteristic curve analysis was performed. Sensitivity, specificity and area under the receiver operating characteristic curve were determined. Improvement obtained by the quantitative imaging method compared to the Society for Fetal Urology grading system and the hydronephrosis index was statistically verified. For the 3 thresholds considered and at 100% sensitivity the specificities of the quantitative imaging method were 94%, 70% and 74%, respectively. Corresponding area under the receiver operating characteristic curve values were 0.98, 0.94 and 0.94, respectively. Improvement obtained by the quantitative imaging method over the Society for Fetal Urology grade and hydronephrosis index was statistically significant (p <0.05 in all cases). Quantitative imaging analysis of renal sonograms in children with hydronephrosis can identify thresholds of clinically significant washout times with 100% sensitivity to decrease the number of diuretic renograms in up to 62% of children. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

PubMed

Crary, Michael A; Carnaby, Giselle D; Shabbir, Yasmeen; Miller, Leslie; Silliman, Scott

2016-02-01

Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

Echo and BNP serial assessment in ambulatory heart failure care: Data on loop diuretic use and renal function.

PubMed

Dini, Frank Lloyd; Simioniuc, Anca; Carluccio, Erberto; Ghio, Stefano; Rossi, Andrea; Biagioli, Paolo; Reboldi, Gianpaolo; Galeotti, Gian Giacomo; Lu, Fei; Zara, Cornelia; Whalley, Gillian; Temporelli, Pier Luigi

2016-12-01

We compared the follow-up data on loop diuretic use and renal function, as assessed by serum creatinine levels, and the estimated glomerular filtration rate (eGFR), of two groups of consecutive ambulatory HF patients: 1) the clinically-guided group, in which management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department of Pisa (standard of care) and 2) the echo and B-type natriuretic peptide (BNP) guided group (patients conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group: Pisa, Perugia, Pavia; Verona, Auckland, and Veruno), in which therapy was delivered according to the serial assessment of BNP and echocardiography. Patients whose follow-up was based on standard of care had a significant higher prevalence of worsening renal function, that was likely related to higher diuretic dosages, whilst, a better management of renal function was observed in the echo-BNP-guided group. The data is related to "Echo and natriuretic peptide guided therapy improves outcome and reduces worsening renal function in systolic heart failure: An observational study of 1137 outpatients" (A. Simioniuc, E. Carluccio, S. Ghio, A. Rossi, P. Biagioli, G. Reboldi, G.G. Galeotti, F. Lu, C. Zara, G. Whalley, P.G. Temporelli, F.L. Dini, 2016; K.J. Harjai, H.K. Dinshaw, E. Nunez, M. Shah, H. Thompson, T. Turgut, H.O. Ventura, 1999; A. Ahmed, A. Husain, T.E. Love, G. Gambassi, L.J. Dell׳Italia, G.S. Francis, M. Gheorghiade, R.M. Allman, S. Meleth, R.C. Bourge, 2006) [1], [2], [3].

The association between drugs frequently used by the elderly and vitamin D blood levels: a review of observational and experimental studies.

PubMed

van Orten-Luiten, Anne Claire B; Janse, André; Dhonukshe-Rutten, Rosalie A M; Witkamp, Renger F

2014-02-01

The risk of adverse drug reactions (ADRs) rises with increasing age. In the field of ADRs, drug-nutrient interactions (DNIs) are a relatively unexplored area. More knowledge will contribute to the simple prevention of this type of ADR. As the prevalence of vitamin D deficiency in the elderly is high, the primary objective of this review is to evaluate the literature on the relationship between drug use and vitamin D status, focusing on medicines commonly used by the elderly. PubMed was searched for human epidemiological and clinical studies published until early 2013, investigating the relationship between vitamin D blood levels and use of drugs from one of the following groups: proton pump inhibitors (PPIs), biguanides, vitamin K antagonists, platelet aggregation inhibitors, thiazide diuretics, loop diuretics, beta-blocking agents, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II antagonists, statins, benzodiazepines, and antidepressants. A total of 63 publications were identified. Thiazide diuretics, statins, and calcium channel blocking agents were the most frequently studied drug groups. Associations between thiazides and vitamin D were mixed (n = 22), statins had no or positive associations (n = 16) and calcium blockers were not associated or were negatively associated with vitamin D (n = 10). In conclusion, several knowledge gaps exist on the relationship between drug use and vitamin D blood levels. Available data are scarce (particularly for the aged), study characteristics are highly variable, and found associations may be confounded by, amongst other things, the underlying disease. Nonetheless, this review provides a basis for future research on ADRs that contribute to nutrient deficiencies.

The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states

PubMed Central

Alshahrani, Saeed; Rapoport, Robert M.; Zahedi, Kamyar; Jiang, Min; Nieman, Michelle; Barone, Sharon; Meredith, Andrea L.; Lorenz, John N.; Rubinstein, Jack

2017-01-01

Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ. HCTZ (20mg/kg s.c.) lowered BP in 1) NCC KO on a salt restricted diet but not with normal diet; 2) in volume depleted but not in volume resuscitated pendrin/NCC dKO mice; the BP reduction occurs without any enhancement in salt excretion or reduction in cardiac output. HCTZ still lowered BP following treatment of NCC KO on salt restricted diet with paxilline (8 mg/kg, i.p.), a BK channel blocker, and in BK KO and BK/NCC dKO mice on salt restricted diet. In aortic rings from NCC KO mice on normal and low salt diet, HCTZ did not alter and minimally decreased maximal phenylephrine contraction, respectively, while contractile sensitivity remained unchanged. These results demonstrate 1) the non-diuretic hypotensive effects of thiazides are augmented with volume depletion and 2) that the BP reduction is likely the result of HCTZ inhibition of vasoconstriction through a pathway dependent on factors present in vivo, is unrelated to BK channel activation, and involves processes associated with intravascular volume depletion. PMID:28719636

Ultrasound based computer-aided-diagnosis of kidneys for pediatric hydronephrosis

NASA Astrophysics Data System (ADS)

Cerrolaza, Juan J.; Peters, Craig A.; Martin, Aaron D.; Myers, Emmarie; Safdar, Nabile; Linguraru, Marius G.

2014-03-01

Ultrasound is the mainstay of imaging for pediatric hydronephrosis, though its potential as diagnostic tool is limited by its subjective assessment, and lack of correlation with renal function. Therefore, all cases showing signs of hydronephrosis undergo further invasive studies, like diuretic renogram, in order to assess the actual renal function. Under the hypothesis that renal morphology is correlated with renal function, a new ultrasound based computer-aided diagnosis (CAD) tool for pediatric hydronephrosis is presented. From 2D ultrasound, a novel set of morphological features of the renal collecting systems and the parenchyma, is automatically extracted using image analysis techniques. From the original set of features, including size, geometric and curvature descriptors, a subset of ten features are selected as predictive variables, combining a feature selection technique and area under the curve filtering. Using the washout half time (T1/2) as indicative of renal obstruction, two groups are defined. Those cases whose T1/2 is above 30 minutes are considered to be severe, while the rest would be in the safety zone, where diuretic renography could be avoided. Two different classification techniques are evaluated (logistic regression, and support vector machines). Adjusting the probability decision thresholds to operate at the point of maximum sensitivity, i.e., preventing any severe case be misclassified, specificities of 53%, and 75% are achieved, for the logistic regression and the support vector machine classifier, respectively. The proposed CAD system allows to establish a link between non-invasive non-ionizing imaging techniques and renal function, limiting the need for invasive and ionizing diuretic renography.

Elucidation of the Strongest Predictors of Cardiovascular Events in Patients with Heart Failure.

PubMed

Fukuda, Hiroki; Shindo, Kazuhiro; Sakamoto, Mari; Ide, Tomomi; Kinugawa, Shintaro; Fukushima, Arata; Tsutsui, Hiroyuki; Ito, Shin; Ishii, Akira; Washio, Takashi; Kitakaze, Masafumi

2018-06-20

In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan-Meier analysis was used to investigate the importance of the combinations. In a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). Among 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan-Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. Patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference.

PubMed

Temperini, Claudia; Cecchi, Alessandro; Scozzafava, Andrea; Supuran, Claudiu T

2009-02-01

Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide. Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM). Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV. Examining the four X-ray crystal structures of their CA II adducts, we observed several (2-3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity. Indeed, indapamide bound to CA II has no interactions with active site water molecules. Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications.

Micellar versus hydro-organic mobile phases for retention-hydrophobicity relationship studies with ionizable diuretics and an anionic surfactant.

PubMed

Ruiz-Angel, M J; Carda-Broch, S; García-Alvarez-Coque, M C; Berthod, A

2004-03-19

Logarithm of retention factors (log k) of a group of 14 ionizable diuretics were correlated with the molecular (log P o/w) and apparent (log P(app)) octanol-water partition coefficients. The compounds were chromatographed using aqueous-organic (reversed-phase liquid chromatography, RPLC) and micellar-organic mobile phases (micellar liquid chromatography, MLC) with the anionic surfactant sodium dodecyl sulfate (SDS), in the pH range 3-7, and a conventional octadecylsilane column. Acetonitrile was used as the organic modifier in both modes. The quality of the correlations obtained for log P(app) at varying ionization degree confirms that this correction is required in the aqueous-organic mixtures. The correlation is less improved with SDS micellar media because the acid-base equilibriums are shifted towards higher pH values for acidic compounds. In micellar chromatography, an electrostatic interaction with charged solutes is added to hydrophobic forces; consequently, different correlations should be established for neutral and acidic compounds, and for basic compounds. Correlations between log k and the isocratic descriptors log k(w), log k(wm) (extrapolated retention to pure water in the aqueous-organic and micellar-organic systems, respectively), and psi0 (extrapolated mobile phase composition giving a k = 1 retention factor or twice the dead time), and between these descriptors and log P(app) were also satisfactory, although poorer than those between log k and log P(app) due to the extrapolation. The study shows that, in the particular case of the ionizable diuretics studied, classical RPLC gives better results than MLC with SDS in the retention hydrophobicity correlations.

Clinical Evaluation of 68Ga-PSMA-II and 68Ga-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm.

PubMed

Wangerin, Kristen A; Baratto, Lucia; Khalighi, Mohammad Mehdi; Hope, Thomas A; Gulaka, Praveen K; Deller, Timothy W; Iagaru, Andrei H

2018-06-06

Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions. The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68 Ga-RM2 and 68 Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale. The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68 Ga-RM2 and for 68 Ga-PSMA-11 in the kidneys and bladder regions. Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68 Ga PET, indicating that the use of diuretics may be avoided.

Labetalol compared with propranolol in the treatment of black hypertensive patients.

PubMed

Saunders, E; Curry, C; Hinds, J; Kong, B W; Medakovic, M; Poland, M; Roper, K

1987-09-01

A double-blind parallel group study was conducted to examine the effects of oral labetalol, in doses from 100 to 800 mg BID, and propranolol, 40 to 320 mg, in patients with mild to moderate hypertension. The doses of labetalol (n = 74) and propranolol (n = 79) were titrated weekly to achieve a sitting diastolic blood pressure (DBP) of less than 90 mmHg or at least a 10-mmHg decrease from placebo baseline on two consecutive visits. A 2-month fixed-dose maintenance phase followed in which a diuretic could be added if the sitting DBP was greater than or equal to 100 mmHg on maximum doses of either drug. BP and heart rate were measured 8-12 hours after a dose in the sitting and standing positions. Labetalol was significantly more effective at the end of monotherapy than propranolol was in lowering both the sitting (p less than .05) and standing (p less than .04) DBP. The reduction in the systolic, although more pronounced for those on labetalol, was not significantly different; 53% of patients had a "good" response to labetalol compared with 30% of the propranolol group. Propranolol significantly (p less than 0.01) lowered heart rate compared with labetalol. Nine patients in the labetalol group and 10 in the propranolol group required a diuretic. The decrease in BP after the addition of a diuretic was comparable. Changes in plasma lipids were not significant, but HDL increased 9% with labetalol and decreased 2% with propranolol. Triglycerides increased 25% with labetalol and 31% with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Gout

MedlinePlus

... which are taken to rid the body of excess fluid in condition like hypertension, edema, and heart disease. Diuretics reduce the amount of uric acid passed in the urine. Drugs with salicylate, such as aspirin. Niacin, a vitamin also known as nicotinic acid. Cyclosporine, a medication ...

Patterns of postnatal weight changes in infants with very low and extremely low birth weights.

PubMed

Smith, S L; Kirchhoff, K T; Chan, G M; Squire, S J

1994-01-01

To describe (1) short-term postnatal weight loss and gain patterns in infants with very low and extremely low birth weights and (2) the variables that may affect these weight change patterns. Descriptive, retrospective review. University hospital in the intermountain western United States. Sixty-two charts of infants admitted to a university neonatal intensive care unit from July 1990 through November 1992 were reviewed. Infants who weighed 1000 grams or less were categorized as extremely low birth weight (ELBW) and infants weighing 1001 to 1500 grams were categorized as very low birth weight (VLBW). Each group was comprised of 31 infants. Fifty percent of the sample were male, and 50% were female. Eighty-five percent of the sample were Anglo-American, and 15% were non-Anglo-American. Data were collected on a three-part data collection tool and included demographic and treatment variables. A significant difference was found in the maximum percent weight lost between the two groups, with the ELBW group losing a mean of 14.77% of birth weight and the VLBW group losing a mean of 11.35% of birth weight (t = 2.45, p < 0.05). The day the infants reached their nadir weight was significantly different between the two groups. The ELBW group reached their nadir on day of life 7, and the VLBW group reached their nadir on day of life 6 (t = 2.00, p < 0.05). No significant difference was noted in the time to return to birth weight between the two groups, with a mean of 15 days to return to birth weight. Factors associated with postnatal weight changes were intraventricular hemorrhage, use of diuretics and steroids, day of life when nadir weight occurred, and maximum percent of weight lost. Many of the independent variables were significantly interrelated to each other (r = -0.90 to r = 0.91, p < 0.01 to p < 0.001). However, only the variables that correlated with time to return to birth weight were entered into the regression analysis. These variables included number of days diuretics were given before return to birth weight, maximum percent of weight lost, and day of life the infants reached their nadir weight. Number of days diuretics were given before return to birth weight correlated significantly with time to return to birth weight (r = 0.77, F = 26.66, p < 0.0001) although maximum percent of weight lost and day of life the infants reached their nadir weight had a minimal effect. Further research into the effects of diuretic therapy on weight changes in this population of infants may lead to interventions to minimize the negative effects of diuretics on return to birth weight. In addition, the older growth charts may not be applicable to this population of infants. Generation of new growth charts that provide growth curves based on these data could be useful in developing nutritional therapies that would promote growth and possibly decrease the length of hospital stay for these infants.

Diuretics and Gout: What's the Connection?

MedlinePlus

... Limiting beverages that are sugar sweetened and limiting foods and beverages that contain high fructose corn syrup Losing weight and maintaining a healthy weight based on your body mass index To ... also limit your intake of foods rich in the compound purine, which form uric ...

Case 39: Anorexia nervosa

USDA-ARS?s Scientific Manuscript database

Anorexia nervosa is a disease affecting primarily young women who have distorted body images. Although their weight is less than 30 percent under ideal body weight, they see themselves as overweight. Anorectics often use diuretic and laxative agents to accomplish their weight loss. Patients with bul...

Beta-blockers for hypertension

PubMed Central

Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

2017-01-01

Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect). Main results Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol). There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons. Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence). However, there was little or no difference in CHD between beta-blockers and diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS inhibitors (low-certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta-blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate-certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low-certainty evidence). Authors' conclusions Most outcome RCTs on beta-blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta-blocker most used. Current evidence suggests that initiating treatment of hypertension with beta-blockers leads to modest CVD reductions and little or no effects on mortality. These beta-blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people. Beta-blockers for hypertension What is the aim of this review? The aim of this Cochrane Review was to assess whether beta-blockers decrease the number of deaths, strokes, and heart attacks associated with high blood pressure in adults. We collected and analysed all relevant studies to answer this question and found 13 relevant studies. Are beta-blockers as good as other medicines when used for treatment of adults with high blood pressure? Beta-blockers were not as good at preventing the number of deaths, strokes, and heart attacks as other classes of medicines such as diuretics, calcium-channel blockers, and renin-angiotensin system inhibitors. Most of these findings come from one type of beta-blocker called atenolol. However, beta-blockers are a diverse group of medicines with different properties, and we need more well-conducted research in this area. What was studied in the review? Millions of people with high blood pressure have strokes, heart attacks, and other diseases, and many of them die. This situation could be prevented with appropriate treatment. Researchers have tried different medicines for treating high blood pressure. What are the main results of the review? We found 13 studies from high-income countries, mainly Western Europe and North America. In the studies, the people receiving beta-blockers were compared to people who received no treatment or other medicines. The studies showed the following. Beta-blockers probably make little or no difference in the number of deaths among people on treatment for high blood pressure. This effect appears to be similar to that of diuretics and renin-angiotensin system inhibitors, but beta-blockers are probably not as good at preventing deaths from high blood pressure as calcium-channel blockers. Beta-blockers may reduce the number of strokes, an effect which appears to be similar to that of diuretics. However, beta-blockers may not be as good at preventing strokes as renin-angiotensin system inhibitors or calcium-channel blockers. Beta-blockers may make little or no difference to the number of heart attacks among people with high blood pressure. The evidence suggests that this effect may not be different from that of diuretics, renin-angiotensin system inhibitors, or calcium-channel blockers. However, among people aged 65 years and older, the evidence suggests that beta-blockers may not be as good at reducing heart attacks as diuretics. People given beta-blockers are more likely to have side effects and stop treatment than people taking renin-angiotensin system inhibitors, but there may be little or no difference in side effects between beta-blockers and diuretics or calcium-channel blockers. How up-to-date is this review? The review authors searched for studies that had been published up to June 2016. PMID:28107561

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.

[Diuretics and their potential effect on breath-alcohol concentration--a case report].

PubMed

Schmitt, Georg; Skopp, Gisela

2015-01-01

Many objections were raised to breath-alcohol analysis upon its introduction in the field of traffic law enforcement in Germany, but in the meantime this issue has become less relevant in forensic routine work. In the present case, the defending lawyer claimed that the ethanol concentration in the blood and hence in the breath of his client, which was 0.35 mg/l according to the Dräger Alcotest 7110® Evidential and thus above the legal limit of 0.25 mg/l, had been changed by diuretics taken 4 hours before the breath alcohol test, viz. 10 mg of torasemide, a loop diuretic, and 50 mg of spironolactone, a competitive aldosterone antagonist. According to the literature, the maximum urinary output in healthy subjects within the first 4 hours after 10 mg torasemide was 1450 ml. In patients suffering from heart failure, the urinary volume was reduced by a factor of 2.5-3; after chronic intake of torasemide, water loss did not differ from placebo. Spironolactone, which acts on the distal tubule, has little effect on urinary output. In a publication, the loss of water in excess within 24 hours was 90 ml. Co-administration of 100 mg spironolactone and 20 mg furosemide, which roughly compares to 10 mg torasemide, resulted in a mean urinary volume of 1566 ml within the first 4 hours. In terms of the reported case and provided that no compensatory fluid had been taken, a purely theoretical maximum shift of 0.007 mg/ may occur in the breath-alcohol concentration due to the smaller distribution volume even considering maximum urinary excretion values. On the other hand, already mild levels of dehydration may be associated with negative symptoms affecting driving ability.

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

Diuretic effects of medetomidine compared with xylazine in healthy dogs

PubMed Central

Talukder, Md. Hasanuzzaman; Hikasa, Yoshiaki

2009-01-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 μg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine’s effect is less dose-dependent than xylazine’s effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation. PMID:19794896

Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations

PubMed Central

Al Shibli, Amar; Narchi, Hassib

2015-01-01

Bartter and Gitelman syndromes (BS and GS) are inherited disorders resulting in defects in renal tubular handling of sodium, potassium and chloride. Previously considered as genotypic and phenotypic heterogeneous diseases, recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition. Although they share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia, hyperaldosteronism, the clinical and laboratory manifestations may not always allow distinction between them. Diuretics tests, measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change (< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS, except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists. The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children. Clinical symptoms and biochemical markers of GS and classic form of BS (type III) may overlap and thus genetic analysis may specify the real cause of symptoms. However, although genetic analysis is available, its use remains limited because of limited availability, large gene dimensions, lack of hot-spot mutations, heavy workup time and costs involved. Furthermore, considerable overlap exists between the different genotypes and phenotypes. Although BS and GS usually have distinct presentations and are associated with specific gene mutations, there remains considerable overlap between their phenotypes and genotypes. Thus, they are better described as a spectrum of clinical manifestations caused by different gene mutations. PMID:26140272

First-line first? Trends in thiazide prescribing for hypertensive seniors.

PubMed

Morgan, Steve; Bassett, Kenneth L; Wright, James M; Yan, Lixiang

2005-04-01

Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older) who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most effective and least costly therapeutic options are significant.

[Diuretic treatment in patients with acute pulmonary edema did not produces severe hyponatremia or hypokalemia].

PubMed

Kalužay, Jozef; Pokorná, Veronika; Bodíková, Svetlana; Vahančíková, Natália; Ponťuch, Peter

2016-04-01

One of the risks of diuretic therapy for pulmonary edema is the development of hyponatremia and hypokalemia with pro-arrhythmic potential. The aim of our study was to analyze the incidence of hyponatremia and hypokalemia after the first day of treatment in a real clinical practice. We performed a retrospective analysis of data obtained from medical records. We included all patients with pulmonary edema admitted to the coronary care unit, only patients which died within the first day of treatment were excluded. Absolute dose of administered furosemide, total fluid intake and urine output, saline and pottasium intake were analyzed. Nonparametric paired Wilcoxon test was used to compare natrium and pottasium levels changes. 37 patients were included into analysis. The median dose of furosemide administered during the first day of treatment was 120 mg (IQR 20-300 mg). Median diuresis was 2 400 ml (IQR 1 425-3 225 ml). The median of difference between diuresis and total fluid intake was 315 ml (IQR 538-1 380 ml). Wilcoxon test confirmed a prevailing statistically significant trend of slight rise in serum sodium within the first day of treatment (serum sodium 138.0 IQR 132.8-139.6 vs 138.1 IQR 134,0-141,7 mmol/l, p = 0.0046). The difference in serum potassium was not statistically significant (serum potassium 4.2 IQR 3.9-4.8 vs 4.2, IQR 3.8-4.8 mmol/l). Results did not confirmed the need for a substitution of sodium and potassium losses during the first day of diuretic therapy to prevent hyponatriemia and hypokalemia in patients with pulmonary edema.

Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet.

PubMed

Wang, Bangchen; Wen, Donghai; Li, Huaqing; Wang-France, Jun; Sansom, Steven C

2017-10-01

Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance. We used free-flow micropuncture to measure the [K + ] in the early distal tubule (EDT [K + ]) before and after furosemide treatment. Furosemide increased the EDT [K + ] in WT on CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K + ] of KO on LNaHK or WT on HK. Furosemide-sensitive Na + excretion was significantly greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split-open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but similar density in mice on LNaHK, compared with CTRL. No difference was found in the density or Po of the 30 pS K channels between the two groups. These results indicate mice on LNaHK exhibited furosemide-sensitive net K + secretion in the TAL that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude that furosemide is a K-sparing diuretic by decreasing the TAL net K + secretion in subjects on LNaHK. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

PubMed

Hirsch, Sheldon; Hirsch, Jackie; Bhatt, Udayan; Rovin, Brad H

2012-01-01

Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use. This study is a retrospective review of 48 mostly African-American patients with CKD treated with multiple and/or high-dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low BP and reduction of urine protein. RASI was not reduced in response to initial increases in serum creatinine greater than 30%. A clinically well-tolerated increase in serum creatinine over 30% during the first year occurred in 41% of the patients. Treatment was unaltered, and target goals for BP and urine protein were typically achieved. After the point of maximal serum creatinine in the first year, these patients had minimal progression of disease over the next 6 years, with a long-term estimated glomerular filtration rate slope of only -0.52 ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death. The 30% limitation to initial increases in the serum creatinine still pertains for single RASI at usual doses. However, favorable long-term outcomes suggest that initial increases over 30% should be tolerated in the context of dual goal-directed, more aggressive RASI and diuretic use. Copyright © 2012 S. Karger AG, Basel.

Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system.

PubMed

Nilsson, Erik; Gasparini, Alessandro; Ärnlöv, Johan; Xu, Hairong; Henriksson, Karin M; Coresh, Josef; Grams, Morgan E; Carrero, Juan Jesus

2017-10-15

Hypo- and hyperkalemia in clinical settings are insufficiently characterized and large-scale data from Europe lacking. We studied incidence and determinants of these abnormalities in a large Swedish healthcare system. Observational study from the Stockholm CREAtinine Measurements project, including adult individuals from Stockholm accessing healthcare in 2009 (n=364,955). Over 3-years, we estimated the incidence of hypokalemia, defined as potassium<3.5mmol/L, hyperkalemia, defined as potassium>5mmol/L, and moderate/severe hyperkalemia, defined as potassium>5.5mmol/L. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Of 364,955 participants, 69.4% had 1-2 potassium tests, 16.7% had 3-4 tests and the remaining 13.9% had >4potassiumtests/year. Hypokalemia occurred in 49,662 (13.6%) individuals, with 33% recurrence. Hyperkalemia occurred in 25,461 (7%) individuals, with 35.7% recurrence. Moderate/severe hyperkalemia occurred in 9059 (2.5%) with 28% recurrence. The frequency of potassium testing was an important determinant of dyskalemia risk. The incidence proportion of hyperkalemia was higher in the presence of diabetes, lower eGFR, myocardial infarction, heart failure (HF), or use of renin angiotensin-aldosterone system inhibitors (RAASi). In adjusted analyses, women and use of loop/thiazide diuretics were associated with lower hyperkalemia risk. Older age, lower eGFR, diabetes, HF and use of RAASi were associated with higher hyperkalemia risk. On the other hand, women, younger age, higher eGFR and baseline use of diuretics were associated with higher hypokalemia risk. Hypo- and hyperkalemia are common in healthcare. Optimal RAASi and diuretics use and careful potassium monitoring in the presence of certain comorbidities, especially lower eGFR, is advocated. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large Health System

PubMed Central

Chang, Alex R.; Sang, Yingying; Leddy, Julia; Yahya, Taher; Kirchner, H. Lester; Inker, Lesley A.; Matsushita, Kunihiro; Ballew, Shoshana H.; Coresh, Josef; Grams, Morgan E.

2016-01-01

Little is known about the frequency and patterns of hyperkalemia in clinical settings. We evaluated the association between baseline antihypertensive medications that may affect potassium levels (angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, loop/thiazide diuretics, and potassium-sparing diuretics) and hyperkalemia, defined by potassium >5 mEq/L and >5.5 mEq/L, over a 3-year time period in 194,456 outpatients in the Geisinger Health System, as well as actions taken after an episode of hyperkalemia. The proportions of patients with 0, <2, 2–4, and ≥4 potassium measurements per year were 20%, 58%, 16%, and 6%. Potassium levels >5 mEq/L and >5.5 mEq/L occurred in 10.8% and 2.3% of all patients over the 3-year period; among patients with ≥4 measurements per year, corresponding values were 39.4% and 14.6%. Most cases of hyperkalemia occurred only once during follow-up. The antihypertensive medication class most strongly associated with hyperkalemia was ACEIs. Among patients with a measurement of potassium >5.5 mEq/L, only 24% were seen by a nephrologist and 5.2% were seen by a dietician during the 3-year period. Short-term actions after a potassium measurement >5.5 mEq/L included emergency room visit (3.1% within 7 days), re-measurement of potassium (44.3% with 14 days), and change in a potassium-altering medication (26.4% within 60 days). The most common medication changes were discontinuation/dose reduction of an ACEI/ARB or potassium-sparing diuretic, which occurred in 29.1% and 49.6% of persons taking these medications, respectively. In conclusion, hyperkalemia is common. Future research may enable optimal RAAS inhibitor use with improved management of hyperkalemia. PMID:27067721

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Jaski, Brian E; Bart, Bradley A; Heywood, James T; Anand, Inder S; Smelser, James M; Kaneshige, Alan M; Chomsky, Don B; Adler, Eric D; Haas, Garrie J; Watts, James A; Nabut, Jose L; Schollmeyer, Michael P; Fonarow, Gregg C

2016-02-01

The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trial's untimely termination, additional AUF investigation is warranted. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Effects of In-Hospital Intravenous Cold Saline in Postcardiac Arrest Patients Treated with Targeted Temperature Management.

PubMed

Suppogu, Nissi; Panza, Gregory A; Kilic, Sena; Gowdar, Shreyas; Kallur, Kamala R; Jayaraman, Ramya; Lundbye, Justin; Fernandez, Antonio B

2018-03-01

Recent data suggest that rapid infusion of intravenous (IV) cold saline for Targeted Temperature Management (TTM) after cardiac arrest is associated with higher rates of rearrest, pulmonary edema, and hypoxia, with no difference in neurologic outcomes or survival when administered by Emergency Medical Services. We sought to determine the effects of IV cold saline administration in the hospital setting in postcardiac arrest patients to achieve TTM and its effect on clinical parameters and neurologic outcomes. A cohort of 132 patients who completed TTM after cardiac arrest in a single institution was retrospectively studied. Patients who did not receive cold saline were matched by age, gender, Glasgow coma scale, downtime, and presenting rhythm to patients who received cold saline. Demographics, cardiac rearrest, diuretic use, time to target temperature, and Cerebral Performance Category (CPC) scores were recorded among other variables. Patients who received cold saline achieved target temperature sooner (280 vs. 345 minutes, p = 0.05), had lower lactate levels on day 1 (4.2 ± 3.5 mM vs. 6.0 ± 4.9 mM, p = 0.019) and day 2 (1.3 ± 2.2 mM vs. 2.2 ± 3.2 mM, p = 0.046), increased incidence of pulmonary edema (51.5% vs. 31.8%, p = 0.006), and increased diuretic utilization (63.6% vs. 42.4%, p = 0.014). There was no significant difference in cardiac rearrest, arterial oxygenation, and CPC scores (ps > 0.05). Infusion of IV cold saline is associated with shorter time to target temperature, increased incidence of pulmonary edema, and diuretic use, with no difference in cardiac rearrest, survival, and neurologic outcomes.

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Qualitative and quantitative analysis of the diuretic component ergone in Polyporus umbellatus by HPLC with fluorescence detection and HPLC-APCI-MS/MS.

PubMed

Zhao, Ying-Yong; Zhao, Ye; Zhang, Yong-Min; Lin, Rui-Chao; Sun, Wen-Ji

2009-06-01

Polyporus umbellatus is a widely used anti-aldosteronic diuretic in Traditional Chinese medicine (TCM). A new, sensitive and selective high-performance liquid chromatography-fluorescence detector (HPLC-FLD) and high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS/MS) method for quantitative and qualitative determination of ergosta-4,6,8(14),22-tetraen-3-one(ergone), which is the main diuretic component, was provided for quality control of P. umbellatus crude drug. The ergone in the ethanolic extract of P. umbellatus was unambiguously characterized by HPLC-APCI, and further confirmed by comparing with a standard compound. The trace ergone was detected by the sensitive and selective HPLC-FLD. Linearity (r2 > 0.9998) and recoveries of low, medium and high concentration (100.5%, 100.2% and 100.4%) were consistent with the experimental criteria. The limit of detection (LOD) of ergone was around 0.2 microg/mL. Our results indicated that the content of ergone in P. umbellatus varied significantly from habitat to habitat with contents ranging from 2.13 +/- 0.02 to 59.17 +/- 0.05 microg/g. Comparison among HPLC-FLD and HPLC-UV or HPLC-APCI-MS/MS demonstrated that the HPLC-FLD and HPLC-APCI-MS/MS methods gave similar quantitative results for the selected herb samples, the HPLC-UV methods gave lower quantitative results than HPLC-FLD and HPLC-APCI-MS/MS methods. The established new HPLC-FLD method has the advantages of being rapid, simple, selective and sensitive, and could be used for the routine analysis of P. umbellatus crude drug.

Extreme metabolic alkalosis with fludrocortisone therapy.

PubMed Central

Burns, A.; Brown, T. M.; Semple, P.

1983-01-01

We present an unusual case of extreme metabolic alkalosis resulting from severe hypokalaemia caused by unmonitored fludrocortisone therapy. Biochemical aspects of the disorder are discussed, as is the successful treatment with diuretics and potassium replacement. Some dangers of this therapy and necessary precautions are emphasized. PMID:6622340

Characterization of the interaction between furosemide and bovine serum albumin

NASA Astrophysics Data System (ADS)

Zhou, Neng; Liang, Yi-Zeng; Wang, Ping

2008-01-01

The interaction of furosemide (FU), one kind of potent diuretic, with bovine serum albumin (BSA) has been investigated at physiological acidity (pH 7.40) by fluorescent technique. Displacement experiment with site markers and Synchronous fluorescence clearly reveal that there are non-specific binding sites of FU with BSA. This conclusion was supported by the binding studies in the presence of the hydrophobic probe 1-anilinonaphthalene-8-sulfonic acid (ANS) and in different ionic strength. The binding sites number n and binding constant K were measured. The thermodynamic parameters Δ H°, Δ G°, Δ S° at different temperatures were calculated. The effects of other four diuretics, some common metal ions and bioactive components from herbal medicine on the binding are also considered. The results show only bumetanide has strong effect on FU's binding. Moreover, several data processing methods presently used were evaluated with Data of the same set. Quite different results were obtained from these methods suggesting more attention should be paid to the data processing methods.

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

Farina, R.; Brandao-Mello, C.E.; Oliveira, A.R.

In September 1987, the Goiania radiological accident involving a source of {sup 137}Cs culminated in about 140 victims who presented internal and/or external contamination and/or external exposure to radiation and/or radiation burns. Internal contamination was verified through analysis of urine and fecal samples. Internal contamination was also evaluated by measurements performed at the whole-body counter installed in Goiania in November 1987. To enhance the decorporation of 137Cs, patients were treated with the following: (1) Prussian Blue, oral administration, in 46 patients; (2) diuretics, oral administration, in 17 patients; (3) induced perspiration, increasing {sup 137}Cs elimination. These procedures were done undermore » rigorous clinical evaluation and considering the data from assay of excreta and data obtained from the whole-body counter. The doses of Prussian Blue exceeded about 6.5 times the dose previously indicated in the literature. It was the first time diuretics were used in humans to treat {sup 137}Cs internal contamination. The results of these procedures are discussed.« less

Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2

PubMed Central

Konopacka, Agnieszka; Qiu, Jing; Yao, Song T.; Greenwood, Michael P.; Greenwood, Mingkwan; Lancaster, Thomas; Inoue, Wataru; de Souza Mecawi, Andre; Vechiato, Fernanda M.V.; de Lima, Juliana B.M.; Coletti, Ricardo; Hoe, See Ziau; Martin, Andrew; Lee, Justina; Joseph, Marina; Hindmarch, Charles; Paton, Julian; Antunes-Rodrigues, Jose; Bains, Jaideep

2015-01-01

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution—rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats. PMID:25834041

Practical aspects in the management of hypokalemic periodic paralysis

PubMed Central

Levitt, Jacob O

2008-01-01

Management considerations in hypokalemic periodic paralysis include accurate diagnosis, potassium dosage for acute attacks, choice of diuretic for prophylaxis, identification of triggers, creating a safe physical environment, peri-operative measures, and issues in pregnancy. A positive genetic test in the context of symptoms is the gold standard for diagnosis. Potassium chloride is the favored potassium salt given at 0.5–1.0 mEq/kg for acute attacks. The oral route is favored, but if necessary, a mannitol solvent can be used for intravenous administration. Avoidance of or potassium prophylaxis for common triggers, such as rest after exercise, high carbohydrate meals, and sodium, can prevent attacks. Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. Potassium, water, and a telephone should always be at a patient's bedside, regardless of the presence of weakness. Perioperatively, the patient's clinical status should be checked frequently. Firm data on the management of periodic paralysis during pregnancy is lacking. Patient support can be found at . PMID:18426576

When to increase or reduce sodium loading in the management of fluid volume status during acute decompensated heart failure.

PubMed

Hirotani, Shinichi; Masuyama, Tohru

2014-12-01

Sodium restriction has been believed to be indispensible to manage fluid overload during acute decompensated heart failure (ADHF). However, recently, it was reported that a change in aggression of sodium and water restriction did not affect the outcome of ADHF. In contrast, current data suggest that small amount of hypertonic saline solution with high-dose furosemide produces an improvement in haemodynamic and clinical parameters without any severe adverse effects. In this perspective, first, we are going to describe the effects of sodium loading on neurohormonal activation, body's sodium balance, and renal function in chronic heart failure and the efficacy of loop diuretics in ADHF. Then, we are going to explain the possible mechanisms by which sodium loading enhances the efficacy of loop diuretics and about the clinical conditions during which sodium loading should be avoided. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Phytochemical and pharmacological review of Lagenaria sicereria

PubMed Central

Prajapati, Rakesh P.; Kalariya, Manisha; Parmar, Sachin K.; Sheth, Navin R.

2010-01-01

Lagenaria siceraria (Molina) standley (LS) (Family: Cucurbitaceae) is an annual herbaceous climbing plant with a long history of traditional medicinal uses in many countries, especially in tropical and subtropical regions. Since ancient times the climber has been known for its curative properties, and has been utilized for treatment of various ailments, including jaundice, diabetes, ulcer, piles, colitis, insanity, hypertension, congestive cardiac failure (CCF), and skin diseases. Its fruit pulp is used both as an emetic and purgative, and for its cooling, diuretic, antibilious, and pectoral properties. Boiled in oil this pulp is used to treat rheumatism and insomnia. A wide range of chemical compounds including sterols, terpenoids, flavonoids, and saponins have been isolated from the species. Its extracts have been found to possess various pharmacological activities. Below, we give a comprehensive review of its ethnomedical uses, chemical constituents, and pharmacological profile as a medicinal plant. Particular attention is given to its analgesic, anti-inflammatory, antihyperlipidemic, diuretic, hepatoprotective, anthelmintic, and antibacterial effects so that its potential uses in pharmaceutics can be better evaluated. PMID:21731373

Mineral content of Chinese medicinal herbs used as diuretic treatments for Taiwanese children.

PubMed

Chen, Chien-Yi

2005-01-01

Eighteen major, minor and trace elements in 12 Chinese medicinal herbs commonly consumed by Taiwanese Children as diuretics were determined by instrumental neutron activation analysis (INAA). Dried and powdered herb samples were irradiated in a neutron flux of ca. 2 x 10(12) n/cm2 s under separate short and long irradiation schemes. Lichen (IAEA-336) was used as the reference standard, and tomato leaves (NIST-SRM 1570a) were employed for cross-checking the accuracy of the results. INAA was shown to be a reliable multi-element analytical method for determining the content of both toxicologically and nutritionally important minerals in Chinese medicinal herbs. Determined elements were present in the dried herbs in concentrations ranging from 10(4) to 10(-3) microg/g. The mineral contents and the maximum daily intake values of the tested herbs were compared with published values and with the recommended daily intakes for Taiwanese children as specified by the World Health Organization.

Resistant hypertension and hyperaldosteronism.

PubMed

Gonzaga, Carolina C; Calhoun, David A

2008-12-01

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.

Efficacy of azilsartan medoxomil with chlorthalidone in hypertension.

PubMed

Baker, William L; Nigro, Stefanie C; White, William B

2014-07-01

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events.

Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors

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

Y Cho; J Vermeire; J Merkel

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are blood-feeding, intestinal nematode parasites that infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a 'proof-of-concept' for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibitionmore » of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analog that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity.« less

Delineating the Effects of Spironolactone on Two Small Fish Species

EPA Science Inventory

Spironolactone is a pharmaceutical that acts as an anti-androgen in humans to treat certain conditions such as hirsutism and female pattern hair loss. This drug is also used to treat hypertension, various dermatologic conditions, and as a diuretic. With its common usage for vario...

Medications and Characteristics of Drugs Causing Ototoxicity.

ERIC Educational Resources Information Center

Pappas, Dennis G.; Pappas, Dennis G., Jr.

1997-01-01

This article discusses medications which, by entering the confines of the inner ear, can be toxic and destroy the structures of hearing. Medications that may produce ototoxicity are explained and include aminoglycosides, quinine, salycilates, and diuretics. Factors that should be considered relating to ototoxicity are provided. Contains…

The identification and quantitation of triamterene in blood and urine from a fatal aircraft accident.

DOT National Transportation Integrated Search

1992-07-01

Triamterene, a diuretic drug used in combination with other drugs for the treatment of hypertension, was found in the blood and urine of a fatal aircraft accident victim. The extraction and identification of triamterene is difficult. It exhibits poor...

Molecular analysis of the glutamate decarboxylase locus in Streptococcus thermophilus ST110

USDA-ARS?s Scientific Manuscript database

GABA ('-aminobutyric acid) is generated from glutamate by the action of glutamic acid decarboxylase (GAD) and characterized by hypotensive, diuretic and tranquilizing effects in humans and animals. The production of GABA by lactic acid starter bacteria would enhance the functionality of fermented da...

Detection and transfer of the glutamate decarboxylase gene in Streptococcus thermophilus

USDA-ARS?s Scientific Manuscript database

GABA (gamma-aminobutyric acid) is generated from glutamate by the action of glutamic acid decarboxylase (GAD) and characterized by hypotensive, diuretic and tranquilizing effects in humans and animals. The production of GABA by lactic acid starter bacteria would enhance the functionality of fermen...

Cross species sensitivity to a novel androgen receptor agonist of potential environmental concern, spironolactone

EPA Science Inventory

Spironolactone (SPL) is a pharmaceutical that is used in humans as an androgen receptor (AR) antagonist to treat conditions like hirsutism, various dermatologic afflictions, and female pattern hair loss, in addition to its common usage as a diuretic to treat hypertension. Althoug...

Identification of a novel androgen receptor agonist (or “androgen mimic”) of environmental concern: spironolactone

EPA Science Inventory

Spironolactone is a pharmaceutical that acts as an androgen receptor (AR) antagonist in humans to treat certain conditions such as hirsutism, various dermatologic afflictions, and female pattern hair loss. The drug is also used to treat hypertension as a diuretic. With this commo...

Hypertension. Part 2: The Role of Medication.

ERIC Educational Resources Information Center

Tanji, Jeffrey L.

1990-01-01

Discusses the differences between exercise alone and exercise with medication (e.g., diuretics, beta blockers, and ACE inhibitors) for treating hypertensive patients. Guidelines are presented for physicians wanting to change the therapeutic regimen or to step down from medical therapy, noting exercise must always be part of the program. (SM)

[Pseudo-Bartter syndrome--2 cases].

PubMed

Jóźwiak, Lucyna; Jaroszyński, Andrzej; Baranowicz-Gaszczyk, Iwona; Borowicz, Ewa; Ksiazek, Andrzej

2010-01-01

Bartter syndrome represents the group of renal disturbances characterized by hypokaliemia and metabolic alkalosis. Some diseases could display hypokalemic metabolic alkalosis without primary tubular dysfunction. These disorders are called pseudo-Bartter syndrome. In this paper we present 2 cases of pseudo-Bartter syndrome related among to other things to overuse of diuretic drugs.

The control of Malpighian tubule secretion in a predacious hemipteran insect, the spined soldier bug Podisus maculiventris (Heteroptera, Pentatomidae)

USDA-ARS?s Scientific Manuscript database

Spined soldier bugs, Podisus maculiventris, are heteropteran insects that feed voraciously on other insects, particular the soft bodied larval forms of Lepidoptera and Coleoptera. The response of P. maculiventris Malpighian tubules (MT) to serotonin and known diuretic and antidiuretic peptides has b...

The Molecular Characterization of the Kinin Transcript and the Physiological Effects of Kinins in the Blood-Gorging Insect Rhodnius prolixus

USDA-ARS?s Scientific Manuscript database

The dramatic feeding-related activities of the Chagas' disease vector, Rhodnius prolixus are under neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect kinins, possess diuretic, digestive and myotropic activities in many insects. In this study...

Into the Unknown: The Logistics Preparation of the Lewis and Clark Expedition

DTIC Science & Technology

2003-06-06

boils), “pox” (syphilis, also called Lues or French Disease), “char lick” ( colic ), and “biliousness.” Lewis and Clark had a rudimentary knowledge of...secretion producing dark stools; also a diuretic; given orally, has an anti-syphilitic action; ingredient of Dr. Rush’s Bilious Pills. Cream of tartar

Myxedema coma leading to respiratory depression in a dog.

PubMed

Atkinson, Kathryn; Aubert, Isabelle

2004-04-01

A 10-year-old, intact male, cocker spaniel was presented with hypothermia, without shivering, and progressive stupor leading to coma. Myxedema coma, potentially precipitated by diuretic therapy, was tentatively diagnosed and treatment initiated, but progressive respiratory depression led to the decision to euthanize. Postmortem findings supported the diagnosis of myxedema coma.

Myxedema coma leading to respiratory depression in a dog

PubMed Central

2004-01-01

Abstract A 10-year-old, intact male, cocker spaniel was presented with hypothermia, without shivering, and progressive stupor leading to coma. Myxedema coma, potentially precipitated by diuretic therapy, was tentatively diagnosed and treatment initiated, but progressive respiratory depression led to the decision to euthanize. Postmortem findings supported the diagnosis of myxedema coma. PMID:15144105

Topical wound-healing effects and phytochemical composition of heartwood essential oils of Juniperus virginiana L., Juniperus occidentalis Hook., and Juniperus ashei Juniperus Buchholz

USDA-ARS?s Scientific Manuscript database

Ethnobotanical surveys indicated that several Juniperus species are utilized as an antihelmintic, diuretic, stimulant, antiseptic, carminative, antirheumatic, antifungal and for wound healing. In the present study, essential oils obtained from heartwood samples of Juniperus virginiana L., J. occide...

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

Kramer, L.

The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Camore » 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.« less

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

Berkowitz, L.R.; Orringer, E.P.

Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, /sup 86/Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments withmore » hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin CC cells. The increased K flux in hemoglobin AA cells was likewise sensitive to anion replacement and to loop diuretics and did not require the presence of Na. These data indicate that a volume-activated K pathway with similar transport characteristics exists in both hemoglobin CC and AA red cells.« less

Pharmacogenomics Study of Thiazide Diuretics and QT Interval in Multi-Ethnic Populations: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)

PubMed Central

Seyerle, Amanda A; Sitlani, Colleen M; Noordam, Raymond; Gogarten, Stephanie M; Li, Jin; Li, Xiaohui; Evans, Daniel S; Sun, Fangui; Laaksonen, Maarit A; Isaacs, Aaron; Kristiansson, Kati; Highland, Heather M; Stewart, James D; Harris, Tamara B; Trompet, Stella; Bis, Joshua C; Peloso, Gina M; Brody, Jennifer A; Broer, Linda; Busch, Evan L; Duan, Qing; Stilp, Adrienne M; O’Donnell, Christopher J; Macfarlane, Peter W; Floyd, James S; Kors, Jan A; Lin, Henry J; Li-Gao, Ruifang; Sofer, Tamar; Méndez-Giráldez, Raúl; Cummings, Steven R; Heckbert, Susan R; Hofman, Albert; Ford, Ian; Li, Yun; Launer, Lenore J; Porthan, Kimmo; Newton-Cheh, Christopher; Napier, Melanie D; Kerr, Kathleen F; Reiner, Alexander P; Rice, Kenneth M; Roach, Jeffrey; Buckley, Brendan M; Soliman, Elsayed Z; de Mutsert, Renée; Sotoodehnia, Nona; Uitterlinden, André G; North, Kari E; Lee, Craig R; Gudnason, Vilmundur; Stürmer, Til; Rosendaal, Frits R; Taylor, Kent D; Wiggins, Kerri L; Wilson, James G; Chen, Yii-Der I; Kaplan, Robert C; Wilhelmsen, Kirk; Cupples, L Adrienne; Salomaa, Veikko; van Duijn, Cornelia; Jukema, J Wouter; Liu, Yongmei; Mook-Kanamori, Dennis O; Lange, Leslie A; Vasan, Ramachandran S; Smith, Albert V; Stricker, Bruno H; Laurie, Cathy C; Rotter, Jerome I; Whitsel, Eric A; Psaty, Bruce M; Avery, Christy L

2017-01-01

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common SNPs modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic, and cross-phenotype genome-wide analyses of European (66%), African American (15%), and Hispanic (19%) populations (N=78,199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5×10−8), we found suggestive evidence (P<5×10−6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (e.g. NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions. PMID:28719597

Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: pathophysiological hypothesis.

PubMed

Kimura, Genjiro

2016-03-01

Primarily the sodium-glucose cotransporter 2 (SGLT2) inhibitors suppress the cotransport of glucose and sodium from the tubular lumen of proximal tubules to the blood and enhance the glucose excretion into urine. Therefore, glucose and caloric balances become negative, making the blood glucose level as well as insulin secretion both reduced. On the other hand, the proximal tubular fluid, constituting with low chloride concentration because of SGLT2 inhibition, is transferred to the loop of Henle. On the low chloride conditions, the reabsorption mechanisms in the loop of Henle do not work, as if loop diuretics are given. Finally, blood pressure is also lowered secondarily due to the loop diuretic action by SGLT2 inhibitions. Thus, the metabolic and hemodynamic combined systems synergistically interact further to suppress the risks leading to atherosclerosis and organs damage. Precise mechanisms for SGLT2 inhibitors to work in various aspects especially in preventing organ damage and cardiovascular events must be clarified further. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Drug-induced abnormalities of potassium metabolism.

PubMed

Kokot, Franciszek; Hyla-Klekot, Lidia

2008-01-01

Pharmacotherapy has progressed rapidly over the last 20 years with the result that general practioners more and more often use drugs which may influence potassium metabolism at the kidney or gastrointestinal level, or the transmembrane transport of potassium at the cellular level. Potassium abnormalities may result in life-theatening clinical conditions. Hypokalemia is most frequently caused by renal loss of this electrolyte (thiazide, thiazide-like and loop diuretics, glucocorticoids) and the gastrointestinal tract (laxatives, diarrhea, vomiting, external fistula), and may be the result of an increased intracellular potassium influx induced by sympathicomimetics used mostly by patients with asthma, or by insulin overdosage in diabetic subjects. The leading symptoms of hypokalemia are skeletal and smooth muscle weakness and cardiac arrhythmias. Hyperkalemia may be caused by acute or end-stage renal failure, impaired tubular excretion of potassium (blockers of the renin-angiotensin-aldosterone system, nonsteroidal anti-inflammatory drugs, cyclosporine, antifungal drugs, potassium sparing diuretics), acidemia, and severe cellular injury (tumor lysis syndrome). Hyperkalemia may be the cause of severe injury of both skeletal and smooth muscle cells. The specific treatment counteracting hyperkalemia is a bolus injection of calcium salts and, when necessary, hemodialysis.

Comparison of Body Weight Trend Algorithms for Prediction of Heart Failure Related Events in Home Care Setting.

PubMed

Eggerth, Alphons; Modre-Osprian, Robert; Hayn, Dieter; Kastner, Peter; Pölzl, Gerhard; Schreier, Günter

2017-01-01

Automatic event detection is used in telemedicine based heart failure disease management programs supporting physicians and nurses in monitoring of patients' health data. Analysis of the performance of automatic event detection algorithms for prediction of HF related hospitalisations or diuretic dose increases. Rule-Of-Thumb and Moving Average Convergence Divergence (MACD) algorithm were applied to body weight data from 106 heart failure patients of the HerzMobil-Tirol disease management program. The evaluation criteria were based on Youden index and ROC curves. Analysis of data from 1460 monitoring weeks with 54 events showed a maximum Youden index of 0.19 for MACD and RoT with a specificity > 0.90. Comparison of the two algorithms for real-world monitoring data showed similar results regarding total and limited AUC. An improvement of the sensitivity might be possible by including additional health data (e.g. vital signs and self-reported well-being) because body weight variations obviously are not the only cause of HF related hospitalisations or diuretic dose increases.

Correlates of diuretic renography in experimental hydronephrosis

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

Kekomaeki, M.R.; Rikalainen, H.; Ruotsalainen, P.

1989-02-01

We studied the correlations between diuretic renographs and kidney function in experimental hydronephrosis in rabbits. Features of furosemide-stimulated /sup 99m/Tc-diethylenetriamine-pentaacetic acid renographs were compared to the growth rate, thirst test and endogenous creatinine clearance rate in a chronic solitary-kidney animal model. Intravenous pyelograms, done four weeks after laparotomy, left nephrectomy, bladder resection and constriction of the right pyeloureteric junction, showed signs of obstruction in all the 12 animals of the experimental group. An absent tracer washout after intravenous furosemide, found in five animals, was associated with retarded growth, isosthenuria and an abnormal creatinine clearance. In all of the other sevenmore » animals, a distinct tracer washout after intravenous furosemide was accompanied with a normal growth rate and creatinine clearance. However, no one of these seven animals had a normal ability to retain water and concentrate urine in the thirst test. We conclude that, in this experimental model, a furosemide-induced tracer washout from the kidney pelvis cannot be taken as a proof of the absence of any upper urinary tract obstruction.« less

[Hypercalciuria].

PubMed

Périmenis, P; Wémeau, J-L; Vantyghem, M-C

2005-12-01

The frequency of hypercalciuria is increasing in western countries with an incidence of nephrolithiasis which can reach 13%. Hypercalciuria appears as an alteration of the calcium transport system (kidney, bowel, bone) which is regulated by calcitriol and parathormone. The aim of this review was to screen etiologies of hypercalciuria taking into account recent genetic advances (calcium epithelial channel and calcium sensing receptor). Hypercalciuria may be favored by nutritional causes (diet rich in calcium, sodium, carbohydrates, proteins, poor in phosphates and potassium). It may also be related to an increase in calcium absorption (vitamin D excess, primary hyperparathyroidism, sarcoidosis, lymphoma, estrogens, and certain genetic causes), an increase in osteoresorption (bone metastasis, myeloma, Paget, hyperthyroidism, immobilization, hypercortisolism and corticosteroid therapy), or a decrease of kidney tubular resorption (diuretics, Cacci and Ricci, acromegally, Bartter, familial dominant hypocalcemia, Fanconi, Dent, familial hypomagnesemia-hypercalciuria syndrome, type 1 distal tubular acidosis, pseudohypoaldosteronism, diabetes). If no cause is identified, persistence of hypercalciuria after instituting a correct diet is defined as idiopathic hypercalciuria. Treatment of the cause is essential in secondary hypercalciuria, in addition to diet (low sodium intake, normocalcic diet, hydration), associated with thiazide diuretics and biphosphonates if necessary.

Bartter's syndrome with type 2 diabetes mellitus.

PubMed

See, Ting-Ting; Lee, Siu-Pak

2009-02-01

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

PubMed Central

Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

2017-01-01

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

PubMed

Vasco, Raquel F V; Reis, Eduardo T; Moyses, Rosa M A; Elias, Rosilene M

2017-12-01

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.

Generic sample preparation combined with high-resolution liquid chromatography-time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories.

PubMed

Peters, R J B; Oosterink, J E; Stolker, A A M; Georgakopoulos, C; Nielen, M W F

2010-04-01

A unification of doping-control screening procedures of prohibited small molecule substances--including stimulants, narcotics, steroids, beta2-agonists and diuretics--is highly urgent in order to free resources for new classes such as banned proteins. Conceptually this may be achieved by the use of a combination of one gas chromatography-time-of-flight mass spectrometry method and one liquid chromatography-time-of-flight mass spectrometry method. In this work a quantitative screening method using high-resolution liquid chromatography in combination with accurate-mass time-of-flight mass spectrometry was developed and validated for determination of glucocorticosteroids, beta2-agonists, thiazide diuretics, and narcotics and stimulants in urine. To enable the simultaneous isolation of all the compounds of interest and the necessary purification of the resulting extracts, a generic extraction and hydrolysis procedure was combined with a solid-phase extraction modified for these groups of compounds. All 56 compounds are determined using positive electrospray ionisation with the exception of the thiazide diuretics for which the best sensitivity was obtained by using negative electrospray ionisation. The results show that, with the exception of clenhexyl, procaterol, and reproterol, all compounds can be detected below the respective minimum required performance level and the results for linearity, repeatability, within-lab reproducibility, and accuracy show that the method can be used for quantitative screening. If qualitative screening is sufficient the instrumental analysis may be limited to positive ionisation, because all analytes including the thiazides can be detected at the respective minimum required levels in the positive mode. The results show that the application of accurate-mass time-of-flight mass spectrometry in combination with generic extraction and purification procedures is suitable for unification and expansion of the window of screening methods of doping laboratories. Moreover, the full-scan accurate-mass data sets obtained still allow retrospective examination for emerging doping agents, without re-analyzing the samples.

Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large Health System.

PubMed

Chang, Alex R; Sang, Yingying; Leddy, Julia; Yahya, Taher; Kirchner, H Lester; Inker, Lesley A; Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef; Grams, Morgan E

2016-06-01

Little is known about the frequency and patterns of hyperkalemia in clinical settings. We evaluated the association between baseline antihypertensive medications that may affect potassium levels (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, loop/thiazide diuretics, and potassium-sparing diuretics) and hyperkalemia, defined by potassium >5 mEq/L and >5.5 mEq/L, over a 3-year time period in 194 456 outpatients in the Geisinger Health System, as well as actions taken after an episode of hyperkalemia. The proportions of patients with 0, <2, 2 to 4, and ≥4 potassium measurements per year were 20%, 58%, 16%, and 6%. Potassium levels >5 mEq/L and >5.5 mEq/L occurred in 10.8% and 2.3% of all patients over the 3-year period; among patients with ≥4 measurements per year, corresponding values were 39.4% and 14.6%. Most cases of hyperkalemia occurred only once during follow-up. The antihypertensive medication class most strongly associated with hyperkalemia was angiotensin-converting enzyme inhibitors. Among patients with a measurement of potassium >5.5 mEq/L, only 24% were seen by a nephrologist and 5.2% were seen by a dietician during the 3-year period. Short-term actions after a potassium measurement >5.5 mEq/L included emergency room visit (3.1% within 7 days), remeasurement of potassium (44.3% with 14 days), and change in a potassium-altering medication (26.4% within 60 days). The most common medication changes were discontinuation/dose reduction of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or potassium-sparing diuretic, which occurred in 29.1% and 49.6% of people taking these medications, respectively. In conclusion, hyperkalemia is common. Future research may enable optimal renin-angiotensin-aldosterone system inhibitor use with improved management of hyperkalemia. © 2016 American Heart Association, Inc.

Fluid overload in the ICU: evaluation and management.

PubMed

Claure-Del Granado, Rolando; Mehta, Ravindra L

2016-08-02

Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients. In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies. In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.

Signs, symptoms, and treatment patterns across serial ambulatory cardiology visits in patients with heart failure: insights from the NCDR PINNACLE® registry.

PubMed

Allen, Larry A; Tang, Fengming; Jones, Philip; Breeding, Tracie; Ponirakis, Angelo; Turner, Stuart J

2018-05-03

Due to a relative lack of outpatient heart failure (HF) clinical registries, we aimed to describe symptoms, signs, and medication treatment among ambulatory patients with heart failure (HF) over time. Using health records from 234 PINNACLE (Practice Innovation and Clinical Excellence) U.S. cardiology practices (2008-2014), serial visits for patients with HF were characterized. Symptoms, signs, and HF medications (angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARB], beta blockers [BB], and diuretics) were compared between visits. Among 763,331 patients with HF, 550,581 had ≥2 clinic visits < 1 year apart, with 2,998,444 visit pairs. In the 12 months following an index visit, patients had a mean of 2.5 ± 2.3 additional visits. Recorded index visit symptoms ranged from dyspnea (53.6%) to orthopnea (23.1%); signs ranged from peripheral edema (52.2%) to hepatomegaly (0.6%). Of those with ejection fraction < 40%, ACEI was prescribed in 58.6%, ARB in 18.5%, BB in 85.2%, and diuretics in 70.0%. Between-visit recorded changes were infrequent: dyspnea appeared in 3.8%, resolved in 2.7%; NYHA class increased in 2.9%, decreased in 2.9%; number of signs increased in 6.0%, decreased in 5.1%; ACEI/ARB or BB added in 6.4%, removed in 6.2%; diuretic added in 3.7%, removed in 3.8%. Changes in recorded symptoms were rarely associated with initiation or discontinuation in HF medication classes. Ambulatory HF care in U.S. cardiology practices seldom recorded changes in symptoms, signs, and medication class. Although templated medical records and absence of medication dosing likely underestimated the degree to which clinical changes occur over serial visits for HF, these PINNACLE data suggest opportunities for greater symptom-based and therapy-focused visits.

Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

PubMed

Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

2013-09-01

Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.

PubMed

Miller, Wayne L; Mullan, Brian P

2014-06-01

This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. The accurate assessment and management of volume overload in patients with DCHF remains problematic. TBV was measured by a radiolabeled-albumin dilution technique with intravascular volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine interstitial volume contribution to total fluid loss. Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular volume post-diuretic therapy despite large reductions in body weight. Mobilization of interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular volume, however, remained increased at dismissal. The extent, composition, and distribution of volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed volume management with respect to a goal of treating to euvolemia. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Hemodynamic and metabolic effects of estrogen plus progestin therapy in hypertensive postmenopausal women treated with an ACE-inhibitor or a diuretic.

PubMed

Posadzy-Malaczynska, Anna; Rajpold, Katarzyna; Woznicka-Leskiewicz, Lucyna; Marcinkowska, Justyna

2015-01-01

The aim of the study was to assess the hemodynamic and metabolic actions of estrogen plus progestin therapy (EPT) in hypertensive, postmenopausal women treated with perindopril (ACEI) or hydrochlorothiazide (HCTZ). A group of normotensive postmenopausal women was also studied. 100 hypertensive and 40 normotensive postmenopausal women were recruited for the study. The hypertensive females were randomly assigned to receive ACEI or HCTZ for 12 months. The patients of the ACEI group and the patients of the HCTZ group, as well as normotensives, were further subdivided into two subgroups each. One subgroup received estrogen plus progestin therapy (EPT+), the other subgroup received no hormone replacement (EPT-). Combined hormone replacement with transdermal patches releasing 17β-estradiol and norethisterone was used. Office and 24-hour ambulatory blood pressure was measured at baseline and during follow-up. Renal plasma flow (RPF) was measured using the clearance of [125I]-iodohippuran. Pulse wave velocity (PWV) was determined with an automatic device. In normotensive postmenopausal women, transdermal estrogen plus progestin therapy increases RPF and insulin sensitivity, decreases PWV, decreases total and LDL cholesterol, and decreases uric acid serum levels. Perindopril (4 mg/day) and hydrochlorothiazide (25 mg/day) were equally effective in reducing blood pressure in postmenopausal, hypertensive subjects. In these females, perindopril increased RPF and decreased PWV and plasma insulin levels. These effects of the ACEI were not altered by estrogen plus progestin therapy. Hydrochlorothiazide decreased RPF and increased plasma insulin and uric acid concentrations in hypertensive subjects whom were not receiving estrogen plus progestin therapy. The unfavorable metabolic and hemodynamic actions of the diuretic were counteracted by estrogen plus progestin therapy. Concomitant estrogen plus progestin therapy may be a method to avoid unfavorable hemodynamic and metabolic effects of thiazide diuretics in hypertensive, postmenopausal women.

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).

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.

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

PubMed Central

2014-01-01

Introduction Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. Methods Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. Results A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04). Conclusions In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months. Trial registration ClinicalTrials.gov NCT01441245. Registered 23 September 2011. PMID:24974232

Diuretics for transient tachypnoea of the newborn.

PubMed

Kassab, Manal; Khriesat, Wadah M; Anabrees, Jasim

2015-11-21

Transient tachypnoea of the newborn (TTN) results from delayed clearance of lung liquid and is a common cause of admission of full-term infants to neonatal intensive care units. The condition is particularly common after elective caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid may shorten the duration of the symptoms and reduce complications. To determine whether diuretic administration reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants presenting with transient tachypnoea of the newborn. An updated search was carried out in September 2015 of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 9, 2015), MEDLINE via Ovid, EMBASE, PubMed, and CINAHL via OVID. We included randomised and quasi-randomised controlled trials that compared the effect of diuretics administration versus placebo or no treatment in infants of less than seven days of age, born at 37 or more weeks of gestation with the clinical picture of transient tachypnoea of the newborn. We extracted and analysed data according to the methods outlined in the latest Cochrane Handbook for Systematic Reviews of Interventions. Two review authors assessed trial quality in each potentially eligible manuscript and two review authors extracted data. Our previous systematic review included two trials enrolling a total of 100 infants with transient tachypnoea of the newborn (Wiswell 1985; Karabayir 2006). The updated search revealed no new trials. Wiswell 1985 randomised 50 infants to receive either oral furosemide (2 mg/kg body weight at time of diagnosis followed by a 1 mg/kg dose 12 hours later if the tachypnoea persisted) or placebo. Karabayir 2006 randomised 50 infants to receive either intravenous furosemide (2 mg/kg body weight) or an equal volume of normal saline placebo. Neither trial reported on the need for respiratory support. Neither trial demonstrated a statistically significant impact of furosemide on transient tachypnoea of the newborn regarding duration of symptoms or length of hospitalisation. Diuretics cannot be recommended as treatment for transient tachypnoea of the newborn and it should not be used unless additional data become available. This finding suggests that either furosemide is not effective in promoting resorption of lung fluid, or factors other than delayed resorption of this fluid contribute to the pathogenesis of transient tachypnoea of the newborn. The question remains as to whether furosemide given to the infant (or even to the mother before caesarean section) might shorten the duration of the illness. As elective caesarean section continues at a high level, these two interventions might be worthy of trials.

Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

PubMed

Ahn, Hee Jung; Chung, Jong-Hoon; Kim, Dong-Min; Yoon, Na-Ra; Kim, Choon-Mee

2018-03-05

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

Cirrhosis related chylous ascites successfully treated with TIPS.

PubMed

de Vries, G J; Ryan, B M; de Bièvre, M; Driessen, A; Stockbrugger, R W; Koek, G H

2005-04-01

We describe a patient with chylous ascites, who was extensively investigated for the cause. No malignant or lymphatic disease could be found, but a liver biopsy revealed liver cirrhosis. The chylous ascites was unsuccessfully treated with a sodium restriction diet, diuretics and a medium chain triglyceride diet. After the placement of a transjugular intrahepatic portosystemic shunt the ascites disappeared.

Isolation, expression analysis and functional characterization of the first anti-diuretic hormone receptor in insects

USDA-ARS?s Scientific Manuscript database

Diuresis following blood-gorging in Rhodnius prolixus is the major process leading to the transmission of Chagas' disease. We have cloned the cDNA of the first receptor known to be involved in an antidiuretic strategy in insects; a strategy that prevents diuresis. This receptor belongs to the insect...

Active diuretic peptidomimetic insect kinin analogs that contain Beta-turn mimetic motif 4-aminopyroglutamate and lack native peptide bonds

USDA-ARS?s Scientific Manuscript database

The multifunctional arthropod 'insect kinins' share the evolutionarily conserved C-terminal pentapeptide core sequence Phe-X1-X2-Trp-Gly-NH2, where X1 = His, Asn, Ser, or Tyr and X2 = Ser, Pro, or Ala. Insect kinins regulate diuresis in many species of insects, including the cricket. Insect kinins...

A case of Fournier gangrene complicating idiopathic nephrotic syndrome of childhood.

PubMed

Wright, A J; Lall, A; Gransden, W R; Joyce, M R; Rowsell, A; Clark, G

1999-11-01

A 10-year-old boy presenting with steroid resistant nephrotic syndrome developed Fournier gangrene of the scrotum. Antimicrobial drug therapy, intravenous albumin, excision of necrotic scrotum and left orchidectomy followed by skin grafting 3 weeks later led to an excellent cosmetic and medical result. Six months later he remains nephrotic on diuretic and angiotensin converting enzyme inhibitor medication.

The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

USDA-ARS?s Scientific Manuscript database

In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

Potassium transport in monkey erythrocytes.

PubMed

Stewart, G W; Blackstock, E J; Hall, A C; Ellory, J C

1989-01-01

K transport in Rhesus and Cynomolgus monkey erythrocytes has been characterised and compared to that in human erythrocytes. Transport due to the NaK pump, residual (diffusional) leak, volume-, pressure- and N-ethyl-maleimide-stimulated KCl system and internal Ca2+-stimulated K channel were similar to that in man but in the monkey it differed, in lacking the loop-diuretic-sensitive NaKCl cotransport system.

Genetic variability for phenotype, seed production, oil content, and fatty acid composition among 17 Roselle (Hibiscus sabdariffa) accessions

USDA-ARS?s Scientific Manuscript database

Seed oil and fatty acids in plants have human health implications. Oil from roselle (Hibiscus sabdariffa L.) seeds are used in Taiwan as a diuretic, laxative, and tonic. The objectives of this study were to evaluate seeds from 17 roselle accessions for oil and fatty acid variation in a greenhouse. S...

Postoperative vesicoureteral reflux after high-pressure balloon dilation of the ureterovesical junction in primary obstructive megaureter. Incidence, management and predisposing factors.

PubMed

García-Aparicio, Luis; Blázquez-Gómez, Eva; de Haro, Irene; Garcia-Smith, Natalie; Bejarano, Miguel; Martin, Oriol; Rodo, Joan

2015-12-01

To describe the incidence, predisposing factors and management of postoperative vesicoureteral reflux (VUR) after high-pressure balloon dilation to treat primary obstructive megaureter (POM). We have reviewed patients that underwent endoscopic treatment for POM from May 2008 to November 2013. All patients were evaluated with renal ultrasound, voiding cystourethrography and diuretic renogram. Endoscopic treatment was done with high-pressure balloon dilation of the ureterovesical junction under general anesthesia; a double-J stenting was done in all patients. Follow-up was performed with ultrasonography, voiding cystourethrography and a diuretic renogram in all patients. Fifteen boys and five girls with a mean age of 14.18 months (3-103) were reviewed. A total of 22 ureters underwent HPBD to treat POM. Ureterohydronephrosis improves in 19 ureters. After endoscopic treatment, six ureters developed VUR. Four ureters were managed surgically, and in the other two, VUR disappeared in a second cystogram. The presence of parameatal diverticulum in the preoperative cystography and those patients with bilateral POM are factors related to postoperative VUR (p < 0.05). Urinary tract infection after HPBD was observed in four patients, but only one of them was affected with VUR.

Low central venous pressure with milrinone during living donor hepatectomy.

PubMed

Ryu, H-G; Nahm, F S; Sohn, H-M; Jeong, E-J; Jung, C-W

2010-04-01

Maintaining a low central venous pressure (CVP) has been frequently used in liver resections to reduce blood loss. However, decreased preload carries potential risks such as hemodynamic instability. We hypothesized that a low CVP with milrinone would provide a better surgical environment and hemodynamic stability during living donor hepatectomy. Thirty-eight healthy adult liver donors were randomized to receive either milrinone (milrinone group, n = 19) or normal saline (control group, n = 19) infusion during liver resection. The surgical field was assessed using a four-point scale. Intraoperative vital signs, blood loss, the use of vasopressors and diuretics and postoperative laboratory data were compared between groups. The milrinone group showed a superior surgical field (p < 0.001) and less blood loss (142 +/- 129 mL vs. 378 +/- 167 mL, p < 0.001). Vital signs were well maintained in both groups but the milrinone group required smaller amounts of vasopressors and less-frequent diuretics to maintain a low CVP. The milrinone group also showed a more rapid recovery pattern after surgery. Milrinone-induced low CVP improves the surgical field with less blood loss during living donor hepatectomy and also has favorable effects on intraoperative hemodynamics and postoperative recovery.

Diuretic activity of Maydis stigma extract in rats.

PubMed

Maksimović, Z; Dobrić, S; Kovacević, N; Milovanović, Z

2004-12-01

Maydis stigma (corn silk) is a herbal drug reputed for the treatment of urinary ailments in various traditional medicine systems. To determine its influence on urinary volume and the excretion of sodium, potassium and chloride, 5% and 10% decoctions were administered daily to adult male Wistar rats for eight days. The concentration of electrolytes and urea in plasma, the influence of treatment on urinary pH value as well as creatinine clearance were also investigated. Daily oral administration of 5% decoction at the dose of 10 ml/kg led to a significant and acute diuresis in rats, reaching the peak value in the first 24 h of treatment. Over a similar period, application of 10% decoction did not affect urinary excretion of water, but significantly increased the pH value of excreted urine. A significant decrease in sodium and chloride plasma levels was observed in both treated groups. The creatinine clearance was markedly increased after the treatment with both extracts. Our findings indicate that the diuretic effect of 5% aqueous Maydis stigma extract is in accordance with the increase in glomerular filtration rate and inhibition of sodium and chloride tubular reabsorption, caused a by still unidentified intrinsic factor, but not the salt-loading effect.

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.

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.

Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.

PubMed

Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

2012-08-14

The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.

Servo-control of water and sodium homeostasis during renal clearance measurements in conscious rats.

PubMed

Thomsen, Klaus; Shirley, David G

2007-01-01

Servo-controlled fluid and sodium replacement during clearance studies is used in order to prevent loss of body fluid and sodium following diuretic/natriuretic procedures. However, even under control conditions, the use of this technique is sometimes associated with increases in proximal tubular fluid output (assessed by lithium clearance) and excretion rates. The present study examined the reason for these increases. The first series of experiments showed that one cause is volume overloading. This can occur if the servo system is activated from the start, i.e., during the establishment of a suitably high urine flow rate by constant infusion of hypotonic glucose solution. The second series of experiments showed that replacement of blood samples with donor blood can also lead to increases in fractional lithium excretion and accompanying increases in water and sodium excretion, a problem not seen when blood samples are replaced with the animal's own red blood cells resuspended in isotonic saline. When these pitfalls are avoided, servo-controlled sodium and fluid replacement is a reliable technique that makes it possible to study the effects of natriuretic and/or diuretic stimuli without interference from unwanted changes in extracellular volume. 2007 S. Karger AG, Basel

Parsley: a review of ethnopharmacology, phytochemistry and biological activities.

PubMed

Farzaei, Mohammad Hosein; Abbasabadi, Zahra; Ardekani, Mohammad Reza Shams; Rahimi, Roja; Farzaei, Fatemeh

2013-12-01

To summarize comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of parsley. Databases including PubMed, Scopus, Google Scholar, and Web of Science were searched for studies focusing on the ethnomedicinal use, phytochemical compounds and biological and pharmacological activities of parsley. Data were collected from 1966 to 2013. The search terms were: "Parsley" or "Petroselinum crispum" or "Petroselinum hortence". Parsley has been used as carminative, gastro tonic, diuretic, antiseptic of urinary tract, anti-urolithiasis, anti-dote and anti-inflammatory and for the treatment of amenorrhea, dysmenorrhea, gastrointestinal disorder, hypertension, cardiac disease, urinary disease, otitis, sniffle, diabetes and also various dermal disease in traditional and folklore medicines. Phenolic compounds and flavonoids particularly apigenin, apiin and 6"-Acetylapiin; essential oil mainly myristicin and apiol; and also coumarins are the active compounds identified in Petroselinum crispum. Wide range of pharmacological activity including antioxidant, hepatoprotective, brain protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti-platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial and antifungal activities have been exhibited for this plant in modern medicine. It is expectant that this study resulted in improvement the tendencies toward Petroselinum crispum as a useful and important medicinal plant with wide range of proven medicinal activity.

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

PubMed Central

Tan, Chunjiang; Xiao, Lu; Chen, Wenlie

2015-01-01

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes. PMID:25711879

Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes.

PubMed

Suchy-Dicey, Astrid; Heckbert, Susan R; Smith, Nicholas L; McKnight, Barbara; Rotter, Jerome I; Chen, Yd Ida; Psaty, Bruce M; Enquobahrie, Daniel A

2014-01-01

Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development.

Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure

PubMed Central

Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E.; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

2012-01-01

The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema. PMID:22847418

An unusual cause of flash pulmonary oedema

PubMed Central

Palkar, Atul Vijay; Shrivastava, Makardhwaj Sarvadaman; Moulick, Nivedita D

2012-01-01

We report a case of young woman who presented with acute cardiogenic pulmonary oedema and respiratory failure. She underwent emergent endotracheal intubation and was transferred to the intensive care unit. She responded to intravenous diuretics and positive pressure ventilation. Subsequent workup revealed that she had Graves’ disease and was in thyrotoxic crisis. Therapy with propranolol and propylthiouracil was instituted to which she showed remarkable improvement. PMID:22707683

Mineral of the month: potash

USGS Publications Warehouse

Searls, James P.

2005-01-01

In 1807, Sir Humphrey Davy discovered a metal during the electrolysis of potassium hydroxide; he named the metal potassium because it came from potash recovered from wood ashes. The four types of potash are the water-soluble compounds potassium chloride, potassium sulfate, potassium-magnesium sulfate and potassium nitrate. The early uses of potash were in glass and soap manufacturing, as a diuretic, and another form was used in gunpowder.

Investigations on dendrimer space reveal solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs.

PubMed

El Brahmi, Nabil; Mignani, Serge M; Caron, Joachim; El Kazzouli, Saïd; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

2015-03-07

The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively.

Isolation, cloning and expression mapping of a gene encoding an anti-diuretic hormone and other CAPA-related peptides in the disease vector, Rhodnius prolixus

USDA-ARS?s Scientific Manuscript database

Following a blood meal, Rhodnius prolixus undergoes a rapid diuresis in order to eliminate excess water and salts. During the voiding of this primary urine, R. prolixus acts as a vector of Chagas’ disease, with the causative agent, Trypanosoma cruzi, infecting the human host via the urine. Diuresi...

Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study.

PubMed

Gallet, Romain; Meyer, Guy; Ternacle, Julien; Biendel, Caroline; Brunet, Anne; Meneveau, Nicolas; Rosario, Roger; Couturaud, Francis; Sebbane, Mustapha; Lamblin, Nicolas; Bouvaist, Helene; Coste, Pierre; Maitre, Bernard; Bastuji-Garin, Sylvie; Dubois-Rande, Jean-Luc; Lim, Pascal

2015-05-22

In acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure. The Diuretic versus placebo in Pulmonary Embolism with Right ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24 h. It will include: (1) urine output >0.5 mL/kg/min for the past 24 h; (2) heart rate <110 bpm; (3) systolic blood pressure >100 mm Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required. Ethical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. NCT02268903. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The potential value of integrated natriuretic peptide and echo-guided heart failure management

PubMed Central

2014-01-01

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach. PMID:25037453

Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage.

PubMed

Sussman, Rachael D; Blum, Emily S; Sprague, Bruce M; Majd, Massoud; Rushton, H Gil; Pohl, Hans G

2017-03-01

In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99m Tc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters. Infants 6 months or younger with grade 3-4 congenital hydronephrosis who presented between January 2009 and December 2014 were identified from billing data and included in analysis if they underwent at least 1 baseline diuretic renography. Those with structural anomalies were excluded from study. Baseline and followup differential function, diuresis half-time, clearance at 30 minutes and clearance with the patient upright were abstracted and comparisons were made between those with initially indeterminate diuresis half-time who underwent pyeloplasty vs those showing spontaneous improvement. A total of 74 patients (82 renal units) with presumed ureteropelvic junction obstruction met inclusion/exclusion criteria. All 10 renal units with initial diuresis half-time less than 5 minutes resolved spontaneously and all 25 renal units with initial diuresis half-time greater than 75 minutes underwent pyeloplasty. Therefore, we defined the indeterminate group as the 47 renal units with initial half-time between 5 and 75 minutes. Of those 47 renal units with indeterminate initial diuresis half-time 23 (47%) underwent pyeloplasty and 25 (53%) resolved spontaneously. Indications for pyeloplasty included worsening in 17 cases, persistent obstruction in 4 and urinary tract infection in 1. Among renal units with indeterminate drainage clearance while upright and clearance at 30 minutes were the only variables that differed significantly between surgical cases and those that resolved spontaneously. Radiotracer clearance with the patient upright and clearance at 30 minutes are more predictive of surgical management than diuresis half-time or differential function for renal units with indeterminate drainage. They should be included in the standard assessment of ureteropelvic junction obstruction. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

PubMed

Sharma, Abhishek; Mete, Uttam K; Sood, Ashwani; Kakkar, Nandita; Gorla, Arun K R; Mittal, Bhagwant R

2017-04-01

Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUV max ) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUV max of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUV max with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUV max of the early dynamic imaging showing tumour perfusion was independent from the SUV max of delayed imaging. High-grade tumours showed higher SUV max than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUV max than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

Short-term reconsultation, hospitalisation, and death rates after discharge from the emergency department in patients with acute heart failure and analysis of the associated factors. The ALTUR-ICA Study.

PubMed

Miró, Òscar; Gil, Víctor; Martín-Sánchez, Francisco Javier; Herrero, Pablo; Jacob, Javier; Sánchez, Carolina; Xipell, Carolina; Aguiló, Sira; Llorens, Pere

2018-03-09

The aim of this study was to define the following in patients with acute heart failure (AHF) discharged directly from accident and emergency (A&E): rates of reconsultation to A&E and hospitalisation for AHF, and all-cause death at 30 days, rate of combined event at 7 days and the factors associated with these rates. The study included patients consecutively diagnosed with AHF during 2 months in 27 Spanish A&E departments who were discharged from A&E without hospitalisation. We collected 43 independent variables, monitored patients for 30 days and evaluated predictive factors for adverse events using Cox regression analysis. We evaluated 785 patients (78±9) years, 54.7% women). The rates of reconsultation, hospitalisation, and death at 30 days and the combined event at 7 days were: 26.1, 15.7, 1.7 and 10.6%, respectively. The independent factors associated with reconsultation were no endovenous diuretics administered in A&E (HR 2.86; 95% CI 2.01-4.04), glomerular filtration rate (GFR)<60ml/min/m 2 (1.94; 1.37-2.76) and previous AHF episodes (1.48; 1.02-2.13); for hospitalisation these factors were no endovenous diuretics in A&E (2.97; 1.96-4.48), having heart valve disease (1.61; 1.04-2.48), blood oxygen saturation at arrival to A&E<95% (1.60; 1.06-2.42); and for the combined event no endovenous diuretics in A&E (3.65; 2.19-6.10), GFR<60ml/min/m 2 (2.22; 1.31-3.25), previous AHF episodes (1.95; 1.04-3.25), and use of endovenous nitrates (0.13; 0.02-0.99). This is the first study in Spain to describe the rates of adverse events in patients with AHF discharged directly from A&E and define the associated factors. These data should help establish the most adequate approaches to managing these patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Effect of lemongrass tea consumption on estimated glomerular filtration rate and creatinine clearance rate.

PubMed

Ekpenyong, Christopher E; Daniel, Nyebuk E; Antai, Atim B

2015-01-01

The existing research findings regarding the effects of lemongrass (Cymbopogon citratus) tea on renal function indices are conflicting and inconclusive. In the present study, we investigated the effects of infusions prepared from C citratus leaves on creatinine clearance rate (CCr) and estimated glomerular filtration rate (eGFR) in humans. One hundred five subjects (55 men and 50 women) aged 18 to 35 years were randomly assigned to groups set to orally receive infusions prepared from 2, 4, or 8 g of C citratus leaf powder once daily, for 30 days. Serum and urinary levels of urea, creatinine, pH, specific gravity, uric acid, electrolytes, diuretic indices, and eGFR were assessed at days 0, 10, and 30 after the initiation of treatment. Results obtained on days10 and 30 were compared with baseline values. CCr and eGFR decreased significantly at day 30 in both male and female subjects in all the groups and in females treated with infusion prepared from 8 g of C citratus leaf powder for 10 days. At day 10, CCr and eGFR were unchanged in those treated with infusions prepared from 2 or 4 g of the leaf powder, whereas diuretic indices (urine volume, urination frequency, diuretic action, and saliuretic indices) increased above the baseline levels. Serum and urinary creatinine levels significantly increased (P < .05) in both male and female subjects in all the groups. Serum urea significantly increased in the groups treated with infusions prepared from 4 or 8 g of the leaf powder (P < .05) for 30 days. Serum electrolytes remained unchanged, but their urinary levels increased. We observed dose- and time-dependent adverse effects of C citratus on CCr and eGFR. At a high dose or with prolonged treatment with a low dose, eGFR decrease may be followed by a decline in the other renal function indices. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Formation of the diuretic chlorazanil from the antimalarial drug proguanil--implications for sports drug testing.

PubMed

Thevis, Mario; Geyer, Hans; Thomas, Andreas; Tretzel, Laura; Bailloux, Isabelle; Buisson, Corinne; Lasne, Francoise; Schaefer, Maximilian S; Kienbaum, Peter; Mueller-Stoever, Irmela; Schänzer, Wilhelm

2015-11-10

Chlorazanil (Ordipan, N-(4-chlorophenyl)-1,3,5-triazine-2,4-diamine) is a diuretic agent and as such prohibited in sport according to the regulations of the World Anti-Doping Agency (WADA). Despite its introduction into clinical practice in the late 1950s, the worldwide very first two adverse analytical findings were registered only in 2014, being motive for an in-depth investigation of these cases. Both individuals denied the intake of the drug; however, the athletes did declare the use of the antimalarial prophylactic agent proguanil due to temporary residences in African countries. A structural similarity between chlorazanil and proguanil is given but no direct metabolic relation has been reported in the scientific literature. Moreover, chlorazanil has not been confirmed as a drug impurity of proguanil. Proguanil however is metabolized in humans to N-(4-chlorophenyl)-biguanide, which represents a chemical precursor in the synthesis of chlorazanil. In the presence of formic acid, formaldehyde, or formic acid esters, N-(4-chlorophenyl)-biguanide converts to chlorazanil. In order to probe for potential sources of the chlorazanil detected in the doping control samples, drug formulations containing proguanil and urine samples of individuals using proguanil as antimalarial drug were subjected to liquid chromatography-high resolution/high accuracy mass spectrometry. In addition, in vitro simulations with 4-chlorophenyl-biguanide and respective reactants were conducted in urine and resulting specimens analyzed for the presence of chlorazanil. While no chlorazanil was found in drug formulations, the urine samples of 2 out of 4 proguanil users returned findings for chlorazanil at low ng/mL levels, similar to the adverse analytical findings in the doping control samples. Further, in the presence of formaldehyde, formic acid and related esters, 4-chlorophenyl-biguanide was found to produce chlorazanil in human urine, suggesting that the detection of the obsolete diuretic agent was indeed the result of artefact formation and not of the illicit use of a prohibited substance. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study.

PubMed

De Vecchis, Renato; Ariano, Carmelina; Di Biase, Giuseppina; Noutsias, Michel

2017-11-01

An alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study. However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs, as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs. The purpose of this retrospective study was to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients aged 65 or over. In this two-center retrospective study, we followed up a cohort of female patients with (n = 80) and without (n = 158) thiazide-induced hyponatremia. A total of 48 osteoporotic fractures were recorded during a median follow-up period of 57.5 months. By means of univariate regression analysis, an association was found between thiazide-induced hyponatremia and increased risk of vertebral fractures (odds ratio (OR): 7.6; 95% confidence interval (CI): 3.755 - 15.39; P < 0.0001). Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI: 1.211 - 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 - 0.645) were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatremia and risk of fracture was noticeable in the final model. Because thiazide-induced hyponatremia was associated with spinal fractures in univariate but not multivariate analysis, a possible explanation is that hyponatremia may be a confounder of the relation between body mass and spinal fractures. Indeed, reduced body mass especially among elderly women with small body build may confer heightened risk of thiazide-induced hyponatremia because of decreased bone sodium available for exchange with the serum sodium. Thus, occurrence of hyponatremia could only serve as an indirect surrogate marker for osteoporosis risk.

Identification of the Pro orientation of CAP2b peptides for antidiuretic activity in the stink bug Acrosternum hilare

USDA-ARS?s Scientific Manuscript database

The CAP2b neuropeptide family plays an important role in the regulation of the processes of diuresis and/or antidiuresis in a variety of insects. While Manse-CAP2b (pELYAFPRVamide) and native CAP2bs elicit diuretic activity in a number of species of flies, native CAP2b sequences have been shown to ...

The Impact of Hyperthermia and Hypohydration on Circulation, Strength, Endurance, and Health,

DTIC Science & Technology

1988-02-05

in the laboratory. The authors concluded that pre-exercise passive heating, diuretic use, and prior exercise interact to reduce physical exercise...school and college wrestling coach. Water. Carbohydrate , and Salt Intake Most of the aforementioned strength and endurance studies have examined the...than 1 - 2 hours, however, dilute sugar additives (6 - 8% carbohydrate in solution) may be required to postpone the development of fatigue, to reduce

Immediate and Delayed Drug Therapy Effects on Low Dose Sarin Exposed Mice Myocardial Performance

DTIC Science & Technology

2011-03-01

to phosphorylate the serine hydroxyl residue in the active pocket of AChE, forming either a phosphoric or phosphonic acid ester which is extremely...London 2006). Brain natriuretic peptide exerts its 15 natriuretic, diuretic, and vasorelaxant effects through activation of its common receptor...exposed to asymptomatic levels would show no issues during normal activities , such garrison or non-field operations. However, this would quickly change

Clinical types and drug therapy of renal impairment in cirrhosis

PubMed Central

Rodés, J.; Bosch, J.; Arroyo, V.

1975-01-01

Four separate types of renal failure in cirrhosis are described: functional renal failure; diuretic induced uraemia; acute tubular necrosis; chronic intrinsic renal disease. Functional renal failure may arise spontaneously or be precipitated by such factors as haemorrhage, surgery, or infection. It carries a poor prognosis but preliminary results of treating this condition with plasma volume expansion in combination with high doses of furosemide are encouraging. PMID:1234328

Change of oxygen pressure in glioblastoma tissue under various conditions.

PubMed

Beppu, Takaaki; Kamada, Katsura; Yoshida, Yuki; Arai, Hiroshi; Ogasawara, Kuniaki; Ogawa, Akira

2002-05-01

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.

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

Yagci, Cemil, E-mail: cemil.yagci@medicine.ankara.edu.tr; Ustuner, Evren, E-mail: evrenustuner@hotmail.com; Atman, Ebru Dusunceli, E-mail: ebrumd2001@yahoo.com

Percutaneous nephrostomy (PCN) in a nondilated pelvicaliceal system is technically challenging. We describe an effective method to achieve transient dilatation of the pelvicaliceal system via induction of diuresis using infusion of a diuretic agent in normal saline, therefore allowing easier access to the pelvicaliceal system. Under real-time ultrasound guidance, the technique had been tested in 22 nephrostomies with nondilated system (a total of 20 patients with 2 patients having bilateral nephrostomies) during a 5-year period. Patients were given 40 mg of furosemide in 250 ml of normal saline solution intravenously by rapid infusion. As soon as maximum calyceal dilatation ofmore » more than 5 mm was observed, which is usually 15 min later after the end of rapid infusion, patients were positioned obliquely, and PCN procedure under ultrasound guidance was performed. The procedure was successful in 19 of the nephrostomies in 17 patients with a success rate of 86.36 % per procedure and 85 % per patient in nondilated pelvicaliceal systems. No major nephrostomy-, drug-, or technique-related complications were encountered. The technique failed to work in three patients due to the presence of double J catheters and preexisting calyceal perforation which avoided transient dilation of the pelvicaliceal system with diuresis. Diuretic infusion in saline is a feasible and effective method for PCN in nondilated pelvicaliceal systems.« less

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.

Managing therapeutic competition in patients with heart failure, lower urinary tract symptoms and incontinence.

PubMed

Tannenbaum, Cara; Johnell, Kristina

2014-02-01

Up to 50% of heart failure patients suffer from lower urinary tract symptoms. Urinary incontinence has been associated with worse functional status in patients with heart failure, occurring three times more frequently in patients with New York Heart Association Class III and IV symptoms compared with those with milder disease. The association between heart failure and urinary symptoms may be directly attributable to worsening heart failure pathophysiology; however, medications used to treat heart failure may also indirectly provoke or exacerbate urinary symptoms. This type of drug-disease interaction, in which the treatment for heart failure precipitates incontinence, and removal of medications to relieve incontinence worsens heart failure, can be termed therapeutic competition. The mechanisms by which heart failure medication such as diuretics, angiotensin-converting enzyme (ACE) inhibitors and β-blockers aggravate lower urinary tract symptoms are discussed. Initiation of a prescribing cascade, whereby antimuscarinic agents or β3-agonists are added to treat symptoms of urinary urgency and incontinence, is best avoided. Recommendations and practical tips are provided that outline more judicious management of heart failure patients with lower urinary tract symptoms. Compelling strategies to improve urinary outcomes include titrating diuretics, switching ACE inhibitors, treating lower urinary tract infections, appropriate fluid management, daily weighing, and uptake of pelvic floor muscle exercises.

Gene expression in thiazide diuretic or statin users in relation to incident type 2 diabetes

PubMed Central

Suchy-Dicey, Astrid; Heckbert, Susan R; Smith, Nicholas L; McKnight, Barbara; Rotter, Jerome I; Chen, YD Ida; Psaty, Bruce M; Enquobahrie, Daniel A

2014-01-01

Thiazide diuretics and statins are used to improve cardiovascular outcomes, but may also cause type 2 diabetes (T2DM), although mechanisms are unknown. Gene expression studies may facilitate understanding of these associations. Participants from ongoing population-based studies were sampled for these longitudinal studies of peripheral blood microarray gene expression, and followed to incident diabetes. All sampled subjects were statin or thiazide users. Those who developed diabetes during follow-up comprised cases (44 thiazide users; 19 statin users), and were matched to drug-using controls who did not develop diabetes on several factors. Supervised normalization, surrogate variable analyses removed technical bias and confounding. Differentially-expressed genes were those with a false discovery rate Q-value<0.05. Among thiazide users, diabetes cases had significantly different expression of CCL14 (down-regulated 6%, Q-value=0.0257), compared with controls. Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls. These genes comprise potential targets for future expression or mechanistic research on medication-related diabetes development. PMID:24596594

Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy.

PubMed

Watanabe, Kenichi; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Giridharan, Vijayasree V; Antony, Shanish; Harima, Meilei; Nakamura, Masahiko; Suzuki, Kenji; Suzuki, Hiroshi; Sone, Hirohito; Arumugam, Somasundaram

2017-03-01

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Beta-blockers for hypertension.

PubMed

Wiysonge, C S; Bradley, H; Mayosi, B M; Maroney, R; Mbewu, A; Opie, L H; Volmink, J

2007-01-24

Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance. Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs. The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

Weight Loss Behaviors Used by Active Duty Air Force Personnel to Maintain Compliance with Weight Control Standards

DTIC Science & Technology

1997-05-01

lose weight. The methods of weight loss reported were exercising , skipping meals, using diet pills, and self- induced vomiting. In each case, females...Restrictive Diet Popular Diet Self- induced Vomifing Laxatives Diuretics Diet Pills Exercise Other Note- N = frequency of resf were allowed to...Rate 69 Demographic Data 69 Exercise 70 Weight Loss Beliefs and Practices 71 Additional Data Collected 76 Implications for Military Health Care

Hyponatraemia and Moduretic-grand mal seizures: a review.

PubMed Central

Johnston, C; Webb, L; Daley, J; Spathis, G S

1989-01-01

Three cases are presented which emphasize the importance of hyponatraemia as a cause of grand mal seizures. The combination of hydrochlorothiazide and amiloride appears to increase the risk of hyponatraemia. We discuss the aetiology and treatment of hyponatraemia and review the necessity for such combination therapy. We recommend caution in prescribing diuretics and preparations such as Moduretic should be used only in those few patients shown to need potassium supplementation. PMID:2506346

[Therapeutic use of Cannibis Sativa L. in Arab medicine].

PubMed

Lozano, I

1997-01-01

Arab scientists were various centuries ahead of our current knowledge of the curative power of hemp (Cannabis sativa L., Cannabaceae). Modern scientific literature ignores their contribution on the subject. We review in this paper the therapeutic uses of the plant in Arabic medicine from the 8th to the 18th century. Arab physicians knew and used its diuretic, anti-emetic, anti-epileptic, anti-inflammatory, pain-killing and antipyretic properties, among others.

A Quick Reference on Hyperkalemia.

PubMed

Kogika, Márcia Mery; de Morais, Helio Autran

2017-03-01

The clinical signs of hyperkalemia usually are less evident than hypokalemia. Arrhythmia and bradycardia could be the first changes noticed. Most cases of persistent hyperkalemia are associated with renal retention of potassium. Common causes for hyperkalemia include hypoadrenocorticism, ruptured bladder, and urethral or bilateral ureteral obstruction. Drug such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, and nonsteroidal antiinflammatory drugs can also lead to hyperkalemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute hypersensitivity to mannitol: a case report

NASA Astrophysics Data System (ADS)

Siahaan, A. M.; Fithrie, A.

2018-03-01

Mannitol is an osmotic diuretic agent that has been considered a main therapeutic option in cerebral edema for the past several decades. The most common adverse effect reported is acute kidney injury and electrolyte imbalance. Hypersensitivity associated with mannitol is not a usual finding. Here we describe a case of a traumatic brain injury patient who had a hypersensitivity reaction to mannitol. It is the first reported case report about hypersensitivity to Mannitol in Indonesia.

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

Ogawa, E.; Suzuki, S.; Fukuda, R.

Pharmacological means to accelerate the elimination of Cs-137 introduced into the living organism are studied. Male dd mice and male Wistar rats are individually housed in metal metabolism cages, and provided with commercial solid diet and water. Radioactivity is determined in urine, and feces for 24 hours and 4 days after subcutaneous injection of a tracer dose of Cs/sup 137/Cl, and in various organs after sacrifices at the ends of these periods. Effects of various chemicals on these results are compared. Twenty five chemicals were investigated. They include inorganic Na salts such as Na bicarbonate, Na carbonate, Na suliate, Namore » thiosulfate, primary and secondary Na phosphates, and organic Na salts such as Na lactate, lactated Ringer, Na acetate, Na glucuronate, Na salt of thioctic acid, ATP Na, and Na pentobarbiturate. Na bicarbonate, Na phosphates, Na sulfate, and Na thiosulfate are found as eifective, especially Na bicarbonate, K bicarbonate shows scarcely any effect, nor do other K salts. It is therefore assumed that Cs will exchange with Na ion in the tubular cells. LiCl is found to accelerate the excretion of Cs-137 from mice and rats. This result is of interest with respect to the periodic law, since it is known that for the elimination of Sr-90, Ca salts are ineffective or slightly effective, whereas Mg salts are effective. Of the diuretics, chlorothiazide, which is considered to increase the excretion of K, does nor increase the elimination of Cs-137 in any dose. This result is different from that of Diamox, a diuretic of the same nature. Cardiac glycosides and xanthine derivatives are effective. Out of digitalis preparations, Digitamin (Shionogi), Digilanogen C (Fujisawa), Digosin (Chugai) are effective. Digitoxin and strospeside are ineffective, and after their application, retention of Cs-137 is observed in the heart muscle. G- strophanthin is ineffective in a smaller dose, but increases the elimination of Cs-137 in a larger dose. Caffeine and sodium benzoate are also effective, but theophylline and theobromine are not so effective. Out of osmotic diuretics, Na ferrocyanate alone increases fecal excretion of Cs-137, and decreases the retention in the body. NaI and KI have scarcely any effect. Phosphomolybdic acid inhibits the elimination of Cs-137 and increases its retention. The above mentioned effective chemicals are also investigated for effects on the elimination of Sr-90. (JAIF)« less

Renal function on admission modifies prognostic impact of diuretics in acute heart failure: a propensity score matched and interaction analysis.

PubMed

Matsue, Yuya; Shiraishi, Atsushi; Kagiyama, Nobuyuki; Yoshida, Kazuki; Kume, Teruyoshi; Okura, Hiroyuki; Suzuki, Makoto; Matsumura, Akihiko; Yoshida, Kiyoshi; Hashimoto, Yuji

2016-12-01

Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 on admission, and the cohort was divided into a high-dose furosemide (≥100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high-dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73-2.16, P = 0.408). However, there was a qualitative difference in OR for in-hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96-3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05-1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide (P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment.

Proof of principle: hydration by low-osmolar mannitol-glucose solution alleviates undesirable renal effects of an iso-osmolar contrast medium in rats.

PubMed

Seeliger, Erdmann; Ladwig, Mechthild; Sargsyan, Lilit; Cantow, Kathleen; Persson, Pontus B; Flemming, Bert

2012-04-01

Saline infusion is widely used to prevent contrast media (CM)-induced acute kidney injury, because it fosters diuresis. Osmodiuretics have a stronger diuretic effect than saline, yet previous trials indicate that osmodiuretic mannitol tends to promote rather than to prevent CM-induced acute kidney injury. However, these studies used hypertonic mannitol solutions that will result in rebound volume contraction. We hypothesize that combining the osmodiuretic effects of a nonhypertonic mannitol solution with sustained volume expansion alleviates undesirable renal effects of CM. Forty-four anesthetized rats were studied by 4 protocols. Urine flow rate, urine viscosity, and glomerular filtration rate (GFR) were measured. Intravenous infusions of hydration solutions were initiated 60 minutes before CM administration and continued throughout the observation period. Hydration by a 3.2% mannitol and 3.2% glucose solution infused at 12 mL/kg per hour (Mannit-Gluc regimen) was compared with a standard regimen of isotonic saline at 4 mL/kg per hour (NaCl regimen); greater infusion rates are required for the Mannit-Gluc regimen because of the profound diuretic effect of mannitol. Two CM were studied: iso-osmolar iodixanol (320 mg I/mL) and low-osmolar iopromide (370 mg I/mL), they were administered as 1.5-mL bolus injection into the thoracic aorta. The Mannit-Gluc regimen resulted in higher urine flow rates than the standard NaCl regimen, yet maintained a good volume status. By virtue of its stronger diuretic effect, the Mannit-Gluc regimen greatly diminished the increase in urine viscosity and completely prevented the transient decrease in GFR caused by iodixanol with the NaCl regimen. After iopromide, the differences between the hydration regimens were much less, as iopromide increased urine flow rates much more than iodixanol, thus resulting in a much smaller increase in viscosity than iodixanol and no decrease in GFR even with the NaCl regimen. This proof of principle study shows that a hydration regimen that combines the osmodiuretic effect of a low-osmolar mannitol-glucose solution with sustained volume expansion is effective in reducing high urine viscosity and preventing GFR reduction caused by iso-osmolar iodixanol. For low-osmolar CM, the beneficial effects seem negligible, because these compounds per se exert greater osmodiuretic action.

Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins

DTIC Science & Technology

2006-09-01

lowering agents (gemfibrozil, clofibric acid ), diuretic agents (furosemide)and the antiepileptic drug valproic acid (Benet et al, 1993; see Bailey and...exposure to the insecticide permethrin is usually performed by analysis of its urinary metabolite 3-phenoxybenzoic acid (3- PBA). However, chronic low...permethrin metabolites 3-PBA and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis/trans-Cl2CA) will form persistent

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

Chaudhuri, T.K.; Fink, S.

The records of 18 consecutive patients referred to a Veterans Administration Hospital nuclear medicine service for renal scintigraphic tests to rule out renovascular hypertension were reviewed. The men were elderly (mean age, 62 years), and risk factors for untoward reactions, including long-standing hypertension, severe peripheral vascular disease, diabetes, chronic renal failure, and recent diuretic use were present. Despite these risks, there was no test morbidity, and the authors conclude that the renal scintigraphic test with captopril enhancement is well tolerated and deserves continued application and evaluation.

Influence of furosemide on the detection of flunixin meglumine in horse urine samples.

PubMed

Araújo, A C; Salvadori, M C; Velletri, M E; Camargo, M M

1990-01-01

The possibility of false negative results from TLC when a diuretic is administered concomitantly with flunixin was studied. Samples were subjected to solvent extraction from acidic aqueous solutions; duplicate samples were also subjected to alkaline hydrolysis at pH 12.5. The internal standard was flufenamic acid. The quantification of flunixin was performed by HPLC and the results confirmed by GC/MS. The data show that furosemide influences the urinary concentration of flunixin.

Impact of Disordered Eating and Psychological Functioning on Overweight Adolescents Participating in a Placebo-Controlled Medication and Behavioral Weight Loss Trial

DTIC Science & Technology

2009-11-23

1997; Sothern et al., 2000)), and therefore induce greater and faster weight loss compared to other hypocaloric diets . However, similar to other...between VLCD and a hypocaloric diet +behavior modification and their combination. International Journal of Obesity and Related Metabolic Disorders, 21(7...taking diet pills, self-induced vomiting, and using laxatives or diuretics, as well as “unhealthy” weight control behaviors, including fasting