Efficacy of Tamsulosin, Oxybutynin, and their combination in the control of double-j stent-related lower urinary tract symptoms

PubMed Central

Maldonado-Avila, Miguel; Garduño-Arteaga, Leopoldo; Jungfermann-Guzman, Rene; Manzanilla-Garcia, Hugo A.; Rosas-Nava, Emmanuel; Procuna-Hernandez, Nestor; Vela-Mollinedo, Alejandro; Almazan-Treviño, Luis; Guzman-Esquivel, Jose

2016-01-01

ABSTRACT Introduction and objective Indwelling double J ureteral stents are used routinely in the resolution of ureteral obstruction caused by different etiologies. Evaluation of urinary symptoms related to double-J stent, indicate that these affect 73-90% of patients. We conducted a prospective, randomized study, to evaluate the efficacy of tamsulosin, oxybutinin and combination therapy in improving the urinary symptoms. Methods Patients who underwent ureteral stent placement after ureterolithotripsy (total 51), were randomized into three groups: Group I: Tamsulosin 0.4 mg. once per day(17 patients), Group II: Oxybutinin 5 mg. once per day (17 patients), Group III: Tamsulosin+ oxybutynin once per day (17 patients). All the groups received the drugs for three weeks and completed a Spanish validated Ureteral Stent Symptom Questionnaire (USSQ) at day 7 and 21. Results Repeated measures ANOVA showed mean urinary symptom index score was 22.3 vs. 15.5 in group three (p<0.001) at day 7 and 21 respectively. The mean work performance index was 6.6 vs 8.1 (p=0.049) favoring tamsulosin group, the mean sexual score was 0.5 vs 1.5 (p=0.03). Among additional problems the mean was 7.2 vs 6.2 (p=0.03). No significant difference was noted among pain and general health index. No side effects were reported. Conclusions Combination therapy with tamsulosin and oxybutynin improved irritative symptoms and work performance as well as sexual matters. Combination therapy should be considered for patients who complained of stent related symptoms. PMID:27286111

Treatment of Distal Ureteral Calculi Using Extracorporeal Physical Vibrational Lithecbole Combined with Tamsulosin: A New Option to Speed Up Obstruction Relief.

PubMed

Liu, Guanlin; Cheng, Yue; Wu, Weijie; Jia, Xiaolong; Hu, Jiasheng; Xie, Guohai; Chen, Xueqin

2018-02-01

The obstruction of the urinary tract by calculi at the narrowest anatomical areas leads to impaired drainage and severe pain. The aim of this study was to evaluate a new technology, extracorporeal physical vibrational lithecbole (EPVL) combined with tamsulosin, as a treatment for distal ureteral calculi (DUC). Between July 2013 and July 2014, 672 patients diagnosed with DUC were randomly divided into three groups; a group receiving EPVL plus 0.4 mg oral tamsulosin daily (PO qd) (experimental group, n = 236), a group receiving 0.4 mg tamsulosin PO qd (n = 222), and a group receiving EPVL only (n = 214) (control groups). There were no significant differences in general characteristics between the three groups. Stone diameters ranged from 0.32 to 1 cm. In the EPVL plus tamsulosin group, 60.1% of patients showed detectable fragment expulsion at 48 hours, and 91.1% were stone free at 7 days. Compared with the two control groups, these rates were significantly higher (EPVL group was 0% and 50.5% and medical expulsive therapy group was 0% and 50.0%, p < 0.05). The stone-free rates were similar in the three groups 2 weeks later (94.5%, 93.6%, and 93.5%; p > 0.05). Patients in the EPVL plus tamsulosin group achieved similar stone-free rates compared with the other two groups, but the speed of the stone expulsion was quicker for both sexes and all age groups (about a week; p < 0.05). This indicates that EPVL plus tamsulosin could be used as an effective, but faster treatment option for patients with DUC, alleviating the symptoms of DUC in a shorter period of time.

Comparison of Prophylactic Naftopidil, Tamsulosin, and Silodosin for {sup 125}I Brachytherapy-Induced Lower Urinary Tract Symptoms in Patients With Prostate Cancer: Randomized Controlled Trial

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

Tsumura, Hideyasu, E-mail: sugan@pd5.so-net.ne.jp; Satoh, Takefumi; Ishiyama, Hiromichi

2011-11-15

Purpose: To compare the efficacy of three {alpha}{sub 1A}/{alpha}{sub 1D}-adrenoceptor (AR) antagonists-naftopidil, tamsulosin, and silodosin-that have differing affinities for the {alpha}{sub 1}-AR subtypes in treating urinary morbidities in Japanese men with {sup 125}I prostate implantation (PI) for prostate cancer. Methods and Materials: This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacymore » variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). Results: Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. Conclusions: Silodosin has a greater impact on improving PI

Elucidation of the Pattern of the Onset of Male Lower Urinary Tract Symptoms Using Cluster Analysis: Efficacy of Tamsulosin in Each Symptom Group.

PubMed

Aikawa, Ken; Kataoka, Masao; Ogawa, Soichiro; Akaihata, Hidenori; Sato, Yuichi; Yabe, Michihiro; Hata, Junya; Koguchi, Tomoyuki; Kojima, Yoshiyuki; Shiragasawa, Chihaya; Kobayashi, Toshimitsu; Yamaguchi, Osamu

2015-08-01

To present a new grouping of male patients with lower urinary tract symptoms (LUTS) based on symptom patterns and clarify whether the therapeutic effect of α1-blocker differs among the groups. We performed secondary analysis of anonymous data from 4815 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan. Data on 7 International Prostate Symptom Score (IPSS) items at the initial visit were used in the cluster analysis. IPSS and quality of life (QOL) scores before and after tamsulosin treatment for 12 weeks were assessed in each cluster. Partial correlation coefficients were also obtained for IPSS and QOL scores based on changes before and after treatment. Five symptom groups were identified by cluster analysis of IPSS. On their symptom profile, each cluster was labeled as minimal type (cluster 1), multiple severe type (cluster 2), weak stream type (cluster 3), storage type (cluster 4), and voiding type (cluster 5). Prevalence and the mean symptom score were significantly improved in almost all symptoms in all clusters by tamsulosin treatment. Nocturia and weak stream had the strongest effect on QOL in clusters 1, 2, and 4 and clusters 3 and 5, respectively. The study clarified that 5 characteristic symptom patterns exist by cluster analysis of IPSS in male patients with LUTS. Tamsulosin improved various symptoms and QOL in each symptom group. The study reports many male patients with LUTS being satisfied with monotherapy using tamsulosin and suggests the usefulness of α1-blockers as a drug of first choice. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparing the efficacy of mydriatic cocktail-soaked sponge and conventional pupil dilation in patients using tamsulosin - a randomized controlled trial.

PubMed

Hargitai, János; Vezendi, László; Vigstrup, Jørgen; Eisgart, Finn; Lundbye-Christensen, Søren; Hargitai, Bálint; Vorum, Henrik

2013-12-20

A strong association exists between the use of tamsulosin and the occurance of intraoperative floppy iris syndrome. Several methods were advocated to overcome the progressive intraopertive miosis.Our purpose was to investigate the effect of a mydriatic-cocktail soaked cellulose sponge on perioperative pupil diameter in tamsulosin-treated patients undergoing elective cataract surgery. Patients using tamsulosin were dilated either with mydriatic-cocktail soaked sponge (group 1) or with conventional eyedrop regimen (group 2). Control patients not taking any α1 adrenergic receptor inhibtors were also dilated with mydriatic sponge (group 3).In all groups oxybuprocain 0.4%, cocain 4%, tropicamide 1%, phenylephrine 10%, diclophenac 0.1% along with chloramphenicol 0.5% were used preoperatively.Pupil diameter (mm) was measured preoperatively, after nucleus delivery, and before IOL implantation. Adverse effects associated with the use of sponge, minor and major intraoperative complications, the use of iris retractors and operation time were recorded.Differences in general between groups were analyzed with a one way analysis of variance (ANOVA); differences between groups in proportions were assessed by Fisher's exact test. Mean pupil diameter (mm) was preopertively: 7.52 ± 1.21, 7.30 ± 1.55 and 7.99 ± 0.96 (ANOVA: p = 0.079); after nucleus delivery: 6 ± 1.20, 6.29 ± 1.12 and 6.52 ± 0.81 (ANOVA: p = 0.123); before IOL implantation: 5.46 ± 1.06, 5.83 ± 1.09 and 6.17 ± 0.89 (ANOVA: p = 0.0291).No adverse effect related to sponge use was detected. Frequency of minor complications, and iris hook use was similar in the two tamsulosin treated group. Operation time did not differ significantly in the three groups. We have found that using a mydriatic cocktail-soaked wick - an alternative way to achieve intraoperative mydriasis for cataract surgery - was as effective and safe as the conventional repeated eyedrops regiment for tamsulosin treated patients. Current Controlled

Comparison and Efficacy of Low-Dose and Standard-Dose Tamsulosin and Alfuzosin in Medical Expulsive Therapy for Lower Ureteral Calculi: Prospective, Randomized, Comparative Study

PubMed Central

Cha, Woo Heon; Choi, Jae Duck; Seo, Young Jin; Lee, Kyungseop

2012-01-01

Purpose Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. Materials and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. Results There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone. PMID:22670195

[Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room].

PubMed

Montiel-Jarquín, Álvaro J; Rocha-Rocha, Valeria M; Solís-Mendoza, Hugo A; Romero-Figueroa, María S; Etchegaray-Morales, Ivet; Alvarado-Ortega, Ivan

2017-01-01

Ureteric colic is the most common symptom of lithiasis. It is caused by the presence of stones accumulated in the renal papillae. These stones often migrate down the ureter, causing a ureteric colic, characterized by a severe pain in the lumbar region. The aim of this study was to compare the use of ketorolac and nifedipine vs. ketorolac and tamsulosin for the medical treatment of pain caused by stones in the lower ureter. Longitudinal study of 150 patients of 21-years or older with stones in the lower third of the ureter. 50% received ketorolac and nifedipine and the other 50%, ketorolac and tamsulosin. The Numeric Pain Rating Scale (NPRS) was used for the assessment of pain at admission and 4 and 12 hours after the treatment was administered. We used descriptive and inferential statistics (Mann-Whitney-Wilcoxon, chi-squared and Poisson regression). Mean age was 38.17 years; 54.7% were male and 45.3% female. NPRS mean was 9.69 (initially), 7.42 (at 4 hours) and 2.05 (at 12 hours). There were no significant differences in the initial measurement of pain between groups (p < 0.005); four and 12 hours later the pain decreased more in patients managed with ketorolac and nifedipine, p = 0.0041. There were no complications nor side effects in both treatments. The use of ketorolac and nifedipine is more effective than the use of ketorolac and tamsulosin for the management of pain caused by lower ureteral colic during the first 12 hours of treatment.

Comparing the efficacy of mydriatic cocktail-soaked sponge and conventional pupil dilation in patients using tamsulosin – a randomized controlled trial

PubMed Central

2013-01-01

Background A strong association exists between the use of tamsulosin and the occurance of intraoperative floppy iris syndrome. Several methods were advocated to overcome the progressive intraopertive miosis. Our purpose was to investigate the effect of a mydriatic-cocktail soaked cellulose sponge on perioperative pupil diameter in tamsulosin-treated patients undergoing elective cataract surgery. Methods Patients using tamsulosin were dilated either with mydriatic-cocktail soaked sponge (group 1) or with conventional eyedrop regimen (group 2). Control patients not taking any α1 adrenergic receptor inhibtors were also dilated with mydriatic sponge (group 3). In all groups oxybuprocain 0.4%, cocain 4%, tropicamide 1%, phenylephrine 10%, diclophenac 0.1% along with chloramphenicol 0.5% were used preoperatively. Pupil diameter (mm) was measured preoperatively, after nucleus delivery, and before IOL implantation. Adverse effects associated with the use of sponge, minor and major intraoperative complications, the use of iris retractors and operation time were recorded. Differences in general between groups were analyzed with a one way analysis of variance (ANOVA); differences between groups in proportions were assessed by Fisher’s exact test. Results Mean pupil diameter (mm) was preopertively: 7.52 ± 1.21, 7.30 ± 1.55 and 7.99 ± 0.96 (ANOVA: p = 0.079); after nucleus delivery: 6 ± 1.20, 6.29 ± 1.12 and 6.52 ± 0.81 (ANOVA: p = 0.123); before IOL implantation: 5.46 ± 1.06, 5.83 ± 1.09 and 6.17 ± 0.89 (ANOVA: p = 0.0291). No adverse effect related to sponge use was detected. Frequency of minor complications, and iris hook use was similar in the two tamsulosin treated group. Operation time did not differ significantly in the three groups. Conclusion We have found that using a mydriatic cocktail-soaked wick – an alternative way to achieve intraoperative mydriasis for cataract surgery – was as effective and safe as

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PubMed

Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

2016-01-01

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

Role of combined use of potassium citrate and tamsulosin in the management of uric acid distal ureteral calculi.

PubMed

El-Gamal, Osama; El-Bendary, Mohamed; Ragab, Maged; Rasheed, Mohamed

2012-06-01

In this article, we investigated the effect of the combined use of tamsulosin and potassium citrate (Uralyt-U(®)) for the treatment of uric acid stones in the distal ureter. The study was designed as a prospective, double blind randomized controlled trial. A total of 191 adult patients with radiolucent distal ureteral calculi were recruited. We included patients with solitary stones ≥5 mm with mild or moderate hydronephrosis and a normal contralateral tract. The patients were randomized into four equal groups (the placebo, tamsulosin, Uralyt-U(®), and the combined treatment groups). The patients were treated for a maximum duration of 4 weeks or until stone expulsion. The stone size in all groups ranged from 5 to 11 mm (7.69 ± 1.7 mm). The total expulsion rate of the stones was significantly lower in the control group (26.1%) compared with that of any of the other three groups (68.8, 58.7, and 84.8% respectively) (P < 0.05). Meanwhile, the difference between the Uralyt-U(®) group and the combined treatment group was also statistically significant (P < 0.05). When we studied the patients with stones >8 mm as a separate subgroup to find the effect of the used drugs on the relatively large stones, we detected that the expulsion rate of these stones was significantly higher in the patients who received the combined treatment in comparison with any of the other three groups (P < 0.05). In conclusion, the use of urinary alkalization with tamsulosin can increase the frequency of spontaneous passage of distal ureteral uric acid stones especially those of 8-11 mm.

The influence of Surelease and sodium alginate on the in-vitro release of tamsulosin hydrochloride in pellet dosage form.

PubMed

Kim, Min-Soo; Jun, Seoung Wook; Lee, Sibeum; Lee, Tae Wan; Park, Jeong-Sook; Hwang, Sung-Joo

2005-06-01

The objective of this study was to prepare controlled-release pellets containing 0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers with Surelease and sodium alginate. The release of tamsulosin HCl from pellets coated with the commercial aqueous ethylcellulose dispersion (Surelease) was investigated at different coating loads. In addition, the effect of sodium alginate on drug release was investigated by varying the ratio of sodium alginate to microcrystalline cellulose (MCC). Dissolution studies were first performed in 500 mL simulated gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross sections were examined by scanning electron microscopy (SEM). Apparently, the spherical pellets were prepared using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from Surelease-coated pellets were significantly affected by changing the content of Surelease, the pH of the dissolution medium and the ratio of sodium alginate to MCC. The drug release rates not only decreased with increase in the coating load, but also increased when the pH of the dissolution medium was increased from 1.2 to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results suggest that Surelease and sodium alginate would be useful excipients in the preparation of controlled-release pellets with the desired release profiles.

Treatment satisfaction with tadalafil or tamsulosin vs placebo in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH): results from a randomised, placebo-controlled study.

PubMed

Oelke, Matthias; Giuliano, François; Baygani, Simin K; Melby, Thomas; Sontag, Angelina

2014-10-01

To assess treatment satisfaction with tadalafil or tamsulosin vs placebo in a 12-week, randomised, double-blind study of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). After a 4-week placebo lead-in period, men aged ≥45 years with an International Prostate Symptom Score (IPSS) of ≥13 and a maximum urinary flow rate of ≥4 to ≤15 mL/s received placebo (172 men), tadalafil 5 mg (171), or tamsulosin 0.4 mg (168) once daily for 12 weeks. Treatment Satisfaction Scale-BPH (TSS-BPH) responses were assessed based on median treatment differences using the van Elteren test. Overall treatment satisfaction was greater for tadalafil vs placebo (P = 0.005), based on greater satisfaction with efficacy (P = 0.003); neither overall treatment satisfaction nor satisfaction with efficacy was greater for tamsulosin vs placebo (P ≥ 0.409). For individual questions, 66.5% of men rated tadalafil treatment as 'effective/very effective' (Question 1, Q1) vs placebo (P = 0.011), 72.6% would 'definitely/probably recommend their treatment' (Q3; P = 0.043), 71.8% were generally 'very satisfied/satisfied with their medication' (Q8; P < 0.003), and 65.0% would 'definitely/probably continue therapy' (Q10; P = 0.035). With tamsulosin, differences vs placebo were not statistically significant. Subgroup analyses of overall TSS-BPH by baseline age (≤65/>65 years), history of erectile dysfunction (yes/no), LUTS/BPH severity (IPSStamsulosin and placebo. © 2014 The Authors. BJU International

Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH - a double-blind randomized trial.

PubMed

Manohar, Chikka Moga Siddaiah; Nagabhushana, Mahadevappa; Karthikeyan, Vilvapathy Senguttuvan; Sanjay, Ramachandra Pudakalkatti; Kamath, Ananth Janardhan; Keshavamurthy, Ramaiah

2017-06-30

Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p <0.001) and 12 (1.2 ±0.66, p <0.001) weeks in Group S. The mean Qmax improvement was the maximum (13.76 ±2.44, p = 0.028) in Group S at 1 week. Reduction in PVR was the maximum in Group S, but it was not statistically significant. Adverse drug events (ADE) were observed in 20.07% (54/269) patients and distribution was similar in the three groups with decreasing incidence with progression of time. Silodosin is the most efficacious AB with rapid onset of action. Silodosin also improves the quality of life in patients with LUTS due to BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin.

Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.

PubMed

Giuliano, François; Oelke, Matthias; Jungwirth, Andreas; Hatzimouratidis, Konstantinos; Watts, Steven; Cox, David; Viktrup, Lars

2013-03-01

Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH. To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH). A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control. The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning. Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699). Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving

Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial).

PubMed

Morgia, Giuseppe; Russo, Giorgio I; Voce, Salvatore; Palmieri, Fabiano; Gentile, Marcello; Giannantoni, Antonella; Blefari, Franco; Carini, Marco; Minervini, Andrea; Ginepri, Andrea; Salvia, Giuseppe; Vespasiani, Giuseppe; Santelli, Giorgio; Cimino, Sebastiano; Allegro, Rosalinda; Collura, Zaira; Fragalà, Eugenia; Arnone, Salvatore; Pareo, Rosaria M

2014-11-01

Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies. PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS. © 2014 Wiley Periodicals, Inc.

Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH – a double-blind randomized trial

PubMed Central

Manohar, Chikka Moga Siddaiah; Nagabhushana, Mahadevappa; Sanjay, Ramachandra Pudakalkatti; Kamath, Ananth Janardhan; Keshavamurthy, Ramaiah

2017-01-01

Introduction Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Material and methods Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). Results IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p <0.001) and 12 (1.2 ±0.66, p <0.001) weeks in Group S. The mean Qmax improvement was the maximum (13.76 ±2.44, p = 0.028) in Group S at 1 week. Reduction in PVR was the maximum in Group S, but it was not statistically significant. Adverse drug events (ADE) were observed in 20.07% (54/269) patients and distribution was similar in the three groups with decreasing incidence with progression of time. Conclusions Silodosin is the most efficacious AB with rapid onset of action. Silodosin also improves the quality of life in patients with LUTS due to BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin. PMID:28721281

The effects of tamsulosin and alfuzosin on iris morphology: an ultrasound biomicroscopic comparison.

PubMed

Aktas, Zeynep; Yuksel, Nilay; Ceylan, Gurhan; Polat, Fazli; Hasanreisoglu, Murat; Hasanreisoglu, Berati

2015-03-01

It is well known that Alpha-1 adrenergic receptor antagonists affect the receptors in the prostate and also iris dilator muscle, leading to loss of iris muscle tone. To compare morphological alterations of iris secondary to tamsulosin and alfuzosin use. Patients included in the study were grouped as follows: 16 patients treated with tamsulosin (Group 1), 14 patients treated with alfuzosin (Group 2) and 18 untreated controls (Group 3). All patients underwent ultrasound biomicroscopic and pupillometric examination. Iris thickness was measured at the dilator muscle region (DMR; measured at half of the distance between the scleral spur and the pupillary margin) and sphincter muscle region (SMR; Standardized at 0.75 mm from the pupillary margin). DMR/SMR was also calculated for each patient. Differences among groups were analysed. Main outcome measures were DMR, SMR, DMR/SMR and pupillary diameter. Mean duration of treatments were 2.4 ± 0.96 years (1-4) and 2.3 ± 1.01 years (1-4) in Groups 1 and 2. Pupillary diameters were reduced in Groups 1-2 compared to Group 3 (p < 0.001, p < 0.001). The SMR was similar in Groups 1 and 2 (p: 0.114). These values were not significantly different from that of Group 3 (p: 0.196, p: 0.209). However, thickness in the DMR in Groups 1-2 were significantly lower than that of controls (Group 3) whereas there was no significant difference between Groups 1 and 2 (p: 0.041, p: 0.039 and 0.986, respectively). Mean DMR/SMR ratios were significantly lower in Groups 1-2 than that of Group 3 (p: 0.040 and p: 0.040, respectively). In patients using these medications, the iris seems to be thinner at the dilator muscle region, but preserving the sphincter muscle region.

Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart.

PubMed

Kojima, Yoshiyuki; Sasaki, Shoichi; Imura, Makoto; Kubota, Yasue; Hayashi, Yutaro; Kohri, Kenjiro

2012-01-01

The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. Eighty-two patients (mean age: 70.9 ± 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP. Copyright © 2011 Wiley Periodicals, Inc.

Dutasteride plus tamsulosin fixed-dose combination first-line therapy versus tamsulosin monotherapy in the treatment of benign prostatic hyperplasia: a budget impact analysis in the Greek healthcare setting.

PubMed

Geitona, Maria; Karabela, Pinelopi; Katsoulis, Ioannis A; Kousoulakou, Hara; Lyberopoulou, Eleni; Bitros, Eleftherios; Xaplanteris, Loukas; Papanicolaou, Sotiria

2014-09-26

The purpose of this study was to explore the budget impact of dutasteride plus tamsulosin fixed-dose combination (DUT + TAM FDC) versus tamsulosin monotherapy, in the treatment of patients with benign prostatic hyperplasia (BPH) from the perspective of the Greek healthcare insurance system. A Microsoft Excel-based model was developed to estimate the financial consequences of adopting DUT + TAM FDC within the Greek healthcare setting. The model, compared six mutually exclusive health states in two alternative treatment options: current standard of care and the introduction of DUT + TAM FDC in the market. The model used clinical inputs from the CombAT study; data on resource use associated with the management of BPH in Greece were derived from expert panel, and unit cost data were derived from official reimbursement tariffs. A payer perspective was taken into account. As patient distribution data between public and private sectors are not available in Greece two scenarios were investigated, considering the whole eligible population in each scenario. A 4 year time horizon was taken into account and included treatment costs, number of transurethral resections of the prostate (TURPs) and acute urinary retention (AUR) episodes avoided. The clinical benefit from the market adoption of DUT + TAM FDC in Greece was 1,758 TURPs and 972 episodes of AUR avoided cumulatively in a four year period. The increase in total costs from the gradual introduction of DUT + TAM FDC to the Greek healthcare system ranges from €1.3 million in the first year to €5.8 million in the fourth year, for the public sector, and €1.2 million to €4.0 million, for the private sector. This represents an increase of 1.91% to 7.94% for the public sector and 1.10% 3.29% in the private sector, during the 4-year time horizon. Budget impact analysis (BIA) results indicated that the gradual introduction of DUT + TAM FDC, would increase the overall budget of the disease, however providing

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

PubMed

Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Kilonzo, Mary; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; Norrie, John; McPherson, Gladys; McDonald, Alison; Shearer, Kirsty; Gillies, Katie; Anson, Kenneth; Boachie, Charles; N'Dow, James; Burgess, Neil; Clark, Terry; Cameron, Sarah; McClinton, Samuel

2015-08-01

Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. Urology departments in 24 UK NHS hospitals. Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

PubMed

McClinton, Sam; Starr, Kathryn; Thomas, Ruth; McLennan, Graeme; McPherson, Gladys; McDonald, Alison; Lam, Thomas; N'Dow, James; Kilonzo, Mary; Pickard, Robert; Anson, Ken; Burr, Jennifer

2014-06-20

Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a

A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of rasagiline and tamsulosin.

PubMed

Brenna, Davide; Pirola, Margherita; Raimondi, Laura; Burke, Anthony J; Benaglia, Maurizio

2017-12-01

The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Murraya koenigii- and Tribulus terrestris-based oral formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in men aged >50 years: a double-blind, double-dummy, randomized controlled trial.

PubMed

Sengupta, Gairik; Hazra, Avijit; Kundu, Anup; Ghosh, Anirban

2011-12-01

Drug treatment can defer surgical intervention in benign prostatic hyperplasia (BPH), a common disorder in elderly men, and is widely practiced. Various herbal formulations have been used for the treatment of BPH, but few have been compared with established modern medicines in head-to-head clinical trials. We compared the effectiveness and tolerability of an oral formulation, comprising standardized extracts of Murraya koenigii and Tribulus terrestris leaves being marketed in India under Ayurvedic license, versus tamsulosin in the treatment of symptomatic BPH. A double-blind, double-dummy, parallel-group, randomized controlled trial was conducted with treatment-naive ambulatory patients with BPH aged >50 years. Patients received either the plant drug in a dose of 2 capsules BID or tamsulosin 400 μg once daily for 12 weeks with 2 interim follow-up visits at the end of 4 and 8 weeks. The double-dummy technique was used to ensure double-blinding. The primary effectiveness measure was reduction in the International Prostate Symptom Score (IPSS). Proportion of patients becoming completely or relatively symptom free (IPSS <8), change in prostate volume (assessed by using ultrasonography conducted by a radiologist blinded to the nature or duration of treatment), and peak urinary flow rate (assessed by using uroflowmetry) were secondary measures. Treatment-emergent adverse events, changes in weight, vital signs, and routine laboratory safety parameters were recorded. Forty-six patients were randomized (23 per group); 19 completed all study visits in the plant drug group and 21 in the tamsulosin group. However, applying modified intention-to-treat criterion, 23 and 21 patients, respectively, were considered for effectiveness analysis. Mean (SD) age and baseline weight were 58.5 (14.0) years and 57.5 (10.5) kg in the plant drug arm, and 62.9 (6.3) years and 59.8 (9.9) kg in the tamsulosin arm, respectively. Median (interquartile range) symptom duration was 12.0 (12

Polymorphism in R-tamsulosin (an alpha blocker): The unexpected manifestation of a sulfonamide⋯o-diethoxybenzene heterosynthon

NASA Astrophysics Data System (ADS)

Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, Krishnan

2014-12-01

A two point Nsbnd H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P21, C2, and P21 space groups respectively with two molecules in the asymmetric unit (Z‧ = 2), whereas, form III of freebase crystallize in the orthorhombic P212121 space group with Z‧ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯o-diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring

Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.

PubMed

Drake, Marcus J; Chapple, Christopher; Sokol, Roman; Oelke, Matthias; Traudtner, Klaudia; Klaver, Monique; Drogendijk, Ted; Van Kerrebroeck, Philip

2015-02-01

Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size <75 ml, and postvoid residuals ≤ 150 ml, who completed the 12-wk, double-blind NEPTUNE study could continue in the 40-wk, open-label NEPTUNE II study. FDC of Soli 6 mg plus TOCAS 0.4 mg, or Soli 9 mg plus TOCAS 0.4mg; patients could switch between doses in NEPTUNE II. Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period. Primary efficacy end points were total International Prostate Symptom Score (IPSS) and total urgency and frequency score (TUFS); secondary end points included IPSS storage and voiding subscores, micturition diary variables, and quality of life parameters. In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from

Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.

PubMed

Matsushima, H; Watanabe, T; Higuchi, S

2000-04-01

The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM. Copyright 2000 Wiley-Liss, Inc.

[Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe].

PubMed

Chapple, Ch R; Montorsi, F; Tammela, T L J; Wirth, M; Koldewijn, E; Fernandez Fernandez, E

2012-01-01

Silodosin is a new selective therapy with a high pharmacologic selectivity for the a (1A)-adrenoreceptor. Our aim was to test silodosin's superiority to placebo and noninferiority to tamsulosin and discuss the findings in the context of a comprehensive literature review of the new compound silodosin. We conducted a multicenter double-blind, placebo-and active-controlled parallel group study. A total of 1228 men > or = 50 yr of age with an International Prostate Symptom Score (IPSS) < or = 13 and a urine maximum flow rate (Q(max))> 4 and < or = 15 ml/s were selected at 72 sites in 11 European countries. The patients were entered into a 2-wk wash-out and a 4-wk placebo run-in period. A total of 955 patients were randomized (2:2:1) to silodosin 8 mg (n = 381), tamsulosin 0.4 mg (n = 384), or placebo (n = 190) once daily for 12 wk. We calculated the change from baseline in IPSS total score (primary), storage and voiding subscores, quality of life (QoL) due to urinary symptoms, and Q(max). Responders were defined on the basis of IPSS and Q(max) by a decrease of > or = 25% and an increase of > or = 30% from baseline, respectively. The change from baseline in the IPSS total score with silodosin and tamsulosin was significantly superior to that with placebo (p < 0.001): difference active placebo of -2.3 (95% confidence interval [CI], -3.2, -1.4) with silodosin and -2.0 (95% CI, -2.9, -1.1) with tamsulosin. Responder rates according to total IPSS were significantly higher (p < 0.001) with silodosin (66.8%) and tamsulosin (65.4%) than with placebo (50.8%). Active treatments were also superior to placebo in the IPSS storage and voiding subscore analyses, as well as in QoL due to urinary symptoms. Of note, only silodosin significantly reduced nocturia versus placebo (the change from baseline was -0.9, -0.8, and -0.7 for silodosin, tamsulosin, and placebo, respectively; p = 0.013 for silodosin vs placebo). An increase in Q(max) was observed in all groups. The adjusted mean

Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe.

PubMed

Chapple, Christopher R; Montorsi, Francesco; Tammela, Teuvo L J; Wirth, Manfred; Koldewijn, Evert; Fernández Fernández, Eldiberto

2011-03-01

Silodosin is a new selective therapy with a high pharmacologic selectivity for the α(1A)-adrenoreceptor. Our aim was to test silodosin's superiority to placebo and noninferiority to tamsulosin and discuss the findings in the context of a comprehensive literature review of the new compound silodosin. We conducted a multicenter double-blind, placebo- and active-controlled parallel group study. A total of 1228 men ≥50 yr of age with an International Prostate Symptom Score (IPSS) ≥13 and a urine maximum flow rate (Q(max)) >4 and ≤15 ml/s were selected at 72 sites in 11 European countries. The patients were entered into a 2-wk wash-out and a 4-wk placebo run-in period. A total of 955 patients were randomized (2:2:1) to silodosin 8 mg (n=381), tamsulosin 0.4 mg (n=384), or placebo (n=190) once daily for 12 wk. We calculated the change from baseline in IPSS total score (primary), storage and voiding subscores, quality of life (QoL) due to urinary symptoms, and Q(max). Responders were defined on the basis of IPSS and Q(max) by a decrease of ≥25% and an increase of ≥30% from baseline, respectively. The change from baseline in the IPSS total score with silodosin and tamsulosin was significantly superior to that with placebo (p<0.001): difference active placebo of -2.3 (95% confidence interval [CI], -3.2, -1.4) with silodosin and -2.0 (95% CI,-2.9, -1.1) with tamsulosin. Responder rates according to total IPSS were significantly higher (p<0.001) with silodosin (66.8%) and tamsulosin (65.4%) than with placebo (50.8%). Active treatments were also superior to placebo in the IPSS storage and voiding subscore analyses, as well as in QoL due to urinary symptoms. Of note, only silodosin significantly reduced nocturia versus placebo (the change from baseline was -0.9, -0.8, and -0.7 for silodosin, tamsulosin, and placebo, respectively; p=0.013 for silodosin vs placebo). An increase in Q(max) was observed in all groups. The adjusted mean change from baseline to end point

α1-Adrenergic receptor antagonists and gynecomastia. A case series from the Italian spontaneous reporting system and VigiBase(™).

PubMed

Viola, Ermelinda; Opri, Sibilla; Moretti, Ugo; Leone, Roberto; Casini, Maria Luisa; Ruggieri, Sara; Minore, Claudia; Conforti, Anita

2014-08-01

The aim of this study was to analyze the cases of gynecomastia associated with α1A-adrenergic receptor antagonists (α1-ARAs) in the Italian spontaneous reporting system database (Rete Nazionale di Farmacovigilanza or RNF) and in the World Health Organization ICSRs database (VigiBase(™)), focusing on tamsulosin use. We analyzed the spontaneous reports of gynecomastia related to the use of α1-ARAs and collected from the RNF and from VigiBase(™) up to December 2012. Cases of gynecomastia have been defined as reports associated with gynecomastia according with Medical Dictionary for Regulatory Activities (MedDRA). Reporting odds ratio (ROR) and Information Component (IC) were calculated as measures of disproportionality in RNF and VigiBase(™), respectively. Up to December 2012, about 186,000 reports were recorded in the RNF. Among these, 902 reports of adverse drug reaction (ADR) have been associated with the use of at least one α1-ARAs. Of these, in 15 cases, gynecomastia was a listed ADR: in 10, the suspected drug was tamsulosin (in eight, it was the sole suspect); in two, doxazosin and alfuzosin, respectively; and in one, terazosin. ROR for tamsulosin was 5.3 (95% CI 1.8, 15.7). In VigiBase(™), 84 reports of gynecomastia indicated tamsulosin as suspected drug. Tamsulosin-associated gynecomastia showed the highest IC value within this class of drugs (IC 95% 2.43). In this study, we highlight a possible association between gynecomastia and tamsulosin use. To our knowledge, this association has not been described before and could represent a potential signal.

[Intraoperative floppy iris syndrome].

PubMed

Mazal, Z

2007-04-01

In the year 2005, Chang and Cambell described unusual reaction of the iris during the cataract surgery in patients treated with tamsulosine. This was named as IFIS, an acronym for the Intraoperative Floppy Iris Syndrome. In its advanced stage, the syndrome is characterized by insufficient mydfiasis before the surgery, narrowing of the pupil during the surgery, its impossible dilatation during the surgery by means of stretching, unusual elasticity of the pupilar margin, surging and fluttering iris with tendency to prolapse. The same manifestations we observed in our patients and we confirm the direct connection with tamsulosine hydrochloride treatment. Tamsulosine is the antagonist of alpha 1A adrenergic receptors whose are present, except in the smooth musculature of the prostate gland and the urinary bladder, in the iris dilator as well. At the same time we observed this syndrome rarely in some patients not using tamsulosine. In most cases, these patients were treated with antipsychotic drugs.

Alpha 1-Adrenoceptor Blocker May Improve Not Only Voiding But Also Storage Lower Urinary Tract Symptoms Caused by 125I Brachytherapy for Prostate Cancer

PubMed Central

Aoki, Yoshitaka; Ito, Hideaki; Miwa, Yoshiji; Akino, Hironobu; Shioura, Hiroki; Kimura, Hirohiko; Yokoyama, Osamu

2014-01-01

Purpose. To assess changes in lower urinary tract symptoms (LUTS) within 1 year after brachytherapy in patients receiving alpha 1-adrenoceptor antagonists. Methods. We retrospectively evaluated 116 patients who underwent 125I prostate brachytherapy in our institute. Seventy-one patients were treated with a combination of external beam radiation therapy and brachytherapy. Alpha 1-adrenoceptor antagonists were prescribed to all patients after brachytherapy. International Prostate Symptom Score (IPSS) forms and postvoid residual urine volume were recorded at all follow-up visits. Results. Forty-nine patients were given tamsulosin hydrochloride, 32 were given silodosin hydrochloride, and 35 were given naftopidil for up to 6 months after seed implantation. Patients given tamsulosin or naftopidil tended to show a higher peak IPSS and slower recovery to baseline values than those given silodosin. The patients given naftopidil showed an insufficient recovery in storage symptoms in naftopidil group in comparison with tamsulosin group at 3 months and with silodosin group at 6 and 9 months. Conclusions. In the management of LUT after brachytherapy, silodosin may provide a more favorable improvement. Silodosin and tamsulosin may have an advantage in improving not only voiding but also storage lower urinary tract symptoms after brachytherapy. PMID:25006516

The effect of competing direct-to-consumer advertising campaigns on the use of drugs for benign prostatic hyperplasia: time series analysis.

PubMed

Skeldon, Sean C; Kozhimannil, Katy B; Majumdar, Sumit R; Law, Michael R

2015-04-01

Direct-to-consumer advertising (DTCA) remains a controversial issue, with concerns that it leads to unnecessary and inappropriate prescribing. Whether DTCA shifts prescribing from first-line (guideline-recommended) therapy to second-line drugs has not been studied. The purpose of this study was to determine the impact of sequential DTCA campaigns for two drugs used to treat benign prostatic hyperplasia (BPH): one newer agent, dutasteride (Avodart(®)), and one older first-line agent, tamsulosin (Flomax(®)). Interrupted time series analysis was used to assess the impact of each DTCA campaign using data on consumer "response" from Google Trends and dispensed prescriptions from IMS Health. We analyzed data for the United States from January 2003 to December 2007. DTCA for dutasteride and tamsulosin commenced on July, 2005 and April, 2006, respectively. Monthly Internet search volume (scaled from 0 to 100) for the advertised trade name of each drug and monthly U.S. prescription rates per 1,000 population were analyzed. The dutasteride campaign was associated with an increase in Internet searches for both "Avodart" (level change +31.3 %, 95 % CI: 27.2-35.4) and "Flomax" (level change +8.3 %, 95 % CI: 0.9-15.7), whereas the tamsulosin campaign was associated with increased "Flomax" searches (level change +25.3 %, 95 % CI: 18.7-31.8). The dutasteride campaign was associated with an increase in the prescription of dutasteride (trend = 0.45/month, 95 % CI: 0.33-0.56), but a larger impact was observed with tamsulosin prescriptions (trend = 0.76/month, 95 % CI: 0.02-1.50). Similarly, the tamsulosin campaign was associated with an immediate fourfold increase in the prescribing of tamsulosin (level change +5.76 units, 95 % CI: 1.79-9.72) compared to dutasteride (level change +1.47 units, 95 % CI: 0.79-2.14). DTCA was associated with the utilization of drugs to treat symptomatic BPH. However, both campaigns were associated with greater increases in the use of the guideline

Non-Adrenergic, Tamsulosin-Insensitive Smooth Muscle Contraction is Sufficient to Replace α1 -Adrenergic Tension in the Human Prostate.

PubMed

Hennenberg, Martin; Acevedo, Alice; Wiemer, Nicolas; Kan, Aysenur; Tamalunas, Alexander; Wang, Yiming; Yu, Qingfeng; Rutz, Beata; Ciotkowska, Anna; Herlemann, Annika; Strittmatter, Frank; Stief, Christian G; Gratzke, Christian

2017-05-01

Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia may be caused by prostate smooth muscle contraction. Although α 1 -blockers may improve symptoms by prostate smooth muscle relaxation, their efficacy is limited. This may be explained by non-adrenergic mediators causing contraction in parallel to α 1 -adrenoceptors. However, little is known about the relevance and cooperative actions of non-adrenergic mediators in the prostate. Prostate tissues were obtained from radical prostatectomy (n = 127 patients). Contractile responses were studied in an organ bath. Endothelin-1 and noradrenaline induced contractions of similar magnitude (116 ± 23 and 117 ± 18% of KCl-induced contractions). Endothelin-2- and -3-induced maximum contractions of 63 ± 8.6 and 71 ± 19% of KCl, while contractions by the thromboxane analog U46619 amounted up to 63 ± 9.4%. Dopamine-induced contractions averaged to 22 ± 4.5% of KCl, while maximum contractions by serotonin, histamine, and carbachol stayed below 10% of KCl-induced. While noradrenaline-induced contractions were inhibited by tamsulosin (300 nM), endothelin-1-, -2-, or -3-induced contraction were not. No additive effects were observed if endothelins and noradrenaline were applied consecutively to the same samples. If endothelin-1 was applied after U46619, resulting tension (172 ± 43% of KCl) significantly exceeded noradrenaline-induced contraction. Tensions following combined application of endothelin-2 or -3 with U46619 stayed below noradrenaline-induced contractions. Tension following combined application of all three endothelins with U46619 resembled maximum noradrenaline-induced tone. Contractions following concomitant confrontation of human prostate tissue with noradrenaline and endothelin-1 are not additive. Endothelin-1 is sufficient to induce a smooth muscle tone resembling that of noradrenaline. This may replace lacking α 1 -adrenergic tone under therapy with

Superparamagnetic graphene oxide-based dispersive-solid phase extraction for preconcentration and determination of tamsulosin hydrochloride in human plasma by high performance liquid chromatography-ultraviolet detection.

PubMed

Pashaei, Yaser; Ghorbani-Bidkorbeh, Fatemeh; Shekarchi, Maryam

2017-05-26

In the present study, superparamagnetic graphene oxide-Fe 3 O 4 nanocomposites were successfully prepared by a modified impregnation method (MGO mi ) and their application as a sorbent in the magnetic-dispersive solid phase extraction (M-dSPE) mode to the preconcentration and determination of tamsulosin hydrochloride (TMS) in human plasma was investigated by coupling with high performance liquid chromatography-ultraviolet detection (HPLC-UV). The structure, morphology and magnetic properties of the prepared nanocomposites were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and vibrating sample magnetometry (VSM). Some factors affecting the extraction efficiency, including the pH value, amount of sorbent, extraction time, elution solvent and its volume, and desorption time were studied and optimized. Magnetic nanocomposites plasma extraction of TMS following HPLC analyses showed a linear calibration curve in the range of 0.5-50.0ngmL -1 with an acceptable correlation coefficient (R 2 =0.9988). The method was sensitive, with a low limit of detection (0.17ngmL -1 ) and quantification (0.48ngmL -1 ). Inter- and intra-day precision expressed as relative standard deviation (n=3) and the preconcentration factor, were found to be 5.6-7.2%, 2.9-4.2% and 10, respectively. Good recoveries (98.1-101.4%) with low relative standard deviations (4.2-5.0%) indicated that the matrices under consideration do not significantly affect the extraction process. Due to its high precision and accuracy, the developed method may be a HPLC-UV alternative with M-dSPE for bioequivalence analysis of TMS in human plasma. Copyright © 2017 Elsevier B.V. All rights reserved.

Ten years of intraoperative floppy iris syndrome in the era of α-blockers

PubMed Central

Mohamad Al-Ali, Badereddin; Radmayr, Christian; Weber, Maria; Horninger, Wolfgang; Findl, Oliver; Plas, Eugen

2017-01-01

Introduction The use of alpha-1 receptor antagonists in the treatment of benign prostatic hyperplasia (BPH) has created a problem in ophthalmic surgery, the so-called intraoperative floppy iris syndrome (IFIS). This consists of a billowing iris, insufficient pupillary dilation with progressive intraoperative miosis, and protrusion of iris tissue through the tunnel and side port incision that are made for access to the anterior chamber during surgery. IFIS presents particular difficulties in cataract surgery which is carried out through the pupil with manipulations in the immediate vicinity of the iris. The complications range from poor visibility of the operative field to iris damage with the surgical instruments and to rupture of the posterior capsule, with loss of lens material into the vitreous body. Material and methods A comprehensive literature review was performed using MEDLINE with MeSH terms and keywords ‘benign prostatic hyperplasia’, ‘intraoperative floppy iris syndrome’, ‘adrenergic alpha-antagonist’ and ‘cataract surgery’. In addition, reference lists from identified publications were reviewed to identify reports and studies of interest from 2001 to 2017. Results The A total of 95% of experienced ophthalmologic surgeons reported that systematic treatment with tamsulosin represents a challenging surgical condition increasing the risk of complications. Alpha-blockers are commonly prescribed, with 1,079,505 packages of tamsulosin prescribed each month in 2014 in Austria. Dose modification may be one way to reduce the risk of IFIS. A lower incidence of IFIS was reported in patients on tamsulosin in Japan, but the recommended dosage was lower than that used in Europe and the US (0.2 mg vs. 0.4 mg). Conclusions We showed that not all patients taking tamsulosin experience IFIS. Moreover, larger investigations with a prospective design are needed, including studies to monitor the pre- and post-therapeutic ophthalmologic changes under tamsulosin

The effects of the combined use of a PDE5 inhibitor and medications for hypertension, lower urinary tract symptoms and dyslipidemia on corporal tissue tone.

PubMed

Lee, J H; Chae, M R; Park, J K; Jeon, J H; Lee, S W

2012-01-01

ED is closely associated with its comorbidities (hypertension, dyslipidemia and lower urinary tract symptoms (LUTS)). Therefore, several drugs have been prescribed simultaneously with PDE5 inhibitors. If a specific medication for ED comorbidities has enhancing effects on PDE5 inhibitors, it offers alternative combination therapy in nonresponders to monotherapy with PDE5 inhibitors and allows clinicians to treat ED and its comorbidities simultaneously. To establish theoretical basis of choosing an appropriate medication for ED and concomitant disease, we examined the effects combining a PDE5 inhibitor with representative drugs for hypertension, dyslipidemia and LUTS on relaxing the corpus cavernosum of rabbits using the organ-bath technique. The effect of mirodenafil on relaxing phenylephrine-induced cavernosal contractions was significantly enhanced by the presence of 10(-4) M losartan, 10(-6) M nifedipine, 10(-6) M amlodipine, 10(-7) M doxazosin and 10(-9) M tamsulosin (P<0.05). The maximum relaxation effects were 47.2±3.8%, 57.6±2.6%, 64.0±3.7%, 76.1±5.7% and 71.7±5.4%, respectively. Enalapril and simvastatin had no enhancing effects. The relaxation induced by sodium nitroprusside alone (39.0±4.0%) was significantly enhanced in the presence of the 10(-4) M losartan (66.0±6.0%, P<0.05). Tetraethylammonium (1 mM) significantly inhibited the enhancement effects of tamsulosin and doxazosin on mirodenafil-induced relaxation (doxazosin: 76.1±5.7% vs 45.3±2.3%; tamsulosin: 71.7±5.4% vs 48.1±3.5%). On the basis of these findings, losartan seemed to induce synergistic effects through an interaction with nitric oxide. In addition, K(+) channel activation could be one of the mechanisms for the synergistic effect of combining mirodenafil with doxazosin or tamsulosin. We believe that the combination of a PDE5 inhibitor with losartan, nifedipine, amlodipine, doxazosin or tamsulosin could be a pharmacologic strategy for simultaneously treating ED and

Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia in men with LUTS suggestive of BPH: re-evaluation of four controlled clinical studies.

PubMed

Oelke, Matthias; Berges, Richard; Schläfke, Sandra; Burkart, Martin

2014-10-01

To determine the effects of the herbal fixed-dose combination PRO 160/120 (extracts from saw palmetto fruits and stinging nettle roots) on nocturnal voiding frequency, as measured by question 7 of the IPSS questionnaire, in patients with moderate-to-severe LUTS/BPH after 24 weeks of treatment compared to placebo, to the α-blocker tamsulosin, or to the 5α-reductase inhibitor finasteride. The study is about post hoc evaluation of four published randomized, double-blind clinical trials on PRO 160/120, two compared with placebo, one with finasteride and one with tamsulosin. In addition, a pooled data analysis of the two placebo-controlled trials was conducted. We analyzed data from a total of 922 patients with a mean age of 66 years and a mean baseline nocturnal voiding frequency of 2.1. In the pooled analysis of placebo-controlled trials, nocturnal voids improved by 0.8 (29 %) with PRO 160/120 compared to 0.6 (18 %) with placebo (p = 0.015, Wilcoxon test, one-tailed). The 69 % responder rate to PRO 160/120 was significantly superior to the placebo response (52 %; p = 0.003, χ (2)-test, two-tailed). The majority of responders improved by 1 void/night. Absolute improvements and response rates were consistently higher with PRO 160/120 than with placebo over a range of baseline nocturnal voiding frequencies. There were no differences between PRO 160/120 and finasteride or tamsulosin regarding absolute improvement of nocturnal voids or responds rates. PRO 160/120 significantly improved nocturnal voiding frequency compared to placebo and similar to tamsulosin or finasteride.

Naftopidil for the treatment of urinary symptoms in patients with benign prostatic hyperplasia

PubMed Central

Masumori, Naoya

2011-01-01

Naftopidil, approved only in Japan, is an α1-adrenergic receptor antagonist (α1-blocker) used to treat lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Different from tamsulosin hydrochloride and silodosin, in that it has higher and extremely higher affinity respectively, for the α1A-adrenergic receptor subtype than for the α1D type, naftopidil has distinct characteristics because it has a three times greater affinity for the α1D-adrenergic receptor subtype than for the α1A subtype. Although well-designed large-scale randomized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined, previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other α1-blockers such as tamsulosin. On the other hand, the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the α1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white, black and Hispanic men having LUTS/BPH in western countries. PMID:21753885

Multichannel impedance monitoring for evaluation of alpha-adrenoblocker effect on the ureteral function in patients with stone disease

NASA Astrophysics Data System (ADS)

Apolikhin, O. I.; Khodyreva, L. A.; Mudraya, I. S.; Kirpatovsky, V. I.; Serdyuk, A. A.

2010-04-01

The study of distal ureter function was carried out on patients with stones in the upper urinary tract, who underwent ureteroscopy and lithotripsy procedures. The parameters of ureteral peristalsis such as peristalsis amplitude, peristalsis rate, ureteral wall tone, contractile wave duration, and its direction obtained by multichannel impedance ureterography were assessed and compared from two groups of patients. The group I patients received tamsulosin in addition to standard regimen, while the group II patients matched according to the stone size and location were managed without tamsulosin medical therapy. In comparison with group II, the group I patients demonstrated smaller average peristalsis amplitude (0.60±0.08 vs 0.81±0.06 Ohm), shorter contractions (7.1±0.3 vs 7.7±0.3 s), greater peristalsis rate (3.3±0.3 vs 2.8±0.2 per minute), and diminished ureteral tone (4.0±0.5 vs 4.7±0.2 Ohm-1). Incidence of the retrograde contractile waves was two-fold greater in the group II, while normal antegrade regular contractions were 30% more frequent in the group I. In addition, our results showed that the effect of tamsulosin on ureteral function was manifested in the patients with different stone size and location in the upper urinary tract, and it depended pronouncedly on individual ureteral tone and contractility parameters.

Silodosin is effective for treatment of LUTS in men with BPH: a systematic review

PubMed Central

Ding, Hui; Du, Wan; Hou, Zi-Zhen; Wang, Han-Zhang; Wang, Zhi-Ping

2013-01-01

The aim of this study was to systematically review the evidence on the efficacy and safety of silodosin treatments on lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) from randomized controlled trials. We searched PubMed (1966–December 2011), Embase (1974–December 2011) and the Cochrane Library Database (2011, Issue 12). The assessed outcome measures were the change from baseline for the International Prostate Symptom Score (IPSS), quality of life (QoL) score, peak urine maximum flow rate (Qmax), QoL related to urinary symptoms and adverse effects. Two authors independently assessed the study quality and extracted data. All data were analysed using RevMan 5.1. The meta-analysis included four randomized controlled trials with a total of 2504 patients. The study durations were each 12 weeks. At the follow-up end points, the pooled results showed that the change from baseline for the silodosin group was significantly higher than the placebo group for the IPSS, QoL score and Qmax(mean difference (MD)=−2.78, P<0.00001; MD=−0.42, P=0.004; MD=1.17, P<0.00001,respectively) and patients felt more satisfied with QoL related to urinary symptoms in the silodosin group than the placebo group. Ejaculation disorder was the most commonly reported adverse effect. The pooled results also showed that the silodosin group was superior to the 0.2 mg tamsulosin group with respect to the IPSS and QoL score (IPSS: MD=−1.14, P=0.02; QoL score: MD=−0.26, P=0.02) and inferior to the 0.2 mg tamsulosin group with respect to Qmax (MD=−0.85, P=0.01). In contrast, there was no significant difference in the incidence of ejaculation disorder and dizziness between the silodosin and 0.2 mg tamsulosin groups. The current meta-analysis suggested that silodosin is an effective therapy for LUTS in men with BPH and is not inferior to 0.2 mg tamsulosin. PMID:23223034

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

PubMed

Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; McPherson, Gladys; McDonald, Alison; Anson, Kenneth; N'Dow, James; Burgess, Neil; Clark, Terry; Kilonzo, Mary; Gillies, Katie; Shearer, Kirsty; Boachie, Charles; Cameron, Sarah; Norrie, John; McClinton, Samuel

2015-07-25

Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78

Effects of specific alpha-1A/1D blocker on lower urinary tract symptoms due to double-J stent: a prospectively randomized study.

PubMed

Wang, Chung-Jing; Huang, Shi-Wei; Chang, Chien-Hsing

2009-06-01

The aim of our study was to evaluate the effect of tamsulosin in improving symptoms in patients with indwelling double-J ureteral stents. This prospective study lasted from April 2006 to March 2008. All the patients with symptomatic lower ureteral stones with <15 mm diameter were enrolled, and were prospectively randomized (random numbers table) into two groups. A total of 154 patients, with insertion of a double-J ureteral stent after ureteroscopic stone removal. In group 1, 75 patients were enrolled and received placebo for 2 weeks. Group 2 included 79 patients who received 0.4 mg of tamsulosin, once daily for 2 weeks. All patients completed the validated ureteral stent symptom questionnaire (USSQ) and quality of life of international prostate symptom scale (IPSS) for evaluating the symptoms of double-J stents and quality of life after double-J stent insertion and removal, respectively. The analysis of the questionnaire at W1 revealed a significant difference in the main score index of urinary symptoms, body pain and general health between groups 1 and 2. When comparing W1 evaluation with that of W4 after double-J removal, both groups showed significant worsening of urinary symptoms, body pain, general health and work performance, except sexual performance. The mean score of quality of life in IPSS was 4.21 in group 1 and 1.6 in group 2. Tamsulosin can improve a subset of stent-related urinary symptoms and quality of life effectively and may be applied in routine clinical practice.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead

PubMed Central

2016-01-01

Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1–6. A high throughput screen against LPA1 gave compound 7a as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH). In contrast to tamsulosin, compound 17a had no impact on the mean blood pressure at this dose. These results suggest that LPA1 antagonists could be used to treat BPH without affecting the blood pressure. Herein, we report the hit-to-lead optimization of a unique series of LPA1 antagonists and their in vivo efficacy. PMID:27774128

[Clinical efficacy of Shuganyiyang capsule combined with Western medicine for the treatment of type III prostatitis complicated by erectile dysfunction].

PubMed

Feng, Yi-Geng; Chen, Lei; Zhou, Zhi-Heng

2013-11-01

To investigate the clinical efficacy of Shuganyiyang Capsule combined with conventional Western medicine (tamsulosin hydrochloride sustained release tablets + prostat tablets) for the treatment of type III prostatitis complicated by erectile dysfunction (ED). Eighty patients with type III prostatitis complicated by ED were equally randomized to an experimental and a control group, the former treated with Shuganyiyang Capsule combined with tamsulosin hydrochloride sustained release tablets and prostat tablets, while the latter with tamsulosin hydrochloride and prostat only, both for 8 weeks. Then the prostatitis symptoms, erectile function and psychological conditions of the patients were evaluated using NIH-CPSI, IIEF-5, and hospital anxiety and depression scale (HADA and HADD) respectively. The rates of recovery, excellence, effectiveness and ineffectiveness were calculated. The scores on NIH-CPSI, IIEF-5, HADA and HADD obtained at 4 and 8 weeks after treatment showed statistically significant differences between the two time points as well as from the baseline (P < 0.01). At 8 weeks, the scores on NIH-CPSI, IIEF-5, HADA and HADD were 6.83 +/- 4.96, 21.03 +/- 2.54, 6.05 +/- 1.62, and 5.35 +/- 3.30 in the experimental group, as compared with 7.55 +/- 4.89, 17.68 +/- 4.15, 6.88 +/- 2.45, and 7.85 +/- 3.77 in the control (P < 0.05). The rate of effectiveness was significantly higher in the experimental than in the control group (90% [36/40] vs 70% [28/40], P < 0.05). Shuganyiyang Capsule combined with conventional Western medicine, such as alpha blockers and galenica, produces definite effect on chronic prostatitis complicated by ED, improves the psychological conditions of the patient, and enhances the therapeutic efficiency of chronic prostatits.

77 FR 7167 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel Multi-Center Study of Tamsulosin for Ureteral Stones in the Emergency Department. Date: March 26, 2012. Time: 11 a.m. to 12 p.m. Agenda: To...

Various treatment options for benign prostatic hyperplasia: A current update

PubMed Central

Shrivastava, Alankar; Gupta, Vipin B.

2012-01-01

In benign prostatic hyperplasia (BPH) there will be a sudden impact on overall quality of life of patient. This disease occurs normally at the age of 40 or above and also is associated with sexual dysfunction. Thus, there is a need of update on current medications of this disease. The presented review provides information on medications available for BPH. Phytotherapies with some improvements in BPH are also included. Relevant articles were identified through a search of the English-language literature indexed on MEDLINE, PUBMED, Sciencedirect and the proceedings of scientific meetings. The search terms were BPH, medications for BPH, drugs for BPH, combination therapies for BPH, Phytotherapies for BPH, Ayurveda and BPH, BPH treatments in Ayurveda. Medications including watchful waitings, Alpha one adrenoreceptor blockers, 5-alpha reductase inhibitors, combination therapies including tamsulosin-dutasteride, doxazosin-finasteride, terazosin-finasteride, tolterodine-tamsulosin and rofecoxib-finasteride were found. Herbal remedies such as Cernilton, Saxifraga stolonifera, Zi-Shen Pill (ZSP), Orbignya speciosa, Phellodendron amurense, Ganoderma lucidum, Serenoa Repens, pumpkin extract and Lepidium meyenii (Red Maca) have some improvements on BPH are included. Other than these discussions on Ayurvedic medications, TURP and minimally invasive therapies (MITs) are also included. Recent advancements in terms of newly synthesized molecules are also discussed. Specific alpha one adrenoreceptor blockers such as tamsulosin and alfuzosin will remain preferred choice of urologists for symptom relief. Medications with combination therapies are still needs more investigation to establish as preference in initial stage for fast symptom relief reduced prostate growth and obviously reduce need for BPH-related surgery. Due to lack of proper evidence Phytotherapies are not gaining much advantage. MITs and TURP are expensive and are rarely supported by healthcare systems. PMID:22923974

Molecular cloning and functional expression of the guinea pig alpha(1a)-adrenoceptor.

PubMed

González-Espinosa, C; Romero-Avila, M T; Mora-Rodríguez, D M; González-Espinosa, D; García-Sáinz, J A

2001-08-31

In the present paper, the cloning and expression of the guinea pig alpha(1A)-adrenoceptor is presented. The nucleotide sequence had an open reading frame of 1401 bp that encoded a 466 amino-acid protein with an estimated molecular mass of approximately 51.5 kDa. When the clone was expressed in Cos-1 cells, specific high-affinity binding of [(3)H]prazosin and [(3)H]tamsulosin was observed. Chloroethylclonidine treatment of membranes slightly decreased the total binding with both radioligands. Binding competition experiments using [(3)H]tamsulosin showed the following potency order: (a) for agonists: oxymetazoline >epinephrine>norepinephrine>methoxamine, and (b) for antagonists: prazosin> or 5-methyl-urapidil=benoxathian>phentolamine>BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione). Photoaffinity labeling using [(125)I-aryl]azido-prazosin revealed a major broad band with a molecular mass between 70 and 80 kDa. The receptor was functional, as evidenced by an epinephrine-increased production of [(3)H]inositol phosphates that was blocked by prazosin.

Silodosin: treatment of the signs and symptoms of benign prostatic hyperplasia.

PubMed

Curran, Monique P

2011-05-07

Silodosin is an α-adrenoceptor antagonist with high selectivity for α(1A)- relative to α(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving the total IPSS. Silodosin was significantly more effective than placebo (all three phase III trials) and tamsulosin (European phase III trial) in simultaneously improving nocturia, frequency and incomplete emptying, according to a post hoc analysis. Long-term, open-label extension trials demonstrated that silodosin provided sustained relief of the signs and symptoms of BPH for up to 1 year. Silodosin was generally well tolerated, and was associated with minimal cardiovascular adverse effects. Abnormal ejaculation, a class effect of α(1A)-adrenoceptor antagonists, was the most common silodosin-associated adverse reaction, but resulted in treatment withdrawal of only a limited number of patients. © 2011 Adis Data Information BV. All rights reserved.

[Intraoperative floppy iris syndrome after treatment with duloxetine: coincidence, association, or causality?].

PubMed

González-Martín-Moro, J; González-López, J J; Zarallo-Gallardo, J; Fernández-Miguel, Y

2015-02-01

The case is presented of a severe Intraoperative Floppy Iris Syndrome (IFIS) in a patient that had been treated with duloxetine. Tamsulosin is the main etiological agent involved in IFIS. However several cases of IFIS, supposedly secondary to drugs of different groups have recently been reported in the literature. The authors use this case report as a means to discuss why most of these cases should be considered anecdotal evidence. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

[Profile of silodosin].

PubMed

Montorsi, Francesco

2013-01-01

Silodosin is a highly selective alpha1A-adrenoceptor antagonist approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. Its clinical pharmacology profile offers a number of advantages, including uroselectivity, once-daily (QD) dosing, a standard dose of 8 mg QD that does not need to be adjusted according to age, and the feasibility of concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors and antihypertensive agents. Three phase 3 double-blind, randomised trials using the dosage regimen of 8 mg QD in > 800 patients have shown that silodosin is significantly more effective than placebo (p < 0.001) and at least as effective as tamsulosin (0.4 mg QD) in improving International Prostate Symptom Score (IPSS) total score, storage subscore, and voiding subscore. It is significantly more effective than tamsulosin in inducing simultaneous improvement of bothersome lower urinary tract symptoms such as incomplete emptying, frequency, and nocturia (p = 0.03). Safety data collected in 1581 patients exposed to chronic treatment with silodosin 8 mg QD have shown that the drug is safe and well tolerated. As was to be expected with a uroselective compound, cardiovascular effects have been minimal. The most common adverse reaction is "retrograde ejaculation" (anejaculation), which led to treatment discontinuation in only 3.9% of patients. The rare, drug class-related safety issue of intraocular floppy iris syndrome can be satisfactorily managed by warning patients simply to inform their ophthalmologist that they are or were on treatment with an alpha1-adrenoceptor blocker.

α1-Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a prospective randomized study.

PubMed

Minardi, Daniele; Pellegrinelli, Francesco; Conti, Alessandro; Fontana, Donatella; Mattia, Michela; Milanese, Giulio; Muzzonigro, Giovanni

2015-01-01

To evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding. A total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), α1-adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with α1-adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures. The incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post-void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up. In women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life. © 2014 The Japanese Urological Association.

Efficacy of phosphodiesterase type 5 inhibitors for the treatment of distal ureteral calculi: A systematic review and meta-analysis

PubMed Central

García-Perdomo, Herney Andrés

2017-01-01

Purpose To determine the efficacy of phosphodiesterase type 5 inhibitors (PDE5i) as medical expulsive therapy (MET) for the treatment of distal ureteral calculi. Materials and Methods A search strategy was conducted in the MEDLINE, CENTRAL, and Embase databases. Searches were also conducted in other databases and unpublished literature. Clinical trials were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. An analysis of random effects due to statistical heterogeneity was conducted. The primary outcome was the expulsion rate of the distal ureteral calculus in 28 days. The secondary outcomes were the time to expulsion, side effects of treatment, and amount (mg) of nonopioid analgesia. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were PDE5i vs. placebo, tadalafil vs. placebo, and tadalafil vs. tamsulosin. Results Four articles were included in the qualitative and quantitative analysis. Records of 580 patients were found among the four studies. A low risk of bias was shown for the majority of the study items. The calculi expulsion rate had an RD of 0.26 (95% CI, 0.15–0.37) and a less prolonged expulsion as a secondary outcome with a mean difference of -4.39 days (95% CI, -6.69 to -2.09) in favor of PDE5i compared with the placebo. No significant difference was found for these outcomes when comparing tadalafil with tamsulosin. Conclusions Compared with a placebo, PDE5i could be effective as MET for the treatment of distal ureter calculi. PMID:28261676

Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard?

PubMed

Silva, João; Silva, Carlos Martins; Cruz, Francisco

2014-01-01

The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is based on alpha-blockers and 5α-reductase inhibitors isolated or in combination. Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical paradigm is being challenged by antimuscarinics, 5-phosphodiesterase inhibitors (PDE5i) and β3-adrenoreceptor agonists. Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head comparison of tadalafil 5 mg/day with tamsulosin 0.4 mg/day showed that these agents provided the same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact, previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not tamsulosin improved sexual function. Mirabegron, the first β3-adrenoreceptor agonist, while improving BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure. The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination. In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept of standard treatment for BPH/LUTS.

Medication Effects on Periurethral Sensation and Urethral Sphincter Activity

PubMed Central

Greer, W. Jerod; Gleason, Jonathan L.; Kenton, Kimberly; Szychowski, Jeff M.; Goode, Patricia S; Richter, Holly E

2014-01-01

Aim To characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to one of six medications for 2 weeks (pseudoephedrine ER 120mg, imipramine 25mg, cyclobenzaprine 10mg, tamsulosin 0.4mg, solifenacin 5mg or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle EMG (CNE) of the urethral sphincter using automated Multi-Motor Unit Action Potential (MUP) software; current perception threshold (CPT) testing to measure periurethral sensation; and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results 56 women had baseline testing; 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean 34.3 ± 10.1), BMI (mean 31.8 ± 7.5), parity (median 1, range 0–7), or race (14% Caucasian, 80% African American). PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5 Hz stimulation level, was observed following treatment with pseudoephedrine (0.15 to 0.09 mA at 5Hz; P=0.03). Conclusion In women without LUTS, pseudoephedrine improved urethral sensation, but not urethral neuromuscular function on CNE or pressure flow studies. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function. PMID:25185603

[Ejaculatory disorders except premature ejaculation, orgasmic disorders].

PubMed

Rigot, J-M; Marcelli, F; Giuliano, F

2013-07-01

Disorders of ejaculation and orgasm apart from premature ejaculation are pretty uncommon. Medical literature was reviewed and combined with expert opinion of the authors. The semiology of these disorders is essential: aspermia, hypospermia, retrograde ejaculation, delayed or absent ejaculation with or without orgasm. Whether this is a lifelong or acquired condition, it is essential to assess the side-effects of medications i.e. psychotropic drugs, including antidepressant, neuroleptics, tramadol, alphablockers: tamsulosin and silodosin must always be surveyed. The management is often difficult, especially with a parenthood perspective. The management of lifelong disorders must rely on psychosexual therapies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Open-label, 9-month extension study investigating the uro-selective alpha-blocker silodosin in men with LUTS associated with BPH.

PubMed

Osman, Nadir I; Chapple, Christopher R; Tammela, Teuvo L; Eisenhardt, Andreas; Oelke, Matthias

2015-05-01

To evaluate the long-term safety (primary objective) and efficacy/impact on quality of life (QoL, secondary objectives) of silodosin 8 mg once daily in men with LUTS/BPH. Men who completed the 12-week double-blind study with silodosin 8 mg, tamsulosin 0.4 mg, or placebo were offered to continue with the 9-month open-label study during which all patients received silodosin 8 mg once daily. Safety was assessed by analysing vital signs, electrocardiograms, laboratory tests, and adverse events. Efficacy was evaluated with the International Prostate Symptom Score (IPSS), IPSS voiding and storage sub-scores, IPSS-QoL, and maximum urinary flow rate (Q max). A total of 500 patients (mean age 66 years) entered the 9-month open-label study. Treatment-emergent adverse events (TEAE) were experienced by 33.4% patients. Ejaculation dysfunction was the most common TEAE (9.0%) but led to study discontinuations in only 1.6% of patients. Dizziness without orthostatic hypotension occurred in 0.8%. A marked reduction in total IPSS (-2.7 ± 3.8) was documented at the first visit of this extension phase in patients having de novo silodosin compared with lesser improvement in patients previously treated with silodosin (-0.82 ± 4.2) or tamsulosin (-0.83 ± 3.8). Improvements were maintained throughout the open-label phase. QoL also improved, with the greatest improvement in de novo silodosin patients. No relevant changes in Q max occurred. Long-term treatment with silodosin was safe and efficacious. Abnormal ejaculation was the most common TEAE, but led to treatment discontinuation in only 1.6% of patients. Orthostatic hypotension was not seen, and only a few patients experienced dizziness.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Alpha blockers v calcium blockers to increase spontaneous passage of renal calculi.

PubMed

Stewart, Alexander; Ferguson, Craig

2013-02-01

A short cut review was carried out to establish the administration of an alpha-1 receptor antagonist or a calcium channel blocker would facilitate the most rapid and successful expulsion of a stone from a patient with uncomplicated renal colic. 597 articles were found using the reported search, of which five trials were selected as providing the best evidence to answer this question. The authors, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that in a patient with an uncomplicated ureteric calculus tamsulosin is more effective than nifedipine in promoting speedy and successful expulsion of the stone.

Systematic Review of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Zhou, Jing; Liu, Zhishun

2016-01-01

Abstract Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The aim of the study was to assess the effects and safety of the use of acupuncture for CP/CPPS. MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wang-Fang Database, JCRM, and CiNii were searched from their inception through 30 November 2015. Grey literature databases and websites were also searched. No language limits were applied. Only randomized controlled trials (RCTs) with CP/CPPS treated by acupuncture were included. Two reviewers extracted data and assessed the risk of bias of RCTs using the Cochrane Risk of Bias Tools, respectively. Seven trials were included, involving 471 participants. The result of meta-analysis indicated that compared with sham acupuncture (MD: −6.09 [95%CI: −8.12 to −5.68]) and medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) (MD: −4.57 [95%CI: −7.58 to −1.56]), acupuncture was more effective at decreasing the total NIH-CPSI score. Real acupuncture was superior to sham acupuncture in improving symptoms (pain, voiding) and quality of life (Qof) domain subscores. Compared to sham acupuncture and medicine, acupuncture appears to be more effective at improving the global assessment. Two trials found that there is no significant difference between acupuncture and sham acupuncture in decreasing the IPSS score. Acupuncture failed to show more favorable effects in improving both symptoms and the Qof domain compared with medicine. Overall, current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Based on the meta-analysis, acupuncture is superior to sham acupuncture in improving symptoms and Qof. Acupuncture might be similar to medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) in its long-term effects, but evidence was limited due to high ROB among included trials as well as

The effect of sodium alginate on physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer.

PubMed

Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

2007-11-01

The aim of this study was to investigate the effect of sodium alginate on the physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The mean values of the shape factor (e(R)) and the aspect ratio of Surelease-matrix pellets were 0.615-0.625 and 1.06-1.070, respectively, indicating good sphericity of the pellets. The drug release rate increased as the amount of sodium alginate increased due to hydration, swelling, and erosion within the Surelease-matrix pellets. In addition, the porosity of pellets also increased with increasing sodium alginate content. The results of this study show that sodium alginate has a greater effect on the drug release rate than the drug release mechanism within the Surelease-matrix for sparingly water-soluble drug, such as tamsulosin hydrochloride.

Efficacy of α-Adrenergic Receptor Blockers in the Treatment of Male Lower Urinary Tract Symptoms

PubMed Central

Roehrborn, Claus G

2009-01-01

Male lower urinary tract symptoms (LUTS) are one of the most common causes for a consultation with a health care provider, and one of the most common causes of male LUTS is benign prostatic hyperplasia (BPH). In recent decades, medical therapy has established itself as viable and cost effective for the majority of men. For the treatment of male LUTS in the United States, the 5 currently available α-adrenergic receptor blockers are alfuzosin, doxazosin, silodosin, terazosin, and tamsulosin. α-Blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit an early onset of efficacy (within less than 1 week) with regard to both symptoms and flow rate improvement, maintain such improvements in open-label and controlled trials for up to 5 years, and have been shown to prevent symptomatic progression. PMID:20126606

Saw palmetto and benign prostatic hyperplasia.

PubMed

Gong, Edward M; Gerber, Glenn S

2004-01-01

Benign prostatic hyperplasia (BPH) is a common health issue that affects 8% of all men at the age of 40, 60% of men in their 70s, and 90% of those greater than 80 years of age. One-fourth of these men will develop moderate to severe lower urinary tract symptoms that greatly affect their quality of life. Recent evidence suggests that the use of saw palmetto leads to improvements in urinary function for those suffering from BPH. The favorable comparison of saw palmetto with tamsulosin, a well-known first line agent in the treatment of urinary tract symptoms, demonstrates promise towards a beneficial effect of this herbal agent, with very few, if any, adverse effects. However, what degree of this beneficial activity is due to placebo effects is yet to be determined. In addition, the precise mechanism of action of saw palmetto in men with BPH remains unclear.

Prostate cell membrane chromatography-liquid chromatography-mass spectrometry for screening of active constituents from Uncaria rhynchophylla.

PubMed

He, Jianyu; Han, Shengli; Yang, Fangfang; Zhou, Nan; Wang, Sicen

2013-01-01

Uncaria rhynchophylla is a traditional Chinese medicinal herb used to treat hypertension and convulsive disorders such as epilepsy. Rat prostate cell membrane chromatography combined with liquid chromatography-mass spectrometry (LC-MS) was used to identify active constituents from U. rhynchophylla extracts. Four compounds (corynoxeine, isorhynchophylline, isocorynoxeine and rhynchophylline) were discovered. Competitive binding assay results indicated that the four compounds were in direct competition at a single common binding site and interacted with α1A adrenergic receptors (α1A-AR) in a manner similar to tamsulosin. Affinity constant values of the four compounds binding with α1A-AR were also measured using rat prostate cell membrane chromatography (CMC). Finally, their pharmacodynamic effects were tested on rat caudal arteries. This CMC combined LC-MS system offers a means of drug discovery by screening natural medicinal herbs for new pharmacologically active molecules targeting specific receptors.

Evolving Guidance on Ureteric Calculi Management in the Acute Setting.

PubMed

Makanjuola, Jonathan K; Rintoul-Hoad, Sophie; Bultitude, Matthew

2016-03-01

Ureteric colic is a common presentation to acute emergency services. The gold standard test for the diagnosis of acute ureteric colic is a non-contrast computer tomography of the kidneys ureters and bladder (CT KUB). Non-steroidal anti-inflammatory drugs (NSAIDs) should be used as first-line analgesia, with studies showing that there is no role for steroid or phosphodiesterase-5 inhibitors. There is emerging evidence that a high body mass index (BMI) is a risk factor. The drugs used to facilitate stone passage are known as medical expulsive therapy (MET). The most evaluated being alpha-blockers. The Spontaneous Urinary Stone Passage Enabled by Drugs (SUSPEND) trial was designed to evaluate the use of MET (tamsulosin and nifedipine). This trial showed that there was no difference with MET and placebo for the spontaneous passage of ureteric stones. There is an emerging role for the use of primary ureteroscopy in the management of non-infective ureteric stones.

The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study

PubMed Central

McArthur, Eric; Fraser, Lisa-Ann; Hayward, Jade; Dixon, Stephanie; Hwang, Y Joseph; Ordon, Michael

2015-01-01

Study question Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? Methods Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147 084 men aged ≥66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. Study answer and limitations The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs

The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study.

PubMed

Welk, Blayne; McArthur, Eric; Fraser, Lisa-Ann; Hayward, Jade; Dixon, Stephanie; Hwang, Y Joseph; Ordon, Michael

2015-10-26

Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147,084 men aged ≥ 66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥ 66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs. Prostate-specific α antagonists are associated with

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-06-01

(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates.

PubMed

Capitanio, U; Salonia, A; Briganti, A; Montorsi, F

2013-06-01

As the clinical effects of the available α1-adrenoceptors (ARs) blockers are usually considered comparable for treatment in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic enlargement, officially recognised guidelines do not make specific recommendations regarding the choice of which agent should be considered according to the patient's characteristics. To analyse data supporting the use of silodosin, a highly selective once-daily dosing α1-ARs blocker, in different daily clinical practice scenarios. A structured literature review was performed using data retrieved from articles assessing the role of silodosin in the management of LUTS secondary to benign prostatic hyperplasia (BPH). A literature search of English language publications was performed using MEDLINE(®) and Web of Science from 2000 to 2012 using the terms LUTS; BPH; silodosin; α1-ARs blockers. The papers with the highest level of evidence were identified and represent the basis of the present review. Available data coming from basic research analyses, randomised trials and prospective studies showed that silodosin is efficacious for the initial management of patients with LUTS. Clinical developmental safety data from patients receiving silodosin with concomitant antihypertensive therapy do not indicate an increase in risk of orthostatic hypotension. In this context, a recent study demonstrated that silodosin can be safely administered to patients who are consensually assuming phosphodiesterase type 5 inhibitors. A recent randomised crossover study comparing the efficacy of silodosin and tamsulosin in patients with LUTS showed that further significant improvement was observed after switching to silodosin treatment, while worsening or little improvement was observed after switching to tamsulosin treatment. Preliminary results seem to demonstrate a potential role of silodosin in the treatment of chronic prostatitis/chronic pelvic pain syndrome and to facilitate

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon® ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): Systematic review and meta-analysis of randomized controlled trials and observational studies.

PubMed

Vela-Navarrete, Remigio; Alcaraz, Antonio; Rodríguez-Antolín, Alfredo; Miñana López, Bernardino; Fernández-Gómez, Jesús M; Angulo, Javier C; Castro Díaz, David; Romero-Otero, Javier; Brenes, Francisco J; Carballido, Joaquín; Molero García, José M; Fernández-Pro Ledesma, Antonio; Cózar Olmos, José Manuel; Manasanch Dalmau, José; Subirana Cachinero, Isaac; Herdman, Michael; Ficarra, Vincenzo

2018-04-25

To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon), at a dose of 320 mg daily, as monotherapy for the treatment of LUTS/BPH. Systematic review and meta-analysis of randomized and observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge [ISI], Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data was collected on IPSS score, peak urinary flow (Qmax), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADR). Data obtained from randomized controlled trials (RCT) and observational studies (OS) were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies which included patients on longer-term treatment (≥one year). Data from 27 studies (15 RCTs and 12 OS) were included for meta-analysis (total N=5,800). Compared with placebo, the HESr was associated with 0.64 (95% CI -0.98 to -0.31) fewer voids per night (p=0.0001) and an additional mean increase in Qmax of 2.75 mL/s (95% CI 0.57 to 4.93; p=0.01). When compared with alpha-blockers, the HESr showed similar improvements on IPSS (WMD 0.57; 95%CI, -0.27 to 1.42; p=0.18) and a comparable increase in Qmax to tamsulosin (WMD -0.02; 95%CI, -0.71 to 0.66; p=0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5ARIs. Analysis of all available published data for the HESr showed a mean improvement in IPSS score from baseline of -5.73 points (95% CI -6.91 to -4.54; p<0.0001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on PSA. Prostate volume decreased slightly. Similar efficacy results were observed in patients treated for ≥1 year (n=447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

PubMed

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-08-11

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

PubMed Central

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-01-01

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

Plant extracts: sense or nonsense?

PubMed

Madersbacher, Stephan; Berger, Ingrid; Ponholzer, Anton; Marszalek, Martin

2008-01-01

To assess the current role of plant extracts in the medical management of lower urinary tract symptoms due to benign prostatic enlargement/benign prostatic obstruction. In 2006, two clinical trials meeting the WHO benign prostatic hyperplasia consensus conference criteria (randomized against placebo/standard therapy, study duration 12 months) were published. One trial compared a saw palmetto extract with placebo. This industry-independent trial published in the New England Journal of Medicine was negative, that is, this saw palmetto extract had no effect on symptoms, Qmax and postvoid residual volume. In another trial, a saw palmetto/urtica combination was compared with tamsulosin. After 12 months, the improvement of symptoms was identical in both study arms. No detailed data were presented, however, on Qmax, postvoid residual or prostate volume. The biological mechanisms of plant extracts in vivo are still unknown and the numerous metaanalyses cannot supplement high-quality prospective trials. Further prospective studies according to WHO benign prostatic hyperplasia standards are required to reliably determine the role of plant extracts in contemporary lower urinary tract symptoms management and to be able to answer the question in the title: 'plant extracts: sense or nonsense?' Plant extracts are currently not recommended by the American and European Association of Urology benign prostatic hyperplasia guidelines.

[Posterior capsule opacification, capsular bag distension syndrome, and anterior capsular phimosis: A retrospective cohort study].

PubMed

González-Martín-Moro, J; González-López, J J; Gómez-Sanz, F; Zarallo-Gallardo, J; Cobo-Soriano, R

2015-02-01

To determine the incidence and the risk factors involved in the development of the three main postoperative capsular complications: posterior capsule opacification (PCO), capsular bag distension syndrome (CBDS), and anterior capsular phimosis syndrome (ACP). A retrospective cohort study was conducted on 801 patients submitted to cataract surgery in the ophthalmology unit of Hospital del Henares (Madrid) from March 2, 2009 to February 28, 2010. Computerized clinical charts were reviewed during July 2012. PCO was studied using the Kaplan-Meier method (log rank test). A total of 167 patients developed PCO. No association could be demonstrated between PCO and age, sex, diabetes mellitus, phaco technique, IOL model, tamsulosin intake, glaucoma, and age-related macular degeneration. Three patients developed CBDS, all of them have received and Akreos Adapt AO(®) (Bausch & Lomb). Two of them were young men who had received surgery for posterior subcapsular cataracts. Three patients developed ACP, 2 of whom had received a MicroSlim(®) IOL (PhysIOL). No association was found between PCO and any of the studied variables. Male gender, young age, subcapsular cataract and large non-angulated lens such as Akreos Adapt AO(®) could be associated with CBDS. ACP could be more frequent when microincision IOLs (like MicroSlim(®)) are implanted. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Benign Prostatic Hyperplasia: from Bench to Clinic

PubMed Central

Cho, Hee Ju

2012-01-01

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

A pharmacoepidemiological approach to investigating inappropriate physician prescribing in a managed care setting in Israel.

PubMed

Kahan, Natan R; Blackman, Shimon; Kutz, Chaim; Waitman, Dan-Andrei

2005-02-01

To identify cases of inappropriate physician prescribing in a managed care setting in Israel that may have resulted from misuse of magnetic-stripe membership cards. Retrospective drug utilization analysis of electronic patient prescription data. In a managed care setting involving approximately 1000 physicians who issue approximately 1.4 million prescriptions annually, the rate of prescription of sex-specific drugs to patients of the opposite sex for which the drugs are indicated was evaluated for 2003. The categories of drugs included in the analysis were drugs for the treatment of benign prostatic hyperplasia or erectile dysfunction that were prescribed to women, as well as oral contraceptives, vaginal pessaries, hormone therapy, or raloxifene hydrochloride prescribed to men. Throughout the study year, 193 different physicians wrote 341 prescriptions that matched the drug inclusion criteria for 210 different patients. The most frequently observed scenario involved the prescription for women of selective alpha-blockers, including alfuzosin hydrochloride, tamsulosin hydrochloride, and terazosin hydrochloride, that are indicated exclusively for the treatment of benign prostatic hyperplasia. The electronic patient record system used in the health maintenance organization studied was programmed to block the prescription of sex-specific drugs for patients of the opposite sex for which they are intended unless proper authorization has been obtained. Furthermore, periodic investigation into prescription impropriety may be easily accomplished through the implementation of pharmacoepidemiological methods commonly used in drug utilization studies.

Benign prostatic hyperplasia and lower urinary tract symptoms. A review of current evidence.

PubMed

Carrero-López, V M; Cózar-Olmo, J M; Miñana-López, B

2016-06-01

The treatment of benign prostatic hyperplasia (BPH) is changing due to a greater understanding of the disease and the development of the functional concept of lower urinary tract symptoms (LUTS). To describe the current state of BPH and the diagnosis and treatment of LUTS. We summarise the issues presented and debated by a group of expert urologists during the First UROVI Congress, sponsored by the Spanish Urological Association. LUTS encompasses filling, voiding and postvoiding symptoms that affect patients' quality of life. The aetiological diagnosis is an important element in starting the most ideal treatment. For this reason, new alternative therapies (both pharmacological and surgical) are needed to help individually address the symptoms in the various patient profiles. There is now a new combination of drugs (6mg of solifenacin and 0.4mg of the tamsulosin oral controlled absorption system) for treating moderate to severe filling symptoms and emptying symptoms associated with BPH in patients who do not respond to monotherapy. Furthermore, new surgical techniques that are increasingly less invasive help provide surgical options for older patients and those with high comorbidity. The availability of drugs that can act on the various LUTS helps integrate the pathophysiological paradigm into the functional one, providing more appropriate treatment for our patients. Copyright © 2016. Publicado por Elsevier España, S.L.U.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, Xianjin; Zhong, Shan; Xu, Tianyuan; Xia, Leilei; Zhang, Xiaohua; Zhu, Zhaowei; Zhang, Minguang; Shen, Zhoujun

2015-02-01

A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.

Intraoperative floppy iris syndrome and its association with various concurrent medications, bulbus length, patient age and gender.

PubMed

Wahl, Michael; Tipotsch-Maca, Saskia M; Vecsei-Marlovits, Pia V

2017-01-01

To evaluate the association between intraoperative floppy iris syndrome (IFIS) and concurrent medications containing selective alpha1A receptor antagonists as well as nonselective alpha1-adrenergic receptor antagonists, bulbus length, patient age and gender. We performed a prospective data acquisition of IFIS occurrence and grading, and retrospective evaluation of concurrent medications, bulbus length, patient age and gender of all patients undergoing cataract surgery over a 6-month period. IFIS was observed in 119 of 947 cases (12.6 %). 31 of those 119 patients (26.1 %) had a concurrent medication with a drug that is associated with a higher risk of causing IFIS. Tamsulosin was the drug most commonly associated with IFIS (n = 11), followed by a combination of drugs (n = 7), doxazosin (n = 4), quetiapine (n = 4), finasterid (n = 2), prothipendyl (n = 2), and mianserin (n = 1). Bulbus length and age did not show any significant association with occurrence or grade of IFIS. Gender distribution among IFIS cases was 57.1 % males (n = 68) and 42.9 % (n = 51) females. The occurrence of IFIS has to be expected with a variety of concurrent medications. The number of IFIS cases and the percentage of females in this series are higher compared to previous reports. The observations might be due to a rising awareness of surgeons or to an increasing number of causative medications on the market.

Saw palmetto extracts potently and noncompetitively inhibit human alpha1-adrenoceptors in vitro.

PubMed

Goepel, M; Hecker, U; Krege, S; Rübben, H; Michel, M C

1999-02-15

We wanted to test whether phytotherapeutic agents used in the treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic properties in vitro. Preparations of beta-sitosterol and extracts of stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several pharmaceutical companies. They were tested for their ability to inhibit [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was also investigated. Up to the highest concentration which could be tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin were without consistent inhibitory effect in all assays. In contrast, all tested saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors and agonist-induced [3H]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active concentrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha1-adrenoceptor antagonists. Saw palmetto extracts have alpha1-adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

Benign prostatic hyperplasia (BPH) management in the primary care setting.

PubMed

Kapoor, Anil

2012-10-01

Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH.

Gateways to Clinical Trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2002-09-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil

Minimal Rectal Toxicity in the Setting of Comorbid Crohn's Disease Following Prostate Cancer Radiotherapy with a Hydrogel Rectal Spacer.

PubMed

Singh, Raj; Jackson, Philip S; Blake, Mollie; Cutlip, James; Sharma, Sanjeev

2017-08-01

We present one of the first cases of a prostate cancer (PCa) patient with inflammatory bowel disease (IBD) treated with intensity-modulated radiotherapy (IMRT) and a hydrogel rectal spacer. A 73-year-old male with a past medical history significant for Crohn's disease (CD) and the recent diagnosis of T1cN0M0 high-risk PCa was referred for definitive radiotherapy. Given the patient's history of CD and the possible increased risk of gastrointestinal (GI) toxicity and disease exacerbation, prior to IMRT, a hydrogel spacer was placed between the prostate and the anterior rectal wall to further minimize irradiation to the rectum. The patient then received IMRT (78 Gy/2 Gy fractions at a 100 percent isodose line). Over the course of treatment, Radiation Therapy Oncology Group (RTOG) Grade 1 GI toxicities of mild diarrhea were noted during the fifth and sixth weeks of treatment as well as an RTOG Grade 1 genitourinary (GU) toxicity of a decrease in the urinary stream that resolved with tamsulosin. At the 3, 6, 9, and 12-month follow-ups, bowel movements and urinary stream were reported to be at baseline with prostate-specific antigen (PSA) levels of 0.18 ng/mL and 0.03 ng/mL at the three and nine-month follow-ups, respectively. As such, this case report suggests that IBD patients with localized PCa may be viable candidates for radiotherapy given the promising results of hydrogel spacers in combination with IMRT in limiting rectal toxicity.

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia.

PubMed

Kawahara, Takashi; Morita, Satoshi; Ito, Hiroki; Terao, Hideyuki; Sakata, Ryoko; Ishiguro, Hitoshi; Tanaka, Katsuyuki; Miyamoto, Hiroshi; Matsuzaki, Junichi; Kubota, Yoshinobu; Uemura, Hiroji

2013-06-12

Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.

Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested?

PubMed

Nderitu, Paul; Van Hemelrijck, Mieke; Ashworth, Mark; Mathur, Rohini; Hull, Sally; Dudek, Alexandra; Chowdhury, Simon

2016-07-12

To investigate the association between factors influencing prostate-specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. Men aged ≥40 years without prostate cancer were included (n=150 481). Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. PSA testing prevalence was 8.2% (2013-2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70-74 years compared to 40-44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. 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/

The detection and upgrade rates of prostate adenocarcinoma following transperineal template-guided prostate biopsy – a tertiary referral centre experience

PubMed Central

Telford, Robert; Viney, Richard; Patel, Prashant

2016-01-01

Introduction We aim to present transperineal template-guided prostate biopsy (template biopsy) outcomes at a tertiary referral centre. Furthermore, to identify the detection rate of prostate cancer in those with a previous negative transrectal ultrasound guided prostate biopsy and the upgrade rate of those on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma. Material and methods We conducted a prospective study of 200 consecutive men who underwent template biopsy over a 22-month period in a tertiary referral centre, using a standard 24 region template prostate biopsy technique. Indications and histology results, as well as complications, were recorded. Results Median age was 67 years and median PSA was 10 ng/mL. Overall detection rate was 47%. 39.5% of cases with previous negative transrectal biopsies were found to have prostate adenocarcinoma. 47.5% of cases on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma were upgraded. The most frequent complication was acute urinary retention at a rate of 12.5%, however, the use of a single prophylactic dose of tamsulosin was found to be beneficial, with 13 cases needed to treat to prevent one episode. Conclusions Template biopsies are safe and efficacious with an overall detection rate of 47% in the present series. Due to the high detection rate, one must consider template biopsy following one negative transrectal biopsy where there is persistent clinical suspicion. Furthermore, those considering active surveillance for Gleason 3 + 3 = 6 disease should be offered template biopsy to confirm the grade of their disease. PMID:27123325

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia

PubMed Central

2013-01-01

Background Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Methods Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. Results The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Conclusions Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH. PMID:23758651

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

PubMed

Oelke, Matthias; Becher, Klaus; Castro-Diaz, David; Chartier-Kastler, Emmanuel; Kirby, Mike; Wagg, Adrian; Wehling, Martin

2015-09-01

we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Management of benign prostatic hyperplasia with silodosin

PubMed Central

Yamanishi, Tomonori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro; Sakakibara, Ryuji; Uchiyama, Tomoyuki

2009-01-01

It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (−)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B-and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia. PMID:24198606

Evaluation of apoptosis indexes in currently used oral alpha- blockers in prostate: a pilot study

PubMed Central

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. PMID:29617082

Efficacy of an alpha1 blocker in expulsive therapy of lower ureteral stones.

PubMed

Wang, Chung-Jing; Huang, Shi-Wei; Chang, Chien-Hsing

2008-01-01

To evaluate the clinical role of an alpha(1a-1d)-specific blocker in the medical expulsive therapy of symptomatic lower ureteral stones. This prospective study was carried out from May 2005 to December 2006 and involved 95 patients. All patients, who had symptomatic lower ureteral stones <10 mm diameter, were enrolled in this prospective study, and were randomly divided into three groups using the statistical software programs Plus 1.0 and Plus 2.10. Group 1 (32 patients) received tamsulosin (0.4 mg daily), group 2 (32 patients) received terazosin (2 mg daily), group 3 (31 patients) acted as controls. All patients were diagnosed with x-rays of the kidneys, ureters, and bladder, urinary ultrasonography, and intravenous urography. All patients received the same analgesic regimen and sublingual buprenorphine on demand. The number of colic episodes, lower urinary tract symptoms, analgesic dosages, and the number of days required for spontaneous passage of the stones were all recorded in a diary. Expulsion was observed in 26 of 32 patients in group 1 (81%), 25 of 32 in group 2 (78%), and 17 of 31 in group 3 (55%). The average expulsion time for groups 1, 2, and 3 were 6.3, 6.3, and 10.1 days, respectively. Mean analgesic dosage per patient in groups 1, 2, and 3 were 231, 256, and 347 mg, respectively. A statistically significant difference was observed between groups 1 and 2 with respect to group 3 for all three of these parameters. Adverse effects were also seen in 5 of 32 patients in group 2 (16%), a statistically significant difference with regard to groups 1 and 3. Medical treatment with alpha(1a-1d)-blocker proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced expulsion time, as well as the need for analgesics.

Adrenoceptor function and expression in bladder urothelium and lamina propria.

PubMed

Moro, Christian; Tajouri, Lotti; Chess-Williams, Russ

2013-01-01

To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study.

PubMed

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Patients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analysis in Java were used for evaluations. Statistical significant p was p<0.05. There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statistical significant difference apoptosis index in immunochemical TUNEL dyeing and image software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. Copyright® by the International Brazilian Journal of Urology.

Sexual function in hypertensive patients receiving treatment.

PubMed

Reffelmann, Thorsten; Kloner, Robert A

2006-01-01

oxide donor (nitrates) is absolutely contraindicated in combination with phosphodiesterase 5 inhibitors, due to significant, potentially life threatening hypotension. Also, a-adrenoceptor blockers, such as doxazosin, terazosin and tamsulosin, should only be combined with phosphodiesterase 5 inhibitors with special caution and close monitoring of blood pressure.

The Use of Medical Expulsive Therapy During Pregnancy: A Worldwide Perspective Among Experts.

PubMed

Lloyd, Granville L; Lim, Amy; Hamoui, Nabeel; Nakada, Stephen Y; Kielb, Stephanie J

2016-03-01

Medical expulsive therapy (MET) is a pharmacologic approach thought to augment the spontaneous passage of ureteral calculi. The usage of MET pharmacologics for presumed ureteral calculi during pregnancy has not been studied and their safety and utility are unknown. We sought to characterize the worldwide usage of MET in the setting of pregnancy with presumed ureteral calculus (P-MET), as well as factors associated with physician use. Experts in stone management were specifically sought. A nine-question survey was delivered through society-administered e-mail. Questions gathered physician's worldwide region, degree of specialization in stone disease, practice type, interval since training, and willingness to use both MET and P-MET. We assessed drugs of choice in those using P-MET and reasons for avoidance in non-P-MET users. Finally, we assessed the impact of physician-perceived medicolegal risk on usage of P-MET. Five hundred sixty-five responses were recorded. Sixty-three percent were US-based practitioners and the remaining represented a worldwide distribution. Worldwide usage of MET was 97.6%, and tamsulosin was globally preferred by over 90% of urologists. P-MET was endorsed by only 44.3%. 23.6% of European practitioners used this strategy compared with 51.1% of US physicians. Time from training and practice type did not significantly interact with adoption of P-MET; experts were less likely to use P-MET. Physician nonuse of MET during pregnancy was adverse outcome related: 76.7% reported either the fear of legal risk (52.8%) or concerns about safety (23.9%). Respondents report impressive worldwide adoption of MET. P-MET is less trusted, and fears of legal risk and safety far outweigh questions about effectiveness. The effectiveness of drugs during pregnancy-induced ureteral dilation is unknown. Still, 44% of global respondents embrace usage of this drug strategy despite a paucity of evidence supporting either safety or effectiveness during pregnancy.

Economic Outcomes Associated with a Pharmacist-Adjudicated Formulary Consult Service in a Veterans Affairs Medical Center.

PubMed

Britt, Rachel B; Hashem, Mohamed G; Bryan, William E; Kothapalli, Radhika; Brown, Jamie N

2016-09-01

Several cost analysis studies have been conducted looking at clinical and economic outcomes associated with clinical pharmacist services in a variety of health care settings. However, there is a paucity of data regarding the economic impact of clinical pharmacist involvement in formulary management at the hospital level. To evaluate economic outcomes of a pharmacist-adjudicated formulary management consult service in a Veterans Affairs (VA) medical center offering outpatient and inpatient services. This VA medical center uses a pharmacist-adjudicated formulary management system for review of restricted drug consults. A retrospective review of electronic medical records was conducted to identify restricted drug consults at this institution between January 1, 2014, and March 31, 2014. Only restricted drug consults that were not approved were included for evaluation in order to best characterize the effects of formulary interventions by pharmacists. Economic outcomes were determined as direct cost savings by comparing the cost of requested drug with the recommended drug and accounting for the cost of pharmacist review. Characteristics of consults that were not approved and pharmacist rationale were also evaluated. Of 1,802 restricted drug consults adjudicated by a pharmacist during the study period, 198 consults in 190 individual patients met criteria for inclusion and were evaluated. The most commonly requested indications were dyslipidemia, pain, and diabetes, while the most commonly requested drugs were rosuvastatin, insulin pens, tamsulosin, varenicline, ezetimibe, and rivaroxaban. The majority of consults were requested for outpatient use. Total cost savings among 195 evaluable consults was $420,324.05, while mean cost savings per consult was $2,229.43 (range: -$3,009.27-$65,982.36). The highest cost savings were seen with outpatient use. A pharmacist-adjudicated formulary consult service in a VA medical center was associated with a substantial cost savings after

A comparative, epidemiological study of acute renal colic presentations to emergency departments in Doha, Qatar, and Melbourne, Australia.

PubMed

Pathan, Sameer A; Mitra, Biswadev; Bhutta, Zain A; Qureshi, Isma; Spencer, Elle; Hameed, Asmaa A; Nadeem, Sana; Tahir, Ramsha; Anjum, Shahzad; Cameron, Peter A

2018-01-03

This study aimed to compare the epidemiology, clinical presentations, management, and outcomes of renal colic presentations in two major academic centers from geographically diverse populations: Qatar (a country in the Afro-Asian stone belt) and South-Eastern Australia (not within a stone belt). We undertook a retrospective cohort study of patients with renal colic who presented to the Hamad General Hospital Emergency Department (HGH-ED), Qatar, and The Alfred ED, Melbourne, Australia, during a period of 1 year from August 1, 2012, to July 31, 2013. Cases were identified using ICD-9-CM codes, and an electronic template was used to record the data on predefined clinical variables. A total of 12,223 from the HGH-ED and 384 from The Alfred ED were identified as renal colic presentations during the study period. The rate of renal colic presentations at the HGH-ED was 27.9 per 1000 ED visits compared to 6.7 per 1000 ED visits at The Alfred ED. Patients presenting to the HGH-ED were significantly younger [34.9 years (29.0-43.4) than The Alfred ED [48 years (37-60); P < 0.001]. The median stone size was larger in the HGH-ED group [6 (4-8) mm] versus The Alfred ED group [4 (3-6) mm, P < 0.001]. The intervention rate in the stone-positive population was significantly higher in the HGH-ED group as opposed to The Alfred ED group (38.7 versus 11.9%, P < 0.001). At the time of discharge, The Alfred ED group received fewer analgesic prescriptions (55.8 versus 83.5%, P < 0.001) and more tamsulosin prescriptions (25.3 versus 11.7%, P < 0.001). Renal colic presentations to the HGH-ED, Qatar, were younger, with larger stone size mostly located in the lower ureter, compared to The Alfred ED, Melbourne, Australia. The findings suggest that the benefits of treatment including medical expulsion therapy will vary between the two populations. Differences in epidemiology and patient mix should be considered while tailoring strategies for effective management of patients

Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

PubMed

Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

2013-01-30

Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

Efficacy and safety of PDE5-Is and α-1 blockers for treating lower ureteric stones or LUTS: a meta-analysis of RCTs.

PubMed

Sun, Xifeng; Guan, Wei; Liu, Haoran; Tang, Kun; Yan, Libin; Zhang, Yangjun; Zeng, Jin; Chen, Zhiqiang; Xu, Hua; Ye, Zhangqun

2018-05-03

Lower ureteric stones and lower urinary tract symptoms are common in urology.Drug treatment is one of standard therapy,but the efficacy was controversial.Thus we aimed to investigate the efficacy and safety of monotherapy or combination therapy of adrenoceptor1 blockers and phosphodiesterase5 inhibitors for treatment. Randomized controlled trials up to November 2016 were retrieved from PubMed, the Cochrane Library, Web of Science and Embase. A total of 17 studies were included. We analyzed data through random or fixed effect models. The heterogeneity between studies was assessed by the I 2 test statistic. As for lower ureter stones, our analysis demonstrated tadalafil had a significantly lower incidence of abnormal ejaculation than adrenoceptor1 blockers (2.31 95%CI 0.22to0.84, P = 0.01),while combination therapy had a higher expulsion rate (2.49 95%CI 1.44to4.29, P = 0.001) and shorter expulsion time (- 1.98 95%CI -3.08to0.88, P = 0.0004) than tamsulosin. As for lower urinary tract symptoms, our analysis indicated adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on decreasing International Prostate Symptom Score (1.96 95%CI 0.03to3.89, P = 0.05) and Post-Void Residual (9.41 95%CI 1.40to14.41, P = 0.02) and phosphodiesterase5 inhibitors showed a greater effect than adrenoceptor1 blockers on improving Erectile Dysfunction (2.23 95%CI 1.24to3.22, P<0.0001).Combination therapy had a significantly better effect on International Prostate Symptom Score (1.47 95%CI 1.25to1.69, P<0.0001), Maximum flow rate (0.87 95%CI 0.71to1.04, P<0.0001), Post-Void Residual (10.74 95%CI 3.53to17.96,P = 0.004) and Quality of life (0.59 95%CI 0.22to0.97, P = 0.002) but was associated with higher incidences of adverse events (3.40 95%CI 1.82to6.36, P = 0.0001) than adrenoceptor1 blockers. Combination therapy had a significantly better effect on International Prostate Symptom Score (4.19 95%CI 3.34to5.04, P<0.0001), Maximum flow

Evaluation and medical management of kidney stones in children.

PubMed

Tasian, Gregory E; Copelovitch, Lawrence

2014-11-01

We review the current literature on the diagnostic evaluation and dietary and pharmacological management of children with nephrolithiasis. We searched MEDLINE(®), Embase(®) and the Cochrane Library from their inceptions to March 2014 for published articles in English on kidney stones and therapy in children 0 to 18 years old. Based on review of the titles and abstracts, 110 of the 1,014 articles (11%) were potentially relevant to the diagnostic evaluation and medical management of nephrolithiasis in children. We summarized this literature and drew on studies performed in adult populations to augment areas in which no studies of sufficient quality have been performed in children, and to highlight areas in need of research. During the last 25 years the incidence of nephrolithiasis in children has increased by approximately 6% to 10% annually and is now 50 per 100,000 adolescents. Kidney stones that form during childhood have a similar composition to those that form in adulthood. Approximately 75% to 80% of stones are composed of predominantly calcium oxalate, 5% to 10% are predominantly calcium phosphate, 10% to 20% are struvite and 5% are pure uric acid. The recurrence rate of nephrolithiasis in patients with stones that form during childhood is poorly defined. Ultrasound should be used as the initial imaging study to evaluate children with suspected nephrolithiasis, with noncontrast computerized tomography reserved for those in whom ultrasound is nondiagnostic and the suspicion of nephrolithiasis remains high. Current treatment strategies for children with kidney stone disease are based largely on extrapolation of studies performed in adult stone formers and single institution cohort or case series studies of children. Tamsulosin likely increases the spontaneous passage of ureteral stones in children. Increased water intake and reduction of salt consumption should be recommended for all children with a history of kidney stones. Potassium citrate is a