多沙唑嗪控释片治疗前列腺增生症的对照研究

目的评价多沙唑嗪控释片、特拉唑嗪片和坦索罗辛片等3种α1受体阻滞剂治疗良性前列腺增生症(BPH)的临床有效性和安全性。方法对入选的183例BPH患者进行了一个前瞻性的随机、双盲和平行对照试验,过程分3个阶段:第一阶段为2周的清洗期,第二阶段为2周的单盲安慰剂导入期,第三阶段为12周的双盲药物治疗期。多沙唑嗪控释片、特拉唑嗪片和坦索罗辛片的起始剂量分别为4 mg/d、1 mg/d和0.4 mg/d,如果治疗4周后最大尿流率(Qmax)增加<3 mL/s,国际前列腺症状评分(IPSS)下降<30%,则将3种药物分别加量为8 mg/d、8 mg/d和0.8 mg/d。主要评价指标为从基线到最后1次随访的IPSS和Qmax的变化值,以及治疗中常见不良事件的发生率。统计方法采用方差分析和χ2检验。结果多沙唑嗪控释片、特拉唑嗪片和坦索罗辛片均能显著减轻BPH的下尿路梗阻症状,增加Qmax(P<0.01),但是前两种药物对IPSS的降低显著优于坦索罗辛片(P<0.05)。多沙唑嗪控释片组没有因为与治疗相关的不良事件而退出试验的患者,并且在头晕、恶心、体位性低血压等主要不良事件的发生率与特拉唑嗪片组和坦索罗辛片组比较,差异有统计学意义(P<0.05)。结论α1受体阻滞剂均能有效缓解BPH的下尿路症状。多沙唑嗪控释片作用全面,有效性和安全性显著提高,是这类药物的首选。     

坦索罗辛与阿呋唑嗪治疗输尿管结石的疗效比较

目的:比较坦索罗辛与阿呋唑嗪治疗输尿管结石的疗效。方法:将156例确诊为输尿管结石的患者随机分为试验组与对照组(各78例),分别给予阿呋唑嗪10 mg、坦索罗辛0.2mg,均为qd,服药2⁴周;患者均每日饮水>2 L,适量运动。比较两组患者的排石率、结石排出时间和药品不良反应发生情况。结果:试验组与对照组的排石率分别为61.5%、83.3%(P<0.05),两组患者的结石排出时间和药品不良反应发生率差异无统计学意义(P>0.05)。结论:坦索罗辛治疗输尿管结石比阿呋唑嗪疗效更好。     

基于openFDA的诺西那生不良反应真实世界研究

目的：基于FDA公共数据开放项目（openFDA）中诺西那生不良事件的数据,分析研究诺西那生的不良反应,为临床安全用药提供参考。方法：收集2016年1月1日至2020年12月31日美国FDA不良事件报告系统（FAERS）中诺西那生相关的不良事件（AE）报告,提取报告数排名前50位不良事件报告,采用报告比值比法（ROR）和比例报告比值法（PRR）挖掘诺西那生不良反应风险信号。结果：设定时段内FAERS共收到以诺西那生为首要怀疑药物的不良事件报告3 497例,对报告数排名前50位不良事件进行药物不良反应风险信号分析,检测出35个不良反应风险信号,其中30个为说明书中未收录的不良事件。不良事件报告数前5位的不良事件依次为头痛、腰穿后综合征、发热、感染性肺炎、呕吐。不良反应风险信号强度排名前5位的依次为腰穿后综合征、脑脊液漏、鼻病毒感染、尿蛋白检出、呼吸道合胞病毒感染。结论：利用诺西那生不良事件的真实世界数据深入分析其潜在的不良反应,提示临床予以关注及进一步进行安全性评价。其中尿蛋白检出不良反应风险信号强度高,建议在每次给药前进行尿蛋白检测。     

基于FAERS对沙库巴曲缬沙坦不良反应的分析研究

目的： 通过挖掘美国食品药品监督管理局不良事件呈报系统（FAERS）数据库中关于沙库巴曲缬沙坦的相关数据,探讨该药潜在的不良反应,为临床安全用药提供依据。方法： 采用报告比值比法（ROR）和比例报告比值法（PRR）同时检测FAERS数据库中沙库巴曲缬沙坦的不良事件信号,检索时限从2015年第3季度该药上市至2019年第3季度共17个季度,并对结果进行分析研究。结果： 经过多重筛查,ROR法与PRR法得到信号均一致合计41个且挖掘出33个未在说明书收录的警戒信号。其中较强的信号主要集中在低血压、室性心动过速、血管性水肿、听觉迟钝、高钾血症等,系统器官分类（SOC）涉及信号个数最多的主要集中在神经系统疾病和心脏疾病等,同时也挖掘出该药可能引起认知功能障碍等不良事件。结论： 利用挖掘FAERS数据可较全面深入地分析研究沙库巴曲缬沙坦上市后的不良反应,进而有效地降低临床用药风险。     

唑吡坦对老年不稳定性心绞痛伴自述失眠患者的临床疗效评价

目的：观察唑吡坦对老年不稳定性心绞痛（UAP）伴自述失眠（SRI）患者治疗30 d临床疗效及预后的影响。方法：选取2016年6月至2019年6月收治的99例老年UAP伴SRI患者,随机分为对照组50例和治疗组49例,2组均给予常规冠心病二级预防用药。治疗组同时加用唑吡坦5 mg每晚睡前口服,对照组则给予安慰剂,2组疗程均为30 d。运用匹兹堡睡眠质量指数（PSQI）评估患者睡眠质量及SRI临床疗效,比较2组患者肌钙蛋白I（cTnI）、心型脂肪酸结合蛋白（H-FABP）和脑钠肽（BNP）水平,评价UAP临床疗效。同时观察2组患者30 d心血管事件发生情况。结果：治疗30 d后2组的PSQI评分均有下降（P<0.05）,治疗组下降程度高于对照组（P<0.05）;治疗组SRI治疗总有效率（89.8%）优于对照组（68.0%）,组间比较存在差异（P<0.05）。治疗后2组cTnI、H-FABP和BNP水平均有所下降（P<0.05）,治疗组比对照组下降明显（P<0.05）;治疗组UAP治疗总有效率（91.8%）优于对照组（72.0%）,组间比较差异显著（P<0.05）。治疗组30 d心血管事件发生率为10.2%,优于对照组的18.0%（P<0.05）。结论：唑吡坦对老年UAP伴SRI患者具有心肌保护作用,能够明显改善患者的SRI疗效,并能在常规冠心病二级预防用药基础上明显改善患者UAP治疗效果,降低30 d心血管事件发生率、改善患者预后。     

槲皮素通过调节TGF-β1/Smad抑制增生性瘢痕的形成

目的：探讨槲皮素对人增生性瘢痕成纤维细胞（HSFb）及其介导的TGF-β₁/Smad信号通路中相关蛋白表达的影响。方法：提取人增生性瘢痕成纤维细胞进行原代培养并鉴定;采用CCK-8法检测不同浓度的槲皮素（50~600 μmol·L^-1）处理后的HSFb细胞活力;Western blot检测α-SMA、COL-Ⅲ、TGF-β₁、Smad2、Smad7的蛋白表达,免疫荧光检测α-SMA的表达以及HSF和HSFb中波形蛋白的表达。结果：与模型组相比,槲皮素（250,500 μmol·L^-1）可降低α-SMA蛋白的表达（P<0.05）并显著下调COL-Ⅲ蛋白的表达（P<0.05或P<0.01）,其中500 μmol·L^-1槲皮素组对HSFb细胞Ⅲ-型胶原分泌的抑制作用最强,并显著降低TGF-β₁和Smad2的蛋白表达;显著上调Smad7蛋白表达并且呈浓度依赖性,差异均具有统计学意义（P<0.05或P<0.01）。结论：槲皮素主要通过抑制COL-Ⅲ、α-SMA、TGF-β₁/Smad通路的活化从而抑制增生性瘢痕的形成。     

基于FAERS数据库的奥司他韦神经精神不良事件数据挖掘研究

目的：通过美国FDA不良事件报告系统（FAERS）数据库,挖掘奥司他韦神经精神学不良事件（neuropsychiatric adverse events,NPAEs）信号,为用药监护提供依据。方法：采用报告比值比（reporting odds ration,ROR）法对FAERS 数据库中于2004-2020年上报的奥司他韦NPAEs进行挖掘及分析。结果：共获得奥司他韦NPAEs报告3 469例,年龄主要在7~35岁,男性多于女性,报告国家以日本和美国为主。采用ROR法共得到奥司他韦NPAEs信号65个,主要表现为异常行为、妄想、幻觉、谵妄、睡眠障碍、自我伤害等。结论：奥司他韦引发NPAEs的风险极高,临床使用时应加强早期监测。     

基于FAERS的多粘菌素B安全信号挖掘研究

目的： 基于美国FDA不良事件报告系统（FAERS）,对多粘菌素B的不良事件进行挖掘,为临床安全使用多粘菌素B提供参考。方法： 下载2004年1季度至2019年4季度一共64季度的FAERS数据,经过MedEx药品名称标准化、MedDRA不良事件系统分类等数据清洗后,提取多粘菌素B相关不良事件,采用报告比值比法（ROR）和比例报告比值法（PRR）进行信号检测。结果： 共提取到多粘菌素B不良事件报告记录947例,包含4 042个报告事项。发生不良事件的男女比值为0.8,患者中位年龄为48岁。美国、日本和巴西是报告例数最多的前3位国家。检测到不良事件信号188个,包含1 889项事件。各类检查、感染及侵袭类疾病、血液及淋巴系统疾病、眼器官疾病和胃肠系统疾病的报告事项最多。（移植物）植入综合征、（移植物）植入失败、肝静脉闭塞等的ADE信号最强。结论： 使用多粘菌素B期间应关注患者的凝血功能、继发性感染和呼吸肌麻痹等不良事件的发生,特别应重视患有血液系统疾病和移植术后的患者,保障患者用药安全。     

基于openFDA数据对阿贝西利不良事件的信号检测与分析

目的：基于openFDA数据分析阿贝西利的不良事件报告,为临床安全用药提供参考。方法：通过访问openFDA药物不良事件端点,检索2018年2月26日至2021年9月15日期间阿贝西利的不良事件报告并进行描述性统计分析,采用报告比值比（reporting odds ratio, ROR）法和比例报告比值法（proportional reporting ratio, PRR）2种方法,按药物不良反应术语集的首选系统器官分类（system organ classification, SOC）和首选术语（preferred term, PT）对阿贝西利的不良事件（adverse events, AE）进行分类并挖掘可疑风险信号。结果：检索时段中阿贝西利的不良事件报告共4 734份,患者首发AE年龄平均为63.55岁,集中在50~74岁;女性患者占绝大部分;主要上报国家是美国;消费者或非健康专业人员为主要上报人;适应证多为乳腺癌;严重不良事件占44.70%。根据阳性标准共筛选出45个不良反应风险信号,涉及11个SOC分类。腹泻、肺炎、间质性肺病、血肌酐增加、肝功能异常和白细胞减少症等25个信号较强,另外说明书未提及的治疗改变、乳腺癌转移、疾病进展、脱水和肝病等20个可疑信号需给予关注。结论：对阿贝西利真实世界的不良事件数据进行挖掘,有助于发现潜在不良反应风险信号,提示临床除关注说明书提及的不良反应外,对说明书未提及的信号应引起重视,并采取干预措施,保障患者用药安全。     

基于美国FAERS数据库的卡格列净不良反应信号挖掘

目的：利用大样本数据对卡格列净的不良反应（adverse drug reactions,ADR）信号进行挖掘分析,为临床合理安全用药提供参考。方法：收集美国FDA不良事件报告系统中2015年第一季度至2021年第二季度共26季度的卡格列净的ADR报告,采用报告比值比（reporting odds ratio,ROR）法和比例报告（proportional reporting ratio,PRR）法对其进行数据挖掘。利用国际医学用语词典（Medical Dictionary for Drug Regulatory Activities,MedDRA）分析药物不良事件安全信号。结果：共提取到卡格列净相关ADR报告14 039份,除去信息未知的情况,其中女性5 439例（38.7%）,男性5 824例（41.5%）;年龄主要分布在45~64岁（3 779例,占26.92%）。挖掘到该药相关ADR信号主要表现为截肢、酮症酸中毒、泌尿生殖系统感染等事件,且截肢好发于男性及高龄患者;泌尿生殖系统感染好发于女性。将信号进行规整比对,还挖掘出骨髓炎、特发性阴囊坏死、胰腺炎、排尿障碍等药品说明书中尚未提及的ADR。结论：利用FAERS数据库可较全面深入地分析卡格列净的ADR,为临床安全合理用药提供参考。     

A randomized,comparative, open-label study of efficacy and tolerability of alfuzosin,tamsulosin and silodosin in benign prostatic hyperplasia

Objectives:

Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS.

Methods:

Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks.

Results:

IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P < 0.001) at 12 weeks. Improvement in QLS was >75% in all the three groups (P < 0.001). A significant improvement in Qmax was seen with alfuzosin and tamsulosin (P = 0.025 and P < 0.001) but not with silodosin (P = 0.153). However, the intergroup differences in IPSS, QLS, and Qmax were not significant. Ejaculatory dysfunction was more common with silodosin and corrected QT (QTc) prolongation occurred only with alfuzosin (two subjects) and tamsulosin (three subjects).

Conclusion:

Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse event as there are no reports of QTc prolongation with tamsulosin in any of the previous studies.KEY WORDS: α1-blockers, alfuzosin, benign prostatic hyperplasia, clinical trial, silodosin, tamsulosin     

Tamsulosin potently and selectively antagonizes human recombinant α(1A/1D)-adrenoceptors: slow dissociation from the α(1A)-adrenoceptor may account for selectivity for α(1A)-adrenoceptor over α(1B)-adrenoceptor subtype

We determined the binding affinity of tamsulosin, a selective α(1)-adrenoceptor antagonist, for human α(1)-adrenoceptor subtypes in comparison with those of other α(1)-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [(3)H]tamsulosin for recombinant human α(1)-adrenoceptor subtypes were compared with those of [(3)H]prazosin. Tamsulosin competitively inhibited [(3)H]prazosin binding to human α(1A)-, α(1B)- and α(1D)-adrenoceptors (pK(i) values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human α(1A)-adrenoceptor than those for α(1B)- and α(1D)-adrenoceptors, respectively. The affinity of tamsulosin for the human α(1A)-adrenoceptor was, respectively, 5, 9.9, 38, 120, 280, 400, 1200 and 10000 fold higher than those of silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, naftopidil, urapidil and BMY7378, respectively. [(3)H]Tamsulosin dissociated from the α(1A)-adrenoceptor slower than from the α(1B)- and α(1D)-adrenoceptors (α(1B)>α(1D)>α(1A)). Moreover, [(3)H]tamsulosin dissociated slower than [(3)H]prazosin from the α(1A)-adrenoceptor and faster from the α(1B)- and α(1D)-adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized α(1A/1D)-adrenoceptor ligand binding, and slowly dissociated from the α(1A)-adrenoceptor subtype.     

In vivo study on the effects of alpha1-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in male dogs

Alpha-adrenoceptor antagonists are used worldwide for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Recently, abnormal ejaculation, an adverse effect associated with their use, has attracted attention. Here, we simultaneously investigated the effects of alpha(1)-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in anesthetized male dogs, and compared their tissue selectivity. Phenylephrine, an alpha(1)-adrenoceptor agonist, induced simultaneous increases in intraurethral and intraluminal pressure. Alfuzosin, naftopidil, prazosin, silodosin and tamsulosin dose-dependently inhibited both responses. Comparison of ED(50) values in both tissues showed that silodosin had the highest selectivity for the vas deferens (7.5-fold), followed by naftopidil (4.3-fold), alfuzosin (3.8-fold), tamsulosin (2.6-fold) and prazosin (2.5-fold). These results suggest that alpha(1)-adrenoceptor antagonists inhibit contraction of not only the urethra but also the vas deferens in a dose-dependent fashion, and that their high tissue selectivity for the vas deferens over the urethra may contribute to the incidence of abnormal ejaculation.     

Evaluation of silodosin in comparison to tamsulosin in benign prostatic hyperplasia: A randomized controlled trial

Objectives:

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in elderly men. Selective alfa₁-adrenergic antagonists are now first-line drugs in the medical management of BPH. We conducted a single-blind, parallel group, randomized, controlled trial to compare the effectiveness and safety of the new alfa₁-blocker silodosin versus the established drug tamsulosin in symptomatic BPH.

Materials and Methods:

Ambulatory male BPH patients, aged above 50 years, were recruited on the basis of International Prostate Symptom Score (IPSS). Subjects were randomized in 1:1 ratio to receive either tamsulosin 0.4 mg controlled release or silodosin 8 mg once daily after dinner for 12 weeks. Primary outcome measure was reduction in IPSS. Proportion of subjects who achieved IPSS <8, change in prostate size as assessed by ultrasonography and changes in peak urine flow rate and allied uroflowmetry parameters, were secondary effectiveness variables. Treatment emergent adverse events were recorded.

Results:

Data of 53 subjects – 26 on silodosin and 27 on tamsulosin were analyzed. Final IPSS at 12-week was significantly less than baseline for both groups. However, groups remained comparable in terms of IPSS at all visits. There was a significant impact on sexual function (assessed by IPSS sexual function score) in silodosin arm compared with tamsulosin. Prostate size and uroflowmetry parameters did not change. Both treatments were well-tolerated. Retrograde ejaculation was encountered only with silodosin and postural hypotension only with tamsulosin.

Conclusions:

Silodosin is comparable to tamsulosin in the treatment of BPH in Indian men. However, retrograde ejaculation may be troublesome for sexually active patients.KEY WORDS: Benign prostatic hyperplasia, international prostate symptom score, randomized controlled trial, silodosin, tamsulosin     

Tamsulosin: an update of its role in the management of lower urinary tract symptoms.

Tamsulosin is a selective alpha1A- and alpha1D-adrenoceptor antagonist. These alpha1-receptors are predominant in the prostate, prostatic capsule, prostatic urethra and bladder. The relaxation of prostate and bladder smooth muscles may result in improvement in maximum urine flow (Qmax) and reduction of lower urinary tract symptoms (LUTS). Tamsulosin 0.4 and 0.8 mg/day in a modified-release formulation was significantly more effective than placebo in large (n >250) double-blind, randomised, multicentre, 12- to 13- week clinical trials in patients with LUTS. A greater increase in Qmax from baseline was seen in patients receiving tamsulosin 0.4 or 0.8 mg/day (1.4 to 1.79 ml/sec from a baseline of 9.46 to 10.7 ml/sec) than in placebo recipients (0.4 to 0.93 ml/sec from a baseline of 9.75 to 10.4 ml/sec); the between-group difference was significant in two of three studies. Tamsulosin 0.4 or 0.8 mg/day improved total Boyarsky symptom scores from baseline by a significantly greater extent (by 3.0 to 5.2 points from a baseline of 9.5 to 11.1 points) than placebo (1.9 to 3.2 points from a baseline of 9.3 to 11.0 points). In noncomparative extension studies, the improvement in efficacy parameters with tamsulosin treatment was maintained for up to 4 years. Tamsulosin is effective in patients with mild to severe LUTS, patients with diabetes mellitus or those aged > or = 65 years and does not interfere with the antihypertensive action of nifedipine, enalapril or atenolol. Tamsulosin 0.4 mg/day for 12 weeks and tamsulosin 0.2 mg/day for 4 weeks were as effective as alfuzosin 2.5mg three times daily and terazosin 2 mg/day, respectively, in improving Qmax and symptom scores in randomised comparative trials. With the exception of a numberically greater incidence of abnormal ejaculation, dizziness and rhinitis, the incidence of adverse events with tamsulosin 0.4 mg/day was similar to that seen with placebo in randomised, double-blind studies. The overall incidence of symptoms indicative of orthostasis was 1.4% with tamsulosin 0.4 or 0.8 mg/day treatment. Tamsulosin had less effect on blood pressure than alfuzosin or terazosin. CONCLUSION: Tamsulosin, an alpha1-adrenoceptor antagonist, has a well established place in the treatment of LUTS and has a tolerability profile similar to that of placebo (apart from a higher incidence of abnormal ejaculation, dizziness and rhinitis). Comparative data have shown tamsulosin to be as effective as other alpha1-adrenoceptor antagonists at increasing Qmax and improving symptom scores. However, tamsulosin is unlikely to produce orthostatic hypotensive adverse effects or interfere with concomitant antihypertensive drug therapy. Therefore, tamsulosin is a useful therapeutic option in the management of patients with moderate to severe LUTS.     

Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia

Alpha1-adrenoceptor antagonists are clinically useful for the improvement of urinary obstruction due to benign prostatic hyperplasia (BPH), and their therapeutic effects are mediated through the blockade of prostatic alpha(1)-adrenoceptors. The present study was undertaken to predict the magnitude and duration of alpha(1)-adrenoceptor occupancy in the human prostate after oral alpha(1)-adrenoceptor antagonists. Prostatic alpha(1)-adrenoceptor-binding parameters of silodosin were estimated by measuring specific [(3)H]prazosin binding in rat prostate after oral administration of this drug. The plasma concentration of silodosin after oral administration in rats and healthy volunteers was measured using a high-performance liquid chromatographic method. The alpha(1)-adrenoceptor-binding affinities (K(i)) of silodosin, tamsulosin, and terazosin in the human prostate and plasma concentrations of tamsulosin and terazosin were obtained from the literature. Using the alpha(1)-adrenoceptor binding parameters of silodosin in rat prostate, alpha(1)-adrenoceptor occupancy in the human prostate was estimated to be around 60-70% at 1-6 h after oral administration of silodosin at doses of 3.0, 8.1, and 16.1 micromol. Thereafter, the receptor occupancy was periodically decreased, to 24% (8.1 micromol) and 54% (16.1 micromol) 24 h later. A similar magnitude and time course of alpha(1)-adrenoceptor occupancy by silodosin in the human prostate were estimated using alpha(1)-adrenoceptor-binding affinities (K(i)) in the human prostate. Despite about two orders of differences in the plasma unbound concentrations after clinically effective oral dosages of silodosin, tamsulosin, and terazosin, there was a comparable magnitude of prostatic alpha(1)-adrenoceptor occupancy by these drugs. In conclusion, the prediction of alpha(1)-adrenoceptor occupancy in the human prostate by alpha(1)-adrenoceptor antagonists may provide the rationale for the optimum dosage regimen of these drugs in the therapy of BPH.     

Effects of alpha(1)-adrenoceptor antagonists on male sexual function

alpha(1)-Adrenoceptor antagonists such as alfuzosin, doxazosin, tamsulosin and terazosin are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), but are only second-line agents (doxazosin and terazosin only) for the treatment of arterial hypertension. Sexual function is complex and includes multiple domains such as sexual desire (libido), erectile function and ejaculatory function. Erectile and ejaculatory functions are frequently reduced in patients with BPH and can impact on their quality of life. Therefore, the treatment of BPH should aim to maintain or even restore sexual function.alpha(1)-Adrenoceptor antagonists lack major effects on sexual desire in placebo-controlled studies. Reports on erectile function are inconsistent, with both beneficial and adverse effects being reported, but impotence can occur in some patients without clear differences between drugs. Ejaculatory dysfunction during treatment may represent (relative) an ejaculation. It occurs more frequently with tamsulosin than with other drugs of this class, but the differences are not big enough to be consistently detectable in directly comparative studies. We propose that such differences between drugs should be weighed against differences in cardiovascular tolerability when choosing the optimal treatment for each patient.     

Comorbid LUTS and erectile dysfunction: optimizing their management

ABSTRACT

Background and scope: Lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), and sexual dysfunction such as erectile dysfunction (ED), are highly prevalent in men over the age of 50. LUTS and ED have a negative impact on sexual function and when comorbid, result in reduced quality of life. The goal of this article is to discuss the relationship between ED and LUTS, describe the diagnostic workup of these disorders, explore the current treatment options, and examine how treatments may affect this population. Medline (1980–2006), Cochrane reviews, and the American Urological Association 2006 General Meeting abstracts were searched for relevant clinical trials and reviews with the terms: benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction, sexual dysfunction, α-adrenergic receptor antagonists, α-blockers, 5α-reductase inhibitors, phosphodiesterase type-5 inhibitors, transurethral resection of the prostate, transurethral microwave thermotherapy, transurethral needle ablation, adverse events, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, sildenafil, tadalafil, vardenafil. However, because of the volume of literature, this article is not a systematic review.

Findings: Although age is an independent risk factor for both LUTS and ED, studies report that LUTS is also an independent risk factor for ED. Treatments for LUTS include pharmacologic, minimally invasive, and surgical therapies. Among pharmacologic options, α₁-adrenergic receptor (α₁-AR) antagonists provide effective treatment with a low risk of sexual side-effects; some of these drugs have been reported to improve sexual function. The treatment of LUTS may improve ED. Phosphodiesterase type 5 inhibitors (PDE-5s) are considered first-line therapy for ED. Comorbid LUTS and ED are treated with an α₁-AR antagonist and a PDE-5; however, this combination must be used with caution because of vasodilatory adverse events associated with both classes of drugs.

Conclusions: Optimal management includes screening to identify patients with comorbid LUTS and ED, and the use of treatments that minimize both vasodilatory and sexual side-effects.     

Efficacy and safety of silodosin in the medical expulsion therapy for distal ureteral calculi: a systematic review and meta‐analysis

Aims

Using a selective α‐adrenoceptor blocker for medical expulsive therapy (MET) is an effective treatment approach widely used for ureteral stones. The aim of the review was to assess the efficacy and safety of silodosin in medical expulstion therapy compared with placebo and tamsulosin.

Methods

A systematic search was performed in PubMed, Cochrane Library and Embase to identify randomized controlled trials that compared silodosin with a placebo or tamsulosin for ureteral calculi.

Results

Eight publications involving a total of 1048 patients were used in the analysis, which compared silodosin with placebo and tamsulosin. We found that silodosin was effective in treating ureteral calculi in our meta‐analysis and was superior to tamsulosin in its efficacy. The expulsion rate of all ureteral stones (OR 1.59, 95% CI 1.08, 2.36, P = 0.02), the expulsion rate of distal ureteral stones (OR 2.82, 95% CI 1.70, 4.67, P < 0.0001) and the expulsion time (days) of distal ureteral stones (standard mean difference (SMD) −4.71, 95% CI −6.60, −2.83, P < 0.00001) indicated that silodosin was more effective than the placebo. Moreover, expulsion rate (OR 2.54, 95% CI 1.70, 3.78, P < 0.00001), expulsion time (days) (SMD −2.64, 95% CI −3.64, −1.64, P < 0.00001) and pain episodes (P < 0.00001) indicated that silodosin was more effective than the tamsulosin. Even though silodosin had a significant increase in abnormal ejaculation compared with tamsulosin, no significant differences were observed for complications (OR 1.00, 95% CI 0.58, 1.74, P = 1.00).

Conclusions

This meta‐analysis indicated that silodosin was superior to placebo or tamsulosin in the efficacy for distal ureteral calculi with better control of pain. The safety profile of silodosin was similar to tamsulosin though retrograde ejaculation was worse for silodosin use. We conclude that silodosin might have potential as a MET for ureteral stones.     

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

Purpose

The aim of this study was to analyze the cases of gynecomastia associated with α_1A-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.

Methods

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.

Results

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).

Conclusion

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.