特拉唑嗪、坦洛新及非那雄胺治疗良性前列腺增生症的安全性评价

目的:评价特拉唑嗪、非那雄胺及坦洛新治疗良性前列腺增生症(benignprostatichyperlasia,BPH)的安全性。方法:应用系统评价方法,检索关于该三种药物中任意两药对比或两药联用与单用对比,治疗良性前列腺增生的文献。纳入与药物安全性有关的随机对照试验(RCT)、临床对照试验(CCT)、队列研究及报道严重不良反应的个案报道和病案分析。评价纳入文献质量并提取资料,进行Meta分析或作定性系统评价。结果:共纳入10篇RCT/CCT及3篇其他类型临床研究。分析发现:特拉唑嗪比坦洛新更易引起头晕、头痛、血压降低、症状明显的直立性低血压,因不良反应退出试验的人数也更多,差异有统计学意义;两者在引起胃肠道不适、胸闷心慌、皮疹及皮肤瘙痒方面的差异无统计学意义。特拉唑嗪比非那雄胺更易引起头晕,差异有统计学意义;两药在阳痿、性欲减退方面无统计学差异,但尚须开展更多临床试验以获得确切结论。坦洛新与非那雄胺不良反应比较仅1篇,结果表明坦洛新安全性优于非那雄胺,差异有统计学意义。两药联用与单用的不良反应比较有2篇,结果不一致。结论:特拉唑嗪引起头晕、头痛、血压降低、症状明显的直立性低血压等不良反应的发生率较其它两种药物高。关于非那雄胺最易引起阳痿、性欲减退暂无足够证据。坦洛新引起不良反应最少,因不良反应停药和退出试验者也最少,提示其可接受性最佳。有研究显示两药联用的副作用高于单药,但现有的研究证据过少,无法做出判断。     

After ALLHAT: doxazosin for the treatment of benign prostatic hyperplasia

Doxazosin mesylate is an α₁-adrenoceptor antagonist that was used to treat hypertension until a major study (ALLHAT; Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) showed that it increased the risk of progressing to heart failure. Doxazosin is now being used to treat benign prostatic hyperplasia (BPH). Noradrenaline acts on α₁-adrenoceptors to contract the smooth muscle in the prostate and bladder, and by opposing these actions, doxazosin is beneficial in BPH. Doxazosin also increases apoptosis in the prostate. Although the standard preparation is suitable for once-daily dosing in BPH, it has to be titrated through three steps to its final dose. The controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin is more convenient to use as it only has to be titrated through one step. In the treatment of BPH, standard doxazosin reduced both obstructive and irritative symptoms and increased peak urinary flow rate. The main side effects with doxazosin are those commonly associated with lowering blood pressure, although doxazosin lowers blood pressure to a lesser extent in normotensives than hypertensives. There is some evidence that in addition to being easier to use, doxazosin GITS may cause less adverse effects than the standard preparations. The benefits of doxazosin and the 5α-reductase inhibitor, finasteride, may be additive in BPH especially in men with large prostates. Further trials are necessary in order to determine whether doxazosin GITS is superior to other α₁-adrenoceptor antagonists in BPH.     

After ALLHAT: doxazosin for the treatment of benign prostatic hyperplasia

Doxazosin mesylate is an alpha1-adrenoceptor antagonist that was used to treat hypertension until a major study (ALLHAT; Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) showed that it increased the risk of progressing to heart failure. Doxazosin is now being used to treat benign prostatic hyperplasia (BPH). Noradrenaline acts on alpha1-adrenoceptors to contract the smooth muscle in the prostate and bladder, and by opposing these actions, doxazosin is beneficial in BPH. Doxazosin also increases apoptosis in the prostate. Although the standard preparation is suitable for once-daily dosing in BPH, it has to be titrated through three steps to its final dose. The controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin is more convenient to use as it only has to be titrated through one step. In the treatment of BPH, standard doxazosin reduced both obstructive and irritative symptoms and increased peak urinary flow rate. The main side effects with doxazosin are those commonly associated with lowering blood pressure, although doxazosin lowers blood pressure to a lesser extent in normotensives than hypertensives. There is some evidence that in addition to being easier to use, doxazosin GITS may cause less adverse effects than the standard preparations. The benefits of doxazosin and the 5alpha-reductase inhibitor, finasteride, may be additive in BPH especially in men with large prostates. Further trials are necessary in order to determine whether doxazosin GITS is superior to other alpha1-adrenoceptor antagonists in BPH.     

Combination of finasteride and doxazosin for the treatment of benign prostatic hyperplasia

Finasteride, which inhibits the enzyme 5 alpha-reductase, reduces prostate size and relieves the symptoms of benign prostatic hyperplasia (BPH) in men with enlarged prostates. alpha 1 -Adrenoceptor antagonists, such as doxazosin and terazosin, are also effective in the treatment of BPH. Previous clinical studies in which finasteride had little or no effect alone, have shown little or no additive effect with alpha 1 -adrenoceptor antagonists. The Medical Therapy of Prostatic Symptoms study showed a considerable benefit with finasteride alone and an additive effect when administered with doxazosin. One interpretation of these results is that if finasteride is effective alone in BPH, the combination with an alpha 1 -adrenoceptor antagonist will give an additive effect.     

Combination of finasteride and doxazosin for the treatment of benign prostatic hyperplasia

Finasteride, which inhibits the enzyme 5α-reductase, reduces prostate size and relieves the symptoms of benign prostatic hyperplasia (BPH) in men with enlarged prostates. α₁-Adrenoceptor antagonists, such as doxazosin and terazosin, are also effective in the treatment of BPH. Previous clinical studies in which finasteride had little or no effect alone, have shown little or no additive effect with α₁-adrenoceptor antagonists. The Medical Therapy of Prostatic Symptoms study showed a considerable benefit with finasteride alone and an additive effect when administered with doxazosin. One interpretation of these results is that if finasteride is effective alone in BPH, the combination with an α₁-adrenoceptor antagonist will give an additive effect.     

Dutasteride/tamsulosin: in benign prostatic hyperplasia

The 5α-reductase inhibitor dutasteride and the α(1)-adrenergic receptor antagonist tamsulosin are available as a fixed-dose combination for use in men with symptomatic benign prostatic hyperplasia (BPH) and an enlarged prostate. Dutasteride 0.5?mg/day plus tamsulosin 0.4?mg/day improved lower urinary tract symptoms (LUTS) to a significantly greater extent than dutasteride or tamsulosin alone in men with BPH, moderate to severe LUTS and an increased risk of disease progression, according to the results of the randomized, double-blind, multinational CombAT trial. The mean change from baseline in the total International Prostate Symptom Score was significantly greater with dutasteride plus tamsulosin than with dutasteride or tamsulosin alone after 2 years (primary endpoint) and 4 years of therapy. After 4 years' therapy in the CombAT trial, the time to first acute urinary retention or BPH-related surgery (primary endpoint) significantly favoured men with symptomatic BPH who were receiving dutasteride plus tamsulosin versus those receiving tamsulosin alone, with no significant difference between recipients of dutasteride plus tamsulosin and recipients of dutasteride alone. In the CombAT trial, health-related quality of life and treatment satisfaction were improved to a significantly greater extent with dutasteride plus tamsulosin than with dutasteride or tamsulosin alone. Combination therapy with oral dutasteride plus tamsulosin was generally well tolerated in patients with symptomatic BPH in the CombAT trial.     

Finasteride and doxazosin alone or in combination for the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia is an increasingly prevalent condition affecting > 50% of men > 65 years of age. Although it is a condition that is unlikely to be life threatening, it can significantly affect quality of life with distressing lower urinary tract symptoms. Increasingly, medical therapy is being used as first-line treatment for men with moderate-to-severe lower urinary tract symptoms. Two main pharmacological classes of drugs are used: 5alpha-reductase inhibitors and alpha-1 selective blockers. Both these classes of drugs have shown good tolerability and clinical efficacy. This article examines the potential benefit of the use of combination therapy. In particular, what is the evidence for using doxazosin and finasteride therapy together?     

Effects of terazosin in the treatment of benign prostatic hyperplasia. A pilot study

Several reports in the literature suggest that alpha-receptor blockade may have therapeutic value in treating the symptoms of patients with benign prostatic hyperplasia (BPH). Terazosin (Heitrin, Hytrin) is a long acting, highly selective alpha 1-adrenergic blocking agent structurally similar to prazosin. The present study, which also can be regarded as a pilot study, was undertaken as part of a multicenter study to evaluate the safety and efficacy of terazosin in the treatment of patients with BPH. This article presents the results with terazosin in the first 15 patients who completed a dose-ranging, non-comparative single-blind study. These preliminary results confirm that terazosin significantly improved peak as well as mean urine flow rates and significantly reduced residual volume and significantly improved obstructive symptoms in patients with benign prostatic hyperplasia (p less than 0.001). The results of this study support the conclusion that terazosin is beneficial for treatment of symptoms in patients with BPH.     

依立雄胺联合多沙唑嗪治疗良性前列腺增生临床观察

目的 评价依立雄胺联合多沙唑嗪治疗中重度症状的前列腺增生的有效性.方法 选择中重度症状前列腺增生患者70例,联合应用依立雄胺(5mg口服,2次/d)与多沙唑嗪控释片(4mg口服,每晚1次)治疗3个月,观察主客观症状的改善及指标变化.结果 70例患者观察过程中,4例因出现不能耐受的体位性低血压、1例因反复尿潴留改用手术治疗而停药.65例患者治疗3个月后,国际前列腺症状评分[(16.12±5.82)分比(23.21 ±7.61)分]、生活质量评分[(2.65±0.70)分比(4.28±0.60)分]、血清前列腺特异抗原[ (2.43±1.98) μg/L比(2.85±2.23) μg/L]和残余尿量[(33±35) ml比(49 ±40)ml]均比治疗前明显降低(P＜0.01);最大尿流率比治疗前明显增多[(11.63±3.70)比(8.92 ±3.87) ml/s,P＜0.01];前列腺体积减小[ (38±16) ml比(40±13) ml],但与治疗前相比无统计学差异(P＞0.05).结论 依立雄胺联合多沙唑嗪治疗中重度症状的前列腺增生有效,可作为联合用药的一种选择.     

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。     

坦索罗辛联合索利那新治疗良性前列腺增生伴膀胱过度活动症

目的评价坦索罗辛联合索利那新治疗良性前列腺增生伴膀胱活动过度症的疗效。方法选择经临床确诊的良性前列腺增生伴膀胱过度活动患者85例,随机分成单药组和联合组,单药组45例,单用坦索罗辛(0.2 mg,口服,1次/晚);联合组40例,服用坦索罗辛(0.2 mg,口服,1次/晚)和索利那新(5 mg,1次/d)。两组分别在治疗前和治疗12周后行国际前列腺症状评分(IPSS)、生活质量评分(QOL)、最大尿流率(Qmax)及膀胱过度活动症状评分(OABSS)测定,并对出现的不良反应进行记录。结果治疗后,单药组IPSS、QOL评分及Qmax均有改善(P<0.05),OABSS无明显改善;联合组IPSS、QOL评分、Qmax及OABSS均有明显改善(P<0.05),且联合组IPSS、QOL评分、OABSS改善情况明显优于单药组。结论坦索罗辛联合索利那新不仅可以改善BPH所导致的梗阻症状,还可以更好地减轻患者的膀胱过度活动症状,改善患者的生活质量。     

前列欣胶囊联合特拉唑嗪治疗前列腺增生症的临床研究

目的 探讨前列欣胶囊联合盐酸特拉唑嗪胶囊治疗前列腺增生症的临床疗效。方法 选取2018年5月-2020年5月在新乡市中心医院治疗的前列腺增生症患者242例,根据用药的差别分为对照组（121例）和治疗组（121例）。对照组口服盐酸特拉唑嗪胶囊,2 mg/次,1次/d;治疗组在对照组基础上口服前列欣胶囊,3.0 g/次,3次/d。两组患者均治疗30 d。观察两组患者临床疗效,同时比较治疗前后两组患者前列腺体积、残余尿量（PVR）、最大尿流率（Q_max）,IPSS、VSS、QOL和USPSS评分,及血清胰岛素样生长因子-1（IGF-1）、B细胞淋巴瘤/白血病-2（Bcl-2）、脂蛋白相关磷脂酶A2（LP-PLA2）和白细胞介素-17（IL-17）水平。结果 治疗后,对照组临床总有效率为80.49%,显著低于治疗组的97.56%,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者前列腺体积、PVR均显著降低（P<0.05）,而Q_max均显著升高（P<0.05）,且治疗组明显好于对照组（P<0.05）。治疗后,两组患者IPSS评分、VSS评分、QOL评分、USPSS评分均显著下降（P<0.05）,且治疗组下降最为明显（P<0.05）。治疗后,两组患者血清IGF-1、Bcl-2、Lp-PLA2、IL-17水平均明显降低（P<0.05）,且治疗组明显低于对照组（P<0.05）。结论 前列欣胶囊联合盐酸特拉唑嗪胶囊治疗前列腺增生症可有效改善患者临床症状,降低血清IGF-1、Bcl-2、Lp-PLA2、IL-17水平,提高患者生活质量,具有一定的临床推广应用价值。     

Abnormal ejaculation associated with tamsulosin in benign prostatic hyperplasia patients

Benign prostatic hyperplasia (BPH) refers to excessive cellular growth of glandular and stromal elements of prostate. It is one of the most common condition affecting men, with incidence increasing dramatically after the age of 50 years. α₁-Adrenoreceptor antagonists have remained the mainstay of pharmacotherapy in patients suffering from moderate-to-severe BPH, due to their rapid onset of action and symptomatic relief of symptoms associated with BPH. Among all of the α-blockers, tamsulosin is the first selective α_1A-adrenoreceptor antagonist approved for clinical use and is the most commonly prescribed drug for the treatment of BPH. Despite an improved tolerability profile over other α₁-blockers, tamsulosin still exhibits high incidence abnormal ejaculation, which can affect the quality of life. The current clinical study demonstrates the recovery of abnormal ejaculation following intermittent tamsulosin treatment in BPH patients.     

度他雄胺联合坦索罗辛治疗老年良性前列腺增生的临床研究

目的探讨度他雄胺联合坦索罗辛治疗老年良性前列腺增生的临床疗效。方法收集2013年1月—2014年1月新疆维吾尔自治区人民医院收治的良性前列腺增生患者183例,随机分为对照组(92例)和治疗组(91例)。对照组口服盐酸坦索罗辛缓释胶囊1粒/次,1次/d。治疗组口服度他雄胺软胶囊,1粒/次,1次/d,同时口服盐酸坦索罗辛缓释胶囊,用法用量同对照组。两组患者均连续治疗24周。比较两组的临床疗效,同时比较两组治疗前,治疗8、16、24周最大尿流率(MFR)、残余尿量(RU)、前列腺体积(PV)、泌尿症状困扰(BS)评分、国际前列腺症状(IPSS)评分的变化。结果对照组和治疗组总有效率分别为81.52%、90.11%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者MFR均较治疗前显著升高,RU、PV、BS评分、IPSS评分均较治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组这些指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。结论度他雄胺联合坦索罗辛治疗老年良性前列腺增生有较好的临床疗效,可以缩小前列腺体积和膀胱残余尿量,改善患者下尿路症状,值得临床推广应用。     

宁泌泰胶囊联合坦索罗辛治疗良性前列腺增生症的临床研究

目的 系统研究藤黄健骨胶囊的主要化学成分,并探讨其发挥药效的主要作用机制,为其药效物质研究提供一定的参考依据。方法 采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱（UHPLC-Q-Orbitrap HRMS）对藤黄健骨胶囊的主要化学成分进行全面分析,根据化合物的一级、二级质谱信息,并与对照品或参考文献进行比对,以实现对药物的化学信息进行快速识别。在此基础上,采用BAT-MAN-TCM数据库对鉴定得到的化学成分进行靶点预测,进一步通过DAVID数据库进行KEGG通路注释分析和GO富集分析,初步筛选出药物的主要药效物质,并探讨其作用机制。结果 从藤黄健骨胶囊中共鉴定出34种化学成分,“成分-靶点”网络分析表明药物中的重要成分山柰酚、大豆苷元、熊果酸、刺芒柄花素和豆甾醇等可作用于Bcl-2、BAX、AKt、PPARG、PTGS1、PTGS2、TNF、IL6、F7及IL1B等关键靶点,结果分析表明破骨细胞分化信号通路、NF-κB信号通路、PI3K-Akt信号通路、肾细胞信号通路以及血小板激活等可能是其发挥壮骨健骨、补肾活血和解痉止痛治疗作用的主要途径。结论 采用UHPLC-Q-Orbitrap HRMS高分辨质谱分析结合网络药理学的方法,初步明确了藤黄健骨胶囊的化学组成及潜在作用机制,为筛选其药效成分及深入阐明作用机制提供了科学的理论依据。     

多沙唑嗪在住院前列腺增生患者中的心血管安全性

目的研究多沙唑嗪在住院前列腺增生患者中的心血管安全性。方法收集首都医科大学宣武医院2016年1-12月诊断为前列腺增生且使用甲磺酸多沙唑嗪缓释片或坦索罗辛缓释胶囊的住院患者的相关资料,分析两组患者使用这2种药物后发生心绞痛、急性心肌梗死、心律失常、心力衰竭等心血管事件的情况。结果共有80例患者符合纳入标准,多沙唑嗪组51例(63.75%),坦索罗辛组29例(36.25%),两组患者基本资料比较差异无统计学意义。使用2种药物后,发生心绞痛、急性心肌梗死、心律失常、心力衰竭等心血管事件共13例(16.25%),多沙唑嗪组12例(心绞痛6例、急性心肌梗死3例、心律失常7例、心力衰竭3例,同时发生急性心肌梗死、心律失常1例,同时发生心绞痛、心律失常1例,同时发生心绞痛、心律失常、心力衰竭2例),坦索罗辛组1例(心绞痛),两组间心血管事件发生率比较差异有统计学意义(23.53%vs.3.45%,P=0.043)。结论多沙唑嗪增加前列腺增生患者发生心绞痛、急性心肌梗死、心律失常、心力衰竭等心血管事件的风险,尤其是心血管危险分层较高的患者;建议前列腺增生患者选用多沙唑嗪前进行心血管危险分层,对于心血管中高危患者选择高选择性的α1受体阻滞剂。     

沙巴棕软胶囊联合特拉唑嗪治疗良性前列腺增生的临床研究

目的探讨沙巴棕软胶囊联合特拉唑嗪治疗良性前列腺增生的临床疗效。方法选取2017年2月—2017年6月郑州市第一人民医院收治的良性前列腺增生患者88例,随机分为对照组(44例)和治疗组(44例)。对照组睡前口服盐酸特拉唑嗪片,2 mg/次,1次/d。治疗组在对照组基础上口服沙巴棕软胶囊,160 mg/次,2次/d。两组患者均经过3月治疗。观察两组患者临床疗效,比较治疗前后两组患者前列腺体积、残余尿量、最大尿流率(Q_(max))、血清指标和国际前列腺症状(IPSS)评分。结果治疗后,对照组临床有效率为79.55%,显著低于治疗组的95.45%。两组比较差异具有统计学意义(P0.05)。治疗后,两组前列腺体积、残余尿量均显著减小,而Q_(max)明显增加,同组比较差异具有统计学意义(P0.05);且治疗组上述指标明显好于对照组(P0.05)。治疗后,两组血清Bcl-2、白细胞介素-6(IL-6)、IL-17水平均明显降低,IL-2水平均明显增加,同组比较差异具有统计学意义(P0.05);且治疗组上述指标明显优于对照组(P0.05)。治疗后,两组患者IPSS评分均明显降低(P0.05);且治疗组比对照组降低的更显著(P0.05)。结论沙巴棕软胶囊联合盐酸特拉唑嗪片治疗良性前列腺增生可有效改善患者临床症状和细胞因子水平,具有一定的临床推广应用价值。     

非那雄安联合特拉唑嗪对前列腺增生症围手术期腺体微血管密度的影响

目的通过对CD34和第Ⅷ因子相关抗原（FⅧ-Rag）在非那雄安联合特拉唑嗪治疗前列腺增生症围手术期中的表达及腺体微血管密度（MVD）的检测,探讨前列腺增生症围手术期非那雄安联合特拉唑嗪治疗后FⅧ-Rag、CD34与MVD的关系及其对手术的影响。方法设在围手术期联合应用非那雄安、特拉唑嗪为实验组,单独服用非那雄安治疗为对照组,采用免疫组化方法检测两组患者术后前列腺组织中CD34、FⅧ-Rag的表达,并检测其微血管密度。结果实验组与对照组CD34的表达值分别为（19.4±3.6）和（21.5±4.7）,FⅧ-Rag的表达值分别为（14.8±2.1）和（18.3±3.5）,差异均有统计学意义（P均〈0.05）。结论在前列腺增生症围手术期应用非那雄安联合特拉唑嗪治疗,可以降低前列腺腺体的微血管密度,有效减少手术中和手术后的出血。