Long-term treatment with doxazosin in men with benign prostatic hyperplasia: 10-year follow-up

INTRODUCTION AND OBJECTIVES: Benign prostatic hyperplasia (BPH) is a progressive condition that is characterized by an increased risk of acute urinary retention and BPH-related surgery. This study evaluates the safety and efficacy of doxazosin over 10 years in men with BPH. MATERIAL AND METHODS: The trial enrolled men (aged 49-83 years--mean 64.0) with symptomatic BPH (clinical stage II according to Alken) and no evidence of prostate cancer. The trial involved a 1.5 year controlled efficacy study with doxazosin (4 mg/day) 64 ambulatory patients with BPH, followed by a 5-year extension. During the study after 1 year 11 pts discontinued it (expense given as reason) and 6 pts underwent surgery. Then 47 pts (100%) receiving doxazosin continued therapy. After 5 years 32 pts (60%) aged 54-92 years--mean 69.4 years continued to be followed for further 5 years, giving a total follow-up of 10 years (next 8 pts underwent surgery; total 14 (26%) pts; and 14 (26%) pts died. RESULTS: Twenty (38%) of the 47 pts (100%) enrolled into doxazosin were judged as being successfully treated during the 10-year follow-up. In further 5 years only 2 pts underwent surgery and 7 pts (13%) died for reasons unrelated to doxazosin treatment. Three pts after 6 years therapy left study. Excluding 14 pts who died plus 14 pts who left the trial it means that after 10 years 20 pts remained successfully treated and 16 pts who had to be surgically treated. Assuming that all group make 36 pts (100%) than long term follow-up showed effective results in doxazosin treated 20 pts (56%) and thus can obviate surgery. Adverse events associated with doxazosin therapy were insignificant. 10 years therapy proved effective in increasing urina flow rates and decreasing residual urine volume--respectively 14.6 ml/s and 57.0 ml (mean value). CONCLUSIONS: 1. Long-term 10 years doxazosin (4 mg/daily) therapy has demonstrated that appropriately selected BPH patients are likely to have an excellent response. 2. The a/m trial indicates that surgery can be obviated in up to half of BPH treated patients. 3. The results of the trial demonstrate that doxazosin is safe, efficacious and well-tolerated.     

Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients

Summary The effect of doxazosin, an a,-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved.After 12 weeks of treatment (mean doxazosin dose 5.6 ± 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mmHg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml - min^–1 - kg^–1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol·1^–1 before and 10.9 mmol·l^–1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mol · 1^–1 Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.     

甲磺酸多沙唑嗪控释片与酚苄明在嗜铬细胞瘤手术前准备及围术期血压控制效果

目的 将甲磺酸多沙唑嗪控释片与酚苄应用于在嗜铬细胞瘤患者的术前准备,比较两者对围术期血压的控制效果.方法 1978-2006年上交通大学医学院附属瑞金医院40例左侧肾上腺嗜铬细胞瘤患者,根据术前的药物准备情况分为3组:组1,手术前未使用a受体阻滞剂进行术前准备;组2,酚苄明20～40 mg/d,分2～3次口服,平均服用天数为(25.1±2.4)d;组3,甲磺酸多沙唑嗪控释片4～8 mg/d顿服,平均服用天数为(10.6±3.9)d.连续挠动脉内监测血压,记录5个时间点的收缩压.分别为手术麻醉诱导前、麻醉后、探查肿瘤时、肿瘤切除后和手术结束时.结果 麻醉前,3组间收缩压的差异有统计学意义(P＜0.01).组2最低,组3次之,组1最高.麻醉后,3组收缩压都有下降,还是以组2最低,组1次之,组3最高,3组间差异有统计学意义(P＜0.01).探查肿瘤时,三组收缩压均升高,依然是组2最低,组3次之,组1最高,3组间差异有统计学意义(P＜0.001),但是组2与组3间差异无统计学意义(P＞0.05).肿瘤切除后,3三组收缩压均下降,组l与组2的差异无统计学意义(P＞0.05),但是与组3的差异均有统计学意义(P值均＜0.01).手术结束时,3组收缩压的差异无统计学意义(P＞0.05).组2、3的最高与最低血压差小于组1(P值均＜0.01),组3显著小于组2(P＜0.01).结论 在左肾上腺嗜铬细胞瘤手术中,术前服用甲磺酸多沙唑嗪控释片可更好地控制术中收缩压的波动,而酚苄明对术前收缩压的控制更佳.     

Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia

It has long been recognised that neural factors are of considerable importance in lower urinary tract function. Whilst reduction in the bulk of the human prostate is feasible, experience on this therapeutic approach proved to be disappointing. Existing trial data with the agent finasteride are reviewed. A number of formulations derived from plant extracts have been advocated but their mechanism of action remain largely obscure and there is a dearth of placebo controlled information to support their efficacy. Experience over the last 10 years has demonstrated efficacy with the use of alpha adrenoceptor blockade in the management of BPH. Alpha adrenoceptor antagonists relax the prostatic smooth muscle by interrupting the sympathetic pathway at the receptor level. Recent developments in this field include the recognition that there are alpha 1 adrenoceptor subtypes. The functional adrenoceptor in the human prostate is predominantly the alpha _1A – subtype. Of the alpha 1-adrenoceptor antagonists only tamsulosin discriminates between the alpha 1-adrenoceptor subtypes. Alpha 1-blockers should be used in first-line medical therapy for BPH and 5-alpha-reductase inhibitors reserved for those patients in whom alpha-blocker therapy fails. Alpha 1-blockers such as doxazosin, tamsulosin, terazosin, alfuzosin are effective in the treatment of BPH both in younger and in older men. The drugs are well tolerated. The majority of side effects were classified as minor and mild. The most common complaints, as with other alpha-blockers, are dizziness, fatigue and headache, and these are often transient. In contrast, finasteride can lead to impotence, reduced libido, gynaecomastia or ejaculatory disorders. Men with small prostates may not be suitable candidates for finasteride therapy. This revised version was published online in September 2006 with corrections to the Cover Date.     

甲磺酸多沙唑嗪质量标准提高的研究

目的: 提高甲磺酸多沙唑嗪的质量标准。方法: 根据生产厂家提供的工艺等资料，按照《中国药典》2010年版二部的相关规定，参考各厂家注册标准及相关文献，考察本品的紫外鉴别、酸度、干燥失重、有关物质、含量测定等项目。结果: 应修订有关物质检测方法，提高杂质限度要求以及修订含量测定方法。结论：提高后的质量标准能更好地控制甲磺酸多沙唑嗪的产品质量，与国际水平接轨。     

多沙唑嗪对高血压患者动态血管平滑肌细胞NO产生的影响

采用高血压患者的肠系膜动脉进行分离培养,检测细胞培养液中的NO含量.结果多沙唑嗪治疗组的NO含量高于对照组(74.56±4.56μmol/L,42.77±6.76μmol/L,P<0.05).认为多沙唑嗪增加了高血压患者动脉血管平滑肌细胞NO的产生.     

可多华联合托特罗定缓解女性OAB患者夜尿频繁的疗效观察

目的探讨可多华(甲磺酸多沙唑嗪控释片)联合托特罗定缓解女性膀胱过度活动症(OAB)夜尿频繁的疗效。方法选择确诊为OAB且口服M受体阻滞剂不明显的患者78例,在继续口服托特罗定片的基础上加服可多华治疗4周,观察用药前后夜尿次数、夜尿单次最大尿量各指标变化。结果联合治疗后日平均夜尿次数、平均单次夜尿最大尿量及OABSS总评分较用药前均明显改善(均P<0.05)。结论可多华联合托特罗定能够有效改善单一口服M受体阻滞剂无效的OAB女性患者夜尿频繁症状,提高患者生活质量。     

多沙唑嗪的致突变作用研究

应用ＣＨＬ细胞染色体畸变试验、Ａｍｅｓ试验 和小鼠骨髓哮多染色细胞微核试验对多沙唑嗪进行了致突变作用研究。结果显示：３１２．５μｇ／皿－５０００μｇ／皿合剂量组ＴＡ９７、ＴＡ９８、ＴＡ１００、ＴＡ１０２等菌株回复突变率未见明显增加；５１３ｍｇ／ｋｇ、１０２５ｍｇ／ｋｇ、２０５０ｍｇ／ｋｇ各剂量组ＰＣＥ微核率分别为１．７‰、２．５‰、２．６‰，与对照组（２．０）‰比较无明显差异（Ｐ〉０．０５）；１０