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α受体拮抗剂在良性前列腺增生治疗中的新作用。

The emerging role of alpha antagonists in the therapy of benign prostatic hyperplasia.

作者信息

Lepor H

机构信息

Department of Urology, Medical College of Wisconsin, Milwaukee 53226.

出版信息

J Androl. 1991 Nov-Dec;12(6):389-94.

PMID:1722795
Abstract

The rationale for using alpha blockade to treat benign prostatic hyperplasia (BPH) is based on the physiology and pharmacology of prostate smooth muscle. Approximately 20% of the area density of the prostate adenoma is smooth muscle. In vitro isometric tension studies have demonstrated that the contractile properties of the human prostate adenoma are mediated primarily by alpha 1 adrenoceptors. Alpha blockers presumably decrease the resistance along the prostatic urethra by relaxing the smooth muscle component of the prostate. Over the past 14 years, at least 16 clinical trials have confirmed the efficacy of alpha blockade in the treatment of BPH. The primary advantage of terazosin over all other commercially available alpha blockers is that its longer half-life allows for a once-daily dosage regimen. Two Phase II studies conducted in the United States, a multicenter dose titration randomized withdrawal study and the author's personal experience with terazosin, are summarized in this report. Overall, the peak urinary flow rate increased 50% and the mean urinary flow rate increased 46% following terazosin therapy. The mean obstructive and irritative scores improved 67% and 35%, respectively. The adverse reactions occurring with an incidence greater than 5% included headache (10%), asthenia (7%), and dizziness (14%). All adverse events were reversible on termination of therapy. The preliminary experiences with alpha blockers for the treatment of BPH has been very encouraging. Yet, the definitive role of alpha blockade in BPH awaits the reporting of multicenter, randomized placebo-controlled studies.

摘要

使用α受体阻滞剂治疗良性前列腺增生(BPH)的理论依据基于前列腺平滑肌的生理学和药理学。前列腺腺瘤的面积密度中约20%是平滑肌。体外等长张力研究表明,人前列腺腺瘤的收缩特性主要由α1肾上腺素能受体介导。α受体阻滞剂可能通过松弛前列腺的平滑肌成分来降低前列腺尿道的阻力。在过去14年中,至少16项临床试验证实了α受体阻滞剂治疗BPH的疗效。与所有其他市售α受体阻滞剂相比,特拉唑嗪的主要优势在于其较长的半衰期允许每日一次给药方案。本报告总结了在美国进行的两项II期研究,一项多中心剂量滴定随机撤药研究以及作者使用特拉唑嗪的个人经验。总体而言,特拉唑嗪治疗后,最大尿流率增加了50%,平均尿流率增加了46%。平均梗阻性和刺激性评分分别改善了67%和35%。发生率大于5%的不良反应包括头痛(10%)、乏力(7%)和头晕(14%)。所有不良事件在治疗终止后均可逆转。α受体阻滞剂治疗BPH的初步经验非常令人鼓舞。然而,α受体阻滞剂在BPH中的明确作用仍有待多中心、随机安慰剂对照研究的报告。

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1
The emerging role of alpha antagonists in the therapy of benign prostatic hyperplasia.α受体拮抗剂在良性前列腺增生治疗中的新作用。
J Androl. 1991 Nov-Dec;12(6):389-94.
2
Alpha adrenergic antagonists for the treatment of symptomatic BPH.用于治疗有症状良性前列腺增生的α肾上腺素能拮抗剂。
Int J Clin Pharmacol Ther Toxicol. 1989 Apr;27(4):151-5.
3
Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study.特拉唑嗪与托特罗定联合治疗良性前列腺增生相关下尿路症状患者的疗效与安全性:一项前瞻性研究。
Chin Med J (Engl). 2007 Mar 5;120(5):370-4.
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A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia.一项多中心、随机、双盲、安慰剂对照研究,以评估特拉唑嗪治疗良性前列腺增生的安全性和有效性。
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The role of combination medical therapy in benign prostatic hyperplasia.联合药物治疗在良性前列腺增生中的作用。
Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. doi: 10.1038/ijir.2008.51.
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Embryologic development of the prostate. Insights into the etiology and treatment of benign prostatic hyperplasia.前列腺的胚胎发育。对良性前列腺增生病因及治疗的见解。
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The safety and efficacy of terazosin for the treatment of benign prostatic hyperplasia.特拉唑嗪治疗良性前列腺增生的安全性和有效性。
Int J Clin Pharmacol Ther Toxicol. 1989 Aug;27(8):392-7.
8
Clinical comparison of selective and non-selective alpha 1A-adrenoceptor antagonists for bladder outlet obstruction associated with benign prostatic hyperplasia: studies on tamsulosin and terazosin in Chinese patients. The Chinese Tamsulosin Study Group.选择性与非选择性α1A肾上腺素能受体拮抗剂治疗良性前列腺增生所致膀胱出口梗阻的临床比较:坦索罗辛与特拉唑嗪在中国患者中的研究。中国坦索罗辛研究组
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Alpha blockade for the treatment of benign prostatic hyperplasia.α受体阻滞用于治疗良性前列腺增生。
Urol Clin North Am. 1995 May;22(2):375-86.
10
Efficacy and safety of alfuzosin 10 mg once daily in the treatment of symptomatic benign prostatic hyperplasia.每日一次服用10毫克阿夫唑嗪治疗有症状的良性前列腺增生的疗效和安全性。
Int J Clin Pract. 2006 Mar;60(3):351-8. doi: 10.1111/j.1368-5031.2005.00830.x.

引用本文的文献

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Hepatic metabolism of two alpha-1A-adrenergic receptor antagonists, phthalimide-phenylpiperazine analogs (RWJ-69205 and RWJ-69471), in the rat, dog and human.两种α-1A-肾上腺素能受体拮抗剂(邻苯二甲酰亚胺-苯基哌嗪类似物,RWJ-69205和RWJ-69471)在大鼠、犬和人体内的肝脏代谢。
Eur J Drug Metab Pharmacokinet. 2006 Oct-Dec;31(4):271-6. doi: 10.1007/BF03190467.
2
Role of Primary Care Clinicians in the Diagnosis and Treatment of LUTS and BPH.基层医疗临床医生在LUTS(下尿路症状)和BPH(良性前列腺增生)诊断与治疗中的作用。
Rev Urol. 2004;6 Suppl 9(Suppl 9):S53-9.
3
Metabolism of the new alpha-1A-adrenergic receptor antagonist, phthalimide-phenylpiperazine analog (RWJ-69442), in rat, dog and human hepatic S9 fractions, and in rats.
新型α-1A-肾上腺素能受体拮抗剂邻苯二甲酰亚胺-苯基哌嗪类似物(RWJ-69442)在大鼠、犬和人肝脏S9组分以及大鼠体内的代谢。
Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):113-20. doi: 10.1007/BF03226416.
4
Metabolism of the alpha-1A-adrenergic receptor antagonist, pyridine-phenylpiperazine analog (RWJ-69597), in rat, dog and human hepatic S9 fractions -API-MS/MS identification of metabolites.α-1A-肾上腺素能受体拮抗剂吡啶-苯基哌嗪类似物(RWJ-69597)在大鼠、犬和人肝脏S9组分中的代谢——代谢产物的API-MS/MS鉴定
Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):105-11. doi: 10.1007/BF03226415.
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Variable selection and specification of robust QSAR models from multicollinear data: arylpiperazinyl derivatives with affinity and selectivity for alpha2-adrenoceptors.从多重共线性数据中选择变量并构建稳健的定量构效关系(QSAR)模型:对α2-肾上腺素能受体具有亲和力和选择性的芳基哌嗪衍生物
J Comput Aided Mol Des. 2004 Jul-Sep;18(7-9):495-509. doi: 10.1007/s10822-004-5203-7.
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A pharmacoeconomic analysis of patients with symptoms of benign prostatic hyperplasia.
Pharmacoeconomics. 1997 Jun;11(6):550-65. doi: 10.2165/00019053-199711060-00004.
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Urol Res. 1997;25 Suppl 1:S13-9. doi: 10.1007/BF00942042.
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Urol Res. 1993;21(5):319-23. doi: 10.1007/BF00296828.