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[血管紧张素转换酶抑制剂(ACEI)和血管紧张素II受体拮抗剂。药理学特性]

[Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor antagonists. Pharmacologic features].

作者信息

Vaz-da-Silva M

机构信息

Instituto de Farmacologia e Terapêutica da Faculdade de Medicina da Universidade do Porto.

出版信息

Rev Port Cardiol. 2000 Dec;19 Suppl 2:II19-32.

Abstract

The development of pharmacological agents that block the renin-angiotensin system (RAS) specifically have helped to define all the components of the system and their contribution to blood-pressure control and to the pathogenesis of hypertension, congestive heart failure and chronic renal failure. The angiotensin converting-enzyme inhibitors (ACEi) are among all available drugs that interfere with the RAS, the most efficient, so far, in the treatment of several cardiovascular diseases, with comfortable posologic schemes and an acceptable safety profile. The most important difference between them are more related to pharmacokinetic profile rather than to pharmacodynamic characteristics. With the use of ACEi the interference with other neurohumoral systems is unavoidable and the controversy has been pharmacologically and clinically installed. With the advent of oral selective AT1 angiotensin II receptor blockers (ARB) the pharmacological interference became eventually much more selective. Their antihypertensive efficacy is identical and their tolerability is better than that showed by ACEi. The ARBs differ mainly in their pharmacokinetics and in their binding capacity to the AT1 angiotensin receptor. The results of several ongoing clinical trials will show if the ARBs as ACEi will be capable to protect target-organs and to promote a significant reduction in cardiovascular morbility and mortality. In parallel there is an intense experimental and clinical research with other groups of drugs which also markedly interfere with RAS: renin inhibitors, chymase inhibitors and simultaneous inhibitors of vasopeptidases (ACE, endothelin converting-enzyme, neutral endopeptidase). From the pharmacological point of view, it is now possible to block effectively RAS with some relevant clinical results that will be certainly widen in the near future.

摘要

特异性阻断肾素 - 血管紧张素系统(RAS)的药物研发,有助于明确该系统的所有组成部分及其在血压控制、高血压、充血性心力衰竭和慢性肾衰竭发病机制中的作用。血管紧张素转换酶抑制剂(ACEi)是所有干扰RAS的可用药物中,目前治疗多种心血管疾病最有效的药物,其给药方案简便且安全性可接受。它们之间最重要的差异更多地与药代动力学特征而非药效学特性相关。使用ACEi时,对其他神经体液系统的干扰不可避免,并且在药理学和临床方面都存在争议。随着口服选择性AT1血管紧张素II受体阻滞剂(ARB)的出现,药理学干扰最终变得更加具有选择性。它们的降压效果相同,耐受性优于ACEi。ARB主要在药代动力学以及与AT1血管紧张素受体的结合能力方面存在差异。几项正在进行的临床试验结果将表明,ARB是否与ACEi一样能够保护靶器官,并显著降低心血管发病率和死亡率。与此同时,针对其他也能显著干扰RAS的药物组开展了大量实验和临床研究:肾素抑制剂、糜酶抑制剂以及血管肽酶(ACE、内皮素转换酶、中性内肽酶)的联合抑制剂。从药理学角度来看,现在已经能够有效阻断RAS,并取得了一些相关临床结果,而且在不久的将来肯定会进一步扩大。

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