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抗血小板药物。一项比较性综述。

Antiplatelet drugs. A comparative review.

作者信息

Schrör K

机构信息

Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.

出版信息

Drugs. 1995 Jul;50(1):7-28. doi: 10.2165/00003495-199550010-00002.

Abstract

Antiplatelet therapy has become a useful means of preventing acute thromboembolic artery occlusions in cardiovascular diseases. The rationale for this is an enhanced activity of circulating platelets and release of platelet-derived vasoactive mediators, probably due to endothelial dysfunction. This review discusses the current status of 4 major classes of antiplatelet compounds: (i) aspirin and related drugs active via cyclo-oxygenase product formation; (ii) thienopyridines (ticlopidine and clopidogrel); (iii) direct thrombin inhibitors (e.g. hirudin); and (iv) GPIIb/IIIa receptor antagonists [e.g. abciximab (c7E3 Fab)]. It is concluded that aspirin is the drug of choice for long term oral treatment, specifically for secondary prevention of myocardial infarction, and is also a suitable basic but not maximally efficient drug in percutaneous transluminal coronary angioplasty (PTCA) and platelet activation during clot lysis. Ticlopidine has a similar indication and may be superior to aspirin in prevention of ischaemic stroke and peripheral arterial occlusion. Direct thrombin inhibitors and glycoprotein GPIIb/IIIa receptor antagonists need further investigation in clinical trials. To date, these compounds have a higher bleeding risk and currently they are available only for short term parenteral application. They are superior to aspirin in acute platelet-dependent ischaemic syndromes, such as unstable angina, and in connection with therapeutic PTCA because of their high potency in preventing platelet-dependent reocclusion. Future developments include more selective thromboxane inhibitors, i.e. combined-mode agents; nonpeptide clot-specific thrombin inhibitors with longer lasting action and nonpeptide fibrinogen receptor antagonists.

摘要

抗血小板治疗已成为预防心血管疾病急性血栓栓塞性动脉闭塞的一种有效手段。其理论依据是循环血小板活性增强以及血小板衍生的血管活性介质释放,这可能是由于内皮功能障碍所致。本综述讨论了4大类抗血小板化合物的现状:(i)通过环氧化酶产物形成发挥作用的阿司匹林及相关药物;(ii)噻吩吡啶类(噻氯匹定和氯吡格雷);(iii)直接凝血酶抑制剂(如水蛭素);(iv)糖蛋白IIb/IIIa受体拮抗剂[如阿昔单抗(c7E3 Fab)]。得出的结论是,阿司匹林是长期口服治疗的首选药物,特别是用于心肌梗死的二级预防,在经皮腔内冠状动脉成形术(PTCA)和血栓溶解过程中的血小板激活方面也是一种合适的基础药物,但并非最有效的药物。噻氯匹定有类似的适应证,在预防缺血性卒中和外周动脉闭塞方面可能优于阿司匹林。直接凝血酶抑制剂和糖蛋白GPIIb/IIIa受体拮抗剂需要在临床试验中进一步研究。迄今为止,这些化合物有较高的出血风险,目前仅可用于短期胃肠外给药。它们在急性血小板依赖性缺血综合征(如不稳定型心绞痛)以及与治疗性PTCA相关的情况下优于阿司匹林,因为它们在预防血小板依赖性再闭塞方面效力较高。未来的发展包括更具选择性的血栓素抑制剂,即联合模式药物;具有更持久作用的非肽类凝块特异性凝血酶抑制剂和非肽类纤维蛋白原受体拮抗剂。

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