van Zwieten P A
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Drugs. 1993 Apr;45(4):509-17. doi: 10.2165/00003495-199345040-00003.
Haemodynamically, the combination of alpha 1- and beta-adrenoceptor antagonists is a logical one. alpha 1-Adrenoceptor blockade causes vasodilatation and hence counteracts elevated peripheral vascular resistance, the most consistent haemodynamic derangement in established essential hypertension. beta-Blockers, which lower elevated blood pressure by a different (not yet clearly understood) mechanism, suppress the reflex tachycardia triggered by vasodilatation. Combined alpha/beta-adrenoceptor blockade can be obtained by the simultaneous administration of both types of adrenoceptor antagonists, but also by giving drugs that possess alpha- and beta-adrenoceptor antagonistic activity in the same molecule. Carvedilol and labetalol are the best known examples of such combined alpha/beta-adrenoceptor antagonists, although their pharmacodynamic profile is a result of different receptor selectivity of their component stereoisomers, rather than combined alpha/beta-blocking activity in a single chemical entity. Both compounds have been investigated clinically in the treatment of essential hypertension in moderate-to-large scale trials. A few newer combined alpha/beta-adrenoceptor antagonists, such as amosulalol, arotinolol and medroxalol have been developed, but clinical data on these compounds are relatively scarce.
从血流动力学角度来看，α1和β肾上腺素能受体拮抗剂联合使用是合理的。α1肾上腺素能受体阻滞可导致血管舒张，从而抵消外周血管阻力升高，这是确诊的原发性高血压中最常见的血流动力学紊乱。β受体阻滞剂通过不同（尚未完全明确）的机制降低血压升高，可抑制血管舒张引发的反射性心动过速。联合α/β肾上腺素能受体阻滞可通过同时给予两种类型的肾上腺素能受体拮抗剂来实现，也可通过给予在同一分子中具有α和β肾上腺素能受体拮抗活性的药物来实现。卡维地洛和拉贝洛尔是这类联合α/β肾上腺素能受体拮抗剂中最知名的例子，尽管它们的药效学特征是其组成立体异构体具有不同受体选择性的结果，而非单一化学实体中联合的α/β阻滞活性。这两种化合物均已在中大规模试验中针对原发性高血压的治疗进行了临床研究。一些较新的联合α/β肾上腺素能受体拮抗剂，如阿唑洛尔、阿罗洛尔和美多心安已被研发出来，但关于这些化合物的临床数据相对较少。
