Taylor S H
Department of Medical Cardiology, General Infirmary, Leeds, United Kingdom.
Am J Med. 1989 Aug 16;87(2A):2S-11S. doi: 10.1016/0002-9343(89)90107-1.
Doxazosin is the latest in a series of highly selective postsynaptic alpha 1-adrenoceptor inhibitors. It is readily absorbed, with high bioavailability and a relatively long plasma half-life, neither of which property is influenced by age. This accounts for the prolonged pharmacologic activity of doxazosin following a single oral dose. Its prime pharmacodynamic activity resides in its ability to counter sympathetic vasoconstriction of the systemic arteriolar resistance vessels and venous capacitance system, which enables the drug to target the major pathophysiologic abnormality in hypertension, i.e., the generalized systemic arteriolar constriction. The widespread vasodilation induced by doxazosin relieves both cardiac preload and afterload and, consequently, reduces left ventricular wall stress and myocardial oxygen consumption. In hypertension, doxazosin reduces blood pressure both at rest and during exercise by reduction of systemic vascular resistance without precipitating substantial reflex cardiac stimulation. The effects are maximal on the standing blood pressure between two and four hours after ingestion; due to doxazosin's relatively slow absorption, postural hypotension is infrequent. Its antihypertensive activity is maintained over 24 hours following a single oral dose, and the optimal dose range is 2 to 8 mg once daily. The antihypertensive efficacy of doxazosin has been shown to be comparable with that of other alpha-adrenoceptor inhibitors, beta-blocking drugs, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors. In contrast to other conventional antihypertensive drugs, a unique feature of alpha-adrenoceptor-inhibiting drugs, including doxazosin, is their ability to reduce the plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and to increase high-density lipoprotein cholesterol concentration. This contrasts with the opposite effect on lipid levels induced by hydrochlorothiazide and atenolol seen in comparative studies. Side effects show no predilection for any organ system, and the overall incidence of such effects compares well with those of other commonly used antihypertensive drugs. This unique combination of antihypertensive efficacy and favorable effect on blood lipid levels indicates that once-daily treatment with doxazosin holds considerable promise in the treatment of hypertension, both from the point of view of its antihypertensive efficacy and also from its primary preventative potential.
多沙唑嗪是一系列高选择性突触后α1肾上腺素能受体抑制剂中的最新药物。它易于吸收，生物利用度高，血浆半衰期相对较长，这两种特性均不受年龄影响。这就解释了单次口服多沙唑嗪后其药理活性的延长。其主要药效学活性在于它能够对抗全身小动脉阻力血管和静脉容量系统的交感神经血管收缩，这使得该药物能够针对高血压的主要病理生理异常，即全身性小动脉普遍收缩。多沙唑嗪引起的广泛血管舒张可减轻心脏前负荷和后负荷，从而降低左心室壁应力和心肌耗氧量。在高血压患者中，多沙唑嗪通过降低全身血管阻力，在静息和运动时均能降低血压，且不会引发明显的反射性心脏刺激。服药后两到四小时对站立位血压的影响最大；由于多沙唑嗪吸收相对较慢，体位性低血压并不常见。单次口服后其降压活性可维持24小时，最佳剂量范围为每日一次2至8毫克。多沙唑嗪的降压疗效已被证明与其他α肾上腺素能受体抑制剂、β受体阻滞剂、利尿剂、钙拮抗剂和血管紧张素转换酶抑制剂相当。与其他传统降压药物相比，包括多沙唑嗪在内的α肾上腺素能受体抑制药物的一个独特特点是它们能够降低甘油三酯、总胆固醇和低密度脂蛋白胆固醇的血浆浓度，并提高高密度脂蛋白胆固醇浓度。这与比较研究中氢氯噻嗪和阿替洛尔对血脂水平的相反作用形成对比。副作用对任何器官系统均无偏好，此类副作用的总体发生率与其他常用降压药物相当。降压疗效和对血脂水平的有利影响这一独特组合表明，从降压疗效及其一级预防潜力的角度来看，每日一次服用多沙唑嗪在高血压治疗中具有很大的前景。
