Davey M J
Pfizer International, Sandwich, Kent, United Kingdom.
Am J Med. 1989 Aug 16;87(2A):36S-44S. doi: 10.1016/0002-9343(89)90112-5.
The drug treatment of mild hypertension has been shown to afford protection against fatal and nonfatal strokes, congestive heart failure, progression to more severe levels of hypertension, and all-cause mortality, but not against the complications of coronary artery disease. The lack of benefit against coronary artery disease may result from failure to reduce other risk factors or because the drugs employed increased coronary risk. It can be taken as axiomatic that effective preventive antihypertensive therapy is more likely with drugs with mechanisms and sites of action that are focused on the underlying pathophysiology than with drugs that lower blood pressure by means unrelated to the hypertensive process. Adrenergic predominance plays a major role in the initiation and maintenance of essential hypertension and, consequently, the alpha-adrenergic receptor inhibitors were among the first substances to receive serious consideration as antihypertensive agents. However, since these drugs are nonselective, feedback control of transmitter norepinephrine was lost and, consequently, the clinical expectations of the early alpha-adrenergic receptor inhibitors in the treatment of high blood pressure were not fulfilled. The discovery of selective postjunctional alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, which preserve feedback control of transmitter norepinephrine release, was the crucially important step in the development of specific drugs to combat the hyperactivity of adrenergic vasoconstrictor nerves in hypertension. These drugs have been shown to normalize hemodynamics in hypertensive patients. They lower blood pressure through a reduction in peripheral resistance at rest and during exercise, independent of changes in heart rate and blood pressure, with minimal reflex activation or tolerance development. Alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, represent an attractive choice for initial therapy in all grades of hypertension and are especially appropriate in hypertensive patients with congestive heart failure, asthma and chronic obstructive airways disease, renal impairment, diabetes mellitus, hyperlipidemia, benign prostatic hyperplasia, or gout, and in those involved in vigorous work, sports, or exercise. There are no known contraindications to these drugs, except in patients who are sensitive to quinazolines.
轻度高血压的药物治疗已被证明可预防致命和非致命性中风、充血性心力衰竭、高血压进展至更严重程度以及全因死亡率，但对冠状动脉疾病的并发症无效。对冠状动脉疾病缺乏益处可能是由于未能降低其他危险因素，或者是因为所使用的药物增加了冠状动脉风险。可以认为，与通过与高血压过程无关的方式降低血压的药物相比，作用机制和作用部位聚焦于潜在病理生理学的药物更有可能实现有效的预防性抗高血压治疗。肾上腺素能占优势在原发性高血压的发生和维持中起主要作用，因此，α-肾上腺素能受体抑制剂是最早被认真考虑作为抗高血压药物的物质之一。然而，由于这些药物是非选择性的，去甲肾上腺素递质的反馈控制丧失，因此，早期α-肾上腺素能受体抑制剂治疗高血压的临床预期未能实现。选择性节后α1-肾上腺素能受体抑制剂如哌唑嗪和多沙唑嗪的发现，保留了去甲肾上腺素递质释放的反馈控制，这是开发对抗高血压中肾上腺素能血管收缩神经功能亢进的特异性药物的关键重要步骤。这些药物已被证明可使高血压患者的血流动力学正常化。它们通过降低静息和运动时的外周阻力来降低血压，与心率和血压变化无关，反射激活或耐受性发展最小。α1-肾上腺素能受体抑制剂如哌唑嗪和多沙唑嗪是各级高血压初始治疗的有吸引力选择，尤其适用于患有充血性心力衰竭、哮喘和慢性阻塞性气道疾病、肾功能损害、糖尿病、高脂血症、良性前列腺增生或痛风的高血压患者，以及从事剧烈工作、运动或锻炼的患者。除了对喹唑啉敏感的患者外，这些药物没有已知的禁忌症。
