Dollery C T
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, U.K.
J Cardiovasc Pharmacol. 1988;11 Suppl 2:S1-4.
beta-Adrenoceptor blocking drugs were originally devised as a treatment for angina pectoris. Their activity as antihypertensive agents was discovered as a result of observations made during angina trials. In the early days of study of these agents, there was a great deal of debate about the relative importance of selectivity for beta 1- and beta 2-receptors, membrane stabilising actions, and the presence or absence of partial agonist activity. It has become clear that these ancillary properties have little effect upon efficacy in angina and hypertension but they have some effect upon the adverse reactions profile. Several secondary prevention trials have established that mortality can be reduced by 25-30% in the first 2-3 years after acute myocardial infarction with drugs such as timolol and propranolol. There have been some negative trials, particularly with oxprenolol, but the pooled evidence suggests a highly significant benefit. The available primary prevention data are mainly derived from trials in hypertensive patients, who have a substantially increased risk of myocardial infarction. Overall, the hypertension trials show only a small reduction in the incidence of acute myocardial infarction, averaging about 6%. This reduction is less than would be expected from the contribution of hypertension as a risk factor for myocardial infarction. Development of new beta-adrenoceptor blocking drugs continues. Development of ancillary properties of agents derived from the labetalol structure has also attracted interest. Various combinations of beta 1-blockade, beta 2-agonist activity, and alpha-receptor blockade seem possible. After 20 years of experience, beta-blockade still presents opportunities for new developments.
β-肾上腺素能受体阻断药最初被设计用于治疗心绞痛。它们作为抗高血压药物的活性是在心绞痛试验期间的观察中发现的。在这些药物研究的早期，关于β1和β2受体选择性、膜稳定作用以及是否存在部分激动剂活性的相对重要性存在大量争论。现已明确，这些辅助特性对心绞痛和高血压的疗效影响不大，但对不良反应谱有一定影响。几项二级预防试验已证实，使用噻吗洛尔和普萘洛尔等药物可在急性心肌梗死后的头2至3年内将死亡率降低25%至30%。也有一些阴性试验，尤其是氧烯洛尔的试验，但汇总证据表明有非常显著的益处。现有的一级预防数据主要来自高血压患者的试验，这些患者发生心肌梗死的风险大幅增加。总体而言，高血压试验显示急性心肌梗死的发生率仅略有降低，平均约为6%。这种降低低于作为心肌梗死危险因素的高血压所预期的降低幅度。新型β-肾上腺素能受体阻断药的研发仍在继续。源自拉贝洛尔结构的药物辅助特性的研发也引起了关注。β1阻断、β2激动剂活性和α受体阻断的各种组合似乎都是可能的。经过20年的经验，β阻断仍然为新的发展提供了机会。
