McDevitt D G
Department of Pharmacology and Clinical Pharmacology, Ninewells Hospital, Dundee, U.K.
Eur Heart J. 1987 Dec;8 Suppl M:9-14. doi: 10.1093/eurheartj/8.suppl_m.9.
Beta-adrenoceptor blocking drugs can be characterised by their pharmacokinetic properties. One of the most important factors appears to be lipid solubility. Lipophilic beta-adrenoceptor antagonists, such as propranolol, oxprenolol and metoprolol, are cleared by the liver and undergo hepatic 'first-pass' metabolism. This results in low bioavailability, substantial interpatient variability in 'steady-state' plasma drug concentrations, rapid elimination half-lives and the possibility of drug interactions with other drugs such as pentobarbitone and cimetidine which affect hepatic enzymes. In addition, lipid soluble drugs are distributed widely within the body and penetrate the brain easily and rapidly. This may result in centrally mediated adverse effects such as vivid dreams. In contrast, the more water-soluble beta-adrenoceptor blocking drugs, such as atenolol, sotalol and nadolol, are cleared by the kidney unchanged. They show less interpatient variation in plasma levels, have longer elimination half-lives and do not interact with drugs affecting hepatic enzymes. They penetrate the central nervous system less easily and cause less central side-effect. Between these two extremes, there are several drugs like betaxolol, bisoprolol and pindolol, which are cleared partly by the liver and partly by the kidney. Their clearance is only altered by severe renal or hepatic disease, and they do not appear to interact with enzyme inducers or inhibitors.
β-肾上腺素受体阻断药可根据其药代动力学特性进行分类。其中一个最重要的因素似乎是脂溶性。亲脂性β-肾上腺素受体拮抗剂，如普萘洛尔、氧烯洛尔和美托洛尔，经肝脏清除并经历肝脏“首过”代谢。这导致生物利用度低、患者间“稳态”血浆药物浓度存在显著差异、消除半衰期短，以及与其他影响肝酶的药物（如戊巴比妥和西咪替丁）发生药物相互作用的可能性。此外，脂溶性药物在体内分布广泛，能迅速且容易地穿透大脑。这可能导致中枢介导的不良反应，如生动的梦境。相比之下，水溶性更强的β-肾上腺素受体阻断药，如阿替洛尔、索他洛尔和纳多洛尔，经肾脏以原形清除。它们在血浆水平上的患者间差异较小，消除半衰期更长，且不与影响肝酶的药物相互作用。它们较难穿透中枢神经系统，引起的中枢副作用也较少。在这两个极端之间，有几种药物，如倍他洛尔、比索洛尔和吲哚洛尔，部分经肝脏清除，部分经肾脏清除。只有在严重的肾脏或肝脏疾病时，它们的清除率才会改变，而且它们似乎不与酶诱导剂或抑制剂相互作用。
