Farmer J A, Gotto A M
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Drug Saf. 1994 Nov;11(5):301-9. doi: 10.2165/00002018-199411050-00002.
The available antihyperlipidaemic drugs are generally safe and effective, and major systemic adverse effects are uncommon. However, because of their complex mechanisms of action, careful monitoring is required to identify and correct potential drug interactions. Bile acid sequestrants are the most difficult of these agents to administer concomitantly, because their nonspecific binding results in decreased bioavailability of a number of other drugs, including thiazide diuretics, digitalis preparations, beta-blockers, coumarin anticoagulants, thyroid hormones, fibric acid derivatives and certain oral antihyperglycaemia agents. Although the incidence is low, nicotinic acid may cause hepatic necrosis and so should not be used with drugs that adversely affect hepatic structure or function. With the HMG-CoA reductase inhibitors, relatively new agents for which clinical data are still being accumulated, the major problems appears to be rhabdomyolysis, associated with the concomitant use of cyclosporin, fibric acid derivatives or erythromycin, and mild, intermittent hepatic abnormalities that may be potentiated by other hepatotoxic drugs. Fibrates also have the potential to cause rhabdomyolysis, although generally only in combination with HMG-CoA reductase inhibitors, and are subject to binding by concomitantly administered bile acid sequestrants. The major interaction involving probucol is a possible additive effect with drugs or clinical conditions that alter the prolongation of the QTc interval, increasing the potential for polymorphic ventricular tachycardia.
现有的降血脂药物一般安全有效，严重的全身性不良反应并不常见。然而，由于其作用机制复杂，需要仔细监测以识别和纠正潜在的药物相互作用。胆汁酸螯合剂是这些药物中最难同时使用的，因为它们的非特异性结合会导致许多其他药物的生物利用度降低，包括噻嗪类利尿剂、洋地黄制剂、β受体阻滞剂、香豆素抗凝剂、甲状腺激素、纤维酸衍生物和某些口服降糖药。虽然烟酸引起肝坏死的发生率较低，但不应与对肝脏结构或功能有不利影响的药物合用。对于HMG-CoA还原酶抑制剂这种临床数据仍在积累的相对较新的药物，主要问题似乎是横纹肌溶解，这与同时使用环孢素、纤维酸衍生物或红霉素有关，以及可能被其他肝毒性药物加重的轻度、间歇性肝脏异常。纤维酸衍生物也有可能导致横纹肌溶解，尽管通常仅在与HMG-CoA还原酶抑制剂合用时发生，并且会受到同时服用的胆汁酸螯合剂的结合作用影响。与普罗布考有关的主要相互作用是，它可能与改变QTc间期延长的药物或临床情况产生相加作用，增加多形性室性心动过速的可能性。
