Woosley R L, Roden D M
Am J Cardiol. 1987 Apr 30;59(11):19E-25E. doi: 10.1016/0002-9149(87)90197-4.
All currently known antiarrhythmic agents can induce or worsen arrhythmias. Inappropriate dosage selection, mistakenly based on pharmacokinetic data from "normal" subjects, may result in adverse reactions when an antiarrhythmic drug is given to patients. Unexpected variations in drug clearance can increase plasma concentration of antiarrhythmic agents and aggravate arrhythmias. Changes in the rate of drug metabolism by the liver, e.g., due to cessation of alcohol or drugs that induce hepatic metabolism, can reduce drug clearance, making a previously well-tolerated dose toxic. Another possible explanation for adverse drug reactions is nonlinear protein binding. Recently, genetic determinants of drug metabolism have been identified as explanations of interindividual variations in drug responsiveness. Finally, the interactions of antiarrhythmic agents may also lead to aggravation of arrhythmias. A better understanding of the pharmacology of antiarrhythmic agents can reduce, if not prevent, the occurrence of potentially lethal proarrhythmic events.
目前已知的所有抗心律失常药物都可能诱发或加重心律失常。基于来自“正常”受试者的药代动力学数据错误地选择不当剂量，在给患者使用抗心律失常药物时可能会导致不良反应。药物清除率的意外变化会增加抗心律失常药物的血浆浓度并加重心律失常。肝脏药物代谢速率的变化，例如由于戒酒或停止使用诱导肝代谢的药物，会降低药物清除率，使先前耐受性良好的剂量变得有毒。药物不良反应的另一个可能解释是非线性蛋白结合。最近，药物代谢的遗传决定因素已被确定为个体间药物反应性差异的解释。最后，抗心律失常药物之间的相互作用也可能导致心律失常加重。更好地了解抗心律失常药物的药理学，即使不能预防，也可以减少潜在致命性促心律失常事件的发生。
