Ehret Georg B, Desmeules Jules A, Broers Barbara
Johns Hopkins University School of Medicine, McKusick Nathans Institute of Genetic Medicine, Baltimore, MD 21205, USA.
Expert Opin Drug Saf. 2007 May;6(3):289-303. doi: 10.1517/14740338.6.3.289.
Methadone is used as the pharmacologic mainstay for substitution for illegal opiates and as analgesic for chronic or cancer-related pain. Given the benefits of methadone substitution for illicit opioids, the finding of an association between methadone and prolongation of cardiac depolarization (QT prolongation) and torsades de pointes is of great concern. QT prolongation can occur with many drugs and is a potentially lethal adverse drug reaction, necessitating risk monitoring and therapeutic alternatives in some patients. Recent studies suggest that QT prolongation with methadone is context dependent: occurrence is more frequent with high doses of methadone, concomitant administration of CYP3A4 inhibitors, hypokalemia, hepatic failure, administration of other QT prolonging drugs and pre-existing heart disease. The valued benefit of methadone substitution therapy on the one hand and the increased cardiovascular risk in particular situations on the other illustrate the difficulties in dealing with drug-induced QT prolongation in general.
美沙酮被用作替代非法阿片类药物的药理学主要药物，以及用于慢性或癌症相关疼痛的镇痛药。鉴于美沙酮替代非法阿片类药物的益处，美沙酮与心脏去极化延长（QT延长）和尖端扭转型室速之间存在关联这一发现令人高度关注。许多药物都可导致QT延长，这是一种潜在致命的药物不良反应，在某些患者中需要进行风险监测并采用其他治疗方法。最近的研究表明，美沙酮引起的QT延长取决于具体情况：高剂量美沙酮、同时使用CYP3A4抑制剂、低钾血症、肝功能衰竭、使用其他导致QT延长的药物以及原有心脏病时，QT延长的发生率更高。一方面美沙酮替代疗法有重要益处，另一方面在特定情况下心血管风险增加，这总体上说明了应对药物引起的QT延长存在困难。
