Tisdale James E
College of Pharmacy, Purdue University, and the School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Can Pharm J (Ott). 2016 May;149(3):139-52. doi: 10.1177/1715163516641136. Epub 2016 Apr 8.
Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration. Pharmacokinetic drug interactions associated with the highest risk of TdP include antifungal agents, macrolide antibiotics (except azithromycin) and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide. Other important pharmacokinetic interactions include antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting with flecainide, quinidine or thioridazine. Pharmacists play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through knowledge of drugs that are associated with a known or possible risk of TdP, individualized assessment of risk of drug-induced QTc interval prolongation, awareness of drug interactions most likely to result in TdP and attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease. Treatment of hemodynamically stable TdP consists of discontinuation of the offending drug(s), correction of electrolyte abnormalities and administration of intravenous magnesium sulfate 1 to 2 g.
尖端扭转型室速（TdP）是一种危及生命的心律失常，与心电图上校正QT（QTc）间期延长有关。加拿大有100多种药物，包括广泛使用的抗生素、抗抑郁药、心血管药物及许多其他药物，可能导致QTc间期延长和TdP。TdP的危险因素包括QTc间期>500毫秒、QTc间期较治疗前值增加≥60毫秒、高龄、女性、急性心肌梗死、射血分数降低的心力衰竭、低钾血症、低镁血症、低钙血症、心动过缓、使用利尿剂治疗以及因药物相互作用导致血浆中QTc间期延长药物浓度升高、肾病患者肾排泄药物剂量调整不当和静脉快速给药。与TdP风险最高相关的药代动力学药物相互作用包括抗真菌药、大环内酯类抗生素（阿奇霉素除外）以及治疗人类免疫缺陷病毒的药物与胺碘酮、丙吡胺、多非利特或匹莫齐特相互作用。其他重要的药代动力学相互作用包括抗抑郁药（安非他酮、度洛西汀、氟西汀、帕罗西汀）与氟卡尼、奎尼丁或硫利达嗪相互作用。药剂师通过了解与已知或可能的TdP风险相关的药物、对药物诱导的QTc间期延长风险进行个体化评估、知晓最有可能导致TdP的药物相互作用以及关注肾病患者肾排泄的QTc间期延长药物的剂量减少，在将药物诱导的QTc间期延长和TdP风险降至最低方面发挥着重要作用。血流动力学稳定的TdP的治疗包括停用相关药物、纠正电解质异常以及静脉注射1至2克硫酸镁。
