非抗心律失常药的致心律失常作用及相关危险因子

Proarrhythmic effects of non-antiarrhythmic agents and related risk factors

获得性QT间期延长综合征 (LQTS)可由抗心律失常药以外的药物引起 ,包括促胃肠动力药、止吐药、抗心律失常药以外的心血管药物、抗菌药、静脉麻醉药、抗精神病药、抗抑郁药、抗组胺药等 ,它们可阻断心脏的电压门控性通道特别是延迟整流钾电流的快速激活成分 (IKr)、延长动作电位时程(APD)及QT间期、诱发尖端扭转型室性心动过速(TdP)等快速型室性心律失常。一些常见的危险因子如女性 ,电解质紊乱 (特别是低钾、低镁 ) ,临床显著的心动过缓或心脏疾病 ,遗传性LQTS ,肝、肾功能障碍 ,与其他药物合用所致的药动学与药效学的相互作用等通过减少复极储备 。

Acquired long QT syndrome can be induced by non-antiarrhythmic agents. These drugs include gastrointestinal prokinetics, antiemetics, non-antiarrhythmic cardiovascular drugs, antibiotics, intravenous anesthetics, antipsychotics, antidepressants, and antihistamines etc. They share the potential to block cardiac voltage-gated potassium channels, particularly the rapid component (I Kr) of the delayed rectifier potassium current (I K), prolong the QT interval and induce the ventricular tachyarrhythmias like torsades de pointes. Several risk factors can facilitate the proarrhythmic effects of these drugs by reducing the repolarization reserve. These risk factors include female gender, electrolyte imbalance (especially hypokalemia, hypomagnesemia), clinically significant bradycardia or heart disease, congenital long QT syndrome, impaired hepatic/renal function and the pharmacokinetic/pharmacodynamic interactions in the combined treatment with other drugs.