Singh B N, Sarma J S
Division of Cardiology 111E, VA Medical Center of West Los Angeles, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
Curr Cardiol Rep. 2001 Jul;3(4):314-23. doi: 10.1007/s11886-001-0086-x.
The decline in the use of sodium channel blockers has led to an expanding use of b-blockers and complex class III agents such as sotalol and amiodarone for controlling cardiac arrhythmias. Success with these agents in the context of their side effects has spurred the development of compounds with simpler ion channel-blocking properties with less complex adverse reactions. The resulting so-called pure class III agents were found to have antifibrillatory effects in atrial fibrillation (AF) and flutter, as well as in ventricular tachyarrhythmias. Pure class III compounds are effective in inducing acute chemical conversion of AF, in preventing paroxysmal AF, and in maintaining sinus rhythm in patients with persistent AF restored to sinus rhythm. Examples of such compounds are dofetilide, which selectively blocks IKr, and ibutilide, available only as an intravenous agent, which blocks the IKr and augments the inactivated Na+ current in atrial myocytes. Dofetilide and ibutilide have been introduced into clinical practice. Azimilide is the first of the class III agents that blocks both components (IKr and IKs) of the delayed rectifier current, which may confer certain electrophysiologic advantages. The potential therapeutic niche of ibutilide, dofetilide, and azimilide in the control of cardiac arrhythmias forms the basis of this review.
钠通道阻滞剂使用的减少导致β受体阻滞剂以及索他洛尔和胺碘酮等复杂的Ⅲ类药物在控制心律失常方面的使用不断增加。这些药物在存在副作用的情况下取得的成功促使人们开发具有更简单离子通道阻滞特性且不良反应更简单的化合物。由此产生的所谓纯Ⅲ类药物被发现对心房颤动(AF)和心房扑动以及室性快速心律失常具有抗纤颤作用。纯Ⅲ类化合物可有效诱导AF的急性化学复律、预防阵发性AF以及维持恢复窦性心律的持续性AF患者的窦性心律。此类化合物的例子包括选择性阻断IKr的多非利特,以及仅作为静脉用药的伊布利特,它可阻断IKr并增强心房肌细胞中失活的Na+电流。多非利特和伊布利特已被应用于临床实践。阿齐利特是首个可阻断延迟整流电流的两个成分(IKr和IKs)的Ⅲ类药物,这可能赋予其某些电生理优势。伊布利特、多非利特和阿齐利特在控制心律失常方面的潜在治疗优势构成了本综述的基础。