Camm A J
Department of Cardiology, St George's Hospital Medical School, London, UK.
Europace. 2000 Jul;1 Suppl C:C16-22.
In the light of studies demonstrating the serious safety problems of antiarrhythmic agents with class I activity, research and development efforts have focused largely on drugs with a class III mechanism of action. Most of the newer agents target the rapid component of the delayed rectifier potassium current (I(Kr)). In the case of dofetilide, the mechanism of action is relatively pure, with single I(Kr) channel blocking activity. Other agents have a wider spectrum of activity. Azimilide blocks both the rapid I(Kr) and slow I(Ks) potassium currents and ibutilide also augments the inward sodium current. Clinical investigation of these agents has shown them to be effective antiarrhythmic drugs with a number of advantages over existing agents, particularly in terms of safety. Dronedarone and tedisamil also have multichannel blocking actions and are in earlier stages of clinical development. Until now, therapeutic choices have been limited and far from ideal. It is hoped that the availability of the newer class III agents will at least provide greater choice of therapy and hopefully will bring us closer to therapeutic ideals in the management of arrhythmia.
鉴于多项研究表明具有I类活性的抗心律失常药物存在严重的安全问题，研发工作主要集中在具有III类作用机制的药物上。大多数新型药物作用于延迟整流钾电流（I(Kr)）的快速成分。就多非利特而言，其作用机制相对单一，具有单一的I(Kr)通道阻断活性。其他药物的活性谱更广。阿齐利特可阻断快速I(Kr)和缓慢I(Ks)钾电流，伊布利特还可增强内向钠电流。对这些药物的临床研究表明，它们是有效的抗心律失常药物，与现有药物相比具有许多优势，尤其是在安全性方面。决奈达隆和替地沙米也具有多通道阻断作用，目前正处于临床开发的早期阶段。到目前为止，治疗选择有限且远非理想。希望新型III类药物的出现至少能提供更多的治疗选择，并有望使我们在心律失常的治疗管理上更接近治疗理想状态。
