Anderson J L, Prystowsky E N
University of Utah and St. Vincent'sHospital, Northside Cardiology, Salt Lake City, USA.
Am Heart J. 1999 Mar;137(3):388-409. doi: 10.1016/s0002-8703(99)70484-9.
Sotalol, the most recently approved oral antiarrhythmic drug, has a unique pharmacologic profile. Its electrophysiology is explained by nonselective beta-blocking action as well as class III antiarrhythmic activity (including fast-activating cardiac membrane-delayed rectifier current blockade), which leads to increases in action potential duration and refractory period throughout the heart and in QT interval on the surface electrocardiogram. Its better hemodynamic tolerance than other beta-blockers may be a result of enhanced inotropy associated with class III activity. Sotalol's ability to suppress ventricular ectopy is similar to that of class I agents and better than that of standard beta-blockers. Unlike class I agents, its use in a postinfarction trial was not associated with increased mortality rate. Therapeutically, it has shown superior efficacy for prevention of recurrent ventricular tachycardia and ventricular fibrillation, which was the basis for its approval. In a randomized study, the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, sotalol was associated with an increased in-hospital efficacy prediction rate (by Holter monitor or electrophysiologic study), reduced long-term arrhythmic recurrence rate with superior tolerance, and lower mortality rate than class I ("standard") antiarrhythmic drugs. Sotalol was 1 of 2 drugs selected for comparison with implantable defibrillators in the recent National Institutes of Health Antiarrhythmics versus Implantable Defibrillator (AVID) study. Sotalol appears to be a preferred drug for use with implantable defibrillators; unlike some other agents (eg, amiodarone) it does not elevate and, indeed, may lower defibrillation threshold. Although unapproved for this use, sotalol is active against atrial arrhythmias. It has shown efficacy equivalent to propafenone and quinidine in preventing atrial fibrillation recurrence, but it is better tolerated than quinidine and provides excellent rate control during recurrence. Sotalol's major side effects are related to beta-blockade and the risk of torsades de pointes (acceptably small if appropriate precautions are taken). Unlike several other antiarrhythmics (eg, amiodarone), it has no pharmacokinetic drug-drug interactions, is not metabolized, and is entirely renally excreted. Initial dose is 80 mg twice daily, with gradual titration to 240 to 360 mg/day as needed. The daily dose must be reduced in renal failure. On the basis of favorable clinical trials and practice experience, sotalol has shown a steadily growing impact on the treatment of arrhythmias during its 5 years of market availability, a trend that is likely to continue.
索他洛尔是最近被批准的口服抗心律失常药物，具有独特的药理学特性。其电生理作用可通过非选择性β受体阻滞作用以及Ⅲ类抗心律失常活性（包括快速激活心脏膜延迟整流电流阻滞）来解释，这会导致整个心脏的动作电位持续时间和不应期增加，以及体表心电图QT间期延长。与其他β受体阻滞剂相比，它具有更好的血流动力学耐受性，这可能是由于Ⅲ类活性相关的心肌收缩力增强所致。索他洛尔抑制室性早搏的能力与Ⅰ类药物相似，且优于标准β受体阻滞剂。与Ⅰ类药物不同，在心肌梗死后试验中使用它并未增加死亡率。在治疗方面，它已显示出预防复发性室性心动过速和心室颤动的卓越疗效，这也是其获批的依据。在一项随机研究即电生理研究与心电图监测（ESVEM）试验中，索他洛尔与住院期间疗效预测率增加（通过动态心电图监测或电生理研究）、长期心律失常复发率降低且耐受性更好以及死亡率低于Ⅰ类（“标准”）抗心律失常药物相关。索他洛尔是最近国立卫生研究院抗心律失常药物与植入式除颤器（AVID）研究中被选用于与植入式除颤器进行比较的两种药物之一。索他洛尔似乎是与植入式除颤器联合使用的首选药物；与其他一些药物（如胺碘酮）不同，它不会提高，实际上可能会降低除颤阈值。虽然未被批准用于此用途，但索他洛尔对房性心律失常有效。在预防房颤复发方面，它已显示出与普罗帕酮和奎尼丁相当的疗效，但耐受性优于奎尼丁，且在复发期间能提供良好的心率控制。索他洛尔的主要副作用与β受体阻滞以及尖端扭转型室速风险有关（如果采取适当预防措施，风险可接受地小）。与其他几种抗心律失常药物（如胺碘酮）不同，它没有药代动力学药物相互作用，不被代谢，完全经肾脏排泄。初始剂量为每日两次，每次80毫克，根据需要逐渐滴定至每日240至360毫克。在肾衰竭时必须减少每日剂量。基于良好的临床试验和实践经验，索他洛尔在上市5年期间对心律失常治疗的影响稳步增长，这一趋势可能会持续下去。
