Vaughan Williams E M
J Clin Pharmacol. 1984 Apr;24(4):129-47. doi: 10.1002/j.1552-4604.1984.tb01822.x.
The past decade has seen the introduction of many new class 1 drugs, restricting fast inward current. Confirmative evidence has been obtained that the antiarrthymic action of lidocaine and diphenylhydantoin is indeed due to their effect as class 1 agents depressing conduction. The original class 3 drug, amiodarone, is increasingly in use as an antiarrhythmic of first choice for WPW and for arrhythmias associated with hypertrophic myopathy, and as a reserve drug in resistant arrhythmias of other types. Other compounds delaying repolarization have proved to be clinically effective as antiarrhythmics. In addition to their class 2 antiarrhythymic action exhibited acutely, on long-term treatment beta blockers have a class 3 action, which might be, at least in part, responsible for the protection of postinfarction patients against sudden death. Recent research suggests that inhibition of slow inward current may lead, as a secondary consequence of lowered [Ca]i, to improved cell-to-cell conduction. Finally, all but one of the new antiarrhythmic drugs, none of which existed in 1972, have turned out to possess one or more of the four classes of action originally described. This can hardly be a coincidence. The single exception, alinidine, a selective bradycardic agent, may restrict anionic currents, which would constitute a fifth class of action, but this is far from proved.
在过去十年中,出现了许多新型1类药物,它们可限制快速内向电流。已有确凿证据表明,利多卡因和苯妥英钠的抗心律失常作用确实归因于它们作为1类药物对传导的抑制作用。最初的3类药物胺碘酮,越来越多地被用作预激综合征(WPW)和肥厚性心肌病相关心律失常的首选抗心律失常药物,以及其他类型难治性心律失常的备用药物。其他延迟复极化的化合物已被证明在临床上作为抗心律失常药物有效。除了它们急性表现出的2类抗心律失常作用外,β受体阻滞剂在长期治疗时还具有3类作用,这可能至少部分地解释了其对心肌梗死后患者预防猝死的保护作用。最近的研究表明,抑制缓慢内向电流可能作为细胞内钙浓度降低的继发结果,导致细胞间传导改善。最后,除了一种新的抗心律失常药物外,所有这些在1972年还不存在的新药都已被证明具有最初描述的四类作用中的一种或多种。这很难说是巧合。唯一的例外是阿利尼定,一种选择性心动过缓药物,它可能限制阴离子电流,这将构成第五类作用,但这一点远未得到证实。