Roden D M, Anderson M E
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232, USA.
Handb Exp Pharmacol. 2006(171):73-97. doi: 10.1007/3-540-29715-4_3.
The concept that antiarrhythmic drugs can exacerbate the cardiac rhythm disturbance being treated, or generate entirely new clinical arrhythmia syndromes, is not new. Abnormal cardiac rhythms due to digitalis or quinidine have been recognized for decades. This phenomenon, termed "proarrhythmia," was generally viewed as a clinical curiosity, since it was thought to be rare and unpredictable. However, the past 20 years have seen the recognition that proarrhythmia is more common than previously appreciated in certain populations, and can in fact lead to substantially increased mortality during long-term antiarrhythmic therapy. These findings, in turn, have moved proarrhythmia from a clinical curiosity to the centerpiece of antiarrhythmic drug pharmacology in at least two important respects. First, clinicians now select antiarrhythmic drug therapy in a particular patient not simply to maximize efficacy, but very frequently to minimize the likelihood of proarrhythmia. Second, avoiding proarrhythmia has become a key element of contemporary new antiarrhythmic drug development. Further, recognition of the magnitude of the problem has led to important advances in understanding basic mechanisms. While the phenomenon of proarrhythmia remains unpredictable in an individual patient, it can no longer be viewed as "idiosyncratic." Rather, gradations of risk can be assigned based on the current understanding of mechanisms, and these will doubtless improve with ongoing research at the genetic, molecular, cellular, whole heart, and clinical levels.
抗心律失常药物会加重正在治疗的心律失常，或引发全新的临床心律失常综合征，这一概念并不新鲜。因洋地黄或奎尼丁导致的异常心律已被认识数十年。这种被称为“致心律失常作用”的现象，通常被视为一种临床奇闻，因为人们认为它罕见且不可预测。然而，在过去20年里，人们认识到致心律失常作用在某些人群中比之前认为的更为常见，并且在长期抗心律失常治疗期间实际上会导致死亡率大幅上升。这些发现进而在至少两个重要方面将致心律失常作用从临床奇闻转变为抗心律失常药物药理学的核心内容。首先，临床医生现在为特定患者选择抗心律失常药物治疗时，不仅是为了最大化疗效，而且非常频繁地是为了最小化致心律失常作用的可能性。其次，避免致心律失常作用已成为当代新型抗心律失常药物研发的关键要素。此外，对该问题严重程度的认识已促使在理解基本机制方面取得重要进展。虽然致心律失常作用在个体患者中仍然不可预测，但它不再能被视为“特异质性的”。相反，根据目前对机制的理解可以划分风险等级，并且随着在基因、分子、细胞、全心和临床层面的持续研究，这些等级无疑会得到改善。
