Antiarrhythmic drugs and torsade de pointes.
In the past decade there has been much progress in understanding the clinical features and associations of drug-induced long QT syndromes, their inter-relationships with other long QT syndromes, and electrophysiological mechanisms that may be involved in the development of torsade de pointes, the major proarrhythmic correlate of prolonged repolarization. The most likely electrophysiologic basis for torsade de pointes is the development of after-depolarizations facilitated by hypokalemia, bradycardia and lengthened QT intervals. Torsade de pointes can be produced by all antiarrhythmic agents that lengthen repolarization, although the precise incidence varies with different agents and is not quantitatively related to the degree of QT prolongation. Quinidine, disopyramide and procainamide (with its metabolite N-acetyl procainamide) are strongly concordant in the production of torsade de pointes. Such concordance suggests that there is an individual predisposition to the induction of early after-depolarizations (EAD) with exposure to agents that prolong repolarization. However, concordance with agents or other classes, such as sotalol, is less certain, and amiodarone appears to be discordant. The discordance between potency in prolonging the QT interval and the proclivity to induce torsade de pointes may hold the key to separating the salutary therapeutic antiarrhythmic effects from adverse proarrhythmic effects of class III agents. There is an optimistic perception that the development of new agents that potently prolong repolarization will give a modern realization of the old concept that prolongation of refractoriness is a uniquely powerful anti-re-entrant, antitachyarrhythmic action.
Lazzara
R
R
University of Oklahoma Health Sciences Center, Oklahoma City.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000145:classification; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D016171:Torsades de Pointes / Q000139:chemically induced*
D000889:Anti-Arrhythmia Agents