Antiarrhythmic drugs: a reorientation in light of recent developments in the control of disorders of rhythm.
Numerous developments in our knowledge of arrhythmias during the past decade or so have had a major influence on antiarrhythmic drug therapy. It has become increasingly evident that arrhythmias merit treatment not only for the relief of symptoms, with improvement in quality of life, but also for the prolongation of survival by decreasing arrhythmic deaths. No longer can mere suppression of arrhythmias, symptomatic or asymptomatic, be equated with prolonged survival. We now know that antiarrhythmic drugs that act by blocking sodium channels can increase mortality and that the most important determinants of arrhythmia mortality are the degree and nature of ventricular dysfunction. To these considerations must be added the advances in nonpharmacologic approaches to controlling cardiac arrhythmias. There has been a shift to the use of implantable devices and of drugs with alternative modes of action, such as beta blockers and class III drugs (e.g., sotalol, amiodarone). However, the side-effect profiles of these 2 classes of compounds have led to the synthesis and characterization of agents that act simply by blocking > or = 1 membrane ion channels. The isolated block of the rapid component of the delayed rectifier potassium current (IKr) has been associated with potent antifibrillatory activity in the atria, with a neutral (e.g., with dofetilide) or deleterious (with d-sotalol) effect on mortality in postinfarct survivors. Therefore, the focus now is on compounds that can block > 1 ion channel (e.g., tedisamil and azimilide). Azimilide is the first of the class III agents that blocks both components of the delayed rectifier potassium current. The drug's overall action is associated with a spectrum of electrophysiologic properties that hold promise in the control of atrial and ventricular arrhythmias, with potential for improving survival in patients at risk for cardiac arrest.
Singh
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Division of Cardiology, Veterans Affairs Medical Center of West Los Angeles, University of California-Los Angeles School of Medicine, 90073, USA.
D000319:Adrenergic beta-Antagonists / Q000145:classification / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000517:prevention & control; D017147:Defibrillators, Implantable; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D007473:Ion Channels