Calcium channel blockers in the treatment of cardiac arrhythmias
- Philip J Podrid, MD, FACC
Philip J Podrid, MD, FACC
- Professor of Medicine, Professor of Pharmacology and Experimental Therapeutics
- Boston University School of Medicine
- Lecturer, Harvard Medical School
Calcium channel blockers (CCBs) are useful antiarrhythmic agents in the management of certain arrhythmias, primarily supraventricular tachyarrhythmias [1-3]. They have diverse electrophysiologic properties and are therefore of variable antiarrhythmic efficacy. The primary settings in which they are useful can be best appreciated from an understanding of their mechanism of action.
This topic will review the electrophysiological properties of calcium channel blockers and their clinical indications in a variety of arrhythmias. More detailed discussions of their use in specific arrhythmias and other treatment options for arrhythmias are presented separately. (See "Atrioventricular nodal reentrant tachycardia" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy" and "Control of ventricular rate in atrial flutter" and "Treatment of symptomatic arrhythmias associated with the Wolff-Parkinson-White syndrome" and "Approach to the management of wide QRS complex tachycardias".)
Calcium channel blockers (CCBs), considered class IV antiarrhythmic drugs (table 1), preferentially affect myocardial tissue that mediates its electrophysiologic properties with a slow action potential (which is mediated by calcium currents) rather than myocardial tissue that mediates its electrophysiologic properties via a fast action potential (mediated by the rapid influx of sodium currents). The sinoatrial and atrioventricular nodes depend upon calcium currents to generate slowly propagating action potentials. In contrast, fast response myocardial tissues (the atria, specialized infranodal conducting system, the ventricles, and accessory pathways) depend upon sodium channel currents. (See "Myocardial action potential and action of antiarrhythmic drugs".)
Certain disorders, such as an acute myocardial infarction, may convert tissue generating a fast action potential, including ventricular myocardium and Purkinje fibers, into tissue that generates a slow action potential. In an animal model, low doses of mibefradil, a T-type CCB with weak effects on the L-type calcium channel, prevented the reduction in the ventricular fibrillation threshold with ischemia, without depressing left ventricular contractility . Higher doses of both mibefradil and verapamil prevented ischemic and reperfusion arrhythmias, an effect associated with depression of left ventricular contractility. It is not clear, however, if CCBs are clinically useful in these settings. Furthermore, mibefradil has been withdrawn from the US market because of toxicity, and it is not known if other T-type calcium channel blockers will be developed.
Calcium channel blockers block the slow calcium channel in a dose-dependent fashion, resulting in the following direct effects [3,5]:
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