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DRUGS THAT PROLONG EFFECTIVE REFRACTORY PERIOD BY PROLONGING THE ACTION POTENTIAL (CLASS 3)
These drugs prolong action potentials, usually by blocking potassium channels in cardiac muscle or by enhancing inward current, eg, through sodium channels. Action potential prolongation by most of these drugs often exhibits the undesirable property of ‚Äúreverse use-dependence‚ÄĚ: action potential prolongation is least marked at fast rates (where it is desirable) and most marked at slow rates, where it can contribute to the risk of torsades de pointes.
Although most drugs in the class evoke QT prolongation, there is considerable variability among drugs in their proarrhythmic ten-dency to cause torsades de pointes despite significant QT-interval prolongation. Recent studies suggest that excessive QT prolonga-tion alone may not be the best predictor of drug-induced torsades de pointes. Other important factors in addition to QT prolongation include action potential stability and development of a triangular shape (triangulation), reverse use-dependence, and dispersion of repolarization.
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