DRUGS THAT PROLONG EFFECTIVE
REFRACTORY PERIOD BY PROLONGING THE ACTION POTENTIAL (CLASS 3)
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.
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