Fig 4.

Dissociation kinetics of Na⁺ channel blockers. Na⁺ channel blockers bind to Na⁺ channels in the open or inactivated states. Dissociation kinetics of the blockers and recovery of channels during diastole determines the extent of Na⁺ channel blockade. (A) Class Ia drugs have an intermediate dissociation rate and Na⁺ channel blockade is influenced by the heart rate. As the heart rate increases, the time available for drugs to dissociate from the channels during diastole is reduced. This increases level of Na⁺ channel blockade and provides heart rate-dependent steady state Na⁺ blockade. (B) Class Ib drugs have rapid dissociation kinetics allowing full recovery of Na⁺ channels before the next action potential. (C) Class Ic drugs have slow dissociation kinetics. The drugs do not completely dissociate from the Na⁺ channels even at low heart rate. This results in steady-state Na⁺ channel blockade even when the cell membrane is fully repolarised.