Mechanism of Action Potential Shortening by Class IB Antiarrhythmics
Class IB antiarrhythmics like lidocaine shorten the action potential (AP) by rapidly binding to and blocking inactivated sodium channels, which accelerates repolarization and decreases the action potential duration. 1
Sodium Channel Binding Characteristics
Class IB agents exhibit distinct binding kinetics that differentiate them from other Class I antiarrhythmics:
Lidocaine, mexiletine, and tocainide primarily block sodium channels during the inactivated state rather than during the open state, which is the predominant mechanism for Class IA agents like quinidine and disopyramide 2
These drugs dissociate rapidly from cardiac sodium channels, with recovery times of 1-2 seconds for lidocaine and 0.71 seconds for phenytoin, compared to much slower dissociation for some agents like amitriptyline (13.6 seconds) 3
The rapid on-off kinetics mean that Class IB agents preferentially affect diseased or rapidly firing tissue while having minimal effects on normal cardiac tissue at physiologic heart rates 4
Effects on Action Potential Parameters
The specific electrophysiological changes induced by Class IB antiarrhythmics include:
Decreased action potential duration (APD) through accelerated repolarization, which distinguishes them from Class IA agents that prolong APD and Class IC agents that have minimal effect on APD 1, 4
Increased refractory period relative to action potential duration, creating a protective effect against reentrant arrhythmias, particularly in ischemic tissue 1
Minimal depression of phase 0 depolarization in healthy cardiac tissue, unlike Class IA or IC agents that significantly slow the maximum upstroke velocity (Vmax) 3
Clinical Implications
The mechanism of AP shortening has important therapeutic consequences:
Class IB agents are particularly effective in ischemic tissue where cells are partially depolarized and sodium channels remain in the inactivated state for longer periods 1
The shortened action potential and increased ventricular fibrillatory threshold make these agents useful for interrupting life-threatening tachycardias caused by reentrant mechanisms 1
Lidocaine can be used as second-line therapy for wide-complex tachycardia refractory to sodium bicarbonate in tricyclic antidepressant overdose, where it may competitively displace slower-acting sodium channel blockers 5, 3