Antiarrhythmic drugs are widely used in clinical electrophysiology to both prevent and terminate arrhythmias. The drugs can also be used to slow arrhythmias to make them hemodynamically tolerated (e.g., atrial fibrillation) or facilitate pacing-mediated termination (e.g., ventricular tachycardia [VT]). Their safe and effective use requires a thorough understanding of their indications and toxicities. Reentry is the predominant mechanism of arrhythmias treated with antiarrhythmic drugs. Although the mechanism by which drugs stop automatic or triggered rhythms and reentrant rhythms involving the atrioventicular (AV) node is understood, it is unclear how drugs terminate reentrant arrhythmias confined to the atrial or ventricular myocardium.

Prevention of a reentrant arrhythmia in the atrium or ventricle is most likely to occur by prolongation of refractoriness without affecting conduction or by abolishing conduction—a more difficult task. Antiarrhythmic drugs are classified according to the predominant ion current they block (Vaughn-Williams classification) (see Table 18-1). There are many limitations to this classification, not least of which is the recognition that many antiarrhythmic drugs block multiple ion currents. In general, blockade of sodium channels depresses the rate of rise of the action potential (V_max) and blockade of potassium channels prolongs repolarization.

Class 1 antiarrhythmic drugs primarily block sodium channels which result in a decrease in the rate of rise of phase 0 of the action potential. Class 1 drugs are further divided into class 1A, 1B, and 1C subclasses which
are distinguished by different rates of drug binding and dissociation from the sodium channel receptor. For example, during tachycardia less time is available for drug dissociation from the sodium receptor. This results in a greater number of blocked channels (see Table 18-2). If more sodium channels are blocked there will be a decrease in conduction velocity with prolongation in depolarization and resultant QRS prolongation. The slower a drug dissociates from a receptor the more drug will be bound at rapid heart rates (i.e., use dependence).

Class 1A sodium channel blocking drugs include quinidine, procainamide, and disopyramide. These drugs predominantly block potassium channels (Ikr) at slow rates and normal concentrations and sodium channels at faster rates and higher concentrations. This pattern of potassium channel blockade at slow rates is called reverse use dependence. This group is distinguished by an intermediate rate of binding and dissociation from the sodium channel.

Class 1B antiarrhythmic drugs include lidocaine and mexilitine. They have rapid binding and dissociation kinetics. They are particularly effective on His-Purkinje fibers with less binding to atrial tissues. Atrial tissues have a shorter action potential duration which accounts for the lesser effect of type 1B agents on atrial tissue compared with ventricular tissue. Binding of type 1B agents to the sodium channel is greater in the inactivated state and in the presence cellular acidosis as occurs during myocardial ischemia.

Class 1C drugs have the slowest binding and dissociation kinetics. Slower dissociation kinetics result in a greater amount of bound drug at rapid heart rates which facilitates the termination of rapid arrhythmias (tachycardias). These drugs slow cardiac conduction to the greatest extent of the class 1 agents.

Class 2 drugs are the β-blockers.

Class 3 drugs prolong refractoriness by prolonging the action potential duration. Most block potassium channels but some also allow persistence of the inward sodium current (e.g., ibutilide). The potassium channel blocking drugs predominantly block Ikr and thereby result in prolongation of repolarization with an increase in refractoriness and action potential duration.

Class 4 drugs are calcium channel blocking drugs. The calcium channel blockers of predominant interest to arrhythmia management are the nondihydropyridine compounds (diltiazem and verapamil).

Digoxin blocks the Na/K pump resulting in an increase in intracellular sodium. This results in increased activity of the Na/Ca exchanger and increased intracellular calcium. Digoxin also is a vagomimetic agent, which accounts for its modest AV and sinus nodal–slowing effects.