Antidysrhythmic agents, which are also known as antiarrhythmic agents, are a broad category of medications that help ameliorate the spectrum of cardiac arrhythmias to maintain normal rhythm and conduction in the heart. Arrhythmias generally arise as a result of abnormal impulse generation or abnormal conduction, or a combination of the two. Abnormal impulse generation falls into one of two categories: abnormal automaticity or triggered activity. Abnormal automaticity is thought to occur due to reduced resting membrane potential, causing the membrane to be closer to the threshold for generating an action potential. Triggered activity, or after-depolarization, occurs during the early stages after depolarization, such as in phase 2 and 3, or in the later stage during phase 4. With either form, it requires a preceding triggering beat to create the abnormal depolarization. Abnormal conduction is usually due to conduction block or a reentry phenomenon, with the latter being the most common cause of dysrhythmias. Antidysrhythmics exert their effect on specific ion channels on the cardiac cell membrane which then alters the shape of the action potential, and thus have inotropic, chronotropic, and toxic actions as a result.
The most common classification system for antidysrhythmic agents is the Harrison modification of Vaughan Williams (Table 166-1). This system classifies each agent based upon its unique electrophysiologic and pharmacological properties. Vaughan Williams classification divides these agents in one of four groups, Class I, II, III, and IV. There is a further subdivision of Class I agents, the so-called sodium channel blockers, into IA, IB, and IC.
++ Table Graphic Jump Location TABLE 166-1Classification of Antidysrhythmic Agents ||Download (.pdf) TABLE 166-1 Classification of Antidysrhythmic Agents
|Vaughan Williams Classification ||Electrocardiographic Effect ||Membrane/Ion Channel ||Examples of Agents |
|IA ||↑QRS and Q-T intervals ||Blocks fast Na+ and intermediate K+ ||Quinidine/procainamide/disopyramide |
|IB ||↓ →Q-T interval ||Fast sodium channel blocker ||Lidocaine/tocainide/mexilitine |
|IC ||↓ QRS Interval ||Sodium channel blocker ||Flecainide/propafanone |
|II ||↓ HR; ↑P-R interval ||β adrenergic receptor blockade ||Propranolol/esmolol/metoprolol |
|III ||↑ Q-T interval ||K+ channel blocker ||Amiodarone/sotalol/ibutilide/dronedarone |
|IV ||↓ HR; ↑ P-R interval ||L-type Ca2+ channel blocker ||Verapamil/diltiazem |
|Digoxin ||↑ P-R interval; ↓ Q-T interval ||Na+/K+ ATPase inhibitor || |
|Adenosine ||↓ HR; ↑ P-R interval ||Purinergic A1 receptor agonist || |
Class I agents block the rapid inward sodium channel, slow the rate of rise of phase 0, and so decrease the rate of depolarization. The subgrouping of Class I agents allows for differentiating their electrophysiologic effects. Class IA drugs (quinidine, procainamide, and disopyramide) prolong the repolarization and the refractoriness of isolated myocardial tissue as well as block the inward sodium current. They also have potassium channel blocking properties, and so increase action potential duration and the effective refractory period. Class IB drugs (lidocaine, tocainide, and mexiletine) produce only modest inhibition of the rapid inward sodium current and so shorten the refractory period, and reduce the action potential duration. ...