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 174-1). This system classifies each agent based on 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.
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. In Class IC agents (flecainide and propafenone), these sodium channel inhibitors increase the QRS interval more than the other Class I drugs, slow the conduction velocity but have little effect on either action potential duration or the refractory period.
Class II agents include the beta-1 selective adrenergic blocking agents, such as metoprolol, atenolol, and bisoprolol, in addition to the nonselective agents such as propranolol, labetalol, carvedilol, and nadolol. These agents block adrenergic stimulation through sympathetic activity and thus decrease conduction velocity.
Class III agents block potassium channels and thus delay repolarization of the action potential during phase 3. They also increase both the effective refractory period and the action potential duration. Drugs in this class include amiodarone, ...