Antiarrhythmic Drug Review

Antiarrhythmic drugs are those that act upon the electrical conduction system of the heart in an attempt to maintain sinus rhythm. They are classified by the Vaughan-Williams classification system as below:

Class IA drugs: Quinidine, Amiodarone, Procainamide, Disopyramide

These drugs block cardiac sodium channels and depress phase 0 of the action potential.

While class IA drugs are effective to treat atrial fibrillation, they are not commonly utilized for this purpose due to side-effects and significant pro-arrhythmia except in special situations.

Procainamide can cause drug-induced lupus erythematosus detected by measuring anti-histone antibodies. It is used to treat atrial fibrillation when Wolff-Parkinson-White syndrome is present and can cause drug-induced lupus erythematosus. Disopyramide is used in vagally mediated atrial fibrillation and in hypertrophic obstructive cardiomyopathy. Quinidine is rarely used and causes cinchonism.

Amiodarone has more class III properties than class I and is used primarily for atrial fibrillation and ventricular tachycardia. Amiodarone toxicity is a concern.

Class IB drugs: Lidocaine, Mexiletine, Tocainide

These drugs block cardiac sodium channels and shorten the action potential.

Lidocaine is used intravenously to treat ventricular tachycardia and ventricular fibrillation. Lidocaine toxicity can occur at higher doses. Mexiletine is available orally to treat ventricular tachycardia. Tocainide is no longer used.

Class IC drugs: Flecainide, Propafenone, Encainide, Moricizine

These drugs block cardiac sodium channels and has no effect on the action potential.

The class IC drugs are commonly used to maintain sinus rhythm in atrial fibrillation patients. Significant coronary artery disease is a contraindication to their use as this increases the risk of proarrhythmia and sudden cardiac death. These agents must be used in combination with an AV blocking agent in order to prevent rapid atrial fibrillation or atrial flutter conduction (1:1 conduction) through the AV node resulting in very fast ventricular rates if a breakthrough episode occurs since class IC drugs also act to increase AV nodal conduction. These drugs may be proarrhythmic in the setting of left ventricular hypertrophy (wall thickness > 1.4 cm).

Flecainide can be used with a “pill-in-the-pocket” approach. If documented to be successful and safe while hospitalized, flecainide can be used on an as-needed basis in the outpatient setting. Note that propafenone is hepatically cleared (not recommended with liver disease) while flecainide is renally cleared. Encainide and moricizine are rarely used.

Class II drugs: Metoprolol, Carvedilol, Atenolol, Propranolol, Bisoprolol

These drugs are known as beta-blockers. They antagonize beta-receptors inhibiting the effect of the sympathetic nervous system resulting in decreased chronotropy (heart rate), inotropy (contractility) and dromotropy (conductivity).

Class III drugs: Amiodarone, Sotalol, Bretylium, Dofetilide, Dronedarone, Ibutilide

These drugs act by blocking cardiac potassium channels.

The class III drugs are used to treat primarily atrial fibrillation, however amiodarone is FDA approved only for the treatment of ventricular tachycardia.

Amiodarone is very effective however amiodarone toxicity is a concern. The half-life of amiodarone is 42 days. Sotalol is proarrhythmic in the setting of left ventricular hypertrophy (wall thickness > 1.4 cm). Amiodarone and dofetilide are preferred in patients with left ventricular systolic dysfunction (reduced ejection fraction). Dronedarone is not safe with systolic heart failure or in the setting of permanent atrial fibrillation. Bretylium is rarely used. Ibutilide can be used as a one time intravenous infusion to cardiovert atrial fibrillation to sinus rhythm chemically.

Class IV drugs: Verapamil, Diltiazem

These drugs are known as non-dihydropyridine calcium channel blockers and act by blocking cardiac calcium uptake. They are used to slow AV nodal conduction decreasing heart rate. They have less of an effect on sinus node activity.

Class V drugs: Those for whom the mechanism of action is unknown.

By Steven Lome