Class III antiarrhythmics

Class III antiarrhythmics

Class III antiarrhythmics are used to treat ventricular arrhythmias. The drugs in this class are amiodarone, dofetilide, ibutilide, and sotalol.

Which class are you in?

Sotalol is a nonselective beta-adrenergic blocker (class II drug) that also has class III properties. Nonselective means that the drug doesn’t have a specific affinity for a receptor. Although sotalol is a class II drug, its class III antiarrhythmic effects are more predominant, especially at higher doses. Therefore, it’s usually listed as a class III antiarrhythmic.

Pharmacokinetics

The absorption of these antiarrhythmics varies widely.

Slow going

After oral administration, amiodarone is absorbed slowly at widely varying rates. The drug is distributed extensively and accumulates in many sites, especially in organs with a rich blood supply and fatty tissue. It’s highly protein-bound in plasma, mainly to albumin.

Dofetilide is very well absorbed from the GI tract, with almost 100% overall absorption. Of that, about 70% is bound to plasma proteins. Ibutilide, which is administered only by I.V., has an absorption of 100%. Sotalol’s absorption is slow and varies between 60% and 100%, with minimal protein-binding.

 

Pharmacodynamics

Although the exact mechanism of action isn’t known, class III antiarrhythmics are thought to suppress arrhythmias by converting a unidirectional block to a bidirectional block. Class III antiarrhythmics have little or no effect on depolarization. Rather, these drugs slow repolarization, prolonging the refractory period and duration of the action potential.

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Pharmacotherapeutics

Class III antiarrhythmics are used for life-threatening arrhythmias. Amiodarone is the first-line drug of choice for ventricular tachycardia and ventricular fibrillation.

 

Drug interactions

• Amiodarone increases phenytoin, procainamide, and quinidine levels.
• Amiodarone also increases the risk of digoxin toxicity.
• Ibutilide shouldn’t be administered within 4 hours of class I or other class III antiarrhythmics because it increases the potential for a prolonged refractory period.
• Dofetilide shouldn’t be administered with cimetidine, ketoconazole, megestrol, prochlorperazine, sulfamethoxazole, trimethoprim, or verapamil because of their potential to induce life-threatening arrhythmias.
• Sotalol shouldn’t be administered with dolasetron or droperidol because of the increased risk of life-threatening arrhythmias.
• Concomitant use of amiodarone and fluoroquinolones, macrolide antibiotics, and azole antifungals may cause prolongation of the QTc interval, leading to cardiac arrhythmias, including torsades de pointes.

Pressure plunge

Severe hypotension may develop from too-rapid I.V. administration of amiodarone. 

Warning!

Adverse reactions to class III antiarrhythmics

Adverse reactions to class III antiarrhythmics, especially amiodarone, vary widely and commonly lead to drug discontinuation. A common adverse effect is aggravation of arrhythmias.

Adverse reactions to amiodarone…

Amiodarone may produce hypotension, nausea, and anorexia. Severe pulmonary toxicity occurs in 15% of patients and can be fatal. Vision disturbances and corneal microdeposits may occur.

… and ibultilide …

Ibutilide may cause sustained ventricular tachycardia, prolongation of the QT interval, hypotension, nausea, and headache.

… and sotalol

Sotalol may cause atrioventricular block, bradycardia, ventricular arrhythmias, bronchospasm, and hypotension.