Class III antiarrhythmics

Class III antiarrhythmics

Class III antiarrhythmics are used to treat ventricular arrhyth-mias. 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 predomi-nant, 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 wide-ly varying rates. The drug is distributed extensively and accumu-lates in many sites, especially in organs with a rich blood supply and fatty tissue. It’s highly protein-bound in plasma, mainly to al-bumin.

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 ab-sorption 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 an-tiarrhythmics are thought to suppress arrhythmias by converting a unidirectional block to a bidirectional block. Class III antiarrhyth-mics have little or no effect on depolarization. Rather, these drugs slow repolarization, prolonging the refractory period and duration of the action potential.

Pharmacotherapeutics

Class III antiarrhythmics are used for life-threatening arrhythmias. Amiodarone is the first-line drug of choice for ventricular tachy-cardia 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, ketocona-zole, megestrol, prochlorperazine, sulfamethoxazole, trimetho-prim, 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 prolonga-tion of the QTc interval, leading to cardiac arrhythmias, including torsades de pointes.

Pressure plunge

Severe hypotension may develop from too-rapid I.V. administra-tion of amiodarone. (See Adverse reactions to class III antiar-rhythmics.)