Class III antiarrhythmics
Class III antiarrhythmics are used to treat ventricular arrhyth-mias. The drugs in this class are amiodarone, dofetilide, ibutilide, and sotalol.
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.
The absorption of these antiarrhythmics varies widely.
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.
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.
Class III antiarrhythmics are used for life-threatening arrhythmias. Amiodarone is the first-line drug of choice for ventricular tachy-cardia and ventricular fibrillation.
§ 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.
Severe hypotension may develop from too-rapid I.V. administra-tion of amiodarone. (See Adverse reactions to class III antiar-rhythmics.)