Amiodarone has multiple effects on myocardial depolarization and repolarization that make it an extremely effective antiarrhythmic drug. Its primary effect is to block the potassium channels, but it can also block sodium and calcium channels and the beta and alpha adrenergic receptors. (See "Myocardial action potential and action of antiarrhythmic drugs".)
The approved clinical use of amiodarone has been limited to refractory ventricular arrhythmias because of a relatively high incidence of side effects that can range in severity from mild to potentially lethal (table 1) . The use of lower doses (200 to 300 mg/day) may allow amiodarone to be given safely and effectively in atrial arrhythmias such as atrial fibrillation or flutter. However, as will be described below, even low doses of therapy are associated with significant adverse effects, particularly thyroid, pulmonary, neurologic, skin, ocular, and bradycardic events (table 1) . Many of these effects are due to the tissue accumulation of amiodarone with long-term oral therapy and are not seen with short-term intravenous therapy.
Guidelines for the use of amiodarone were published by the North American Society of Pacing and Electrophysiology (NASPE) in 2000 . It was estimated that the prevalence of side effects was as high as 15 percent in the first year and as high as 50 percent with long-term therapy. On the other hand, the need to stop amiodarone because of serious adverse effects is thought to be about 20 percent. In a meta-analysis of trials of low-dose therapy, there was a significantly higher rate of drug discontinuation with amiodarone compared to placebo (22.9 versus 15.4 percent) .
The major side effects of amiodarone will be reviewed here. The clinical uses of amiodarone, including recommendations for its use in the treatment of various arrhythmias, are discussed separately. (See "Clinical uses of amiodarone" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'Amiodarone'.)
Intravenous amiodarone is primarily given for short-term management of serious ventricular arrhythmias. It has a different electrophysiologic and pharmacologic profile from oral amiodarone. (See "Clinical uses of amiodarone".)