[Amiodarone].

Abstract

The extraordinary antiarrhythmic efficacy of amiodarone has been well documented in the last few years. Parallel investigations of the electrophysiologic influence of this iodinated benzofuran derivative on myocardial tissue showed that repolarizing as well as depolarizing currents are inhibited. However, the detailed electrochemical aspects of these effects are only partly understood. Likewise, ideas on causes of the differences in hemodynamic and electrophysiologic actions of oral and intravenous amiodarone are still speculative. An understanding of the actions of amiodarone is particularly difficult to achieve because of the unique pharmacokinetics of the drug: it resides in extra-plasmatic compartments for months after discontinuation of treatment, a fact which explains, for example, the lack of an established dose/response relationship. Replacement of amiodarone by another antiarrhythmic drug in the same patient may be problematic, because pharmacokinetic and pharmacodynamic interactions of residual amiodarone with the new antiarrhythmic drug are to be expected. Therefore, amiodarone should be prescribed only in cases where other treatment has failed. This is also advisable in view of the long list of amiodarone-induced adverse reactions. Determinations of plasma concentrations of amiodarone and desethylamiodarone may be useful in some instances, but must never replace clinical evaluation of antiarrhythmic drug efficacy. Although the incidence of some amiodarone-induced adverse reactions increases with dosage and serum drug level, dose-independent factors may play a role in the rare but serious pulmonary and hepatic side effects.