I.V. Amiodarone: What Do We Really Know About It?

Abstract

The mechanism of amiodarone’s antiarrhythmic action is not known. In vitro and clinical studies have demonstrated that it has multiple actions that could potentially contribute to an antiarrhythmic response. These include block of ion channels (sodium, potassium and calcium), receptors (alpha adrenergic, beta adrenergic and muscarinic) and intracellular transduction pathways (phospholipase and thyroid hormone). It is generally speculated that the drug’s large number of actions is responsible for the broad spectrum of arrhythmias that respond to orally administered amiodarone. However, all of these actions may not e operative during i.v. therapy. Numerous studies have demonstrated the electrophysiologic differences between acute and chronically administered amiodarone. Comparison of i.v and oral amiodarone is complicated by the slow tissue accumulation of amiodarone, the possible effects of its active desethyl metabolite, potential anti-thyroid effects and the potential action of the diluent in the intravenous formulation, polysorbate 80 (Tween-80). Although most comparisons of acute and chronically administered amiodarone found greater effects with chronic administration, a recent report found amiodarone to clock L-type calcium channels acutely in cell culture but not in cells harvested from chronically treated animals [1]. The potential importance of this action is supported by a report by Kojima, et al [2] in which they concluded that amiodarone’s anti~brillatory action in isolated perfused rat hearts was due to a reduction in intracellular calcium. Some, but not all, of the known actions of amiodarone can be observed clincally. In some cases the action is not temporally correlated with antiarrhythmic response. For example, QT prolongation (a marker of Class III antiarrhythmic action or potassium channel block) is not seen after acute intravenous administration. High intravenous dosages, $300 mg, have been observed to cause hypotension, heart block or excessive bradycardia but these reactions may be due to Tween-80. The bradycardia that is seen during chronic therapy is most likely due to non-competitive inhibition of beta adrenergic receptors. The electrophysiological actions of amiodarone in humans depend on the route of administration and the duration of therapy. Following acute intravenous amiodarone administration, prolongation of the AH interval and an increase in the refractory periods of the AV node and bypass tracts are seen, but again this may be due to the effects of the Tween-80. No acute changes occur in either sinus rate or atrial or ventricular repolarization or refractoriness, whereas these are prolonged during chronic oral therapy.