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J Am Coll Cardiol. 1984 Apr;3(4):1059-71.

Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects.


Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.

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