What is the mechanism of action of Amiodarone (antiarrhythmic medication)?

From the Guidelines

Amiodarone is a complex antiarrhythmic medication with a multifaceted mechanism of action that includes noncompetitive B-adrenoceptor blockade, calcium channel blockade, blockade of sympathetic efferents, and possible Class Ia effects. Its mechanisms of action when given over the short term are still poorly defined, but it is known to have effects in each of the four Vaughn-Williams classes 1.

Key Mechanisms of Action

• Noncompetitive B-adrenoceptor blockade
• Calcium channel blockade
• Blockade of sympathetic efferents
• Possible Class Ia effects

Clinical Implications

Amiodarone's unique mechanism of action makes it effective for treating frequently recurring ventricular fibrillation (VF) and hemodynamically destabilizing ventricular tachycardia (VT) 1. The drug can be administered intravenously for short-term use, with a recommended starting dose of 500 mg per 24 hours, given in three stages: rapid infusion, early maintenance infusion, and later maintenance infusion 1.

Important Considerations

• Individual variability in response to amiodarone requires dosing to be titrated according to patient response 1.
• Adverse effects such as hypotension, bradycardia, and AV block may occur with intravenous amiodarone 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanisms of Action Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, it exerts a noncompetitive antisympathetic action One of its main effects, with prolonged administration, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node.

The mechanism of action of Amiodarone is multifaceted, involving:

• Blockage of sodium channels at rapid pacing frequencies (class I effect)
• Noncompetitive antisympathetic action (class II effect)
• Lengthening of the cardiac action potential (class III effect)
• Negative chronotropic effect in nodal tissues (class IV effect)
• Blockage of myocardial potassium channels, contributing to slowing of conduction and prolongation of refractoriness
• Blockage of calcium channels, contributing to negative dromotropic effects on the sinus node and slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node 2

From the Research

Mechanism of Action of Amiodarone

The mechanism of action of Amiodarone, an antiarrhythmic medication, is complex and multifaceted. Key aspects include:

• Class III antiarrhythmic agent: Amiodarone is primarily considered a class III antiarrhythmic agent, which means it acts by inhibiting outward potassium currents, resulting in a prolongation of action potential duration in atrial and ventricular muscles, as well as in the sinoatrial and atrioventricular nodes 3.
• Class I, II, and IV actions: In addition to its class III effects, Amiodarone also exhibits class I, II, and IV actions, making it a unique and effective antiarrhythmic agent 4.
• Use-dependent inhibition of inward sodium and calcium currents: Acute Amiodarone therapy results in a use-dependent inhibition of inward sodium and inward calcium currents, as well as a non-competitive alpha- and beta-blockade effect 3.
• Induction of postrepolarization refractoriness: Chronic Amiodarone therapy induces postrepolarization refractoriness via its class I effects on sodium channels, which prevents reentry formation in patients with heart failure 5.
• Vasodilating effect: Amiodarone also exhibits a vasodilating effect, which is mediated by the activation of intracellular calcium binding mechanisms, and can be enhanced by the simultaneous supplementation of calcium channel blockers 6.

Key Effects on the Heart

The effects of Amiodarone on the heart include:

• Prolongation of action potential duration: Amiodarone prolongs the action potential duration in atrial and ventricular muscles, as well as in the sinoatrial and atrioventricular nodes 3.
• Prevention of reentry formation: Amiodarone prevents reentry formation in patients with heart failure by inducing postrepolarization refractoriness via its class I effects on sodium channels 5.
• Vasodilation: Amiodarone exerts a vasodilating effect, which can be beneficial in the treatment of patients with coronary heart disease 6.

Clinical Implications

The clinical implications of Amiodarone's mechanism of action include:

• Effective treatment of ventricular and supraventricular arrhythmias: Amiodarone is effective in the treatment of various forms of supraventricular and ventricular tachycardia 4, 3.
• Use in patients with heart failure: Amiodarone can be used in patients with heart failure, as it does not usually produce significant cardiodepression and has a relatively high antiarrhythmic efficacy 7.
• Potential benefits in preventing sudden death: Amiodarone may have a beneficial effect on mortality and survival in certain groups of patients with ventricular arrhythmias 7.