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

From the Guidelines

Amiodarone works through multiple mechanisms to control abnormal heart rhythms, primarily by blocking potassium channels, sodium channels, and having noncompetitive beta-blocking and calcium channel-blocking effects. This combination of actions makes it effective for both supraventricular and ventricular arrhythmias. The medication has an extremely long half-life (approximately 40-55 days) due to its high lipophilicity and extensive tissue distribution, particularly in adipose tissue, liver, and lungs 1.

Key Mechanisms of Action

• Blocks potassium channels, prolonging cardiac action potential and effective refractory period
• Blocks sodium channels, slowing conduction through cardiac tissue
• Has noncompetitive beta-blocking effects
• Has calcium channel-blocking effects

Clinical Use

Amiodarone is used in various clinical settings, including life-threatening arrhythmias, ventricular arrhythmias, and atrial fibrillation 1. The dosage guidelines for amiodarone vary depending on the indication and administration route, with typical dosages ranging from 150-mg IV bolus to 800-1,600 mg per day in divided doses for oral treatment 1.

Side Effects and Considerations

Amiodarone has numerous potential side effects, including pulmonary fibrosis, thyroid dysfunction, liver abnormalities, and corneal deposits 1. The medication's complex mechanism and multiple ion channel effects explain its efficacy against various arrhythmias but also account for its potential side effects.

Evidence-Based Recommendations

The use of amiodarone is supported by evidence from various studies, including a meta-analysis of 18 RCTs, which showed that amiodarone was similar to other antiarrhythmic drugs in its ability to convert patients to normal sinus rhythm 1. Additionally, a recent study comparing the use of amiodarone and lidocaine in patients with shock-resistant, out-of-hospital ventricular fibrillation showed that amiodarone therapy substantially improves survival and hospital admission rates 1.

From the FDA Drug Label

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 (MOA) of amiodarone is complex and involves:

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

From the Research

Mechanism of Action

• Amiodarone is classified as a class III antiarrhythmic drug, but it also has class I, II, and IV actions, making it a unique and effective anti-arrhythmic agent 3, 4, 5.
• Its leading pharmacologic features include sodium and calcium channel block, nonselective β-adrenergic inhibition, as well as high lipophilicity and a very long plasma half-life 3.
• Amiodarone affects all phases of the cardiac action potential, which contributes to its effectiveness in treating both ventricular and atrial arrhythmias 6.

Therapeutic Uses

• Amiodarone is used to treat symptomatic and life-threatening ventricular arrhythmias and symptomatic supraventricular arrhythmias 4.
• It is effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation and preventing ventricular arrhythmias, such as frequent ventricular extrasystoles or nonsustained runs of ventricular tachycardia 3.
• Amiodarone is also used to prevent sudden cardiac death in patients with increased risk, such as those with severely depressed left ventricular function 3, 7.

Side Effects and Interactions

• Amiodarone has a diverse side effect profile, involving the cardiac, thyroid, pulmonary, hepatic, gastrointestinal, ocular, neurological, and dermatological systems 4, 5, 6.
• Common side effects include thyroid abnormalities, pulmonary fibrosis, and transaminitis, for which routine monitoring is recommended 6.
• Amiodarone interacts with several medications, such as warfarin, simvastatin, and atorvastatin, and many HIV antiretroviral medications, which requires careful management and monitoring 5, 6.