What is the electrophysiological profile of amiodarone?

From the Guidelines

Amiodarone has a complex electrophysiological profile that makes it effective for treating various arrhythmias, primarily functioning as a class III antiarrhythmic drug by blocking potassium channels, but also exhibiting properties of all four Vaughan Williams antiarrhythmic classes. The mechanisms of action of amiodarone when given over the short term are still poorly defined but may include noncompetitive B-adrenoceptor blockade, calcium channel blockade, blockade of sympathetic efferents, and possible Class Ia effects 1. Amiodarone's electrophysiological profile is characterized by its ability to block sodium channels (class I effect), having beta-blocking and calcium channel-blocking properties (class II and IV effects), and inhibiting alpha-adrenergic receptors. This multi-channel blocking activity contributes to its effectiveness in treating both supraventricular and ventricular arrhythmias.

Some key points about the electrophysiological profile of amiodarone include:

• It has a complex mechanism of action that involves multiple ion channels and receptors
• It is effective in treating various types of arrhythmias, including ventricular and atrial fibrillation
• It has minimal negative inotropic effects compared to other antiarrhythmics, making it suitable for patients with heart failure
• It has an extremely long half-life due to its high lipophilicity and tissue accumulation, which explains its delayed onset of action and prolonged effects after discontinuation

The dosage of amiodarone should be kept at the lowest effective level, and potential drug toxicity and interactions must be considered when using long-term amiodarone therapy 1. Laboratory studies to assess liver and thyroid function should be performed at least every six months. The effects of interaction with amiodarone do not peak until seven weeks after the initiation of concomitant therapy, so close attention should be paid to digoxin levels and prothrombin time in patients taking digoxin and warfarin 1.

In terms of specific dosing guidelines, amiodarone can be administered intravenously or orally, with typical dosages provided in the ACLS setting, and the dosage should be titrated according to patient response 1. The recommended starting dose is 500 mg per 24 hours, given in three stages: rapid infusion of 150 mg over 10 minutes, early maintenance infusion of 1 mg/min for 6 hours, and later maintenance infusion of 0.50 mg/min 1.

Overall, amiodarone's complex electrophysiological profile makes it a valuable treatment option for various arrhythmias, but its use requires careful consideration of potential side effects and interactions.

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 electrophysiological profile of amiodarone includes:

• Class I effect: blocking sodium channels at rapid pacing frequencies
• Class II effect: noncompetitive antisympathetic action
• Class III effect: lengthening the cardiac action potential
• Class IV effect: negative chronotropic effect in nodal tissues The effects of amiodarone on the heart include:
• Slowing of conduction
• Prolongation of refractoriness
• Negative dromotropic effects on the sinus node
• Slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node
• Vasodilatory action, which can decrease cardiac workload and consequently myocardial oxygen consumption 2, 2, 2

From the Research

Electrophysiological Profile of Amiodarone

The electrophysiological profile of amiodarone is complex and multifaceted, involving various mechanisms of action that contribute to its antiarrhythmic effects. Some key aspects of its electrophysiological profile include:

• Inhibition of inward and outward currents, including sodium and calcium currents, which suppresses excitability and conductivity of cardiac tissues 3
• Inhibition of voltage- and ligand-gated potassium channel currents, which contributes to the prolongation of the action potential duration (APD) 3
• Moderate APD prolongation with minimal frequency dependence, which is a consistent long-term effect of the drug 3
• Down-regulation of Kv1.5 messenger ribonucleic acid (mRNA) in rat hearts, suggesting a drug-induced modulation of potassium-channel gene expression 3

Effects on Cardiac Tissues

Amiodarone's effects on cardiac tissues are varied and include:

• Prolongation of refractoriness in all cardiac tissues, which contributes to its antiarrhythmic effects 4
• Suppression of automaticity in some fibers, which helps to prevent arrhythmias 4
• Minimal slowing of conduction in fast channel-dependent tissue, which reduces the risk of proarrhythmic effects 4
• Interactions with the autonomic nervous system, which can contribute to its antiarrhythmic effects 5

Clinical Implications

The electrophysiological profile of amiodarone has important clinical implications, including:

• Efficacy in controlling symptomatic ventricular tachycardia and fibrillation (VT/VF) in patients who are refractory to other treatments 5, 6
• Potential to reduce mortality and improve survival in certain groups of patients with ventricular arrhythmias 6, 7
• Low to negligible proarrhythmic actions, which reduces the risk of worsening arrhythmias 7
• Ability to increase left ventricular ejection fraction and improve exercise capacity in patients with heart failure 7