How does amiodarone cause hepatotoxicity?

The cause of amiodarone hepatotoxicity appears to be direct damage to lipid bilayers and disturbance of lysosomal and/or mitochondrial function. Amiodarone appears to be potent inhibitor of phospholipase A accounting for the accumulation of lipid-rich material in lysosomes.

How does amiodarone cause cirrhosis?

The effect of amiodarone on the liver resulting in hepatotoxicity is a recognized complication of amiodarone, but this hepatotoxicity leading to cirrhosis of the liver is unfortunately an underrecognized side effect. Little has been written on amiodarone-induced cirrhosis (AIC) of the liver due to its rarity [1–4].

Is amiodarone metabolized by the liver?

Amiodarone is metabolized to mono-N-desethylamiodarone (DEA) by cytochrome P-450 enzymes (CYP3A4 and 2C8). This active metabolite possesses antiarrhythmic properties. Left ventricular dysfunction prolongs the half-life of DEA. Both amiodarone and DEA accumulate in fatty tissues, including the liver.

Can amiodarone cause hyperbilirubinemia?

Amiodarone-induced hepatotoxicity is a rare adverse reaction, which may progress into hepatic fibrosis and cirrhosis [2]. In this report, we present the case of a 76-year-old patient with amiodarone-induced intrahepatic cholestasis with prolonged hyperbilirubinemia despite the discontinuation of the offending agent.

Is amiodarone bad for liver?

Long-term oral amiodarone is associated with photosensitivity, thyroid dysfunction, and pulmonary and hepatic toxicity. Hepatic toxicity varies from an asymptomatic and transient rise of serum aminotransferases that resolves after dose reduction or withdrawal, to severe liver disease [1].

Is there a substitute for amiodarone?

Multaq® (dronedarone) is a new drug for atrial fibrillation and atrial flutter that is a potential replacement for amiodarone. Multaq® just received priority review status from the US FDA.

What is the mechanism of action of amiodarone?

After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias.

Is there an alternative to amiodarone?

Dronedarone has been viewed as a potential therapeutic alternative for amiodarone because of a lower risk for pulmonary, thyroid, and dermatologic adverse effects. Compared with amiodarone, dronedarone has poor bioavailability and a shorter terminal disposition half-life, which dictates a twice-daily dosing regimen.

Why is amiodarone so bad?

HEART: Amiodarone can cause slow heart rhythm disorders such as slowing of the sinus rate and AV block. You may feel fatigued, lethargic, have poor exercise tolerance, and may experience dizziness and fainting.

What is the primary action of amiodarone?

Amiodarone has multiple effects on myocardial depolarization and repolarization that make it an extremely effective antiarrhythmic drug. Its primary effect is to block the potassium channels, but it can also block sodium and calcium channels and the beta and alpha adrenergic receptors.

Why do we use amiodarone?

Amiodarone (Cordarone) is used to treat and prevent an irregular heartbeat. It slows down nerve activity in the heart and relaxes an overactive heart.

When to be concerned about hepatotoxicity with amiodarone?

Potential hepatotoxicity related to amiodarone therapy is often a concern when deciding whether to initiate or continue treatment with this medication. While mostly associated with long-term oral administration of the drug, toxicity has also been reported early during intravenous administration and months after discontinuation of therapy.

What are mechanisms of hepatocellular toxicity associated with dronedarone?

Amiodarone is a well-known mitochondrial toxicant. The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone. We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h.

How does amiodarone interact with thyroid nuclear receptors?

Amiodarone may interact with thyroid nuclear receptors, but its antiarrhythmic effects are believed to be mediated by its action in blocking membrane ion channels via perturbation of the lipid environment in the membrane bilayer. Amiodarone is highly lipophilic and is concentrated in many tissues and cells, including hepatocytes in the liver.

Where does amiodarone accumulate in the human body?

Amiodarone is highly lipophilic and is concentrated in many tissues and cells, including hepatocytes in the liver. It has a slow onset of action and a long but variable elimination half life (up to 6 months) and can accumulate in tissues including hepatocytes.