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 metabolized?

Amiodarone is metabolized to desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochrome P450 3A4 (CYP3A4) and CYP2C8. The CYP3A4 isoenzyme is present in both the liver and intestines (see “CLINICAL PHARMACOLOGY, Pharmacokinetics”).

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.

Does amiodarone cause nephrotoxicity?

Although there is no objective evidence of Amiodarone-induced nephrotoxicity (like a renal biopsy), in this case, the presence of a strong “temporal association” and lack of any other nephrotoxic agents or conditions significantly raises the possibility of an association between Amiodarone and Acute Kidney Disease.

What is amiodarone toxicity?

The three main complications of long-term amiodarone use are pulmonary toxicity, thyroid disease and liver toxicity. Pulmonary toxicity progresses slowly in the setting of amiodarone use, may be subtle initially and is the most common cause of death related to amiodarone therapy.

What does amiodarone do to potassium?

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.

Is amiodarone renally cleared?

Amiodarone has a clear effect on serum creatinine. Maximum change in parameters of renal function occurs in conjunction with the time that serum concentrations of DEA stabilize during the first year of therapy.

How is amiodarone toxicity diagnosed?

Amiodarone-induced pulmonary toxicity is a diagnosis of exclusion. Pulmonary evaluation with chest X-ray and pulmonary function testing, including diffusion capacity for carbon monoxide is recommended when amiodarone is started.

Is amiodarone renally excreted?

Amiodarone, an antiarrhythmic agent, is hepatically metabolized and with negligible amounts detectable in urine. High dose i.p. administration to rats reduces renal blood flow and creatinine clearance without apparent damage on electron microscopy.

Can amiodarone cause high creatinine levels?

Rising creatinine concentrations correlated with amiodarone concentrations (y = 93.9 + 8.6x, r = 0.51, P < 0.0001). When assessing elevation of serum creatinine in a patient receiving amiodarone, physicians should be aware that it may be related to this drug.

What is the most concerning toxicity of amiodarone?

Amiodarone can cause numerous kinds of lung problems, but in most cases, the problem takes one of four forms. The most dangerous type of amiodarone lung toxicity is a sudden, life-threatening, diffuse lung problem called acute respiratory distress syndrome (ARDS).

Is amiodarone pulmonary toxicity reversible?

One well known serious side effect of amiodarone is pulmonary toxicity which can be acute, sub-acute, or chronic and can be irreversible and fatal.

Is amiodarone toxicity reversible?

For most patients with the less severe forms of lung toxicity (IP, typical pneumonia, or a pulmonary mass), the lungs often eventually improve if the drug is stopped. 2 Amiodarone should also be stopped for people who develop ARDS, but the damage might not be reversible in these cases.

How does amiodarone cause hypokalemia?

The arrhythmogenicity of amiodarone is not well known. This compound lengthens cardiac repolarization. Any electrolyte abnormality, such as hypokalemia or hypomag- nesemia, that may produce instability of the membrane potential may then produce polymor- phous ventricular tachycardia.

Does amiodarone cause hyperkalemia?

Conclusions: In this in-vitro model using human blood, amiodarone and quinidine both attenuated F(-)-induced hyperkalemia.

Does amiodarone cause renal toxicity?

As noted above, amiodarone is also a cationic amphiphilic drug, and its ability to produce similar inclusions in various tissues is not surprising. However, although it is a well-known cause of pulmonary and hepatic toxicity, significant renal toxicity has not been described.

What does amiodarone do to kidneys?

Not much has been studied about the kidney injury seen in amiodarone. Fogoros et al. [5] reported that about 8.8% of patients on oral amiodarone had an elevation of creatinine with a mean increase of 0.81 mg/dL with one among them requiring discontinuation of the medication.

What are signs of amiodarone toxicity?

The clinical presentation of amiodarone pulmonary toxicity is very nonspecific. Common symptoms are shortness of breath, dry cough, fever, respiratory distress, and fatigue; sometimes it can mimic acute respiratory distress syndrome.

What is the cause of amiodarone 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.

What is the mechanism of action of amiodarone?

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.

Can amiodarone be used to treat AFIB in dogs?

On the basis of >20% decrease in heart rate in 76% of the dogs and conversion to sinus rhythm in 35%, it was concluded that amiodarone may be useful in managing AF in dogs. The use of amiodarone in the medical management of AF in dogs warrants further investigation.

What is the prognosis of amiodarone toxicity?

Amiodarone and its derivatives can be detected in plasma and in hepatic tissue, and these levels may remain high for months if not years after stopping. Amiodarone has also been associated with rare cases of Reye Syndrome, usually arising in a child on chronic amiodarone therapy who develops an acute viral syndrome suggesting influenza.