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Amiodarone

Amiodarone is an antiarrhythmic drug used to treat recurrent supraventricular and ventricular arrhythmias. Amiodarone can be administered orally or intravenously. It is lipophilic and taken up extensively by tissue. After long-term therapy, the circulating half- life can range between 60 and 140 days. Amiodarone is metabolized by cytochrome CYP3A4 to N-desethylamiodarone (DEA), which is equally active and has similar pharmacokinetic properties. 

Amiodarone is associated with a relatively high incidence of side effects, making it a complicated drug to use safely. Amiodarone is associated with toxicities involving the lungs, thyroid, liver, eyes, and skin.The most common side effect of amiodarone is hypothyroidism or hyperthyroidism because of its structural similarity to thyroxine. Pulmonary toxicity is responsible for most deaths associated with amiodarone therapy and correlates more closely with the total cumulative dose than with serum drug levels. Gastrointestinal side effects associated include nausea, vomiting, anorexia, diarrhea, and constipation. Amiodarone can directly cause both sinus bradycardia and AV nodal block, due primarily to its calcium channel blocking activity. Corneal microdeposits are caused by the secretion of amiodarone by the lacrimal gland with accumulation on the corneal surface. Skin reactions include photosensitivity and a bluish-gray discoloration. Neurologic toxicity may take many forms including tremor, ataxia, peripheral neuropathy with paresthesias, and sleep disturbances. 

Transient increase in serum aminotransferase concentrations occurs in approximately 25 percent of patients soon after initiation of therapy. The patients are usually asymptomatic, but the drug should be discontinued if there is more than a twofold elevation. The histopathology of amiodarone hepatotoxicity resembles alcoholic liver disease. 

Therapeutic range is 0.5 to 2.0 mcg/mL. Levels that are >2.5 mcg/mL are considered toxic. Current therapeutic ranges are based solely on amiodarone, but most individuals will have roughly equivalent concentrations of DEA at steady state.

Drug levels are measured by liquid chromatography-tandem mass spectrometry. Specimen requirement is a red top tube of blood. 

Reference

Goldschlager N, Epstein AE, Naccarelli GV, et al: A practical guide for clinicians who treat patients with amiodarone. Heart Rhythm 2007;4:1250-1259

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