Clonidine is a centrally active alpha-adrenergic agonist used predominantly as an antihypertensive agent, usually in combination with other agents. Despite wide scale use for many years, clonidine has not been linked definitively to either serum aminotransferase elevations or clinically apparent liver injury.
Clonidine (klon' i deen) is an antihypertensive agent which acts by stimulation of the alpha 2A subtype of alpha adrenergic receptors in the brainstem, causing a reduction in the sympathic outflow of the central nervous system. Decreases in plasma levels of norepinephrine correlate closely with its antihypertensive effects. Clonidine is effective in lowering blood pressure and can be used alone or in combination with other antihypertensive medications. Clonidine is also used in several other conditions in which central nervous system sympathetic activity is believed to contribute including neuropathy, smoking and alcohol cessation, attention deficit disorder, vascular headache, menopausal symptoms, diabetic diarrhea, and restless leg syndrome. Clonidine was approved for use in the United States in 1974 and continues to be widely used with more than 11 million prescriptions being filled yearly. Current approved indications are for treatment of hypertension, but some preparations are also approved for cancer pain management and treatment of attention deficit disorder. Off label uses include treatment of Tourette syndrome, migraine headahces, stress and sleep disorders, and to alleviate symptoms of alcohol, nicotine or narcotic withdrawal. Clonidine is available in tablets of 0.1, 0.2 and 0.3 mg generically and under the brand name of Catapres. Clonidine is also available in fixed combination with diuretics, as a solution for injection and in a transdermal formulation for application once weekly. The typical maintenance dose of clonidine in adults is 0.1 to 0.6 mg daily in 2 to 3 divided doses. Side effects are usually mild and include sedation, fatigue, bradycardia, dry mouth, headaches, dizziness, postural hypotension, male impotence and gastrointestinal upset. Sudden withdrawal can cause rebound hypertension.
Serum aminotransferase elevations during clonidine therapy are uncommon and rates of such elevations have not been reported in the large clinical trials, demonstrating its efficacy in hypertension. Despite many decades of use, clonidine has not been implicated in instances of clinically apparent acute liver injury.
Mechanism of Injury
Clonidine is metabolized by the cytochrome P450 (CYP) system to a major degree but is typically administered in very low doses (less than 1 mg daily) and neither induces or inhibits CYP activity, which may account in part for its relative lack of hepatotoxicity.
Drug Class: Antihypertensive Agents
Clonidine – Generic, Catapres®
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