Prazosin is a nonselective alpha-adrenergic antagonist (alpha-blocker) used in the therapy of hypertension. Prazosin is associated with a low rate of transient serum aminotransferase elevations and has not been clearly linked to clinically apparent acute liver injury.
Prazosin (pray' zoe sin) was the first alpha-adrenergic antagonist to be approved for use in the United States and is still widely used for therapy of hypertension. Prazosin inhibits alpha-adrenergic receptors present on smooth muscle in arterioles (so-called alpha-1b adrenergic receptors) as well as in those in the bladder neck and prostate (alpha-1a adrenergic receptors). The inhibition of alpha-adrenergic tone in blood vessels causes relaxation of arteriolar resistance and lowering of the blood pressure. Prazosin was approved for use in the United States in 1976 and is still used for treatment of hypertension, although rarely as a first line agent and usually in combination with other antihypertensives. Prazosin has not been fully evaluated or approved for therapy of benign prostatic hypertrophy (as have other alpha-1 adrenergic antagonists). Prazosin is available in capsules of 1, 2 and 5 mg generically and under the trade name Minipress. Prazosin is usually started at a dose of 1 mg two or three times daily, with increase in the dose based upon tolerance and clinical response to an average of 5 to 20 mg daily in divided doses. Prazosin is also available in a fixed combination with polythiazide (Minizide). Side effects include dizziness and syncope (particularly with the initial dose), fatigue, headache, palpitations, impotence, incontinence and gastrointestinal upset.
Prazosin has been associated with a low rate of serum aminotransferase elevations that in controlled trials was no higher than with placebo therapy. These elevations were transient and did not require dose modification. There have been no instances of clinically apparent acute liver injury attributed to prazosin in the published literature and current product labelling does not mention hepatic injury. As a group, the alpha-adrenergic blockers have not been linked to instances of clinically apparent liver injury. Thus, acute symptomatic liver injury due to prazosin must be exceedingly rare if it occurs at all.
Mechanism of Injury
The cause of the minor serum aminotransferase elevations associated with prazosin is not known. Prazosin is extensively metabolized by the liver and generation of a mildly toxic intermediate is a possible explanation.
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