indication

For treatment of hypertension, symptomatic benign prostatic hyperplasia, and severe congestive heart failure. May also be used alone or in combination with β-blockers in the preoperative management of signs and symptoms of pheochromocytoma.

pharmacology

Prazosin is an alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, Prazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors. In the human prostate, Prazosin antagonizes phenylephrine (alpha1 agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1c adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that Prazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of Prazosin results from a decrease in systemic vascular resistance and the parent compound Prazosin is primarily responsible for the antihypertensive activity.

mechanism of action

Prazosin acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

biotransformation

Primarily hepatic. Several metabolites have been identified in humans and animals (6- O -demethyl, 7- O -demethyl, 2-[1-piperazinyl]-4-amino-6, 7-dimethoxyquinazoline, 2,4-diamino-6,7-dimethoxyquinazoline).

absorption

Well-absorbed from gastrointestinal tract; bioavailability is variable (50 to 85%).

half life

2-3 hours

route of elimination

Animal studies indicate that prazosin hydrochloride is extensively metabolized, primarily by demethylation and conjugation, and excreted mainly via bile and feces. Less extensive human studies suggest similar metabolism and excretion in man.

drug interactions

Acebutolol: Risk of hypotension at the beginning of therapy

Atenolol: Risk of hypotension at the beginning of therapy

Betaxolol: Beta-Blockers such as betaxolol may enhance the orthostatic hypotensive effect of Alpha1-Blockers such as prazosin. The risk associated with ophthalmic products is probably less than systemic products. Exercise caution if an alpha1-blocker is added to existing beta-blocker therapy. Monitor for hypotension during first few days of concomitant therapy. A priori reduction in alpha1-blocker (especially systemic) dose may be warranted. Administering the first dose of systemic agents at bedtime may help minimize risk of severe hypotension. The risk associated with the use of ophthalmic products in either interacting group is probably less than that associated with systemic agents. If the alpha1-blocker is being used to treat BPH, consider using tamsulosin since its alpha1-A selectivity is least likely to cause hypotension.

Bevantolol: Risk of hypotension at the beginning of therapy

Bisoprolol: Risk of hypotension at the beginning of therapy

Carteolol: Risk of hypotension at the beginning of therapy

Carvedilol: Risk of hypotension at the beginning of therapy

Dabigatran etexilate: P-Glycoprotein inducers such as prazosin may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.

Digoxin: Prazosin increases the effect of digoxin

Esmolol: Risk of hypotension at the beginning of therapy

Labetalol: Risk of hypotension at the beginning of therapy

Metoprolol: Risk of hypotension at the beginning of therapy

Nadolol: Risk of hypotension at the beginning of therapy

Oxprenolol: Risk of hypotension at the beginning of therapy

Penbutolol: Risk of hypotension at the beginning of therapy

Pindolol: Risk of hypotension at the beginning of therapy

Practolol: Risk of hypotension at the beginning of therapy

Propranolol: Risk of hypotension at the beginning of therapy

Sotalol: Risk of hypotension at the beginning of therapy

Tadalafil: Tadalafil may enhance the hypotensive effect of Prazosin. Monitor for hypotension during concomitant therapy.

Tamsulosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Prazosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Timolol: Risk of hypotension at the beginning of therapy

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Vardenafil: Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Prazosin, may occur. Monitor for hypotension during concomitant therapy.

Verapamil: Risk of hypotension at the beginning of therapy