indication

For treatment and management of mild to moderate hypertension and urinary obstruction symptoms caused by BPH.

pharmacology

Doxazosin is an alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, Doxazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors. In the human prostate, Doxazosin 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 Doxazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of Doxazosin results from a decrease in systemic vascular resistance and the parent compound Doxazosin is primarily responsible for the antihypertensive activity.

mechanism of action

Doxazosin 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.

toxicity

Symptoms of overdose include hypotension. Oral LD₅₀ is greater than 1000 mg/kg in mice and rats.

biotransformation

Hepatic.

absorption

65%

half life

22 hours

route of elimination

On average only 4.8% of the dose was excreted as unchanged drug in the feces and only a trace of the total radioactivity in the urine was attributed to unchanged drug.

drug interactions

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

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

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

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