indication

For use alone or in combination with other classes of antihypertensive agents in the management of hypertension. Has also been used for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric patients.

pharmacology

Guanfacine is a phenylacetyl-guanidine derivative hypotensive and a centrally-acting, alpha(2)-adrenergic receptor agonist used alone or in combination with other drugs for the treatment of hypertension.

mechanism of action

Guanfacine selectively stimulates central alpha(2)-adrenergic receptors, resulting in inhibition of sympathetic vasomotor centers, which contributes predominantly to the hypotensive effects of the drug. Central effects of guanfacine lead to reduced peripheral sympathetic nerve impulses from the vasomotor center to the heart and blood vessels. This results in a decrease in peripheral vascular resistance and a reduction in heart rate. The stimulation of peripheral alpha(2)-adrenergic receptors may also contribute to hypotensive effects.

toxicity

Symptoms of overdose include drowsiness, lethargy, bradycardia and hypotension. LD₅₀=165mg/kg (orally in mice)

biotransformation

Hepatic

absorption

Rapid and complete, with an oral bioavailability of approximately 80%.

half life

17 hours (range 10-30 hours)

route of elimination

In individuals with normal renal function, guanfacine and its metabolites are excreted primarily in the urine.

drug interactions

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

Trimipramine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanfacine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanfacine should be withdrawn very gradually to reduce the risk of hypertensive crisis.