Therapeutic Function

Antihypertensive

Biological Activity

Selective α 2A -adrenoceptor agonist (K d = 31 nM). Displays 60-fold selectivity over α 2B -adrenoceptors. Also available as part of the α 2 -Adrenoceptor Tocriset? .

Biochem/physiol Actions

α-2 noradrenergic receptor agonist.

Pharmacokinetics

The pharmacokinetic properties for guanfacine differ from those of clonidine, guanabenz, and α-methyldopa. At pH 7.4, guanfacine is predominately (67%) in the nonionized, lipid-soluble base form, which accounts for its high oral bioavailability (>80%). Following an oral dose, peak plasma concentrations occur in 1 to 4 hours, with a relatively long elimination half-life of 14 to 23 hours. The maximum blood pressure response occurs in 8 to 12 hours after oral administration and is maintained up to 36 hours following its discontinuation. Following IV dosing, guanfacine achieves the highest concentrations in liver and kidney, with low concentrations in the brain. Guanfacine is 64% bound to plasma proteins. In patients with hepatic or renal impairment, its elimination half-life may be prolonged. Guanfacine is metabolized principally by hepatic hydroxylation to its inactive metabolite, 3-hydroxyguanfacine (20%), which is eliminated in the urine as its glucuronide (30%), sulfate (8%), or mercapturic acid conjugate (10%), and 24 to 37% is excreted as unchanged guanfacine. Its nearly complete bioavailability suggests no evidence of any first-pass effect. Guanfacine and its inactive metabolites are excreted principally in urine, with approximately 80% of its oral dose excreted in urine within 48 hours.

Side effects

Overall, although the frequency of troublesome adverse effects produced by guanfacine is similar to that produced by clonidine and the other centrally acting sympatholytics, their incidence and severity are lower with guanfacine. Unlike clonidine, abrupt discontinuation of guanfacine rarely results in rebound hypertension. When a withdrawal syndrome has occurred, its onset was slower and its symptoms less severe than the syndrome observed with clonidine.

General Description

Guanfacine hydrochloride,N-(aminoiminomethyl)-2,6-dichlorobenzeneacetamide(Tenex), is structurally related to clonidine hydrochloride andguanabenz acetate and shares many of their pharmacologicalproperties. The drug has a longer duration of action than eitherclonidine hydrochloride or guanabenz acetate. It lasts upto 24 hours. It also requires much longer (8–12 hours) for apeak effect to occur after the drug is administered.