title: Concentration-dependent blood pressure effects of guanfacine.
abstract: Central alpha 2-adrenoceptor stimulation decreases blood pressure, whereas stimulation of postjunctional peripheral adrenoceptors induces a pressor response. The net blood pressure response during multiple dosing is the sum of these effects and is dependent on drug kinetics, receptor affinity, and receptor occupancy. Guanfacine (2 to 6 mg/day), a selective alpha 2-adrenoceptor agonist, decreased blood pressure in patients with hypertension. At a dose greater than 6 mg/day the antihypertensive response deteriorated. Steady-state kinetics were linear but there was a tendency for a decrease in clearance after the highest dose. These results have practical implications for the therapeutic handling of the drug: Low doses for maximal therapeutic effect and longer dosage intervals at high-dosage schedules are indicated.
authors.forename: M
authors.initials: M
authors.lastname: Frisk-Holmberg
authors.forename: L
authors.initials: L
authors.lastname: Wibell
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D000328:Adult; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine; D006146:Guanidines / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010648:Phenylacetates / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D006146:Guanidines; D010648:Phenylacetates; D016316:Guanfacine