Concentration-dependent blood pressure effects of guanfacine.

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.