Guanfacine hydrochloride: a centrally acting antihypertensive agent

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of guanfacine hydrochloride are reviewed. Guanfacine lowers blood pressure by activating CNS alpha adrenoreceptors, which results in sympathetic outflow leading to reduced vascular tone. However, initial hypotensive response to guanfacine may be caused by stimulation of peripheral presynaptic receptors that inhibit sympathetic nerve function. Guanfacine is rapidly and completely absorbed from the gastrointestinal tract and apparently undergoes extensive distribution to all tissues. Steady-state plasma concentrations may be reached in four days. About 30% is excreted renally; the rest is metabolized hepatically. Its long duration of action is related to a slow elimination half-life. In the few controlled clinical trials of guanfacine versus placebo, systolic and diastolic blood pressures were reduced in patients treated with guanfacine; daily dosages of guanfacine 1, 2, and 3 mg (as the hydrochloride salt) were comparable in efficacy. Several large open trials of guanfacine showed blood pressure reductions of about 16% after one year; some patients received other antihypertensive therapy concomitantly. Guanfacine and clonidine appear to have comparable effects in reducing both systolic and diastolic blood pressure when given as monotherapy and as step-2 therapy; data on the comparative blood-pressure-lowering effects of guanfacine and methyldopa are less consistent. Guanfacine's adverse reactions include dry mouth, sedation, and constipation. Adverse effects and reaction to sudden withdrawal of the drug may be less severe with guanfacine than with clonidine. A daily dose of guanfacine 1 mg (as the hydrochloride salt) at bedtime is recommended; 2 or 3 mg, or divided doses, may be given if needed. Once-daily administration and fewer adverse effects may give guanfacine some advantage over other centrally acting antihypertensive agents. Further study is needed to determine whether it will be adequate as first-line therapy.