Effects of single and multiple doses of guanfacine in essential hypertension.

The effects of oral guanfacine were examined in six patients with essential hypertension. Guanfacine caused a substantial fall in both lying and standing systolic and diastolic blood pressure. The fall in pressure was evident by 6 hr, maximal by 10 to 12 hr, and lasted as long as 36 hr. In four patients satisfactory blood pressure control throughout the day was achieved during inpatient administration with single daily doses of 2 to 4 mg in the evening. The other two patients required twice-daily dosing for optimal control of blood pressure. There was no evidence of tolerance to the hypotensive effect. Sedation and xerostomia were apparent after the first dose but did not limit dose titration. Guanfacine lowered lying and standing plasma norepinephrine; this continued on long-term dosing. Urinary catecholamines were reduced from 59.21 +/- 17.24 (mean +/- SEM) to 28.91 +/- 4.20 micrograms/24 hr after 7 days of treatment. The hemodynamic effects, side effects, and biochemical evidence of reduced sympathetic activity after guanfacine resembled the centrally acting antihypertensive clonidine, although guanfacine appeared to have a longer duration of action.