EFFECTS OF ORAL AND INTRAVENOUS TERAZOSIN AND HEAD-UP TILT ON BLOOD-PRESSURE RESPONSES IN PATIENTS WITH HYPERTENSION

Terazosin is a selective alpha(1)-adrenoceptor antagonist. A double-bl ind, randomized, placebo-controlled, two-period study evaluated the ef fects of posture and of oral and intravenous administration of terazos in on blood pressure and heart rate in patients with hypertension. At least one week after withdrawal of all antihypertensive medications, 3 1 patients with sitting diastolic blood pressure of 95 to 114 mmHg wer e enrolled in the study. After a 24-hour, single-blind, placebo lead-i n phase, the patients were randomized to receive either oral terazosin (1 mg on day 1, 2 mg on day 2, and 5 mg on days 3 and 4), a la-hour i ntravenous infusion of terazosin (2.5 mg, 5 mg, or 7.5 mg), or placebo for 4 consecutive days. Head-up tilt (60 degrees for 20 minutes) eval uations were performed before and 0.5. 1.5, 2.5, 6, 12, and 1 6 hours after start of administration during the placebo lead-in phase and on each of the 4 days of the double-blind treatment phase. Blood pressure and heart rate were monitored every 2 minutes during the 20-minute ti lt. Statistically significantly larger mean changes in blood pressure and heart rate were observed with the 7.5-mg intravenous dose of teraz osin compared with those after oral terazosin or placebo. With respect to intravenous terazosin, the orthostatic changes were maximal on the first day of the 4-day treatment and increased with increasing doses of terazosin. Maximum orthostatic changes in blood pressure after oral administration of tetazosin were not Significantly different from tho se observed with placebo. The most common treatment-emergent adverse e vents during tilt were dizziness and nausea. Dizziness occurred more f requently with intravenous terazosin than with oral terazosin. The res ults of this study indicate that oral dose titration of terazosin rath er than a slower rate of terazosin infusion minimized the postural eff ects on blood pressure and associated symptoms during head-up tilt. Jo urnal of Clinical Pharmacology, 1998;38:545-553 (C) 1998 The American College of Clinical Pharmacology.