In animals, terazosin causes a decrease in blood pressure by decreasing total peripheral vascular resistance. The vasodilatory hypotensive action of terazosin appears to be produced mainly by blockade of alpha-1 adrenoceptors. Terazosin decreases blood pressure gradually within 15 minutes following oral administration.

Patients in clinical trials of terazosin were administered once daily (the great majority) and twice daily regimens with total doses usually in the range of 5 to 20 mg/day, and had mild (about 77%, diastolic pressure 95 to 105 mmHg) or moderate (23%, diastolic pressure 105 to 115 mmHg) hypertension. Because terazosin, like all alpha antagonists, can cause unusually large falls in blood pressure after the first dose or first few doses, the initial dose was 1 mg in virtually all trials, with subsequent titration to a specified fixed dose or titration to some specified blood pressure end point (usually a supine diastolic pressure of 90 mmHg).

Blood pressure responses were measured at the end of the dosing interval (usually 24 hours) and effects were shown to persist throughout the interval, with the usual supine responses 5 to 10 mmHg systolic and 3.5 to 8 mmHg diastolic greater than placebo. The responses in the standing position tended to be somewhat larger, by 1 to 3 mmHg, although this was not true in all studies. The magnitude of the blood pressure responses was similar to prazosin and less than hydrochlorothiazide (in a single study of hypertensive patients). In measurements 24 hours after dosing, heart rate was unchanged.

Limited measurements of peak response (2 to 3 hours after dosing) during chronic terazosin administration indicate that it is greater than about twice the trough (24 hour) response, suggesting some attenuation of response at 24 hours, presumably due to a fall in blood terazosin concentrations at the end of the dose interval. This explanation is not established with certainty, however, and is not consistent with the similarity of blood pressure response to once daily and twice daily dosing and with the absence of an observed dose-response relationship over a range of 5 to 20 mg, i.e., if blood concentrations had fallen to the point of providing less than full effect at 24 hours, a shorter dosing interval or larger dose should have led to increased response.

Further dose response and dose duration studies are being carried out. Blood pressure should be measured at the end of the dose interval; if response is not satisfactory, patients may be tried on a larger dose or twice daily dosing regimen. The latter should also be considered if possibly blood pressure-related side effects, such as dizziness, palpitations, or orthostatic complaints, are seen within a few hours after dosing.

The greater blood pressure effect associated with peak plasma concentrations (first few hours after dosing) appears somewhat more position-dependent (greater in the erect position) than the effect of terazosin at 24 hours and in the erect position there is also a 6 to 10 beat per minute increase in heart rate in the first few hours after dosing. During the first 3 hours after dosing 12.5% of patients had a systolic pressure fall of 30 mmHg or more from supine to standing, or standing systolic pressure below 90 mmHg with a fall of at least 20 mmHg, compared to 4% of a placebo group.

There was a tendency for patients to gain weight during terazosin therapy. In placebo-controlled monotherapy trials, male and female patients receiving terazosin gained a mean of 1.7 and 2.2 pounds respectively, compared to losses of 0.2 and 1.2 pounds respectively in the placebo group. Both differences were statistically significant.

During controlled clinical trials, patients receiving terazosin monotherapy had a small but statistically significant decrease (a 3% fall) compared to placebo in total cholesterol and the combined low-density and very-low-density lipoprotein fractions. No significant changes were observed in high-density lipoprotein fraction and triglycerides compared to placebo.

Analysis of clinical laboratory data following administration of terazosin suggested the possibility of hemodilution based on decreases in hematocrit, hemoglobin, white blood cells, total protein and albumin. Decreases in hematocrit and total protein have been observed with alpha-blockade and are attributed to hemodilution.