Predictability of antihypertensive responsiveness and alpha-adrenoceptor antagonism during prazosin treatment.

This study investigates concentration-effect relationships in nine patients who had essential hypertension treated with prazosin. Antihypertensive responsiveness was determined for each individual patient in terms of millimeters of mercury of blood pressure reduction per nanogram per milliliter of plasma prazosin concentration. The principal findings were that there was significant attenuation of antihypertensive responsiveness, from 11.5 mm Hg per nanogram per milliter after the first dose to 8.7 mm Hg per ng/ml after 1 week of treatment with prazosin. Correspondingly, there was significant attenuation of the degree of alpha 1-antagonism as assessed by the pressor response to intravenous phenylephrine. However, there was no significant further attenuation of either assessment during continued treatment for up to 3 months. These findings suggest that after an early adaptation, which occurs within the first week of treatment, there is no long-term attenuation of the antihypertensive effect of prazosin. Despite this initial adaptive change, the magnitude of the long-term antihypertensive effect of prazosin was predictable from the first dose response in individual patients.