COMBINED TERAZOSIN AND VERAPAMIL THERAPY IN ESSENTIAL-HYPERTENSION - HEMODYNAMIC AND PHARMACOKINETIC INTERACTIONS

alpha-Blockers and calcium antagonists are commonly used in the treatm ent of hypertension, but few data are available concerning first dose or steady state (SS) hemodynamic and pharmacokinetic effects of these drugs when they are used in combination therapy. To examine these inte ractions, we measured supine and standing blood pressure (BP), heart r ate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients a fter 2 weeks of placebo, again after the first dose or 3 weeks of ther apy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazos in (T) titrated weekly to 5 mg daily, and finally when T was added to V (group VT) or V added to T (group TV), acutely and at SS. Changes in supine hemodynamics when T was added to V or when V was added to T we re similar and included a further reduction in BP, a transient increas e in HR, and little or no change in CI. Both groups experienced signif icant decreases in standing blood pressure, especially 0.5 to 2 h foll owing initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV afte r the first dose, but minimum standing systolic BP was not significant ly different between groups (group TV 97 mm Hg at 1 h; group VT 109 mm Hg at 1.5 h, P > .05). Four patients in group TV and two in group VT experienced symptomatic orthostatic hypotension with the first dose of double-agent treatment. Pharmacokinetic interactions, including an in crease in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, th e orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combina tion for the treatment of essential hypertension, but that orthostasis may result when initiating combination therapy. The orthostasis seen in some patients appears to be due to the combined vasodilatory effect s rather than negative ionotropic or chronotropic effects.