title: Combined terazosin and verapamil therapy in essential hypertension. Hemodynamic and pharmacokinetic interactions.
abstract: alpha-Blockers and calcium antagonists are commonly used in the treatment 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 interactions, we measured supine and standing blood pressure (BP), heart rate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients after 2 weeks of placebo, again after the first dose or 3 weeks of therapy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazosin (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 were similar and included a further reduction in BP, a transient increase in HR, and little or no change in CI. Both groups experienced significant decreases in standing blood pressure, especially 0.5 to 2 h following initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV after the first dose, but minimum standing systolic BP was not significantly 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 increase in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, the orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combination 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 effects rather than negative ionotropic or chronotropic effects.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Lenz
authors.forename: J L
authors.initials: JL
authors.lastname: Pool
authors.forename: A R
authors.initials: AR
authors.lastname: Laddu
authors.forename: A
authors.initials: A
authors.lastname: Varghese
authors.forename: W
authors.initials: W
authors.lastname: Johnston
authors.forename: A A
authors.initials: AA
authors.lastname: Taylor
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011187:Posture; D011224:Prazosin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014700:Verapamil / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: C041226:Terazosin; D014700:Verapamil; D011224:Prazosin