On the combination of α‐ and β‐adrenoceptor blockade in hypertension

A randomized double‐blind crossover trial was conducted in 20 patients with moderate to severe hypertension to compare the efficacy of labetalol, which combines α‐ and β‐adrenoceptor blocking properties, with that of metoprolol alone or in combination with prazosin. After placebo for 1 wk, active medication was given in two 6‐wk phases. During one phase, metoprolol (100 to 400 mg/day) was given with prazosin (2 to 4 mg/day) as an option in the last 3 wk, whereas during the other phase, labetalol (200 to 1000 mg/day) was given alone. Satisfactory control of supine blood pressure was obtained in 10 patients with metoprolol and in another four patients after the addition of prazosin. During the labetalol phase, blood pressure control was achieved in 11 of 19 patients tested. Gastrointestinal disturbances, nasal congestion, impotence, failure to ejaculate, scalp tingling, and headache were more prevalent in the labetalol phase than in the other. In four cases these occurred in patients who did not require prazosin. Supine, erect, and exercise pulse rates were reduced by both metoprolol with or without prazosin and by labetalol; the effects were less in the labetalol phase. These differences could arise from an action of labetalol on cardiac presynaptic α‐adrenoceptors. Adjunctive use of prazosin in nonresponders to metoprolol increases the response rate and avoids unnecessary deployment of α‐adrenoceptor blockade in patients whose blood pressure can be controlled by β‐blockade alone. Clinical Pharmacology and Therapeutics (1983) 34, 576–582; doi: 10.1038/clpt.1983.218