Alpha‐adrenoceptor blockade by labetalol during long‐term dosing

The hypotensive effect of short‐term labetalol, the alpha‐ and beta‐adrenoceptor blocker, is greater in subjects in the orthostatic position, possibly because of the α‐adrenoceptor blockade. During prolonged use the orthostatic blood pressure fall disappears. To verify whether or not this is due to reduction in alpha‐blocking activity, phenylephrine‐induced increase in blood pressure was studied in six subjects with mild essential hypertension before and after 3 and 6 days and 1 and 6 mo of continuous treatment with 200 mg labetalol three times a day by mouth. At the same intervals, isoproterenol‐induced tachycardia was followed to assess β‐blockade. After 3 days on labetalol, the log dose‐response curve of phenylephrine‐induced increase in blood pressure shifted to the right and the dose of agonist required to elicit a 20% increase in systolic pressure was 1.7 times that before treatment. There was a progressive decline in the dose of agonist that induced the same increase in pressure so that after 6 mo of continuous labetalol it was the same as control. In contrast, the amount of isoproterenol needed to induce a 20% increase in heart rate was two to three times that before labetalol and did not change throughout 6 mo of therapy. These data indicate a decline in the α‐adrenoceptor‐blocking effect of oral labetalol without concomitant change in the degree of β‐adrenoceptor blockade. This might account for the disappearance of orthostatic hypotension early in the course of treatment and for some decrease in the antihypertensive efficacy of labetalol. Clinical Pharmacology and Therapeutics (1983) 33, 278–282; doi: 10.1038/clpt.1983.33