title: Alpha-adrenoceptor blockade by labetalol during long-term dosing.
abstract: 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 alpha-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 beta-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 alpha-adrenoceptor-blocking effect of oral labetalol without concomitant change in the degree of beta-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.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007545:Isoproterenol / Q000494:pharmacology; D007741:Labetalol / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D004983:Ethanolamines; D010656:Phenylephrine; D007545:Isoproterenol; D007741:Labetalol