Labetalol: A Review of Its Pharmacology, Pharmacokinetics, Clinical Uses and Adverse Effects

Abstract

Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.

Failure of metyrosine therapy for preoperative management of pheochromocytoma: a case report

“…16 Our review of the literature and our previous clinical experience with preoperative preparation of PHEOS guided our choice to use metyrosine alone without concomitant selective competitive alpha-1 blockade-keeping in mind that we did use labetalol, which exerts beta-alpha antagonism in a 3:1 ratio after oral administration. 17,18 While practices in preparation for surgical treatment of malignant PHEOS vary at each institution, we recognize that recent research and review articles suggest that metyrosine is ideally used in combination with alpha blockade, including either competitive or non-competitive agents. 10,11,13 Still, a review of older reports suggests that metyrosine monotherapy is a suitable option for achieving perioperative BP control in both malignant and benign PHEOS.…”

Beta-bloqueadores em anestesiologia: aspectos farmacológicos e clínicos

“…Tem meia-vida de eliminação de 5 a 8 horas. 33 Apresenta mínimos efeitos sobre os fluxos uterino e cerebral 34 . Seu efeito anti-hipertensivo resulta da diminuição da resistência vascular sistêmica, da freqüência cardíaca e da contratilidade do miocárdio.…”

“…Seu efeito anti-hipertensivo resulta da diminuição da resistência vascular sistêmica, da freqüência cardíaca e da contratilidade do miocárdio. Não determina aumento da freqüência cardíaca após a ocorrência de vasodilatação e diminuição da pressão arterial 33 . Tem sido bastante empregado nas cirurgias de feocromocitoma.…”

“…It is conjugated to glucuronic acid in the liver and excreted by urine and feces. Its elimination half-life is 5 to 8 hours 33 . It has minor effects on uterine and cerebral flows 34 .…”

Single dose pharmacokinetics and pharmacodynamics of oral oxazepam during concomitant administration of propranolol and labetalol.

“…The latter shares the same metabolic pathway as the benzodiazepine oxazepam, being metabolised to inactive glucuronides (MacCarthy et al, 1983 (Sonne et al, 1988).…”