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.