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Labetalol is a medication used to treat high blood pressure.
Labetalol’s dual alpha and beta adrenergic antagonism has different physiological effects in short- and long-term situations. In short-term, acute situations, labetalol decreases blood pressure by decreasing systemic vascular resistance with little effect on stroke volume, heart rate and cardiac output.
1 Medical uses
1.1 Special populations
2 Side effects
5.1 Mechanism of action
5.2 Physiological action
7 See also
Labetalol is effective in the management of hypertensive emergencies, postoperative hypertension, pheochromocytoma -associated hypertension, and rebound hypertension from beta blocker withdrawal.
It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.
It is also used as an alternative in the treatment of severe hypertension.
Pregnancy: studies in lab animals showed no harm to the fetus. However, a comparable well-controlled study has not been performed in pregnant women.
Nursing: breast milk has been shown to contain small amounts of labetalol (0.004% original dose). Prescribers should be cautious in the use of labetalol for nursing mothers.
Pediatric: no studies have established safety or usefulness in this population.
Geriatric: the elderly are more likely to experience dizziness when taking labetalol. Labetalol should be dosed with caution in the elderly and counseled on this side effect.
Neurologic: headache (2%), dizziness (11%)
Gastrointestinal: nausea (6%), dyspepsia (3%)
Cholinergic: nasal congestion (3%), ejaculation failure (2%)
Respiratory: dyspnea (2%)
Other: fatigue (5%), vertigo (2%), orthostatic hypotension
Low blood pressure with standing is more severe and more common with IV formulation (58% vs 1%
Drug eruption similar to lichen planus
Hypersensitivity – which may result in a lethal respiratory distress
Labetalol is contraindicated in people with overt cardiac failure, greater-than-first-degree heart block, severe bradycardia, cardiogenic shock, severe hypotension, anyone with a history of obstructive airway disease including asthma, and those with hypersensitivity to the drug.
The minimum requirement for adrenergic agents is a primary or secondary amine separated from a substituted benzene ring by one or two carbons.
Labetalol has two chiral carbons and consequently exists as four stereoisomers.
Stereoisomers of Labetalol
Labetalol acts by blocking alpha and beta adrenergic receptors, resulting in decreased peripheral vascular resistance without significant alteration of heart rate or cardiac output.
The β:α antagonism of labetalol is approximately 3:1.
It is chemically designated in International Union of Pure and Applied Chemistry (IUPAC) nomenclature as 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride.
Mechanism of action
Labetalol is a dual alpha (α1) and beta (β1/β2) adrenergic receptor blocker and competes with other Catecholamines for binding to these sites.
The amount of alpha to beta blockade depends on whether labetalol is administered orally or intravenously (IV). Orally, the ratio of alpha to β blockade is 1:3. Intravenously, alpha to β blockade ratio is 1:7.
Labetalol possesses intrinsic sympathomimetic activity.
Similar to local anesthetics and sodium channel blocking antiarrhythmics, labetalol also has membrane stabilizing activity.
The physiological effects of labetalol when administered acutely (intravenously) are not predictable solely by their receptor blocking effect, i.e. blocking beta1- receptors should decrease heart rate, but labetalol does not. When labetalol is given in acute situations, it decreases the peripheral vascular resistance and systemic blood pressure while having little effect on the heart rate, cardiac output and stroke volume, despite its alpha1-, beta1- and beta2- blocking mechanism.
Long term labetalol use also has different effects from other beta-blocking drugs. Other beta-blockers, such as propranolol, persistently reduce cardiac output during exercise. The peripheral vascular resistance decreases when labetalol is first administered. Continuous labetalol use further decreases peripheral vascular resistance. However, during exercise, cardiac output remains the same due to a compensatory mechanism that increases stroke volume. Thus, labetalol is able to reduce heart rate during exercise while maintaining cardiac output by the increase in stroke volume.
Labetalol, in animal models, was found to cross the blood-brain-barrier in only negligible amounts.
Labetalol was the first drug created that combined both alpha- and beta- adrenergic receptor blocking properties. It was created to potentially fix the compensatory reflex issue that occurred when blocking a single receptor subtype, i.e. vasoconstriction after blocking beta-receptors or tachycardia after blocking alpha receptors. Because the reflex from blocking the single receptor subtypes acted to prevent the lowering of blood pressure, it was postulated that weak blocking of both alpha- and beta- receptors could work together to decrease blood pressure.
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