Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.
Common side effects include low blood pressure with standing, dizziness, feeling tired, and nausea. Serious side effects may include low blood pressure, liver problems, heart failure, and bronchospasm. Use appears safe in the latter part of pregnancy and it is not expected to cause problems during breastfeeding. It works by blocking the activation of β- and α-adrenergic receptors.
Labetalol was patented in 1966 and came into medical use in 1977. It is available as a generic medication. In 2020, it was the 210th most commonly prescribed medication in the United States, with more than 2million prescriptions.
Medical uses
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.
Special populations
Pregnancy: studies in lab animals showed no harm to the baby. 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.
Side effects
Common
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%) and is often the reason larger doses of the oral formulation cannot be used.
Rare
Fever
Muscle cramps
Dry eyes
Heart block
Hyperkalemia
Hepatotoxicity
Drug eruption similar to lichen planus
Hypersensitivity - which may result in a lethal respiratory distress
Contraindications
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.
Pharmacology
Mechanism of action
Labetalol is a beta blocker, or an antagonist of the β-adrenergic receptors. It is specifically a non-selective antagonist of the β1- and β2-adrenergic receptors. Labetalol has intrinsic sympathomimetic activity. It is also an antagonist of the α1-adrenergic receptor, and hence is additionally an alpha blocker. The antagonism of the adrenergic receptors by labetalol is competitive against other catecholamines and its actions on the receptors are potent and reversible.
Labetalol is about equipotent in blocking β1- and β2-adrenergic receptors. The amount of α to β blockade depends on whether labetalol is administered orally or intravenously (IV). Orally, the ratio of α to β blockade is 1:3. Intravenously, α to β blockade ratio is 1:7. Thus, the labetalol can be thought to be a beta blocker with some α-blocking effects. By comparison, labetalol is a weaker β-adrenergic receptor blocker than propranolol, and has a weaker affinity for α-adrenergic receptors compared to phentolamine.
Labetalol's dual α- and β-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. During long-term use, labetalol can reduce heart rate during exercise while maintaining cardiac output by an increase in stroke volume.