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 2023, it was the 232nd most commonly prescribed medication in the United States, with more than 1 million 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. Labetalol is useful in the treatment of acute cardiovascular toxicity (e.g. in overdose) caused by sympathomimetics like amphetamine, methamphetamine, cocaine, ephedrine, and pseudoephedrine. Other beta blockers are also used. However, the controversial yet possible phenomenon of "unopposed α-stimulation" with administration of selective beta blockers to block non-selective sympathomimetics potentially makes dual alpha-1 and beta blockers like labetalol and carvedilol more favorable for such purposes. The rate of unopposed α-stimulation with selective beta blockers has been reported to be 0.4%, whereas no cases of unopposed α-stimulation have been reported with dual alpha and beta blockers like labetalol.
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: Due to an increased likelihood of experiencing orthostatic symptoms such as dizziness, product labelling recommends that elderly patients receive counselling regarding these side effects during labetalol treatment. Furthermore, because drug elimination is reduced in older demographics, lower maintenance doses are typically sufficient to achieve therapeutic effects.
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.
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
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 acts by blocking α- and β-adrenergic receptors, resulting in decreased peripheral vascular resistance without significant alteration of heart rate or cardiac output. 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, 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. Labetalol possesses significant intrinsic sympathomimetic activity (ISA). In particular, it is a partial agonist at β2-adrenergic receptors located in the vascular smooth muscle. Labetalol relaxes vascular smooth muscle by a combination of this partial β2-adrenergic receptor agonism and through α1-adrenergic receptor blockade. Overall, this vasodilatory effect can decrease blood pressure. It was originally reported to lack ISA, but a slight degree of activity was subsequently characterized. Similar to local anesthetics and sodium channel blocking antiarrhythmics, labetalol also has membrane stabilizing activity. By decreasing sodium entry, labetalol decreases action potential firing and thus has local anesthetic activity.
… excerpt ends here. Continue reading the full article.
