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Labetalol is a medication used to treat high blood pressure it can be given intravenously in severe hypertensive situations or by mouth for long term hypertension management its dose and use is limited by its main side effect postural hypotension where there is a substantial drop in blood pressure when standing up labetalol 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 during long-term use labetalol can reduce heart rate during exercise while maintaining cardiac output by an increase
In stroke volume medical uses labetalol is effective in the management of hypertensive emergencies post-operative 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 preeclampsia 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 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 side effects common neurologic headache 2% dizziness 11% gastrointestinal nausea 6%
Dyspepsia 3% cholinergic nasal congestion 3% ejaculation failure 2% respiratory distant other fatigue 5% vertigo 2% orthostatic hypotension low blood pressure with standing is more severe and more common with iv formulation 58% versus 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 over 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 chemistry the minimum requirement for adrenergic agents is a primary or secondary amines separated from a substituted benzene ring by one or two carbons this configuration results in strong agonist activity as the size of the substituent attached to the amine becomes greater particularly with respect
To a t-butyl group then the molecule typically is found to have receptor affinity without intrinsic activity and is therefore an antagonist elevate along with its one methyl three phenyl propyl substituted amine is greater in size relative to a t-butyl group and therefore acts predominantly as an antagonist the overall structure of labetalol is very polar this
Was created by substituting the isopropyl group in the standard beta-blocker structure within a ral chol group including a carboxamide group on the meta position and by adding a hydroxyl group on the para position labetalol has two chiral carbons and consequently exists as four stereo isomers two of these isomers the s s and rs forms are inactive the third the
S are isomers a powerful alpha one blocker the fourth isomer the rr isomer which is also known as de level all is a mixed non-selective beta blocker and selective alpha one blocker labetalol is typically given as a racemic mixture to achieve both alpha and beta receptor blocking activity 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 beta alpha antagonism of labetalol is approximately three to one it is chemically designated in international union of pure and applied chemistry iupac nomenclature is two hydroxy five one hydroxy two one methyl three phenyl propyl amino ethyle bends amide
Mono hydrochloride pharmacology mechanism of action labetalol is a dual alpha alpha one and vada beta-1 beta-2 adrenergic receptor blocker and competes with other catecholamines for binding to the site its action on these receptors are potent and reversible labetalol is highly selective for postsynaptic alpha one adrenergic and non selective for beta adrenergic
Receptors it is about equipment in blocking both beta 1 and beta 2 receptors the amount of alpha to beta blockade depends on whether labetalol is administered orally or intravenously iv orally the ratio of alpha to beta blockade is 1 2 3 intravenously alpha to beta blockade ratio is 1 to 7 thus the labetalol can be thought to be a beta blocker with some alpha
Blocking effects by comparison labetalol is a weaker beta blocker than propranolol and has a weaker affinity for alpha receptors compared to phentolamine labetalol possesses intrinsic sympathomimetic activity in particular it is a partial agonist at baited 2 receptors located in the vascular smooth muscle labetalol relaxes vascular smooth muscle by a combination of
This partial baited 2 agonism and through alpha 1 blockade overall this vasodilatory effect can decrease blood pressure 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 physiological
Action the physiological effects of labetalol when administered acutely intravenously are not predictable solely by their receptor blocking effect ie blocking beta 1 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 alpha 1 beta 1 invaded 2 blocking mechanism these effects are mainly seen when the person is in the upright position 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 pharmacokinetics labetalol in animal models was found to cross the blood-brain barrier in only negligible amounts history 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 ie 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 see also car vada law med rocks law references
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