Labetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.
(RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide
Brands - Normodyne, Trandate
Ab-Lol - from Steadfast , Cebalol - from Health Biotech, Evabet - from Celon, Gravidol - from Mercury Labs, Labesol- from SG Pharma, Labeta - from Geo Pharma, Labil - from Celon (Revilon),
Lobet - from Samarth, Normadate - from GSK ,
Pih - from Dewcare, Talobet - from Celon , Tiplab- from United Biotech ,
Indications
It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.
It is also used to treat chronic and acute hypertension of pheochromocytoma and hypertensive crisis.
Administration
Labetalol is available in 100, 200, and 400 mg tablets and intravenously (available as Trandate) in 5 mg/ml solution. Adults taking tablets usually start with 100 mg twice daily, with a maximum of 2.4 g/day. In cases of emergency, dosage might be higher. Intravenous (IV) doses are usually started at 20 mg over two minutes. Additional doses of 40 mg, then 80 mg may be administered every ten minutes as needed. Additional 80 mg doses can be given to a total maximum dose of 300 mg. Additionally, labetalol can be administered by IV infusion at a rate of 2 mg/minute, with a maximum dose of 300 mg.
Side effects
Side effects may include:
Drowsiness
Fatigue
Weakness
Difficulty sleeping
Diminished sexual function
Orthostatic hypotension (due to alpha receptor blockade)
Scalp tingling
Drug eruption similar to lichen planus
A rare but potentially lethal side effect is respiratory distress.
Contra indications
Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, or those in cardiogenic shock.
Chemistry
For adrenergic agents, when the substituent on the amine nitrogen is greater in size than a t-butyl group, then the molecule typically is found to have receptor affinity without intrinsic activity, and is therefore an antagonist. Labetalol has two chiral carbons and consequently exists as four stereoisomers. Two of these isomers, the (S,S)- and (R,S)- forms are inactive. The third, the (S,R)-isomer, is a powerful α1 blocker. The fourth isomer, the (R,R)-isomer, is a mixed nonselective β blocker and selective α1 blocker.
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.
Mechanism of action
Labetalol combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.
Absorption
Completely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food.
Toxicity
LD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue
Drug Interactions
In one survey, 2.3% of patients taking labetalol HCl in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol HCl alone. The contribution of each of the treatments to this adverse reaction is unknown but the possibility of a drug interaction cannot be excluded.
Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required.
Cimetidine has been shown to increase the bioavailability of labetalol HCl. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol HCl, special care should be used in establishing the dose required for blood pressure control in such patients.
Synergism has been shown between halothane anesthesia and intravenously administered labetalol HCl. During controlled hypotensive anesthesia using labetalol HCl in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure. The anesthesiologist should be informed when a patient is receiving labetalol HCl.
Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur.
Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type.
(RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide
Brands - Normodyne, Trandate
Ab-Lol - from Steadfast , Cebalol - from Health Biotech, Evabet - from Celon, Gravidol - from Mercury Labs, Labesol- from SG Pharma, Labeta - from Geo Pharma, Labil - from Celon (Revilon),
Lobet - from Samarth, Normadate - from GSK ,
Pih - from Dewcare, Talobet - from Celon , Tiplab- from United Biotech ,
Indications
It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.
It is also used to treat chronic and acute hypertension of pheochromocytoma and hypertensive crisis.
Administration
Labetalol is available in 100, 200, and 400 mg tablets and intravenously (available as Trandate) in 5 mg/ml solution. Adults taking tablets usually start with 100 mg twice daily, with a maximum of 2.4 g/day. In cases of emergency, dosage might be higher. Intravenous (IV) doses are usually started at 20 mg over two minutes. Additional doses of 40 mg, then 80 mg may be administered every ten minutes as needed. Additional 80 mg doses can be given to a total maximum dose of 300 mg. Additionally, labetalol can be administered by IV infusion at a rate of 2 mg/minute, with a maximum dose of 300 mg.
Side effects
Side effects may include:
Drowsiness
Fatigue
Weakness
Difficulty sleeping
Diminished sexual function
Orthostatic hypotension (due to alpha receptor blockade)
Scalp tingling
Drug eruption similar to lichen planus
A rare but potentially lethal side effect is respiratory distress.
Contra indications
Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, or those in cardiogenic shock.
Chemistry
For adrenergic agents, when the substituent on the amine nitrogen is greater in size than a t-butyl group, then the molecule typically is found to have receptor affinity without intrinsic activity, and is therefore an antagonist. Labetalol has two chiral carbons and consequently exists as four stereoisomers. Two of these isomers, the (S,S)- and (R,S)- forms are inactive. The third, the (S,R)-isomer, is a powerful α1 blocker. The fourth isomer, the (R,R)-isomer, is a mixed nonselective β blocker and selective α1 blocker.
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.
Mechanism of action
Labetalol combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.
Absorption
Completely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food.
Toxicity
LD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue
Drug Interactions
In one survey, 2.3% of patients taking labetalol HCl in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol HCl alone. The contribution of each of the treatments to this adverse reaction is unknown but the possibility of a drug interaction cannot be excluded.
Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required.
Cimetidine has been shown to increase the bioavailability of labetalol HCl. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol HCl, special care should be used in establishing the dose required for blood pressure control in such patients.
Synergism has been shown between halothane anesthesia and intravenously administered labetalol HCl. During controlled hypotensive anesthesia using labetalol HCl in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure. The anesthesiologist should be informed when a patient is receiving labetalol HCl.
Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur.
Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type.
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