Labetalol
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| Systematic (IUPAC) name | |
| (RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide | |
| Clinical data | |
| Trade names | Trandate |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a685034 |
| Pregnancy cat. | C One of few drugs used for PIH |
| Legal status | ℞ Prescription only |
| Routes | oral iv |
| Pharmacokinetic data | |
| Bioavailability | 25% |
| Protein binding | 50% |
| Metabolism | hepatic pass metabolism, |
| Half-life | Tablet: 6-8 hours; IV: 5.5 hours |
| Excretion | Excreted in urine, not removed by hemodialysis |
| Identifiers | |
| CAS number | 36894-69-6  |
| ATC code | C07AG01 |
| PubChem | CID 3869 |
| DrugBank | APRD01062 |
| ChemSpider | 3734 |
| UNII | R5H8897N95 |
| KEGG | D08106 |
| ChEBI | CHEBI:6343 |
| ChEMBL | CHEMBL429 |
| Chemical data | |
| Formula | C19H24N2O3 |
| Mol. mass | 328.406 g/mol |
| SMILES | eMolecules & PubChem |
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Labetalol (Normodyne, Trandate) is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.[1]
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[edit] Indications
It has a particular indication in the treatment of pregnancy-induced hypertension which is commonly associated with pre-eclampsia.[2]
It is also used to treat chronic and acute hypertension of pheochromocytoma and hypertensive crisis.[3]
[edit] Administration
Labetalol is available in 100, 200, and 300 mg tablets and intravenously (only 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. IV doses are usually started at 20 mg over 2 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.
[edit] Side effects
Side effects may include:
- Drowsiness
- Fatigue
- Weakness
- Difficulty sleeping
- Diminished sexual function
- Scalp tingling which passes after time.
- Drug eruption similar to lichen planus[4]
- A rare but potentially lethal side effect is respiratory distress.
[edit] Contraindications
Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, or those in cardiogenic shock.
[edit] 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.[5] Labetalol has two chiral carbons and therefore exists as four stereoisomers.[6] 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.
Labetolol 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.[3][7]
Labetalol, 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropanol)amino)]ethyl] benzamide is synthesized by the N-alkylation of N-benzyl-N(4-phenyl-2-butyl)amine 5-bromacetylsalicylamide and forming the aminoketone, which is further debenzylated by hydrogen using a palladium–platinum on carbon catalyst into labetalol. Presumably the ketone is also reduced in this last step.
- H.C. Welch, DE 2032642 (1971).
- L.H.C. Lunts, D.T. Collin, U.S. Patent 4,012,444 (1977).
- Clifton, J. E.; Collins, I.; Hallett, P.; Hartley, D.; Lunts, L. H. C.; Wicks, P. D. (1982). "Arylethanolamines derived from salicylamide with .alpha.- and .beta.-adrenoceptor blocking activities. Preparation of labetalol, its enantiomers and related salicylamides". Journal of Medicinal Chemistry 25 (6): 670. doi:10.1021/jm00348a013. PMID 6124636.
[edit] References
- ^ Fahed S, Grum DF, Papadimos TJ (2008). "Labetalol infusion for refractory hypertension causing severe hypotension and bradycardia: an issue of patient safety". Patient Saf Surg 2: 13. doi:10.1186/1754-9493-2-13. PMC 2429901. PMID 18505576. http://www.pssjournal.com/content/2//13.
- ^ http://www.bnf.org/bnf/bnf/56/2488.htm?q=%22labetalol%22
- ^ a b Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical. p. 170. ISBN 0-07-145153-6.
- ^ Shiohara T, Kano Y (2007). "Lichen planus and lichenoid dermatoses". In Bolognia JL. Dermatology. St. Louis: Mosby. p. 161. ISBN 1-4160-2999-0.
- ^ Medicinal Chemistry of Adrenergics and Cholinergics
- ^ Riva E, Mennini T, Latini R (December 1991). "The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers". Br. J. Pharmacol. 104 (4): 823–8. PMC 1908821. PMID 1687367. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1908821.
- ^ D A Richards, J Tuckman, and B N Prichard (October 1976). "Assessment of alpha- and beta-adrenoceptor blocking actions of labetalol". Br J Clin Pharmacol 3 (5): 849–855. PMC 1428931. PMID 9968. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1428931.
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