Labetalol

From Wikipedia, the free encyclopedia
  (Redirected from Dilevalol)
Jump to: navigation, search
Labetalol
Labetalol.svg
Systematic (IUPAC) name
(RS)-2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide
Clinical data
Trade names Normodyne, Trandate
AHFS/Drugs.com monograph
MedlinePlus a685034
Pregnancy
category
  • C
    One of few drugs used for PIH
Legal status
  • (Prescription only)
Routes of
administration
oral iv
Pharmacokinetic data
Bioavailability 25%
Protein binding 50%
Metabolism hepatic pass metabolism,
Biological half-life Tablet: 6-8 hours; IV: 5.5 hours
Excretion Excreted in urine, not removed by hemodialysis
Identifiers
CAS Registry Number 36894-69-6 YesY
ATC code C07AG01
PubChem CID: 3869
IUPHAR/BPS 7207
DrugBank DB00598 YesY
ChemSpider 3734 YesY
UNII R5H8897N95 YesY
KEGG D08106 YesY
ChEBI CHEBI:6343 YesY
ChEMBL CHEMBL429 YesY
Chemical data
Formula C19H24N2O3
Molecular mass 328.406 g/mol
 YesY (what is this?)  (verify)

Labetalol (INN) (/ləˈbɛtəlɔːl/) (trade names Normodyne and Trandate) is a mixed alpha/beta adrenergic antagonist that is used to treat high blood pressure.[1]

Medical uses[edit]

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]

Side effects[edit]

Side effects may include:

Contraindications[edit]

Labetalol has relative contraindications for use in patients with asthma, congestive heart failure, any degree of heart block, bradycardia, hypotension or those in cardiogenic shock.

Chemistry[edit]

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 consequently 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 which is also known as dilevalol, 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.[3][7]

Mechanism of action[edit]

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.

Labetalol has local anesthetic activity.[8]

Labetalol, in animal models, was found to cross the blood-brain-barrier in only negligible amounts.[9]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ http://www.bnf.org/bnf/bnf/56/2488.htm?q=%22labetalol%22
  3. ^ a b Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical. p. 170. ISBN 0-07-145153-6. 
  4. ^ Shiohara T, Kano Y (2007). "Lichen planus and lichenoid dermatoses". In Bolognia JL. Dermatology. St. Louis: Mosby. p. 161. ISBN 1-4160-2999-0. 
  5. ^ Medicinal Chemistry of Adrenergics and Cholinergics
  6. ^ 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. doi:10.1111/j.1476-5381.1991.tb12513.x. PMC 1908821. PMID 1687367. 
  7. ^ 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. doi:10.1111/j.1365-2125.1976.tb00637.x. PMC 1428931. PMID 9968. 
  8. ^ Exam Zone (1 January 2009). Elsevier Comprehensive Guide. Elsevier India. pp. 449–. ISBN 978-81-312-1620-0. 
  9. ^ Detlev Ganten; Patrick J. Mulrow (6 December 2012). Pharmacology of Antihypertensive Therapeutics. Springer Science & Business Media. pp. 147–. ISBN 978-3-642-74209-5.