Labetalol

Labetalol

Labetalol
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
MedlinePlus
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  Y
ATC code C07
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C19H24N2O3
Molecular mass 328.406 g/mol
 Y   

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

Contents

  • Medical uses 1
  • Side effects 2
  • Contraindications 3
  • Chemistry 4
  • Mechanism of action 5
  • See also 6
  • References 7

Medical uses

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

Side effects may include:

Contraindications

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

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

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

References

  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.  
  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.  
  4. ^ Shiohara T, Kano Y (2007). "Lichen planus and lichenoid dermatoses". In Bolognia JL. Dermatology. St. Louis: Mosby. p. 161.  
  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.  
  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.  
  8. ^ Exam Zone (1 January 2009). Elsevier Comprehensive Guide. Elsevier India. pp. 449–.  
  9. ^ Detlev Ganten; Patrick J. Mulrow (6 December 2012). Pharmacology of Antihypertensive Therapeutics. Springer Science & Business Media. pp. 147–.