Levosalbutamol

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Levosalbutamol
Levalbuterol.svg
R-salbutamol-from-xtal-3D-balls.png
Systematic (IUPAC) name
4-[(1R)-2-(tert-butylamino)-1-hydroxyethyl]- 2-(hydroxymethyl)phenol
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. A (AU) C (US)
Legal status -only (US)
Routes Oral, inhalational
Pharmacokinetic data
Metabolism Hepatic
Half-life 3.3-4 hours
Excretion Urinary
Identifiers
CAS number 34391-04-3 N
ATC code R03AC02 R03CC02
PubChem CID 123600
DrugBank DB01001
ChemSpider 110192 YesY
UNII QF8SVZ843E YesY
KEGG D08124 N
ChEBI CHEBI:8746 YesY
ChEMBL CHEMBL1002 YesY
Chemical data
Formula C13H21NO3 
Mol. mass 239.311 g/mol
 N (what is this?)  (verify)

Levosalbutamol (INN) or levalbuterol (USAN) is a short-acting β2-adrenergic receptor agonist used in the treatment of asthma and COPD. It is marketed under the brand name Xopenex, by Sunovion Pharmaceuticals Inc. The drug is the R-enantiomer of its prototype drug salbutamol (INN) or albuterol (USAN). It is available in generic formulations by pharmaceutical companies including Cipla, Teva, and Dey, among others.

There is no reason to use levosalbutamol over salbutamol.[1]

Medical use[edit]

Levosalbutamol's bronchodilator properties give it indications in treatment of Asthma and chronic obstructive pulmonary disease (COPD).

Theoretically, given that the compound is comprised only of the R-enantiomer (the active metabolite responsible for the drug's bronchi-dilating activity[2]) and not the S-enantiomer (hypothesized to activate pro-inflammatory and pro-constrictive pathways in bronchial smooth muscle[3]), Sunovion has implied that the presence of only the R-enantiomer produces fewer side effects (see Preference over Salbutamol section below).

Comparison to salbutamol[edit]

A 2013 systematic review found no benefit of levosalbutamol compared to salbutamol.[1] There also does not appear to be any difference in safety.[1] It should thus probably not be used in asthma[1] as levalbuterol is much more costly.[4][5]

Adverse effects[edit]

Generally, levosalbutamol is well-tolerated. More common side-effects include a fast heart beat. Less commonly, chest pain/tightness, tremor, dizziness, feeling "faint," a high or low blood pressure, shortness of breath and difficulty breathing may occur.[6]

Rarely occurring but of importance with this drug class are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse.

Pharmacology[edit]

Levosalbutamol has similar pharmacokinetic and pharmacodynamic properties to salbutamol.[7]

Mechanism of Action[edit]

Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of cyclic-3', 5' -adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.

Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional agonist that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges.

While it is recognized that beta2-adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta-receptors in the human heart, 10-50% of which are beta2-adrenergic receptors. The precise function of these receptors has not been established. However, all beta-adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure,and restlessness symptoms, and/or electrocardiographic (ECG) changes.

Approval[edit]

Levalbuterol was originally available only as a solution for nebulizer and eventually become available as a CFC-free metered dose inhaler under the trade name "Xopenex HFA (levalbuterol tartrate) Inhalation Aerosol". The FDA approval date was on March 11, 2005.[8]

References[edit]

  1. ^ a b c d Jat, KR; Khairwa, A (Apr 2013). "Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis.". Pulmonary pharmacology & therapeutics 26 (2): 239–48. PMID 23207739. 
  2. ^ Henderson WR, Banerjee ER, Chi EY. Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model. J Allergy Clin Immunol. 2005;116(2):332-40.
  3. ^ Agrawal DK, Ariyarathna K, Kelbe PW. (S)-Albuterol activates pro-constrictory and pro-inflammatory pathways in human bronchial smooth muscle cells. J Allergy Clin Immunol. 2004;113(3):503-10.
  4. ^ Schreck DM, Babin S (November 2005). "Comparison of racemic albuterol and levalbuterol in the treatment of acute asthma in the ED". Am J Emerg Med 23 (7): 842–7. doi:10.1016/j.ajem.2005.04.003. PMID 16291438. 
  5. ^ Hendeles L, Hartzema A (September 2003). "Levalbuterol is not more cost-effective than albuterol for COPD". Chest 124 (3): 1176; author reply 1176–8. doi:10.1378/chest.124.3.1176. PMID 12970057. 
  6. ^ AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2014. Levalbuterol; Accessed on April 16, 2014. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603025.html
  7. ^ Xenopex® [package insert] Marlborough, MA:Sunovion Pharmaceuticals Inc: 2014
  8. ^ (See Official FAQ)