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Salbutamol

Salbutamol
Salbutamol (top) and (S)-salbutamol (bottom)
Systematic (IUPAC) name
(RS)-4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
Clinical data
Licence data US FDA:
Pregnancy
category
  • AU: A
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
Oral, inhalational, IV
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 3.8 - 6 hours
Excretion Renal
Identifiers
CAS Registry Number  Y
ATC code R03 R03
PubChem CID:
IUPHAR/BPS
DrugBank  N
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  N
ChEMBL  Y
Chemical data
Formula C13H21NO3
Molecular mass 239.311 g/mol
 N   

Salbutamol (INN) or albuterol (USAN) is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease (COPD).[2] It is marketed as Ventolin among other brand names.

Salbutamol was the first selective β2-receptor agonist to be marketed in 1968. It was first sold by Allen & Hanburys (UK) under the brand name Ventolin, and has been used for the treatment of asthma ever since.[3] It was approved for use in the US by the Food and Drug Administration (FDA) in May 1982.[4]

The drug is usually manufactured and distributed as the sulfate salt salbutamol sulfate.

Salbutamol is mostly taken by the inhaled route for direct effect on bronchial smooth muscle. This is usually achieved through a metered-dose inhaler (MDI), nebulizer, or other proprietary delivery devices. In these forms of delivery, the maximal effect of salbutamol can take place within five to 20 minutes of dosing, though some relief is immediately seen. Mean duration of effect is roughly 2 hours.[5] It can also be given intravenously.[6] Salbutamol is also available in oral form (tablets, syrup).

It is on the health system.[7] Compliance with the Montreal Protocol, which requires the banning of the use of ozone-layer depleting CFCs, has caused the price of inhalers, however, to increase as much as ten-fold as generics were forced off the market from 2009 to 2013 by new patents obtained by pharmaceutical companies for non-CFC delivery systems.

Contents

  • Medical uses 1
  • Adverse effects 2
  • Chemistry 3
    • Structure and activity 3.1
    • Detection after dosing 3.2
  • Society and culture 4
    • Bodybuilding 4.1
    • Doping 4.2
  • Brand names 5
  • See also 6
  • References 7
    • Additional notes 7.1
  • External links 8

Medical uses

Salbutamol is typically used to treat bronchospasm (due to any cause, allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease.[8] Emergency medical practice commonly treats people presenting with asthma who report taking their salbutamol inhaler as prescribed with salbutamol; in general, people tolerate large doses well.

As a β2-agonist, salbutamol also finds use in obstetrics. Intravenous salbutamol can be used as a tocolytic to relax the uterine smooth muscle to delay premature labor. While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium-channel blocker nifedipine, which is more effective, better tolerated and orally administered.[9]

Salbutamol has been used to treat acute hyperkalemia, as it stimulates potassium flow into cells thus lowering the level in the blood.[10][11]

Salbutamol has also been tested in a trial aimed at treatment of spinal muscular atrophy, where it appears to show modest benefits. The drug is speculated to modulate the alternative splicing of the SMN2 gene, increasing the amount of the SMN protein whose deficiency is regarded as the root cause of the disease.[12][13]

Other potential uses include in cystic fibrosis, and subtypes of congenital myasthenic syndrome associated with mutations in Dok-7.[14]

Adverse effects

The most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation.[15] Other symptoms may include tachycardia, arrhythmia, flushing, myocardial ischemia (rare), and disturbances of sleep and behaviour.[15] Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalaemia, which is of concern especially in patients with renal failure and those on certain diuretics and xanthine derivatives.[15]

Chemistry

Structure and activity

(R)-Salbutamol (top) and (S)-salbutamol

This drug is sold as a racemic mixture. The (R)-enantiomer (CIP nomenclature) is shown in the image at right (top), and is responsible for the pharmacologic activity; the (S)-enantiomer (bottom) blocks metabolic pathways associated with elimination both of it and of the pharmacologically active enantiomer.[16]

With regard to structure-activity relationships, the tertiary butyl group in albuterol/salbutamol makes it more selective for β₂-receptors.

Detection after dosing

Salbutamol may be quantified in blood or plasma; practical needs for this include to confirm a diagnosis of poisoning in hospitalized patients, or to aid in a forensic investigation. As well, urinary salbutamol concentrations are frequently measured in competitive sports programs, for which a level in excess of 1000 μg/L is considered to represent abuse.

The window of detection for urine testing is on the order of just 24 hours, given the relatively short elimination half-life of the drug,[17][18][19] estimated at between 5 and 6 hours following oral administration of 4 mg.[20]

Society and culture

Bodybuilding

Salbutamol has been shown to improve muscle weight in rats [21] and anecdotal reports hypothesise that it might be an alternative to clenbuterol for purposes of fat burning and muscle gain, with multiple studies supporting this claim.[22][23][24][25][26] Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically exceeding 1000 µg/L.[17]

Doping

Clinical studies show no compelling evidence that salbutamol and other β2-agonists can increase performance in healthy athletes.[27] In spite of this, salbutamol required "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the 2010 WADA prohibited list. This requirement was relaxed when the 2011 list was published to permit the use of "salbutamol (maximum 1600 micrograms over 24 hours) and salmeterol when taken by inhalation in accordance with the manufacturers’ recommended therapeutic regimen." [28][29]

According to two small and limited studies, performed on eight and 16 subjects, respectively, salbutamol increases performance on endurance exercise even for a person without asthma.[30][31][32]

Another study contradicts the above findings, however. The double blind, randomised test conducted on 12 non-asthmatic athletes concluded that salbutamol had a negligible effect on endurance performance. Nevertheless, the study also showed that the drug's bronchodilating effect may have improved respiratory adaptation at the beginning of exercise.[33]

Brand names

Ventolin 2 mg tablets made by GSK (Turkey)

Drug forms of this compound are marketed by GlaxoSmithKline as Ventolin, Ventoline, Ventilan, Aerolin, or Ventorlin, depending on the market; by Cipla as Asthalin and Asthavent; by Schering-Plough as Proventil, by Remedica as Salbutamol 4,by Teva as ProAir and Novo-Salbutamol HFA (Canada), Salamol, or Airomir, by Beximco (Bangladesh) as Azmasol by Ad-din Pharma as Ventosol and by Alphapharm as Asmol.

See also

References

  1. ^ Health Canada
  2. ^ "Ventolin". HealthExpress. Retrieved 2013-09-18. 
  3. ^ "Ventolin remains a breath of fresh air for asthma sufferers, after 40 years" (PDF). The Pharmaceutical Journal 279 (7473): 404–405. 
  4. ^ MedicineNet, Inc. http://www.medicinenet.com/albuterol/article.htm
  5. ^ Measured by a 15% increase from baseline in FEV1. "Albuterol Sulfate", Rx List: The Internet Drug Index, 6/12/2008, retrieved 2014-07-13 
  6. ^ "Ventolin Solution for IV Infusion". Retrieved 2013-09-18. 
  7. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  8. ^ "Albuterol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  9. ^ Rossi, S (2004).  
  10. ^ Mahoney, B. A.; Smith, W. A.; Lo, D.; Tsoi, K.; Tonelli, M.; Clase, C. (2005). Clase, Catherine, ed. "Emergency interventions for hyperkalaemia". The Cochrane Library.  
  11. ^ Ahee, P. (2000). "The management of hyperkalaemia in the emergency department". Emergency Medicine Journal 17 (3): 188–191.  
  12. ^ Van Meerbeke, J. P.; Sumner, C. J. (2011). "Progress and promise: The current status of spinal muscular atrophy therapeutics". Discovery medicine 12 (65): 291–305.  
  13. ^ Lewelt, A.; Newcomb, T. M.; Swoboda, K. J. (2011). "New Therapeutic Approaches to Spinal Muscular Atrophy". Current Neurology and Neuroscience Reports 12 (1): 42–53.  
  14. ^ Liewluck, Teerin; Selcen, Duygu; Engel, Andrew G. (November 2011). "Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia". Muscle & Nerve 44 (5): 789–794.  
  15. ^ a b c "3.1.1.1 Selective beta2 agonists – side effects". British National Formulary (57 ed.). London:  
  16. ^ Mehta, Akul. [The tertiary butyl group in salbutamol (or albuterol) makes it more selective for β₂-receptors. http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html "Medicinal Chemistry of the Peripheral Nervous System – Adrenergics and Cholinergics their Biosynthesis, Metabolism, and Structure Activity Relationships"] . Retrieved 2010-10-20. 
  17. ^ a b Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Biomedical Publications. pp. 33–35.  
  18. ^ Berges, Rosa; S; V; F; M; F; M; D (2000). "Discrimination of Prohibited Oral Use of Salbutamol from Authorized Inhaled Asthma Treatment". Clinical Chemistry 46 (9): 1365–75.  
  19. ^ Schweizer, C; Saugy, M; Kamber, M (2004). "Doping test reveals high concentrations of salbutamol in a Swiss track and field athlete". Clin. J. Sport Med. 14 (5): 312–315.  
  20. ^ "Albuterol Sulfate", Rx List: The Internet Drug Index, 6/12/2008, retrieved 2014-07-13 
  21. ^ Carter WJ, Lynch ME (September 1994). "Comparison of the effects of salbutamol and clenbuterol on skeletal muscle mass and carcass composition in senescent rats". Metab. Clin. Exp. 43 (9): 1119–25.  
  22. ^ Caruso, JF; Signorile, JF; Perry, AC; Leblanc, B; Williams, R; Clark, M; Bamman, MM (Nov 1995). "The effects of albuterol and isokinetic exercise on the quadriceps muscle group.". Medicine and science in sports and exercise 27 (11): 1471–6.  
  23. ^ Caruso, J. (20 January 2005). "Albuterol aids resistance exercise in reducing unloading-induced ankle extensor strength losses". Journal of Applied Physiology 98 (5): 1705–1711.  
  24. ^ Caruso, John F.; Hamill, John L.; De Garmo, Nicole (2005). "Oral Albuterol Dosing During the Latter Stages of a Resistance Exercise Program". The Journal of Strength and Conditioning Research 19 (1): 102.  
  25. ^ Caruso, JF; Hamill, JL; Yamauchi, M; Mercado, DR; Cook, TD; Keller, CP; Montgomery, AG; Elias, J (Jun 2004). "Albuterol helps resistance exercise attenuate unloading-induced knee extensor losses.". Aviation, space, and environmental medicine 75 (6): 505–11.  
  26. ^ Caruso, JF; Hamill, JL; De Garmo, N (Feb 2005). "Oral albuterol dosing during the latter stages of a resistance exercise program.". Journal of strength and conditioning research / National Strength & Conditioning Association 19 (1): 102–7.  
  27. ^ Davis, E; Loiacono, R; Summers, R J (2008). "The rush to adrenaline: drugs in sport acting on the β-adrenergic system". British Journal of Pharmacology 154 (3): 584–97.  
  28. ^ "THE 2010 PROHIBITED LIST INTERNATIONAL STANDARD" (PDF). WADA. Retrieved 2010-10-20. 
  29. ^ "THE 2011 PROHIBITED LIST INTERNATIONAL STANDARD" (PDF). WADA. Retrieved 2012-05-22. 
  30. ^ Collomp, K; Candau, R; Lasne, F; Labsy, Z; Préfaut, C; De Ceaurriz, J (2000). "Effects of short-term oral salbutamol administration on exercise endurance and metabolism". Journal of applied physiology (Bethesda, Md.: 1985) 89 (2): 430–6.  
  31. ^ "Salbutamol: Ergogenic effects of salbutamol". Retrieved 2010-10-20. 
  32. ^ Van Baak, MA; De Hon, OM; Hartgens, F; Kuipers, H (2004). "Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes". International journal of sports medicine 25 (7): 533–8.  
  33. ^ Goubault, C; Perault, MC; Leleu, E; Bouquet, S; Legros, P; Vandel, B; Denjean, A (2001). "Effects of inhaled salbutamol in exercising non-asthmatic athletes". Thorax 56 (9): 675–679.  

Additional notes

  1. Moore, NG; Pegg, GG; Sillence, MN (September 1994). "Anabolic effects of the beta 2-adrenoceptor agonist salmeterol are dependent on route of administration". Am. J. Physiol. 267 (3 Pt 1): E475–84.  
  2. Schiffelers, SL; Saris, WH; Boomsma, F; Van Baak, MA (May 2001). "beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men". J. Clin. Endocrinol. Metab. 86 (5): 2191–9.  
  3. Van Baak, MA; Mayer, LH; Kempinski, RE; Hartgens, F (July 2000). "Effect of salbutamol on muscle strength and endurance performance in nonasthmatic men". Med Sci Sports Exerc 32 (7): 1300–6.  
  4. Caruso, JF; Hamill, JL; De Garmo, N (February 2005). "Oral albuterol dosing during the latter stages of a resistance exercise program". J Strength Cond Res 19 (1): 102–7.  
  5. Caruso JF, Signorile JF, Perry AC; et al. (November 1995). "The effects of albuterol and isokinetic exercise on the quadriceps muscle group". Med Sci Sports Exerc 27 (11): 1471–6.   Category:CS1 maint: Explicit use of et al.)
  6. Martineau, L; Horan, MA; Rothwell, NJ; Little, RA (November 1992). "Salbutamol, a beta 2-adrenoceptor agonist, increases skeletal muscle strength in young men". Clin. Sci. 83 (5): 615–21.  S
  7. Desaphy, JF; Pierno, S; De Luca, A; Didonna, P; Camerino, DC (March 2003). "Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders". Mol. Pharmacol. 63 (3): 659–70.  
  8. Maki, KC; Skorodin, MS; Jessen, JH; Laghi, F (June 1996). "Effects of oral albuterol on serum lipids and carbohydrate metabolism in healthy men". Metab. Clin. Exp. 45 (6): 712–7.  

External links

  • Salbutamol at The Periodic Table of Videos (University of Nottingham)
  • Volmax Drug Information
  • Side Effects
  • U.S. National Library of Medicine: Drug Information Portal – Albuterol
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