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Salbutamol

Clinical data
Pregnancy category	AU: A
Routes of administration	Oral, inhalational, IV
ATC code	R03AC02 (WHO) R03CC02 (WHO)
Legal status
Legal status	AU: S3 (Pharmacist only) CA: F (prescription) UK: POM (Prescription only) US: WARNINGRx-only
Pharmacokinetic data
Metabolism	Hepatic
Elimination half-life	1.6 hours
Excretion	Renal
Identifiers
IUPAC name (RS)-4--2-(hydroxymethyl)phenol
CAS Number	18559-94-9
PubChem CID	2083
IUPHAR/BPS	558
DrugBank	APRD00553
ChemSpider	1999
UNII	QF8SVZ843E
KEGG	D02147
ChEMBL	ChEMBL714
ECHA InfoCard	100.038.552
Chemical and physical data
Formula	C13H21NO3
Molar mass	239.311 g·mol
3D model (JSmol)	Interactive image
SMILES OCc1cc(ccc1O)C(O)CNC(C)(C)C
InChI InChI=1S/C13H21NO3/c1-13(2,3)14-7-12(17)9-4-5-11(16)10(6-9)8-15/h4-6,12,14-17H,7-8H2,1-3H3 Key:NDAUXUAQIAJITI-UHFFFAOYSA-N
(verify)

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. It is marketed by GlaxoSmithKline as Ventolin, Aerolin or Ventorlin, depending on the market; by Cipla as Asthalin and Asthavent; by Schering-Plough as Proventil and by Teva as ProAir.

Salbutamol was the first selective β₂-receptor agonist to be marketed — in 1968. It was first sold by Allen and Hanburys under the brand name Ventolin. The drug was an instant success, and has been used for the treatment of asthma ever since.

Salbutamol sulfate is usually given 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 (e.g. Rotahaler or Autohaler). In these forms of delivery, the maximal effect of salbutamol can take place within five to twenty minutes of dosing, though some relief is immediately seen. It can also be given orally as an inhalant or intravenously.

Clinical use

Salbutamol is specifically indicated in the following conditions:

• Acute asthma
• Symptom relief during maintenance therapy of asthma and other conditions with reversible or irreversible airways obstruction (including COPD and bronchitis)
• Protection against exercise-induced asthma
• Can be aerosolized with a nebulizer for patients with cystic fibrosis, along with ipratropium bromide, acetylcysteine, and pulmozyme.
• Subtypes of congenital myasthenic syndromes associated to mutations in Dok-7.

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.

In an emergency, EMS providers consider the administration of salbutamol when they see active wheezing, bronchospasm and a past diagnosis of asthma. The drug is most often administered through a nebulizer with 6-8 liters per minute of oxygen. A normal dose is 2.5mg in 3 mL of respiratory saline.

Structure activity relationship

The tertiary butyl group in salbutamol (or albuterol) makes it more selective for β2-receptors. The drug is sold as a racemic mixture mainly because the S isomer blocks metabolism pathways while the R isomer shows activity.

Side effects / health consequences

The most common side effects are of fine tremor, nervousness, headache, muscle cramps, dry mouth, and palpitation. Other symptoms may be tachycardia (rapid heart rate), arrhythmias, flushing, myocardial ischemia, and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse, while high doses may cause hypokalaemia (low potassium levels), especially in patients with renal failure and those on certain diuretics and xanthine derivatives.

Diet and bodybuilding use

Salbutamol is taken by some as an alternative to clenbuterol for purposes of fat burning, and/or as a performance enhancer. Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically in the 10-500 µg/L range.

Doping

Clinical studies show no compelling evidence that salbutamol and other β₂-agonists can increase performance in healthy athletes. In spite of this, salbutamol requires "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the current WADA prohibited list.

According to two small and limited studies, performed on 8 and 16 subjects, respectively, salbutamol increases the performance even for a person without asthma.

Detection of use

Salbutamol may be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to aid in a forensic investigation. 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.

Ban of CFC-containing inhalers

Template:Globalize/North America The U.S. Food and Drug Administration (FDA) in April 2005 mandated all (including salbutamol) inhalers containing chlorofluorocarbons (CFCs) were to be prohibited in the United States as of December 31, 2008. CFC inhalers had previously been given "essential use" status, exempting it from a CFC-production ban; however, in accordance with the Montreal Protocol, they will be phased out; in many other countries, patients have been transitioned to non-CFC based inhalers using hydrofluoroalkane (HFA) propellant. Pharmaceutical manufacturers were expected to produce adequate supplies of alternative (HFA) inhalers by 2009.

One drawback of this transition to HFA inhalers is that, due to patent restrictions, all HFA salbutamol inhalers are "brand-name" (ProAir, Proventil, and Ventolin). They cost approximately $20 more per inhaler than existing generic CFC salbutamol inhalers. These new formulations are patented. An industry consortium was formed to spread the costs of the FDA safety studies to get propellants such as 134a and 227 approved.

Generic HFA salbutamol inhalers are not expected to reach the United States market until after 2012 due to existing patents.

Salbutamol is widely used, and accounts for anywhere from 78% of all bronchodilator prescriptions in 2005 to 85% in 2008. However, patients in the United States who cannot tolerate the HFA salbutamol inhalers will not have a single salbutamol alternative available to them domestically after December 31, 2008. The FDA did not approve any alternatives to HFA and there are few standard inhaled lung medications in the United States that come in dry powder inhaler (DPI) versions. Noticeably missing is salbutamol in DPI form in the United States, although it is available in most of the rest of the world in salbutamol DPIs.

Synthesis

Collin, David T.; Hartley, David.; Jack, David.; Lunts, Lawrence H. C.; Press, J. C.; Ritchie, Alexander C.; Toon, Paul. (1970). "Saligenin analogs of sympathomimetic catechol amines". Journal of Medicinal Chemistry. 13 (4): 674. doi:10.1021/jm00298a022. PMID 5452431.

See also

• Epinephrine
• Beclometasone dipropionate
• Ipratropium
• Ipratropium/salbutamol
• Levalbuterol

References

1. Health Canada
2. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
3. "Ventolin remains a breath of fresh air for asthma sufferers, after 40 years" (PDF). The Pharmaceutical Journal. 279 (7473): 404-–405.
4. Rossi, S (2004). Australian Medicines Handbook. AMH. ISBN 0957852142.
5. Mehta, Akul. "Medicinal Chemistry of the Peripheral Nervous System - Adrenergics and Cholinergic their Biosynthesis, Metabolism and Structure Activity Relationships". Retrieved 2010-10-20.
6. ^ "3.1.1.1 Selective beta2 agonists -- side effects". British National Formulary (57 ed.). London: BMJ Publishing Group Ltd and Royal Pharmaceutical Society Publishing. 2008. ISBN 0-85369-778-7. {{cite book}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
7. Carter WJ, Lynch ME (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. doi:10.1016/0026-0495(94)90054-X. PMID 7916118. {{cite journal}}: Unknown parameter |month= ignored (help)
8. ^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Biomedical Publications,. pp. 33–35. ISBN 0962652369.{{cite book}}: CS1 maint: extra punctuation (link)
9. 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. doi:10.1038/bjp.2008.164. PMC 2439523. PMID 18500380.
10. "THE 2010 PROHIBITED LIST INTERNATIONAL STANDARD" (PDF). WADA. Retrieved 2010-10-20.
11. 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. PMID 10926623.
12. "Salbutamol: Ergogenic effects of salbutamol". Retrieved 2010-10-20. {{cite journal}}: Cite journal requires |journal= (help)
13. 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. doi:10.1055/s-2004-815716. PMID 15459835.
14. 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. PMID 10973867.
15. 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. doi:10.1097/00042752-200409000-00018. PMID 15377972. {{cite journal}}: |first4= missing |last4= (help)
16. Emily Harrison (August 2008). "Unlikely Victims of Banning CFCs—Asthma Sufferers". Scientific American.
17. "IPAC - International Pharmaceutical Aerosol Consortium".
18. "HFA inhalers replacing generic albuterol inhalers, driving up costs". pharmacist.com.
19. IMS Health Sales & Prescription data for all inhalers sales and prescriptions (July 2008)
20. "FDA Advises Patients to Switch to HFA-Propelled Albuterol Inhalers Now CFC-propelled inhalers no longer available as of Dec. 31, 2008". Retrieved 2010-10-20.

Additional notes

1. Moore, NG; Pegg, GG; Sillence, MN (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. PMID 7943228. {{cite journal}}: Unknown parameter |month= ignored (help)
2. Schiffelers, SL; Saris, WH; Boomsma, F; Van Baak, MA (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. doi:10.1210/jc.86.5.2191. PMID 11344226. {{cite journal}}: Unknown parameter |month= ignored (help)
3. Van Baak, MA; Mayer, LH; Kempinski, RE; Hartgens, F (2000). "Effect of salbutamol on muscle strength and endurance performance in nonasthmatic men". Med Sci Sports Exerc. 32 (7): 1300–6. doi:10.1097/00005768-200007000-00018. PMID 10912897. {{cite journal}}: Unknown parameter |month= ignored (help)
4. Caruso, JF; Hamill, JL; De Garmo, N (2005). "Oral albuterol dosing during the latter stages of a resistance exercise program". J Strength Cond Res. 19 (1): 102–7. doi:10.1519/R-14793.1. PMID 15705021. {{cite journal}}: Unknown parameter |month= ignored (help)
5. Caruso JF, Signorile JF, Perry AC; et al. (1995). "The effects of albuterol and isokinetic exercise on the quadriceps muscle group". Med Sci Sports Exerc. 27 (11): 1471–6. PMID 8587482. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
6. Martineau, L; Horan, MA; Rothwell, NJ; Little, RA (1992). "Salbutamol, a beta 2-adrenoceptor agonist, increases skeletal muscle strength in young men". Clin. Sci. 83 (5): 615–21. PMID 1335400. {{cite journal}}: Unknown parameter |month= ignored (help)S
7. Desaphy, JF; Pierno, S; De Luca, A; Didonna, P; Camerino, DC (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. doi:10.1124/mol.63.3.659. PMID 12606775. {{cite journal}}: Unknown parameter |month= ignored (help)
8. Maki, KC; Skorodin, MS; Jessen, JH; Laghi, F (1996). "Effects of oral albuterol on serum lipids and carbohydrate metabolism in healthy men". Metab. Clin. Exp. 45 (6): 712–7. doi:10.1016/S0026-0495(96)90136-5. PMID 8637445. {{cite journal}}: Unknown parameter |month= ignored (help)

External links

• Volmax Drug Information
• Side Effects
• U.S. National Library of Medicine: Drug Information Portal - Albuterol

• Alcohols
• Sympathomimetic amines
• Asthma
• Beta-adrenergic agonists
• Phenethylamines
• Phenols
• World Health Organization essential medicines