Salbutamol was patented in 1966 in Britain and became commercially available in the United Kingdom in 1969.[10][11] It was approved for medical use in the United States in 1982.[7] It is on theWorld Health Organization's List of Essential Medicines.[12] Salbutamol is available as ageneric medication.[7] In 2023, it was the seventh most commonly prescribed medication in the United States, with more than 59million prescriptions.[13][14]
As a β2 agonist, salbutamol also has use inobstetrics. Intravenous salbutamol can be used as atocolytic to relax theuterinesmooth muscle to delaypremature labor. While preferred over agents such asatosiban andritodrine, its role has largely been replaced by the calcium channel blockernifedipine, which is more effective and better tolerated.[16]
Salbutamol has been used to treat acutehyperkalemia, as it stimulates potassium flow into cells, thus lowering thepotassium in the blood.[8]
Salbutamol metered dose inhalers have been described as the "single biggest source of carbon emissions fromNHS medicines prescribing" due to the propellants used in the inhalers.Dry powder inhalers are recommended as a low-carbon alternative.[20]
The tertiarybutyl group in salbutamol makes it more selective for β2 receptors,[21] which are the predominant receptors on the bronchialsmooth muscles. Activation of these receptors causesadenylyl cyclase to convert ATP tocAMP, beginning thesignalling cascade that ends with the inhibition ofmyosin phosphorylation and lowering the intracellular concentration of calcium ions (myosin phosphorylation and calcium ions are necessary for muscle contractions). The increase in cAMP also inhibits inflammatory cells in the airway, such asbasophils,eosinophils, and most especiallymast cells, from releasing inflammatory mediators and cytokines.[22][23] Salbutamol and other β2 receptor agonists also increase the conductance of channels sensitive to calcium and potassium ions, leading tohyperpolarization and relaxation of bronchial smooth muscles.[24]
Salbutamol is either filtered out by the kidneys directly or is first metabolized into the 4′-O-sulfate, which is excreted in the urine.[9]
(R)-(−)-salbutamol (top) and (S)-(+)-salbutamol (bottom)
Salbutamol is sold as aracemic 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 of itself and of the pharmacologically active enantiomer (R).[25] The slower metabolism of the (S)-(+)-enantiomer also causes it to accumulate in the lungs, which can cause airway hyperreactivity and inflammation.[26] Potential formulation of theR form as anenantiopure drug is complicated by the fact that the stereochemistry is not stable, but rather the compound undergoes racemization within a few days to weeks, depending onpH.[27]
The1972 Munich Olympics were the first Olympics where anti-doping measures were deployed, and at that time β2 agonists were considered to be stimulants with high risk of abuse for doping. Inhaled salbutamol was banned from those games, but by 1986 was permitted (although oral β2 agonists were not). After a steep rise in the number of athletes taking β2 agonists for asthma in the 1990s, Olympic athletes were required to provide proof that they had asthma in order to be allowed to use inhaled β2 agonists.[30]
In February 2020, the U.S.Food and Drug Administration (FDA) approved the first generic of an albuterol sulfate inhalation aerosol for the treatment or prevention of bronchospasm in people four years of age and older with reversible obstructive airway disease and the prevention of exercise-induced bronchospasm in people four years of age and older.[31][32] The FDA granted approval of the generic albuterol sulfate inhalation aerosol to Perrigo Pharmaceutical.[31]
In April 2020, the FDA approved the first generic of Proventil HFA (albuterol sulfate) metered dose inhaler, 90 μg per inhalation, for the treatment or prevention of bronchospasm in patients four years of age and older who have reversible obstructive airway disease, as well as the prevention of exercise-induced bronchospasm in this age group.[33] The FDA granted approval of this generic albuterol sulfate inhalation aerosol to Cipla Limited.[33]
It was first sold byAllen & Hanburys (UK) under the brand name Ventolin, and has been used for the treatment of asthma ever since.[35] The drug is marketed under many names worldwide.[1]
As of 2011[update] there was no evidence that an increase in physical performance occurs after inhaling salbutamol, but there are various reports for benefit when delivered orally or intravenously.[38][39] In spite of this, salbutamol required "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the 2010WADA 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."[40][41]
Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically exceeding 1,000 ng/mL. 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,[42][43][44] estimated at between 5 and 6 hours following oral administration of 4 mg.[22]
Albuterol increasesenergy expenditure by 10 to 15 percent at a therapeutic dose for asthma and around 25 percent at a higher, oral dose. In several human studies, albuterol increased lean body mass, reduced fat mass, and causedlipolysis; it has been studied for use as an anti-obesity and anti-muscle wasting medication when taken orally.[48][49]
Salbutamol's low toxicity makes it safe for other animals and thus is the medication of choice for treating acute airway obstruction in most species.[26] It is usually used to treat bronchospasm or coughs in cats and dogs and used as a bronchodilator in horses withrecurrent airway obstruction; it can also be used in emergencies to treat asthmatic cats.[50][51]
Toxic effects require an extremely high dose, and most overdoses are due to dogs chewing on and puncturing an inhaler or nebulizer vial.[52]
^abcdefghijklm"Albuterol".Drugs.com. The American Society of Health-System Pharmacists.Archived from the original on 8 December 2015. Retrieved2 December 2015.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Bhushan R, Tanwar S (February 2010). "Different approaches of impregnation for resolution of enantiomers of atenolol, propranolol and salbutamol using Cu(II)-L-amino acid complexes for ligand exchange on commercial thin layer chromatographic plates".Journal of Chromatography A.1217 (8):1395–8.doi:10.1016/j.chroma.2009.12.071.PMID20074739.
^Ip EJ, Doroudgar S, Lau B, Barnett MJ (August 2019). "Anabolic steroid users' misuse of non-traditional prescription drugs".Research in Social & Administrative Pharmacy.15 (8):949–952.doi:10.1016/j.sapharm.2018.07.003.PMID31303195.S2CID81614300.
^Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, et al. (January 2011). "β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials".Sports Medicine.41 (1):39–57.doi:10.2165/11537540-000000000-00000.PMID21142283.S2CID189906919.
^Schweizer C, Saugy M, Kamber M (September 2004). "Doping test reveals high concentrations of salbutamol in a Swiss track and field athlete".Clinical Journal of Sport Medicine.14 (5):312–5.doi:10.1097/00042752-200409000-00018.PMID15377972.S2CID30402521.
^Hostrup M, Jacobson GA, Jessen S, Lemminger AK (May 2020). "Anabolic and lipolytic actions of beta2 -agonists in humans and antidoping challenges".Drug Testing and Analysis.12 (5):597–609.doi:10.1002/dta.2728.PMID31960603.S2CID210842115.
^Plumb DC (2011). "Albuterol Sulfate".Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 24–25.ISBN978-0-470-95964-0.
^Cote E (9 December 2014)."Albuterol Toxicosis".Clinical Veterinary Advisor - E-Book: Dogs and Cats. Elsevier Health Sciences. pp. 45–46.ISBN978-0-323-24074-1.Archived from the original on 8 September 2017.
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