Beta2-adrenergic agonist

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Salbutamol (albuterol) — an example of β2 agonist

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for Chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.[1][2]

Mechanism of action[edit]

Activation of β adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation and opening of the airways.[3]

β adrenergic receptors are coupled to a stimulatory G protein of adenylyl cyclase. This enzyme produces the second messenger cyclic adenosine monophosphate (cAMP). In the lung, cAMP decreases calcium concentrations within cells and activates protein kinase A. Both of these changes inactivate myosin light-chain kinase and activate myosin light-chain phosphatase. In addition, β2 agonists open large conductance calcium-activated potassium channels and thereby tend to hyperpolarize airway smooth muscle cells. The combination of decreased intracellular calcium, increased membrane potassium conductance, and decreased myosin light chain kinase activity leads to smooth muscle relaxation and bronchodilation.[3]

Adverse effects[edit]

Findings indicate that β2 stimulants, especially in parenteral administration such as inhalation or injection, can induce adverse effects:

Overuse of β2 agonists and asthma treatment without proper inhaled corticosteroid use has been associated with an increased risk of asthma exacerbations and asthma-related hospitalizations.[8] The excipients, in particular sulfite, could contribute to the adverse effects.

Delivery[edit]

All β2 agonists are available in inhaler form, as either metered-dose inhalers which dispense an aerosolized drug and contains propellants, dry powder inhalers which dispense a powder to be inhaled, or soft mist inhalers which dispense a mist without use of propellants.[9]

Salbutamol (INN) or albuterol (USAN) and some other β2 agonists, such as formoterol, also are sold in a solution form for nebulization, which is more commonly used than inhalers in emergency rooms.[9] Nebulizers continuously deliver aerosolized drug and salbutamol delivered through nebulizer was found to be more effective than IV administration.[10]

Salbutamol and terbutaline are also both available in oral forms.[11] In addition, several of these medications are available in intravenous forms, including both salbutamol and terbutaline. It can be used in this form in severe cases of asthma, but it is more commonly used to suppress premature labor because it also relaxes uterine muscle, thereby inhibiting contractions.[12]

Risks[edit]

On 18 November 2005, the U.S. Food and Drug Administration (FDA) alerted healthcare professionals and patients that several long-acting bronchodilator medicines have been associated with possible increased risk of worsening wheezing in some people, and requested that manufacturers update warnings in their existing product labeling.[medical citation needed]

A 2006 meta-analysis found that "regularly inhaled β agonists (orciprenaline/metaproterenol [Alupent], formoterol [Foradil], fluticasone+salmeterol [Serevent, Advair], and salbutamol/albuterol [Proventil, Ventolin, Volmax, and others]) increased the risk of respiratory death more than two-fold, compared with a placebo," while[vague] used to treat chronic obstructive pulmonary disease.[13] On 11 December 2008, a panel of experts convened by the FDA voted to ban[vague] drugs Serevent and Foradil from use in the treatment of asthma. When these two drugs are used without steroids, they increase the risks of more severe attacks. They said that two other, much more popular, asthma drugs containing long-acting β agonists—Advair and Symbicort—should continue to be used.[14]

Types[edit]

They can be divided into short-acting, long-acting, and ultra-long-acting beta adrenoreceptor agonists:

Generic name—Trade name

Short-acting β2 agonists (SABAs)[edit]

Long-acting β2 agonists (LABAs)[edit]

Ultra-long-acting β2 agonists[edit]

[17][18]

Unknown duration of action[edit]

Research[edit]

New drugs in this class with more selective activity or that act simultaneously as muscarinic receptor antagonists are under development as of 2023.[19]

Society and culture[edit]

β2 agonists are used by athletes and bodybuilders as anabolic performance-enhancing drugs and their use has been banned by the World Anti-Doping Agency except for certain drugs that people with asthma may use; they are also used illegally to try to promote the growth of livestock.[20] A 2011 meta-analysis found no evidence that inhaled β₂-agonists improve performance in healthy athletes and found that the evidence was too weak to assess whether systemic administration of β₂-agonists improved performance in healthy people.[21]

See also[edit]

References[edit]

  1. ^ a b Hsu E, Bajaj T (2022). "Beta 2 Agonists". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31194406. Retrieved 5 April 2022 – via NCBI.
  2. ^ van Geffen, Wouter H.; Tan, Daniel J.; Walters, Julia Ae; Walters, E. Haydn (6 December 2023). "Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 12 (12): CD011600. doi:10.1002/14651858.CD011600.pub3. ISSN 1469-493X. PMC 10698842. PMID 38054551.
  3. ^ a b Proskocil BJ, Fryer AD (1 November 2005). "Beta2-agonist and anticholinergic drugs in the treatment of lung disease". Proceedings of the American Thoracic Society. 2 (4): 305–310. doi:10.1513/pats.200504-038SR. PMID 16267353. S2CID 22198277.
  4. ^ a b Almadhoun K, Sharma S (2020). "Bronchodilators". StatPearls. StatPearls Publishing. PMID 30085570. Retrieved 16 March 2020.
  5. ^ Billington CK, Penn RB, Hall IP (2016). 2 Agonists". Handbook of Experimental Pharmacology. 237: 23–40. doi:10.1007/164_2016_64. ISBN 978-3-319-52173-2. PMC 5480238. PMID 27878470.
  6. ^ Lulich KM, Goldie RG, Ryan G, Paterson JW (July 1986). "Adverse reactions to beta 2-agonist bronchodilators". Medical Toxicology. 1 (4): 286–299. doi:10.1007/bf03259844. PMID 2878344. S2CID 58394547.
  7. ^ McCoshen JA, Fernandes PA, Boroditsky ML, Allardice JG (January 1996). "Determinants of Reproductive Mortality and Preterm Childbirth". In Bittar EE, Zakar T (eds.). Advances in Organ Biology. Vol. 1: Pregnancy and Parturition. Elsevier. pp. 195–223. doi:10.1016/S1569-2590(08)60073-7. ISBN 978-1-55938-639-5.
  8. ^ Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. (January 2022). "Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes". The European Respiratory Journal. 59 (1): 2102730. doi:10.1183/13993003.02730-2021. PMC 8719459. PMID 34667060.
  9. ^ a b Sorino C, Negri S, Spanevello A, Visca D, Scichilone N (May 2020). "Inhalation therapy devices for the treatment of obstructive lung diseases: the history of inhalers towards the ideal inhaler". European Journal of Internal Medicine. 75: 15–18. doi:10.1016/j.ejim.2020.02.023. PMID 32113944. S2CID 211727980.
  10. ^ Gad SE (2014). "Albuterol". Encyclopedia of Toxicology. Elsevier. pp. 112–115. doi:10.1016/b978-0-12-386454-3.00809-5. ISBN 978-0-12-386455-0. Retrieved 24 April 2023.
  11. ^ Jaeggi ET, Tulzer G (2010). "CHAPTER 12 - Pharmacological and Interventional Fetal Cardiovascular Treatment". Paediatric Cardiology (Third ed.). Churchill Livingstone. pp. 199–218. doi:10.1016/B978-0-7020-3064-2.00012-6. ISBN 978-0-7020-3064-2.
  12. ^ Motazedian S, Ghaffarpasand F, Mojtahedi K, Asadi N (2010). "Terbutaline versus salbutamol for suppression of preterm labor: a randomized clinical trial". Annals of Saudi Medicine. 30 (5): 370–375. doi:10.4103/0256-4947.67079. PMC 2941249. PMID 20697169.
  13. ^ Salpeter SR, Buckley NS, Salpeter EE (October 2006). "Meta-analysis: anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD". Journal of General Internal Medicine. 21 (10): 1011–1019. doi:10.1111/j.1525-1497.2006.00507.x. PMC 1831628. PMID 16970553.
  14. ^ Harris G (11 December 2008). "F.D.A. Panel Votes to Ban Asthma Drugs". The New York Times. Retrieved 19 January 2009.
  15. ^ Matera MG, Cazzola M (2007). "ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD?". Drugs. 67 (4): 503–515. doi:10.2165/00003495-200767040-00002. PMID 17352511. S2CID 46976912.
  16. ^ Beier J, Fuhr R, Massana E, Jiménez E, Seoane B, de Miquel G, Ruiz S (October 2014). "Abediterol (LAS100977), a novel long-acting β2-agonist: efficacy, safety and tolerability in persistent asthma". Respiratory Medicine. 108 (10): 1424–1429. doi:10.1016/j.rmed.2014.08.005. PMID 25256258.
  17. ^ Cazzola M, Matera MG, Lötvall J (July 2005). "Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease". Expert Opinion on Investigational Drugs. 14 (7): 775–783. doi:10.1517/13543784.14.7.775. PMID 16022567. S2CID 11930383.
  18. ^ Cazzola M, Calzetta L, Matera MG (May 2011). "β(2) -adrenoceptor agonists: current and future direction". British Journal of Pharmacology. 163 (1): 4–17. doi:10.1111/j.1476-5381.2011.01216.x. PMC 3085864. PMID 21232045.
  19. ^ Matera MG, Rinaldi B, Calzetta L, Rogliani P, Cazzola M (November 2023). "Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update". Expert Opinion on Pharmacotherapy: 1–10. doi:10.1080/14656566.2023.2282673. PMID 37955136. S2CID 265148154.
  20. ^ "Clenbuterol" (PDF). Drug Enforcement Administration. November 2013. Archived from the original (PDF) on 17 October 2019.
  21. ^ 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. PMID 21142283. S2CID 189906919.

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