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, such as Chronic obstructive pulmonary disease (COPD).

Mechanism of action[]

Activation of β adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation and opening of the airways.[1]

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.[1]

Adverse effects[]

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

  • Tachycardia secondary to peripheral vasodilation and cardiac stimulation (Such tachycardia may be accompanied by palpitations.)[2]
  • Tremor, excessive sweating, anxiety, insomnia, and agitation[3]
  • More severe effects include paradoxical bronchospasm, hypokalemia, and in rare cases a myocardial infarction.[2] (More severe effects, such as pulmonary edema, myocardial ischemia, and cardiac arrhythmia, are exceptional.)[4][5][6]

Asthma aggravation has been observed in patients using large doses of β2 agonists, but if it results from spontaneous course of the disease or adverse effect of the drugs is not known. The excipients, in particular sulfite, could contribute to the adverse effects. The possible loss of the bronchodilator activity of β2 mimetics could be attenuated by inhaled corticosteroid intake.

Delivery[]

All β2 agonists are available in inhaler form, either metered-dose inhalers, which aerosolize the drug, or dry powder inhalers, which dispense powder which can be inhaled.

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.[citation needed] Salbutamol and terbutaline are also both available in oral forms. The nebulizer form is as effective as administering the drug intravenously.

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.[7]

Risks[]

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.[8]

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.[9]

Types[]

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)[]

  • bitolterol—Tornalate
  • fenoterol—Berotec
  • isoprenaline (INN) or isoproterenol (USAN)—Isuprel
  • levosalbutamol (INN) or levalbuterol (USAN)—Xopenex
  • orciprenaline (INN) or metaproterenol (USAN)—Alupent
  • pirbuterol—Maxair
  • procaterol
  • ritodrine—Yutopar
  • salbutamol (INN) or albuterol (USAN)—Ventolin
  • terbutaline—Bricanyl
  • albuterol—Ventolin/ Proventil

Long-acting β2 agonists (LABAs)[]

  • arformoterol—Brovana (some consider it to be an ultra-LABA)[10]
  • bambuterol—Bambec, Oxeol
  • clenbuterol—Dilaterol, Spiropent
  • formoterol—Foradil, Oxis, Perforomist
  • salmeterol—Serevent

Ultra-long-acting β2 agonists[]

[12][13]

Unknown duration of action[]

Society and culture[]

β2 agonists are abused 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.[14] 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.[15]

See also[]

References[]

  1. ^ Jump up to: a b Proskocil, Becky J.; Fryer, Allison D. (1 November 2005). "β2-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. ISSN 1546-3222. PMID 16267353.
  2. ^ Jump up to: a b Almadhoun, Khaled; Sharma, Sandeep (2020), "Bronchodilators", StatPearls, StatPearls Publishing, PMID 30085570, retrieved 16 March 2020
  3. ^ Billington, Charlotte K et al. “β2 Agonists.” Handbook of experimental pharmacology vol. 237 (2017): 23-40. doi:10.1007/164_2016_64
  4. ^ Lulich, K. M.; Goldie, R. G.; Ryan, G.; Paterson, J. W. (July 1986). "Adverse reactions to beta 2-agonist bronchodilators". Medical Toxicology. 1 (4): 286–299. doi:10.1007/bf03259844. ISSN 0112-5966. PMID 2878344.
  5. ^ McCoshen, John A.; Fernandes, P. Audrey; Boroditsky, Michael L.; Allardice, James G. (1 January 1996). "Determinants of Reproductive Mortality and Preterm Childbirth". In Bittar, E. Edward; Zakar, Tamas (eds.). Pregnancy and Parturition. Advances in Organ Biology. Pregnancy and Parturition. 1. Elsevier. pp. 195–223. doi:10.1016/S1569-2590(08)60073-7. ISBN 9781559386395.
  6. ^ Hsu, Eric; Bajaj, Tushar (2020), "Beta 2 Agonists", StatPearls, StatPearls Publishing, PMID 31194406, retrieved 18 March 2020
  7. ^ Motazedian, Shahdokht; Ghaffarpasand, Fariborz; Mojtahedi, Khatereh; Asadi, Nasrin (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. ISSN 0256-4947. PMC 2941249. PMID 20697169.
  8. ^ Salpeter SR, Buckley NS, Salpeter EE (October 2006). "Meta-analysis: anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD". J Gen Intern Med. 21 (10): 1011–9. doi:10.1111/j.1525-1497.2006.00507.x. PMC 1831628. PMID 16970553. Lay summary.
  9. ^ Harris, Gardiner (11 December 2008). "F.D.A. Panel Votes to Ban Asthma Drugs". The New York Times. Retrieved 19 January 2009.
  10. ^ Matera, MG; Cazzola, M (2007). "Ultra-Long-Acting β2-Adrenoceptor Agonists: An Emerging Therapeutic Option for Asthma and COPD?". Drugs. 67 (4): 503–15. doi:10.2165/00003495-200767040-00002. PMID 17352511. Retrieved 7 March 2016.
  11. ^ 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. Retrieved 25 March 2016.
  12. ^ Cazzola, Mario; Matera, Maria Gabriella; Lötvall, Jan (15 July 2005). "Ultra long-acting β2-agonists in development for asthma and chronic obstructive pulmonary disease". Expert Opinion on Investigational Drugs. 14 (7): 775–83. doi:10.1517/13543784.14.7.775. PMID 16022567.
  13. ^ Cazzola, Mario; Calzetta, Luigino; Matera, Maria Gabriella (May 2011). "β2-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.
  14. ^ Drug Enforcement Administration. November 2013 Clenbuterol
  15. ^ Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, Zwinderman AH, Scholten RJ (January 2011). "β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials". Sports Med. 41 (1): 39–57. doi:10.2165/11537540-000000000-00000. PMID 21142283.

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