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β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs that act on the beta2-adrenergic receptor, thereby causing smooth muscle relaxation, resulting in dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin.
Mechanism of action
Activation of beta-adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation and opening of the airways.
Beta-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, beta-2 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.
Findings indicate that Beta-2 stimulants, especially in parenteral administration such as inhalation or injection, can induce adverse effects:
- tachycardia secondary to peripheral vasodilation and cardiac stimulation; tachycardia can be accompanied by palpitations.
- tremor, sweats, agitation.
- more severe effects, pulmonary edema, myocardial ischemia, cardiac arrhythmia, are exceptional.
Asthma aggravation has been observed in patients using large dose of beta-2 stimulants, but it is not known if it results from spontaneous course of the disease or adverse effect of the drugs. The excipients, in particular sulphite, could contribute to the adverse effects. The possible loss of the bronchodilator activity of beta-2-mimetic could be attenuated by glucocorticoid intake.
Salbutamol (known as albuterol in the U.S.) also comes in a solution form for nebulization, which is more commonly used in inhalers than in emergency rooms. Salbutamol and terbutaline are also both available in oral forms. 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.
On November 18, 2005, 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.
On June 29, 2006, Cornell University and Stanford University researchers reported that a meta-analysis they conducted found that "regularly inhaled beta-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 twofold, compared with a placebo," while used to treat chronic obstructive pulmonary disease (COPD).
On December 11, 2008, a panel of experts convened by the Food and Drug Administration (FDA) voted to ban the drugs Serevent and Foradil from use in the treatment of asthma. It was shown that, when these two drugs are used without steroids, they increase the risks of more severe attacks. The experts said that two other much more popular asthma drugs containing long-acting beta-agonists, Advair and Symbicort, should continue to be used. The latter contains formoterol as contained in Foradil but also a steroid budesonide.
Short-acting beta2 agonists
generic name (Trade Name)
- salbutamol (albuterol (US name), Ventolin)
- levosalbutamol (levalbuterol (US name), Xopenex)
- terbutaline (Bricanyl)
- pirbuterol (Maxair)
- metaproterenol (Alupent)
- bitolterol mesylate
Long-acting beta2 agonists
- salmeterol (Serevent Diskus)
- formoterol (Foradil, Symbicort)
- olodaterol (Striverdi)
Ultra-long-acting beta2 agonists
- Ramanujan K. Common beta-agonist inhalers more than double death rate in COPD patients, Cornell and Stanford scientists assert. Chronicle Online. June 29, 2006. Available at: http://www.news.cornell.edu/stories/June06/Salpeter.COPD.kr.html. Accessed June 30, 2006.
- Harris G. F.D.A. Panel Votes to Ban Asthma Drugs. "The New York Times". December 11, 2008. Available at: http://www.nytimes.com/2008/12/12/health/policy/12fda.html?ref=health. Accessed January 19, 2009.
- beta-Adrenergic Receptor Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)