Beta₂-adrenergic agonist

Activation of β adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation and opening of the airways.[2]

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.[2]

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.)[3]
• Tremor, excessive sweating, anxiety, insomnia, and agitation[4]
• More severe effects include paradoxical bronchospasm, hypokalemia, and in rare cases a myocardial infarction.[3] (More severe effects, such as pulmonary edema, myocardial ischemia, and cardiac arrhythmia, are exceptional.)[5][6][7]

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.

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. Salbutamol and terbutaline are also both available in oral forms.[8] 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.[9]

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.

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 used to treat chronic obstructive pulmonary disease.[10] On 11 December 2008, a panel of experts convened by the FDA voted to ban 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.[11]

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

Generic name—Trade name

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.[16] 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.[17]

• Discovery and development of β₂ agonists
• β3-adrenergic agonist

• Adrenergic beta-Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)