?2 (beta2) adrenergic receptor agonists, also known as adrenergic ?2 receptor agonists, are a class of drugs that act on the ?2 adrenergic receptor. Like other ? adrenergic agonists, they cause smooth muscle relaxation. ?2 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 COPD.
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Mechanism of action
Activation of ? adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation and opening of the airways.
? 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, ?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.
Adverse effects
Findings indicate that ?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, excessive sweating, anxiety, insomnia and agitation
More severe effects, such as pulmonary edema, myocardial ischemia, cardiac arrhythmia, are exceptional.
Asthma aggravation has been observed in patients using large doses of ?2 agonists, 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 ?2 mimetics could be attenuated by inhaled corticosteroid intake.
Delivery
All ?2 agonists are available in inhaler form, either metered-dose inhalers (MDIs), which aerosolize the drug, or dry powder inhalers (DPIs), which dispense powder which can be inhaled.
Salbutamol (INN) or albuterol (USAN) and some other ?2 agonists, such as formoterol, also come 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. 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.
Risks
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 ? 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 (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 ? agonists, Advair and Symbicort, should continue to be used.
Types
They can be divided into short-acting (SABA), long-acting (LABA) and ultra-long-acting ? (more specifically, ?2) adrenoreceptor agonists:
Generic name -- Trade name
Short-acting ?2 agonists
- 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
Long-acting ?2 agonists
- arformoterol -- Brovana (some consider it to be an ultra-LABA)
- bambuterol -- Bambec, Oxeol
- clenbuterol -- Dilaterol, Spiropent
- formoterol -- Foradil, Oxis, Perforomist
- salmeterol -- Serevent
Ultra-long-acting ?2 agonists
- abediterol
- carmoterol
- indacaterol -- Arcapta Neohaler (U.S.), Onbrez Breezhaler (EU, RU)
- olodaterol -- Striverdi Respimat
- vilanterol
- with umeclidinium bromide -- Anoro Ellipta
- with fluticasone furoate -- Breo Ellipta (U.S.), Relvar Ellipta (EU, RU)
Unknown duration of action
- isoxsuprine
- mabuterol
- zilpaterol -- Zilmax
Society and culture
?2 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. A 2011 meta-analysis found no evidence that inhaled ??-agonists improve performance in healthy athletes and found that the evidence was too weak to assess whether systemic administration of ??-agonists improved performance in healthy people.
Source of the article : Wikipedia
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