?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.
Video Beta2-adrenergic agonist
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.
Maps Beta2-adrenergic agonist
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, and cardiac arrhythmia, are exceptional.
Asthma aggravation has been observed in patients using large doses of ?2 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 ?2 mimetics could be attenuated by inhaled corticosteroid intake.
Delivery
All ?2 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 ?2 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. 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.
Risks
On November 18, 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.
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.
On December 11, 2008, a panel of experts convened by the FDA voted to ban the 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. 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, long-acting, 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.
Salbutamol: Uses:
- It is a selective ?² agonist and is mainly used as a bronchodilator in the treatment of asthma for this purpose it is best used by inhalation with the help of an inhalaer or nebulizer .When use by inhaltion a smaller dose of drug is required to produce the maximum effect.0.25-0.5 can be used by subcutaneous,intramuscular or slow intrvenous.
- It can also be used in Reversible airways obstruction and premature labour.
- It can also be used in patients suffering from chronic bronchitis and emphysema.Bronchospasm in these patients can be treated with salbutamol or other bronchodilator.
Mechanism Of Action: Binding of Salbutamol to beta(2)-receptors in the lungs leads to relaxation of bronchial smooth muscles. it's believed that salbutamol will increase cAMP production by activating adenylate cyclase, and also the actions of salbutamol are mediate by cAMP. enlarged intracellular cyclic AMP will increase the activity of cAMP-dependent protein kinase A, that inhibits the phosphorylation of myosin and lowers intracellular Ca concentrations. A lowered intracellular Ca concentration ends up in a smooth muscle relaxation and bronchodilation. additionally to bronchodilation, salbutamol inhibits the discharge of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance. Side effects: Side effects of beta 2 agonist include
- Nervous tension,
- Bronchial Hyperactivity
- Fine tremor,
- Headache,
- Palpitation,
- Muscle cramps ,
- Tachycardia,
- Arrhythmias,
- Myocardial ischemia,
- Peripheral vasodilation
- Sleep disturbances.
- Angioedma,
- Urticaria,
- Hypotension
- High doses of beta 2 agonist are associated with hypokalaemia.
(Note: These side effects are same for all beta 2 agonist drugs) Pharmacokinetics: It can be given orally, subcutaneusly, intramuscularly and by inhalation.it is well absorbed from GIT and metabolised mainly in the liver by monamine oxidase enzyme.when given by inhalation it produces bronchodilation in a few minutes which last for 3-4 hours and persist for about 6 hours.When given orally bronchodilation effect occur after about 1 hour and persist for about 6 hours.When given subcutenous injection its effect occur in about 5 minutes and persist for 4 hours
2. Terbutaline
Though it is similar to salbutamol but it is sometime longer acting than the salbutamol.It is available in the Tablets of 5 mg and 2.5 mg.Dose of 2.5-5mg three time a day can be used in the treatment of asthma.Terbutaline can be given by inhalation .each inhalation from a meter dose inhalor delivers 200µg of terbuatline.11 inhalation may be used 4-6 hourly.Injection 0.25 mg are also available which can be used by intramuscualr, subcutaneous or slow intravenous injection.
3. Salmeterol
This is available as inhaler.Each puff deleivers 25?g of salmeterol.It has a long plasma half life.its dose is 50?g twice daily which can be increased to 100?g twice daily in severe cases.
4. Formoterol Fumarate
This is also a long acting beta 2 agonist drug and is available as dry powder in capsules, containing 12?g/capsules.Its dose is 12?g twice daily by inhalation and in severe cases 24?g twice daily can also be used. [1]
5. Bambuterol Hydrochloride
This is a prodrug and it is converted in the body into terbutaline.it is available as oral tablets of initially 10 mg one tab is used at bed time for 1-2 weeks,then increased the dose to 20 mg once daily.
See also
- Discovery and development of ?2 agonists
References
- 9 Beta Adrenergic Drugs
External links
- beta-Adrenergic Receptor Agonists at the US National Library of Medicine Medical Subject Headings (MeSH)
Beta 2 Adrenergic Agonists
Source of the article : Wikipedia
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