Long-acting beta-adrenoceptor agonist
Long-acting beta-adrenoceptor agonists (LABAs, more specifically β2-agonists) are usually prescribed for moderate to severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2-agonists such as salbutamol, as they have a duration of action of approximately 12 hours in comparison with the 4- to 6-hour duration of salbutamol, making them candidates for sparing high doses of corticosteroids or treating nocturnal asthma and providing symptomatic improvement in patients with COPD. With the exception of formoterol, long-acting β2-agonists are not recommended for the treatment of acute asthma exacerbations because of their slower onset of action compared to salbutamol. Their long duration of action is due to the addition of a long, lipophilic side-chain that binds to an exosite on adrenergic receptors. This allows the active portion of the molecule to continuously bind and unbind at β2 receptors in the smooth muscle in the lungs.
When combined with inhaled steroids, beta-adrenoceptor agonists can improve symptoms. In children this benefit is uncertain and they may be potentially harmful. They should not be used without an accompanying steroid due to an increased risk of severe symptoms, including exacerbation in both children and adults. At least with formoterol, an increased risk appears to be present even when steroids are used and this risk has not been ruled out for salmeterol.
Some currently available long-acting beta-adrenoceptor agonists are:
Two ultra-long-acting beta-adrenoceptor agonists that have a duration of action of 24 hours, allowing for once-daily dosing are now approved.
- Indacaterol (approved by the European Medicines Agency (EMA) under the trade name Onbrez on November 30, 2009, and by the United States Food and Drug Administration (FDA) under the trade name Arcapta Neohaler, on July 1, 2011)
- Olodaterol (approved in some European countries as Striverdi)
While the use of inhaled LABAs are still recommended in asthma guidelines for the resulting improved symptom control, further concerns have been raised, by a large meta-analysis of the pooled results from 19 trials with 33,826 participants, that salmeterol may increase the small risks of asthma deaths, and this additional risk is not reduced with the additional use of inhaled steroids (e.g., as with the combination product Fluticasone/salmeterol). This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.
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- "FDA Drug Safety Communication: New safety requirements for long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs)". FDA. Feb 2010. "Based on the available information, FDA concludes there is an increased risk for severe exacerbation of asthma symptoms, leading to hospitalizations in pediatric and adult patients as well as death in some patients using LABAs for the treatment of asthma. The agency is requiring the REMS and class-labeling changes to improve the safe use of these products."
- Cates, CJ; Cates, MJ (Apr 18, 2012). "Regular treatment with formoterol for chronic asthma: serious adverse events.". Cochrane database of systematic reviews (Online) 4: CD006923. doi:10.1002/14651858.CD006923.pub3. PMID 22513944.
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- European Public Assessment Report for Onbrez Breezhaler
- "FDA approves Arcapta Neohaler to treat chronic obstructive pulmonary disease" (Press release). U.S. Food and Drug Administration. 2011-07-01. Retrieved 2011-07-02.
- "New once-daily Striverdi (olodaterol) Respimat gains approval in first EU countries". Boehringer-Ingelheim. 18 October 2013.
- British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. Guideline No. 63. Edinburgh:SIGN; 2004. (HTML, Full PDF, Summary PDF)
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- Krishna Ramanujan (June 9, 2006). "Common asthma inhalers cause up to 80 percent of asthma-related deaths, Cornell and Stanford researchers assert". ChronicalOnline - Cornell University.
In 2011, the FDA issued a safety alert for Long-Acting Beta-Agonists (LABAs):