Rapid onset of tolerance to beta-agonist bronchodilation

Haney, Sarah; Hancox, Robert J.

doi:10.1016/j.rmed.2004.10.014

Cited by 70 publications

(53 citation statements)

References 23 publications

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“…Similarly, the ability of short-and long-acting b 2 -adrenoceptor agonists to protect the airways against bronchoconstrictor stimuli and to promote bronchodilatation may be partially lost with time following long-term use [2,129,131,[133][134][135][136][137][138][139][140]. Indeed, there is a greater tendency for bronchodilator tolerance to develop to longacting b 2 -adrenoceptor agonists compared to their short-acting counterparts, which may relate to some aspect of their prolonged duration of agonism [141,142].…”

Section: Long-term Use Of B 2 -Adrenoceptor Agonistsmentioning

confidence: 99%

Beyond the dogma: novel 2-adrenoceptor signalling in the airways

Giembycz

Newton²

2006

European Respiratory Journal

131

118

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b 2 -Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of compounds is believed to involve the stimulation of adenylyl cyclase and subsequent activation of the cyclic adenosine monosphosphate (cAMP)/cAMP-dependent protein kinase cascade.This classical model of b 2 -adrenoceptor-mediated signal transduction is deeply entrenched, but there is compelling evidence that agonism of b 2 -adrenoceptors can lead to the activation of multiple effector pathways, which now compels researchers in academia and the pharmaceutical industry alike to think beyond the traditional dogma. Therefore, the regulation by b 2 -adrenoceptor agonists of responses, including airways smooth muscle tone and the secretory capacity of the epithelium and pro-inflammatory/immune cells, may be highly complex, involving both cAMPdependent and -independent mechanisms that, in many cases, may act in concert.In this article, the current status of b 2 -adrenoceptor-mediated signalling in the airways is reviewed in the context of understanding mechanisms that may underlie both the beneficial and detrimental effects of these drugs in asthma symptom management.

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Section: Long-term Use Of B 2 -Adrenoceptor Agonistsmentioning

confidence: 99%

Beyond the dogma: novel 2-adrenoceptor signalling in the airways

Giembycz

Newton²

2006

European Respiratory Journal

131

118

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“…The minimum dose and frequency required to minimize this loss of effect are recommended. 45 Such tachyphylaxis to their bronchoprotective effects occurs after only a few days of use and is not antagonized by inhaled corticosteroid therapy, which can reduce exercise-induced bronchoconstriction in most people with asthma after a few weeks of regular use. 46 If asthma is not controlled by a low dose of inhaled corticosteroid therapy, current guidelines suggest that a long-acting β 2 -agonist should be prescribed to improve such control.…”

Section: Management Of Asthma In Olympic Athletesmentioning

confidence: 99%

Asthma, outdoor air quality and the Olympic Games

McKenzie¹,

Boulet²

2008

Canadian Medical Association Journal

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“…In this context, prescribing physicians as well as patients need to appreciate the potential variability in degree of protection by a single dose of bronchoprotective agents used before exercise. Moreover, consistent (e.g., daily) use of β-adrenergic agents can lead to relative tolerance to the bronchoprotective effect of these agents (15,(26)(27)(28)(29), although intervals of use of 72 hours or greater abrogate this effect (28). Long-term anti-inflammatory control of asthma can decrease bronchial reactivity to various asthma triggers such as exercise (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%