Tolerance &amp; resistance to β2-agonist bronchodilators

Yim, Robert P.; Koumbourlis, Anastassios C.

doi:10.1016/j.prrv.2012.11.002

Cited by 18 publications

(11 citation statements)

References 38 publications

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“…There is evidence that regular use of inhaled β-2 agonists can modify the response of the β-2 receptor resulting in reduced efficacy 15. This may make the use of intravenous salbutamol less beneficial in some cases, but the clinical significance of this finding in the management of acute exacerbations of asthma remains unclear.…”

Section: Pharmacology Of β-2 Agonistsmentioning

confidence: 99%

Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?

Neame

Aragon

Fernandes

et al. 2015

Arch Dis Child Educ Pract Ed

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Acute, severe exacerbations of asthma present a challenge due to the significant morbidity associated with this presentation. For exacerbations that are refractory to initial treatments with inhaled and oral therapies, there is still doubt about which intravenous therapies are most likely to be helpful. β-2 agonists and aminophylline have differing mechanisms of action that also affect their adverse effects profiles and these are considered. A review of the available randomised control trials suggests that a bolus of intravenous salbutamol may reduce symptoms and hasten recovery. Aminophylline infusions may improve lung function, and in some studies have been shown to improve symptoms, but the evidence is not clear cut. Decisions about which treatment to use should include risk management considerations such as ease of prescription, preparation and administration factors and availability of high-dependency beds.

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Section: Pharmacology Of β-2 Agonistsmentioning

confidence: 99%

Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?

Neame

Aragon

Fernandes

et al. 2015

Arch Dis Child Educ Pract Ed

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“…83 This mechanism occurs with β1-ARs in the heart 84 and it may be responsible for the β2-agonist resistance that occurs in both asthma and COPD. 85,86 In addition to altering β-adrenergic signaling, increasing evidence suggests that HuR could impact on the muscarinic cholinergic system in the airways. In healthy lungs, muscarinic receptors control mucus production, bronchoconstriction, vasodilation, and inflammation.…”

Section: Hur and Airways Diseasementioning

confidence: 99%

Posttranscriptional control of airway inflammation

Ezegbunam

Foronjy

2017

WIREs RNA

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Acute inflammation in the lungs is a vital protective response, efficiently and swiftly eliminating inciters of tissue injury. However, in respiratory diseases characterized by chronic inflammation, such as chronic obstructive pulmonary disease and asthma, enhanced expression of inflammatory mediators leads to tissue damage and impaired lung function. Although transcription is an essential first step in the induction of proinflammatory genes, tight regulation of inflammation requires more rapid, flexible responses. Increasing evidence shows that such responses are achieved by posttranscriptional mechanisms directly affecting mRNA stability and translation initiation. RNA-binding proteins, microRNAs, and long noncoding RNAs interact with messenger RNA and each other to impact the stability and/or translation of mRNAs implicated in lung inflammation. Recent research has shown that these biological processes play a central role in the pathogenesis of several important pulmonary conditions. This review will highlight several posttranscriptional control mechanisms that influence lung inflammation and the known associations of derangements in these mechanisms with common respiratory diseases.

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“…Patients who fall into the "severe" category of asthma are frequently hyporesponsive to bronchodilators [4]. Studies show that β 2 AR tolerance or desensitization occurs after repeated bronchodilator use that diminishes drug efficacy [3,[5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone rescues TGF-β1-mediated β2-adrenergic receptor dysfunction and attenuates phosphodiesterase 4D expression in human airway smooth muscle cells

et al. 2020

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Glucocorticoids (GCs) and β2-adrenergic receptor (β2AR) agonists improve asthma outcomes in most patients. GCs also modulate gene expression in human airway smooth muscle (HASM), thereby attenuating airway inflammation and airway hyperresponsiveness that define asthma. Our previous studies showed that the pro-fibrotic cytokine, transforming growth factor- β1 (TGF-β1) increases phosphodiesterase 4D (PDE4D) expression that attenuates agonist-induced levels of intracellular cAMP. Decreased cAMP levels then diminishes β2 agonist-induced airway relaxation. In the current study, we investigated whether glucocorticoids reverse TGF-β1-effects on β2-agonist-induced bronchodilation and modulate pde4d gene expression in HASM. Dexamethasone (DEX) reversed TGF-β1 effects on cAMP levels induced by isoproterenol (ISO). TGF-β1 also attenuated G protein-dependent responses to cholera toxin (CTX), a Gαs stimulator downstream from the β2AR receptor. Previously, we demonstrated that TGF-β1 treatment increased β2AR phosphorylation to induce hyporesponsiveness to a β2 agonist. Our current data shows that expression of grk2/3, kinases associated with attenuation of β2AR function, are not altered with TGF-β1 stimulation. Interestingly, DEX also attenuated TGF-β1-induced pde4d gene expression. These data suggest that steroids may be an effective therapy for treatment of asthma patients whose disease is primarily driven by elevated TGF-β1 levels.

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Tolerance & resistance to β2-agonist bronchodilators

Cited by 18 publications

References 38 publications

Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?

Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?

Posttranscriptional control of airway inflammation

Dexamethasone rescues TGF-β1-mediated β2-adrenergic receptor dysfunction and attenuates phosphodiesterase 4D expression in human airway smooth muscle cells

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