Interactions of glucocorticoids and beta 2-agonists

Adcock, Ian M.; Da, Stevens; Barnes, Peter J.

doi:10.1183/09031936.96.09010160

Cited by 75 publications

(39 citation statements)

References 78 publications

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“…This means that it is unlikely that patients will use b 2 -agonist treatment at the expense of glucocorticosteroids, which are crucial for inflammatory control. Furthermore, the use of inhaled budesonide together with formoterol may have some synergistic effects on efficacy [9,17,18]. In the present study, there was a tendency towards more rapid improvements in morning and evening PEF, and asthma symptom score with single inhaler therapy compared with separate inhaler therapy.…”

Section: Discussionsupporting

confidence: 58%

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone

et al. 2001

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Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone.In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 mg?day -1 ) received single inhaler budesonide/formoterol (Symbicort1 Turbuhaler1) 160/4.5 mg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers.There was a greater increase in morning peak expiratory flow (PEF) with singleinhaler (35.7 L?min -1 ) and separate-inhaler (32.0 L?min -1 ) budesonide and formoterol, compared with budesonide alone (0.2 L?min -1 ; pv0.001, both comparisons); the effect was apparent after 1 day (pv0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (y15% more, pv0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups.It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

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Section: Discussionsupporting

confidence: 58%

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone

et al. 2001

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“…Indeed, fixed combination inhalers of long-acting ␤ 2 -agonists and corticosteroids are now available and seem to be the most effective way to control asthma because these two classes of drug have complementary and synergistic effects (41). Corticosteroids increase the expression of ␤ 2 -adrenergic receptors in the lung and prevent their downregulation and uncoupling in response to ␤ 2 -agonists (42)(43)(44). Recent studies also show that ␤ 2 -agonists enhance the action of corticosteroids, with an increase in nuclear translocation of glucocorticoid receptors in vitro (45) and enhanced suppression of inflam- Endothelin-1 * GM-CSF ϭ granulocyte-macrophage colony-stimulating hormone; ICAM ϭ intercellular adhesion molecule-1; IL ϭ interleukin; MCP ϭ monocyte chemoattractant protein; MIP ϭ macrophage inflammatory protein; NF-B ϭ nuclear factor-B; RANTES ϭ regulated upon activation, normal cell expressed and secreted; SCF ϭ stem-cell factor; TNF-␣ ϭ tumor necrosis factor-␣; VCAM-1 ϭ vascular cell adhesion molecule-1.…”

Section: Interactions Between Corticosteroids and Other Drugsmentioning

confidence: 99%

How Do Corticosteroids Work in Asthma?

2003

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“…In animals, adrenalectomy results in a generalized loss of responsiveness to catecholamines 75,76 Molecular interactions between the pathways have also gained increasing recognition [77][78][79] For instance, both classes of drugs can activate C/EBP-a and the GR. 80,81 Moreover, both classes of medications combined, even at lower doses, can synchronously activate both transcription factors, resulting in an enhanced antiproliferative effect. 75,[79][80][81][82] b-2 -agonists (particularly long-acting preparations) may affect GR nuclear localization through modulation of GR phosphorylation and, further may prime GR functions within the nucleus by modifying GR or GR-associated protein phosporylation.…”

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confidence: 99%

“…80,81 Moreover, both classes of medications combined, even at lower doses, can synchronously activate both transcription factors, resulting in an enhanced antiproliferative effect. 75,[79][80][81][82] b-2 -agonists (particularly long-acting preparations) may affect GR nuclear localization through modulation of GR phosphorylation and, further may prime GR functions within the nucleus by modifying GR or GR-associated protein phosporylation. 83 Glucocorticoids may in turn regulate b 2 AR function by increasing expression and inhibiting b 2 AR downregulation, thereby directly modulating contraction of airway smooth muscle.…”

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confidence: 99%

Overview of the pharmacogenetics of asthma treatment

et al. 2006

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Asthma affects approximately 300 million individuals worldwide. Medications comprise a substantial portion of asthma expenditures. Despite the availability of three primary therapeutic classes of medications, there are a significant number of nonresponders to therapy. Available data, as well as previous pharmacogenetic studies, suggest that genetics may contribute as much as 60-80% to the interindividual variability in treatment response. In this methodologic review, after providing a broad overview of the asthma pharmacogenetics literature to date, we describe the application of a novel family-based screening algorithm to the analysis of pharmacogenetic data and highlight our approach to identifying and verifying loci influencing asthma treatment response. This approach seeks to address issues related to multiple comparisons, statistical power, population stratification, and failure to replicate from which previous population-based or case-control pharmacogenetic association studies may suffer. Identification of such replicable loci is the next step towards the goal of 'individualized therapy' for asthma. The Pharmacogenomics Journal (2006) 6, 311-326. doi:10.1038/sj.tpj.6500387; published online 25 April 2006Keywords: beta-agonist; leukotriene; corticosteroid; FEV 1 ; genetics IntroductionThe goal of this review is to give a comprehensive assessment of asthma pharmacogenetics and highlight the scientific approach being taken by the pharmacogenetics of asthma treatment (PHAT) research group (http:// www.pharmgat.org/) to this research area. Our approach strives to address many of the potential problems inherent in genetic association studies, including those related to multiple comparisons, lack of statistical power, population stratification, and failure to replicate. Moreover, our group of collaborative investigators is well positioned to investigate the molecular biology and functional genomics of identified candidate gene associations. In this review, we will cover some aspects of asthma health care, pathobiology, and review the available pharmacogenetics literature on the important types and pathways of asthma medications: b-agonists, leukotriene (LT) antagonists, methylxanthines, and corticosteroids. We will then present details of our research approach to finding replicated pharmacogenetic associations and suggest what the future may hold for this research area. Pharmacogenetics -definition and rationalePharmacogenetics is the study of the role of genetic determinants in the variable, interindividual response to medications. Numerous examples of heritable differences in pharmacokinetics (drug distribution and metabolism) in The Pharmacogenomics Journal (2006) 6, 311-326 & 2006 Nature Publishing Group All rights reserved 1470-269X/06 $30.00 www.nature.com/tpj individuals resulting in varied clinical response to medications have been described. 1 Other mechanisms underlying the genetic response to drugs includes alterations in pharmacodynamics (changes in the drug target), idiosyncratic associations (unin...

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Interactions of glucocorticoids and beta 2-agonists

Cited by 75 publications

References 78 publications

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone

How Do Corticosteroids Work in Asthma?

Overview of the pharmacogenetics of asthma treatment

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