Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases

Pharmacology & Therapeutics
Robert NewtonMark A Giembycz

Abstract

Glucocorticoids are widely used to treat various inflammatory lung diseases. Acting via the glucocorticoid receptor (GR), they exert clinical effects predominantly by modulating gene transcription. This may be to either induce (transactivate) or repress (transrepress) gene transcription. However, certain individuals, including those who smoke, have certain asthma phenotypes, chronic obstructive pulmonary disease (COPD) or some interstitial diseases may respond poorly to the beneficial effects of glucocorticoids. In these cases, high dose, often oral or parental, glucocorticoids are typically prescribed. This generally leads to adverse effects that compromise clinical utility. There is, therefore, a need to enhance the clinical efficacy of glucocorticoids while minimizing adverse effects. In this context, a long-acting beta(2)-adrenoceptor agonist (LABA) can enhance the clinical efficacy of an inhaled corticosteroid (ICS) in asthma and COPD. Furthermore, LABAs can augment glucocorticoid-dependent gene expression and this action may account for some of the benefits of LABA/ICS combination therapies when compared to ICS given as a monotherapy. In addition to metabolic genes and other adverse effects that are induced by glucocortic...Continue Reading

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Citations

Nov 13, 2010·Inflammopharmacology·Michael W Whitehouse
Nov 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Neil S HoldenRobert Newton
Jul 30, 2011·The Journal of Biological Chemistry·Peter J Barnes
Sep 17, 2011·American Journal of Respiratory and Critical Care Medicine·Fernando M de Benedictis, Andrew Bush
Aug 21, 2013·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Dora LiuHarold Kim
Jun 12, 2013·European Journal of Pharmacology·Robert Newton
May 28, 2013·Toxicology and Applied Pharmacology·Sofia JonassonAnders Bucht
May 13, 2014·Current Infectious Disease Reports·Tasha D Ramsey, Sean K Gorman
Dec 5, 2014·American Journal of Respiratory and Critical Care Medicine·Gail M GauvreauPaul M O'Byrne
Aug 12, 2014·International Immunopharmacology·Jia-Xin ShiXiao-Mei Li
Oct 24, 2012·Pharmacology & Therapeutics·Bart G J DekkersMartina Schmidt
Sep 8, 2010·Pulmonary Pharmacology & Therapeutics·Thomas Glaab, Christian Taube
Jan 5, 2011·British Journal of Pharmacology·Peter J Barnes
Feb 26, 2013·Current Opinion in Pharmacology·Alaina J Ammit
May 9, 2014·Current Opinion in Pharmacology·Mark A Giembycz, Donald H Maurice
Sep 15, 2014·Pulmonary Pharmacology & Therapeutics·C BoardmanP Sharma
Jun 12, 2016·Pharmacology & Therapeutics·Janet P HapgoodJohnson M Moliki
Apr 30, 2017·Clinical and Experimental Otorhinolaryngology·Hwan Soo KimHyun Hee Kim
Jan 1, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mohammed O AltonsyRobert Newton
Aug 12, 2017·Respiratory Research·Seyed M MoosaviAlaina J Ammit
Mar 31, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claire E TaconRichard Leigh
Dec 17, 2014·Journal of Complementary & Integrative Medicine·Deepa K IngawaleSnehal S Patel
May 31, 2011·The Journal of Pharmacology and Experimental Therapeutics·Christopher F RiderRobert Newton
Mar 17, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Tiina KeränenRiku Korhonen

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