Corticosteroids: potential beta2-agonist and anticholinergic interactions in chronic obstructive pulmonary disease.
Corticosteroids are often used in combination with beta2-agonist and anticholinergic bronchodilators in the treatment of chronic obstructive pulmonary disease (COPD). Corticosteroids activate the beta2-receptor gene, increasing receptor number and decreasing desensitization. Long-acting beta2-agonists prime the glucocorticoid receptor and enhance nuclear translocation via activation of CCAAT enhancer binding protein-alpha. Corticosteroids can also increase prejunctional auto-inhibitory M2-receptor gene expression in airway smooth muscle. There is evidence of a synergistic inhibition of cytokine and chemokine release from alveolar macrophages, epithelial cells, and mucosal glands and enhanced respiratory cytoprotection against viral and bacterial infection when a corticosteroid is combined with salmeterol. In airway smooth muscle, corticosteroids inhibit the contractile effects of acetylcholine, whereas M2-receptor antagonism increases the relaxant activity of isoproterenol. Complementary interactions between corticosteroids and long-acting beta2-agonists and between corticosteroids and anticholinergic bronchodilators may be important if these drugs are combined in the treatment of COPD.
Johnson
Malcolm
M
Respiratory Science, GlaxoSmithKline, Greenford Road, Greenford, Middlesex UB6 0HE, UK. malcolm.w.johnson@gsk.com
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid; D011976:Receptors, Muscarinic