title: Cyclic nucleotide-based therapeutics for chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) defines a group of chronic inflammatory disorders of the airways that are characterised by a progressive and largely irreversible decline in expiratory airflow. Drugs used to treat COPD through actions mediated by cyclic AMP (cAMP) are restricted to long-acting and short-acting β2-adrenoceptor agonists and, in a subset of patients with chronic bronchitis, a phosphodiesterase 4 inhibitor, roflumilast. These agents relax airway smooth muscle and suppress inflammation. At the molecular level, these effects in the airways are mediated by two cAMP effectors, cAMP-dependent protein kinase and exchange proteins activated by cAMP. The pharmacology of newer agents, acting through these systems, is discussed here with an emphasis on their potential to interact and increase therapeutic effectiveness.
authors.affiliation: Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Giembycz
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. Electronic address: mauriced@queensu.ca.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Maurice
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D009712:Nucleotides, Cyclic / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors