title: β2Agonists.
abstract: History suggests β agonists, the cognate ligand of the β2adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations. Despite constituting the cornerstone of asthma and COPD therapy, these drugs are not perfect; significant safety issues have led to a black box warning advising that long acting β agonists should not be used alone in patients with asthma. In addition there are a significant proportion of patients whose asthma remains uncontrolled. In this chapter we discuss the evolution of β agonist use and how the understanding of β agonist actions on their principal target tissue, airway smooth muscle, has led to greater understanding of how these drugs can be further modified and improved in the future. Research into the genetics of the β2adrenoceptor will also be discussed, as will the implications of individual DNA profiles on the clinical outcomes of β agonist use (pharmacogenetics). Finally we comment on what the future may hold for the use of β agonists in respiratory disease.
authors.affiliation: Division of Respiratory Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: Charlotte K
authors.initials: CK
authors.lastname: Billington
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Center for Translational Medicine, Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Penn
authors.affiliation: Division of Respiratory Medicine, University of Nottingham, Nottingham, NG7 2RD, UK. Ian.hall@nottingham.ac.uk.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000627:therapeutic use; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents
keywords: Airway smooth muscle; Asthma; Cyclic AMP; Isoprenaline; β adrenoceptor; β agonists