Cyclic nucleotide-based therapeutics for chronic obstructive pulmonary disease

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 beta(2)-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.