PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast.
Chronic obstructive pulmonary disease is characterized by a rapid decline in lung function due to small airway fibrosis, mucus hypersecretion and emphysema. The major causative factor for COPD is cigarette smoking that drives an inflammatory process that gives rise to leukocyte recruitment, imbalance in protease levels and consequently matrix remodeling resulting in small airway fibrosis and loss of alveolar tissue. Current drug treatment improves symptoms but do not alter the underlying progression of this disease. The failure of antiinflammatory drugs like glucocorticosteroids to have a major impact in this disease has hastened the need to develop novel therapeutic strategies. Phosphodiesterase (PDE) 4 inhibitors are novel anti-inflammatory drugs that have recently been show to document clinical efficacy in this disease, although their utility is hampered by class related side-effects of nausea, emesis and diarrhea. Whilst it is not yet clear whether such drugs will prevent emphysema, this is a distinct possibility provided experimental observations from preclinical studies translate to man. This review will discuss the current standing of PDE4 inhibitors like roflumilast as novel treatments for COPD and the potential for developing nonemetic anti-inflammatory drugs.
The Sackler Institute of Pulmonary Pharmacology, King's College London School of Biomedical and Health Sciences, King's College London, Guys Campus, UK.
Victoria
V
Boswell-Smith
Domenico
D
Spina
D000631:Aminopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D009325:Nausea / Q000139:chemically induced; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000201:enzymology; D019141:Respiratory System Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D019141:Respiratory System Agents; C424423:Roflumilast; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4