Frontrunners in novel pharmacotherapy of COPD.
The mainstay of current drug therapy is long-acting bronchodilators; several longer acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. No treatments reduce the progression or suppress the inflammation of COPD. With better understanding of the inflammatory and destructive process, several new targets have been identified. Several mediator antagonists tested in COPD have been disappointing, but of CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment may be more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a major limitation so that inhaled delivery will be necessary. Perhaps the most promising approach is reversal corticosteroid resistance through increasing HDAC2 activity. This may be achieved by theophylline-like drugs, more effective antioxidants and non-antibiotic macrolides.
Barnes
Peter J
PJ
National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK. p.j.barnes@imperial.ac.uk
D001993:Bronchodilator Agents / Q000627:therapeutic use; D018925:Chemokines / Q000037:antagonists & inhibitors; D015195:Drug Design; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D011480:Protease Inhibitors / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D001993:Bronchodilator Agents; D018925:Chemokines; D016328:NF-kappa B; D058988:Phosphodiesterase 4 Inhibitors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D048051:p38 Mitogen-Activated Protein Kinases