Abstract
Phosphodiesterases (PDEs) are a family of enzymes which catalyse the metabolism of the intracellular cyclic nucleotides, c-AMP and c-GMP that are expressed in a variety of cell types and in the context of respiratory diseases, It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical benefit to patients with asthma or chronic obstructive pulmonary disease (COPD). The orally active PDE4 inhibitor Roflumilast-n-oxide has been approved for treatment of severe exacerbations of COPD as add-on therapy to standard drugs. This review discusses the involvement of PDEs in airway diseases and various strategies that are currently being pursued to improve efficacy and reduce side-effects of PDE4 inhibitors, including delivery via the inhaled route, mixed PDE inhibitors and/or antisense biologicals targeted towards PDE4.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Asthma / drug therapy*
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Asthma / enzymology
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Asthma / metabolism
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Drug Therapy, Combination / adverse effects
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Humans
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Isoenzymes / antagonists & inhibitors
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Molecular Targeted Therapy* / adverse effects
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Phosphodiesterase 3 Inhibitors / adverse effects
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Phosphodiesterase 3 Inhibitors / pharmacology
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Phosphodiesterase 3 Inhibitors / therapeutic use
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Phosphodiesterase 4 Inhibitors / adverse effects
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Phosphodiesterase 4 Inhibitors / pharmacology
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Phosphodiesterase 4 Inhibitors / therapeutic use
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Phosphodiesterase Inhibitors / adverse effects
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Phosphodiesterase Inhibitors / pharmacology
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Phosphodiesterase Inhibitors / therapeutic use*
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Phosphoric Diester Hydrolases / chemistry
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Phosphoric Diester Hydrolases / metabolism
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Pulmonary Disease, Chronic Obstructive / drug therapy*
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Pulmonary Disease, Chronic Obstructive / enzymology
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Pulmonary Disease, Chronic Obstructive / metabolism
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Respiratory System / drug effects*
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Respiratory System / enzymology
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Respiratory System / metabolism
Substances
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Isoenzymes
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Phosphodiesterase 3 Inhibitors
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Phosphodiesterase 4 Inhibitors
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Phosphodiesterase Inhibitors
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Phosphoric Diester Hydrolases