Authors: Maria Gabriella Matera Paola Rogliani Luigino Calzetta Mario Cazzola
Publish Date: 2014/10/10
Volume: 74, Issue: 17, Pages: 1983-1992
Abstract
Phosphodiesterase4 PDE4 inhibitors have broad antiinflammatory activity inhibiting the airway inflammation associated with chronic obstructive pulmonary disease COPD especially by reducing airway neutrophils that are key cells in COPD A careful evaluation of the results of several metaanalyses allows us to consider the use of PDE4 inhibitors as very important in those patients with COPD who are particularly susceptible to exacerbations the socalled ‘frequent exacerbators’ Consequently PDE4 inhibitors should be used earlier and more frequently than is the case today but they are prescribed sporadically because of side effects Several strategies are conceivable to avoid side effects but unfortunately many of these approaches are yet to be successfully translated into clinical effectiveness after several decades of research A novel alternative approach is to administer multiple drugs simultaneously or drugs capable of two distinct primary pharmacological actions based on distinct pharmacophores bifunctional drugs in order to produce additive or synergistic effects and consequently to dispense these drugs at lower doses inducing fewer side effects The fact that we have realized that there is a need to target simultaneously more PDEs unquestionably represents an advance in the possible use of PDE inhibitors Actually the possibility that multivalent multifunctional ligands which feature two or more pharmacophores may deliver superior efficacy is an approach that is being explored Recognizing the role of specific targeted therapy aimed at subcellular domains has changed our understanding of the use of PDE inhibitors and offers an opportunity to improve both the therapeutic tolerability and efficacy of these drugs
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