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Resumen
El roflumilast (3-ciclopropilmetoxi-4-difluorometoxi-N-[3,5-di-cloro-4-piridil]-benzamida) ha sido el primer agente de una nueva clase farmacológica, los inhibidores selectivos de la fosfodiesterasa-4 (IPDE4), aprobado para el tratamiento de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC). El mecanismo molecular de acción del roflumilast es la inhibición de la isoenzima de la PDE4 y el consecuente incremento del monofosfato de adenosina cíclico. Es evidente que el roflumilast muestra varios efectos farmacológicos: antiinflamatorio, antienfisematoso, antifibrótico, inhibidor de la hipertensión pulmonar y mucorregulador. Las acciones farmacológicas responsables de sus efectos son: a) la inhibición de la formación de especies reactivas de oxígeno en las células del epitelio, los neutrófilos y las células del músculo liso; b) la inhibición de la proliferación de las células del músculo liso de la arteria pulmonar, las células endoteliales y, probablemente, algunas células inflamatorias responsables del remodelado vascular pulmonar; c) la inhibición de los fibroblastos, con la consiguiente disminución del remodelado pulmonar, y, finalmente, d) la inhibición de la producción de moco y la mejora del batido ciliar.
En suma, el roflumilast es el primer antiinflamatorio no esteroideo que podrá utilizarse en el tratamiento de la EPOC.
Palabras clave:
Inhibidor de la isoenzima fosfodiesterasa-4
(IPDE4)
Enfermedad pulmonar obstructiva crónica
(EPOC)
Antiinflamatorio
Antienfisematoso
Antirremodelado
Mucorregulación
Roflumilast
Abstract
Roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-n-(3,5-dichloropyrid-4-yl)benzamide) was the first agent of a novel pharmacological class, selective phosphodiesterase 4 (PDE4) inhibitors, approved for the use of chronic obstructive pulmonary disease (COPD). The molecular mechanism of action of roflumilast is inhibition of the PDE4 isoenzyme with a consequent increase of cyclic adenosine monophosphate. Roflumilast evidently has several pharmacological effects: antiinflammatory, anti-emphysema, and antibiotic actions. This drug also inhibits pulmonary hypertension and reduces mucus hypersecretion. The pharmacological actions leading to these effects are: a) inhibition of reactive oxygen species formation in epithelial cells, neutrophils and smooth muscle cells; b) inhibition of smooth muscle cell proliferation in the pulmonary artery, endothelial cells and probably some inflammatory cells causing pulmonary vascular remodeling; c) inhibition of fibroblasts, with a consequent reduction in pulmonary remodeling and, finally, d) inhibition of mucus production and improved ciliary beat frequency. In summary, roflumilast is the first non-steroidal anti-inflammatory drug that can be used in the treatment of COPD.
Keywords:
Phosphodiesterase 4 (PDE4) inhibitor
Chronic obstructive pulmonary disease
(COPD)
Antiinflammatory
Anti-emphysema drug
Anti-remodeling agents
Mucus regulation
Roflumilast
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