Journal Article

Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease

Lea, Simon, Mathioudakis, Alexander G., Singh, Dave

2021

Overview

Phosphodiesterase (PDE) 4 inhibitors prevent the metabolism of cyclic adenosine monophosphate, thereby reducing inflammation. Inhaled PDE4 inhibitors aim to restrict systemic drug exposure to enhance the potential for clinical benefits (in the lungs) versus adverse events (systemically). The orally administered PDE4 inhibitor roflumilast reduces exacerbation rates in the subgroup of chronic obstructive pulmonary disease patients with a history of exacerbations and the presence of chronic bronchitis, but can cause PDE4 related adverse effects due to systemic exposure. CHF6001 is an inhaled PDE4 inhibitor, while inhaled ensifentrine is an inhibitor of both PDE3 and PDE4; antagonism of PDE3 facilitates smooth muscle relaxation and hence bronchodilation. These inhaled PDE inhibitors have both reported positive findings from early phase clinical trials, and have been well tolerated. Longer term trials are needed to firmly establish the clinical benefits of these drugs.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Adenosine / Adenosine monophosphate / Administration, Inhalation / Adverse events / Aminopyridines - administration & dosage / Aminopyridines - adverse effects / Aminopyridines - pharmacology / Animals / Antagonism / Benzamides - administration & dosage / Benzamides - adverse effects / Benzamides - pharmacology / Bronchitis / Bronchodilation / Bronchodilators / Chemokines / Chronic obstructive pulmonary disease / Clinical trials / Cyclic AMP / Cyclic AMP - metabolism / Cyclopropanes - administration & dosage / Cyclopropanes - adverse effects / Cyclopropanes - pharmacology / Cytokines / Humans / Inflammation / Inflammation - drug therapy / Inflammation - pathology / Inhibitors / Internal Medicine / Isoquinolines - administration & dosage / Isoquinolines - adverse effects / Isoquinolines - pharmacology / Leading Article / Ligands / Lung diseases / Lungs / Medicine / Medicine & Public Health / Metabolism / Muscle contraction / Muscles / Neutrophils / Obstructive lung disease / Oral administration / para-Aminobenzoates - administration & dosage / para-Aminobenzoates - adverse effects / para-Aminobenzoates - pharmacology / Pathophysiology / Pharmacology/Toxicology / Pharmacotherapy / Phosphodiesterase / Phosphodiesterase 4 Inhibitors - administration & dosage / Phosphodiesterase 4 Inhibitors - adverse effects / Phosphodiesterase 4 Inhibitors - pharmacology / Phosphodiesterase inhibitors / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Pyrimidinones - administration & dosage / Pyrimidinones - adverse effects / Pyrimidinones - pharmacology / Quality of life / Smooth muscle / Steroids / Subgroups / Sulfonamides - administration & dosage / Sulfonamides - adverse effects / Sulfonamides - pharmacology / Tumor necrosis factor-TNF