Pharmacogenetics Of Theophylline

b2-agonists act by increasing the cAMP content of the cell; control of cAMP breakdown is by tissue phosphodiesterases. Theophylline has been used in the treatment of asthma and COPD for at least 70 years. Theophylline has both bronchodilator and anti-inflammatory properties. The bronchodilator component of the drug action is thought to be at least in part mediated by phosphodiesterase inhibition in airway smooth muscle cells, leading to elevated cAMP levels and hence smooth muscle relaxation. The phosphodiesterase (PDE) 4D subfamily is thought to be the critical family of phosphodiesterases involved in the hydrolysis of cAMP in airway smooth muscle cells and is probably the main target of theophylline. Polymorphism within the PDE4D gene could potentially influence theophylline efficacy, but to date no specific gene polymorphisms have been associated with theophylline efficacy or adverse effects in asthma. The development of selective PDE4 inhibitors for the treatment of COPD will lead to increased interest in this subject area.

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