Theophylline

Abstract

Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is markedly reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) and blood concentrations are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids and in COPD patients with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism.

Pharmacokinetics of a modified, compounded theophylline product in dogs

“…The lack of validated, commercial products can be attributed to the decline of theophylline use in human medicine (Hawkins & Papich, ) because of the narrow therapeutic range (10–20 μg/ml) and high incidence of dose‐dependent adverse effects seen in humans (Barnes, ). In contrast, dogs may be more resistant to theophylline's adverse effects with mild and serious signs only occurring at plasma concentrations exceeding 37 and 90 μg/ml, respectively, without cumulative effects (Hamlin & Sally, ; Munsiff, McKiernan, Neff‐Davis, & Koritz, ; Shibata, Wachi, Kagawa, Kojima, & Onodera, ).…”

“…T 1/2,β and MRT also vary significantly between reports, but this may be a function of breed rather than formulation. It has been hypothesized that the short t 1/2,β of rapid re- It should be noted that theophylline products marketed as slow release or extended release in humans generally do not have extended-release properties in dogs (Bach et al, 2004;Koritz et al, 1986 Papich, 2014) because of the narrow therapeutic range (10-20 μg/ ml) and high incidence of dose-dependent adverse effects seen in humans (Barnes, 2010). In contrast, dogs may be more resistant to theophylline's adverse effects with mild and serious signs only occurring at plasma concentrations exceeding 37 and 90 μg/ml, respectively, without cumulative effects (Hamlin & Sally, 1993;Shibata, Wachi, Kagawa, Kojima, & Onodera, 2000).…”

Assessment of the Airway Smooth Muscle Relaxant Effect of Drotaverine

“…Scientific evidence supports the fact that PDE inhibitors, such as theophylline, have therapeutic potential in the treatment of inflammation-driven obstructive airway diseases like asthma and COPD. Theophylline and other PDE inhibitors not only decrease airway inflammation but also improve pulmonary function [15] by acting directly on bronchial tone to induce bronchodilation. In clinical use, theophylline has also been found to be effective on visceral smooth muscle spasm-induced symptoms [16-18].…”

Voltammetric sensor for theophylline using sol–gel immobilized molecularly imprinted polymer particles

“…For over 70 years it has been used to treat maladies of the airway such as asthma and chronic obstructive pulmonary disease (COPD). Its low cost and high availability have both contributed to make it one of the most widely prescribed drugs for such pathologies [12]. Its simple structure and close similarity to its analogues ( Fig.…”