Theophylline in COPD

The role of theophylline in COPD is as maintenance therapy in non-acutely ill patients. Therapy can be initiated at 200 mg twice daily and titrated upward every 3 to 5 days to the target dose most patients require daily doses of400 to 900 mg. 

Bachmann K, Nunlee M, Martin M, Sullivan T, Jauregui L, DeSante K, Sides GD. Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin. J Clin Pharmacol 1990 30(ll) 1001-5. Bachmann K, Jauregui L, Sides G, Sullivan TJ. Steady-state pharmacokinetics of theophylline in COPD patients treated with dirithromycin. J Clin Pharmacol 1993 33(9) 861-5. 

Bachmann K, Jauregui L, Sides G, Sullivan TJ. Steady-state pharmacc inetics of theophylline in COPD patients treated with dirithromycin. J Clin Pharmacol (1993) 33, 861-5. 

Chronic theophylline use in COPD has been shown to produce improvements in lung function, including vital capacity and FEVj. Subjectively, theophylline has been shown to reduce dyspnea, increase exercise tolerance, and improve respiratory drive. Nonpulmonary effects that may contribute to better functional capacity include improved cardiac function and decreased pulmonary artery pressure. 

Methylxanthines are no longer considered first-line therapy for COPD. Inhaled bronchodilator therapy is preferred over theophylline for COPD because of theophylline s risk for drug interactions and the interpatient variability in dosage requirements. Theophylline may be considered in patients who are intolerant or unable to use an inhaled bronchodilator. A methylxanthine may also be added to the regimen of patients who have not achieved an optimal clinical response to an inhaled anticholinergic and [i2-agonist. 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

Kobayashi M, Nasuhara Y, Betsuyaku T, et al. Effect of low-dose theophylline on airway inflammation in COPD. Respirology. 2004 9 249-254. 

Famotidine 40 mg twice daily for 5 days had no effect on the pharmacokinetics of theophylline (given as intravenous aminophylline) in 10 healthy subjects. In another study, 16 patients with bronchial asthma or chronic obstructive pulmonary disease (COPD) found that famotidine 20 mg twice daily for at least 3 days did not affect the clearance of theophylline. Two further studies also found no interaction between intravenous theophylline and famotidine 20 or 40 mg twice daily for 4 or 9 days in COPD... 

Gaffuri-Riva V, Crippa F, Guf nti EE. Theophylline interacticn with new quinolones and macrolides in COPD patients. AmRevRespirDis (1991) 143, A498. 

Several studies in both healthy adults, " and adults with COPD - did not demonstrate any clinically significant interaction, although two of these studies did find a reduction in the clearance of theophylline in some subjects. ... 

Theophylline is a non-specific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle resulting in bronchodilation. It has a modest bronchodila-tor effect in patients with COPD, and its use is limited due to a narrow therapeutic index, multiple drug interactions, and adverse effects. Theophylline should be reserved for patients who cannot use inhaled medications or who remain symptomatic despite appropriate use of inhaled bronchodilators. 

Theophylline (Fig. 20) is structurally very similar to caffeine and present at a low concentration in tea. It is also known as dimethyl xanthine. It is used for the treatments of asthma and COPD, for more than 50 years despite its many side effects. The mechanism of beneficial effect of theophylline is through HD AC activation. 

A plant-derived compound used in the treatment of asthma and COPD is the methylxanthine-type alkaloid, theophylline (50), found naturally in tea Camellia sinensis Kuntze). This compound demonstrated higher activity when complexed with bases, as in its semisynthetic analogue amino-phylline (51). 5... 

Ohta K, Fukuchi Y, Grouse L, et al. A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD. Resp Med 2004 98 1016-1024. 

The respiratory actions of the methylxanthines may not be confined to the airways, for they also strengthen the contractions of isolated skeletal muscle in vitro and improve contractility and reverse fatigue of the diaphragm in patients with COPD. This effect on diaphragmatic performance—rather than an effect on the respiratory center—may account for theophylline s ability to improve the ventilatory response to hypoxia and to diminish dyspnea even in patients with irreversible airflow obstruction. 

ZuWallack RL, Mahler DA, Reilly D, Church N, Emmett A, Rickard K, Knobil K. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 2001 119(6) 1661-70. 

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