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Theophylline is a methylxanthine compound that is used for the treatment of asthma, chronic obstructive pulmonary disease (COPD; chronic bronchitis and emphysema), and premature apnea. The bronchodilatory effects of theophylline are useful primarily for patients with asthma because bronchospasm is a key component of that disease state.1 The use of theophylline in patients with chronic obstructive pulmonary disease is more controversial because these diseases have different pathophysiologic profiles, although some patients do exhibit a mixed disease profile with a limited reversible airway component. Even COPD patients without significant bronchospasm demonstrate clinical improvement when taking theophylline.2–4 Theophylline is also a central nervous system stimulant which explains its usefulness in the treatment of premature apnea.

In the chronic management of asthma or chronic obstructive pulmonary disease patients, theophylline is now considered to be adjunctive therapy.5–8 Asthma is now recognized as an inflammatory disease, and inhaled corticosteroids are considered the mainstay of therapy.8 Inhaled selective β2-agonists are used as bronchodilators in asthmatic patients. Other drugs that are useful in patients with asthma are cromolyn, nedocromil, oral corticosteroids, inhaled anticholinergics, and leukotriene modifiers. Inhaled bronchodilators are the preferred treatment for COPD patients with selective β2-agonists or anticholinergics considered first line agents.6 Theophylline is considered for use in asthmatic patients and chronic obstructive pulmonary disease patients after their respective therapies have commenced. Theophylline is also useful in these patients when they are unable or unwilling to use multiple metered dose inhaler (MDI) devices or if an intravenous drug is needed. For the treatment of premature apnea, most clinicians prefer to use caffeine, a related methylxanthine agent, instead of theophylline because of smoother apnea control and reduced adverse effects.

The bronchodilatory response via smooth muscle relaxation in the lung to theophylline is postulated to occur by several mechanisms.9 Of these, the two predominate mechanisms of action are inhibition of cyclic nucleotide phosphodiesterases which increases intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and antagonism of adenosine receptors. In addition to bronchodilation, theophylline increases diaphragmatic contractility, increases mucociliary clearance, and exerts some antiinflammatory effects. Theophylline is a general central nervous system stimulant and specifically stimulates the medullary respiratory center. These are the reasons why it is a useful agent in the treatment of premature apnea.

The generally accepted therapeutic ranges for theophylline are 10–20 μg/mL for the treatment of asthma or COPD, or 6–13 μg/mL for the treatment of premature apnea. Clinical guidelines suggest that for initial treatment of pulmonary disease, clinical response to theophylline concentrations between 5–15 μg/mL should be assessed before higher concentrations are used.5,7 Many patients requiring chronic theophylline therapy will derive sufficient bronchodilatory response with a low likelihood of adverse effects at concentrations of 8–12 μg/mL. However, theophylline therapy must be individualized for each patient in order to achieve optimal responses and minimal side effects.

In the upper end of the therapeutic ...

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