Practice ABC of chronic obstructive pulmonary disease

Pharmacological management—oral treatment

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7556.1497 (Published 22 June 2006) Cite this as: BMJ 2006;332:1497
  1. Graeme P Currie, specialist registrar,
  2. Daniel K C Lee, specialist registrar,
  3. Brian J Lipworth, professor
  1. Respiratory Unit, Aberdeen Royal Infirmary, Aberdeen
  2. Department of Respiratory Medicine, Papworth Hospital, Papworth Everard, Cambridge
  3. Asthma and Allergy Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee

    Inhaled treatment forms the cornerstone of drug management of chronic obstructive pulmonary disease (COPD). However, some patients—especially those who are elderly, cognitively impaired, or with upper limb musculoskeletal problems—are unable to use inhaler devices successfully.


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    Some patients may not have the manual dexterity required to use hand held inhaler devices. Unfortunately, there are significant unmet needs in terms of effective, long acting, oral bronchodilators for COPD

    Theophylline

    Theophylline is one of the oldest oral bronchodilators available for the treatment of COPD. It has a similar chemical structure to caffeine, which is also a bronchodilator in large amounts.

    Additive effects of theophylline and the bronchodilator salmeterol on lung function in patients with COPD at day 1 and at 12 weeks after starting treatment

    Theophylline is a non-selective phosphodiesterase inhibitor, and it causes an increase in the intracellular concentration of cyclic AMP in various cell types and organs (including the lung). Increased cyclic AMP concentrations are implicated in inhibition of inflammatory and immunomodulatory cells. One result is that phosphodiesterase inhibition causes smooth muscle relaxation and airway dilation.

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    Adverse effects of theophylline

    Other potentially beneficial mechanisms of action of theophylline in COPD have been suggested, including

    • Reduction of diaphragmatic muscle fatigue

    • Increased mucociliary clearance

    • Respiratory centre stimulation

    • Inhibition of neutrophilic inflammation

    • Suppression of inflammatory genes by activation of histone deacetylases

    • Inhibition of cytokines and other inflammatory cell mediators

    • Potentiation of anti-inflammatory effects of inhaled corticosteroids

    • Potentiation of bronchodilator effects of β2 agonists.

    Clinical use of theophylline

    Consider a long acting theophylline preparation in patients with advanced COPD, especially when symptoms persist despite the use of inhaled long acting bronchodilators or in patients unable to use inhaler devices. Studies have shown that theophylline generally …

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