O2. Oral bronchodilators

O2.1 Methylxanthines

Theophylline has a modest effect on FEV1 and FVC (Molfino 2006) and slightly improves arterial blood gas tensions in moderate to severe COPD.  However, theophyllines have gone out of favour in many countries because of their narrow therapeutic index and potential for significant adverse effects (Chrystyn 1988Ram 2002). Some patients with disabling breathless­ness may, however, derive benefit from their use (Murciano 1989, McKay 1993, Taylor 1985). Therapeutic drug monitoring of theophylline is recommended to reduce the risk of toxicity and to distinguish non adherence, under-treatment and therapeutic failure. Theophyllines may have an anti-inflammatory effect or reduce muscle fatigue (Aubier 1988, Moxham 1988). Recent studies have suggested lower dose preparations than had previously been used (achieving plasma concentrations of 5-10mg/L) may have anti-inflammatory or immuno-modulatory effects (Barnes 2003, Kobayashi 2004, Cosio 2009). A randomised placebo controlled trial in China demonstrated that doses of 100mg twice daily reduced exacerbations compared with placebo (Zhou 2006). Evidence supports only the slow-release formu­lation. Theophylline is effective in COPD but due to its potential toxicity (the most common adverse reactions being gastric irritation, nausea, vomiting, anorexia, epigastric pain, reactivation of peptic ulcer, gastro-oesophageal reflux, haematemesis, tachycardia, palpitations, headache, CNS stimulation, reflex hyperexcitability, insomnia and tremor (MIMS Australia Pty Ltd 2008), inhaled bronchodilators are preferred when available (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006). Theophylline has an extensive drug interaction profile that may present potential adverse effects in patients on some multi-medication regimens. If medications are started or stopped, pharmacokinetic interactions can be detected by changes in theophylline concentrations. For example, erythromycin and clarithromycin inhibit theophylline metabolism with consequent increase in plasma theophylline concentration and decrease in plasma theophylline concentration on stopping.