💊 Theophylline

Theophylline is a methylxanthine bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and severe asthma. It has a narrow therapeutic index.

Theophylline's primary mechanism of action is thought to be non-selective inhibition of phosphodiesterase (PDE) enzymes, leading to an increase in intracellular cyclic AMP (cAMP). This results in bronchodilation, reduced inflammation, and improved diaphragmatic contractility. It also acts as an adenosine receptor antagonist.

In the UK, theophylline is typically reserved for severe, persistent asthma or COPD that remains poorly controlled despite optimal use of inhaled corticosteroids and long-acting bronchodilators. It is considered a third-line or add-on therapy due to its narrow therapeutic window and potential for significant adverse effects. It can be used in both oral and intravenous forms.

Absolute contraindications include hypersensitivity to theophylline or other methylxanthines. It is also contraindicated in patients with acute porphyria. Caution is required in patients with unstable angina, severe uncontrolled hypertension, recent myocardial infarction, severe hepatic impairment, and peptic ulcer disease.

Due to its narrow therapeutic index, adverse effects are common and dose-related, including nausea, vomiting, headache, palpitations, and insomnia. More serious effects at toxic levels include cardiac arrhythmias (e.g., supraventricular tachycardia, ventricular arrhythmias), seizures, and gastrointestinal haemorrhage. Hypokalaemia can also occur.

Therapeutic drug monitoring (TDM) is essential due to the narrow therapeutic window. Plasma theophylline concentrations should be measured regularly, especially after initiating treatment, changing dose, or if toxicity is suspected. Patients should also be monitored for signs of toxicity and electrolyte imbalances, particularly potassium.

Always check for allergies and a comprehensive medication history to identify potential drug interactions that can alter theophylline levels. Counsel patients on the importance of regular blood tests and to report any signs of toxicity immediately. Emphasise consistency in dosage and timing.

Theophylline is a potent bronchodilator but has a narrow therapeutic window, requiring careful monitoring. Watch out for drug interactions that can increase or decrease its levels. Signs of toxicity include nausea, vomiting, arrhythmias, and seizures. Used for severe, refractory asthma/COPD.

SBA questions frequently test the narrow therapeutic index of theophylline and the need for therapeutic drug monitoring. Common traps involve drug interactions (e.g., with erythromycin, cimetidine, phenytoin, rifampicin) that alter theophylline levels, or the signs of toxicity. Its role as a 'last resort' in severe asthma/COPD is also a key point.