Makindo Medical Notes

💊 Theophylline is a methylxanthine bronchodilator used as an adjunct in asthma and COPD. It has a narrow therapeutic index — plasma monitoring is essential. 🧠 Smokers metabolise it faster (require higher doses), whereas elderly or those with heart failure or liver disease need lower doses. ⚠️ Always prescribe by brand (e.g. Uniphyllin Continus, Nuelin SA) — formulations differ in bioavailability and release characteristics. Complex interactions with many drugs; always check co-prescriptions carefully.

📘 About

• Always check the BNF entry here for exact dosing, brands, and monitoring guidance.
• Metabolised hepatically via CYP1A2 — metabolism affected by smoking, illness, and interacting drugs.
• Therapeutic range: 10–20 mg/L (≈55–110 µmol/L) — toxic effects may occur above this.
• Role in modern care is limited; often reserved for patients uncontrolled by inhaled therapy.

⚙️ Mode of Action

• Inhibits phosphodiesterase (PDE) → increases intracellular cAMP → bronchial smooth muscle relaxation.
• Enhances diaphragmatic contractility and respiratory drive.
• Also antagonises adenosine receptors, contributing to both bronchodilation and cardiac stimulation (side-effects).

🎯 Dosing & Therapeutic Target

• Therapeutic plasma concentration: 10–20 mg/L (55–110 µmol/L).
• Measure levels 4–6 hours after oral modified-release dose (steady-state trough).
• Monitor after dose changes, illness, smoking cessation, or addition of interacting drugs.

💊 Indications & Typical Doses

• Asthma / COPD (adjunctive therapy): 250–500 mg every 12 hours (dose varies by preparation).
• Uniphyllin Continus®: 200–400 mg twice daily.
• Nuelin SA 250®: 250–500 mg twice daily.
• Nuelin SA 175®: 175–350 mg twice daily.
• Adjust according to plasma levels, age, smoking status, and comorbidities.

🔄 Interactions

• Increased levels (toxicity risk): heart failure, hepatic impairment, viral infections, macrolides (erythromycin), ciprofloxacin, cimetidine, fluvoxamine.
• Reduced levels: smoking (induces CYP1A2), chronic alcohol use, rifampicin, carbamazepine, phenytoin.
• Synergistic hypokalaemia risk: with β₂-agonists, corticosteroids, and diuretics.

⚠️ Cautions

• Very narrow therapeutic window — toxicity may occur even at “therapeutic” levels in elderly or hypoxic patients.
• Avoid abrupt cessation of smoking without review — may precipitate toxicity due to reduced clearance.
• Consider lower starting doses in elderly, hepatic, or cardiac impairment.
• Monitor potassium in patients receiving high-dose β₂-agonists concurrently.

🚫 Contraindications

• Porphyria (may precipitate attack).
• Hypersensitivity to xanthines (e.g. caffeine, aminophylline).
• Active peptic ulcer disease (stimulates gastric acid secretion).

💥 Adverse Effects

• Early: nausea, vomiting, tremor, agitation, insomnia, headache.
• Cardiac: sinus tachycardia, supraventricular or ventricular tachycardia, hypotension.
• Neurological: seizures (may occur suddenly, even without prodrome).
• Metabolic: hypokalaemia, hyperglycaemia.
• Severe toxicity → haematemesis, hyperthermia, convulsions, arrhythmia, and cardiac arrest.

🧠 Teaching Note

Theophylline illustrates the challenges of drugs with narrow therapeutic margins and variable metabolism. Always interpret plasma levels in clinical context, and remember smoking, infection, and drug interactions can shift concentrations dramatically. In modern asthma/COPD management, it is mainly a third-line adjunct when inhaled options fail.

📚 References

• BNF: Theophylline
• GOLD 2024: Global Initiative for COPD
• GINA 2024: Global Strategy for Asthma Management
• UKCPA Perioperative Medicines Handbook (2024)