Methylxanthines
Theophylline, aminophylline and caffeine: old bronchodilators and breathing stimulants with a narrow margin between effect and toxicity.
What they are
Methylxanthines are purine derivatives related to the caffeine in coffee and tea. Theophylline (oral) and aminophylline (theophylline with ethylenediamine, for intravenous use) are now add-on or last-line drugs for asthma and COPD, because inhaled bronchodilators and corticosteroids are safer. Caffeine citrate is the drug of choice for apnea of prematurity. Theophylline matters for exams because of its narrow therapeutic range, its many interactions through the liver enzyme CYP1A2, and its toxicity: vomiting, arrhythmias and seizures.
Mechanism of action
Methylxanthines inhibit phosphodiesterases (mainly PDE3 and, less, PDE4), so cyclic AMP rises in bronchial smooth muscle and inflammatory cells. They also block adenosine A1 and A2 receptors; adenosine normally constricts airways in asthma, slows the heart and depresses the brain and breathing. Adenosine blockade explains the stimulation of the respiratory centre, as well as the tachycardia, arrhythmias, tremor and seizures in toxicity. At low concentrations theophylline also activates histone deacetylase, which may help corticosteroids work.
Target: Phosphodiesterases (PDE3, PDE4) and adenosine receptors (A1, A2A)
Drugs in this class
- TheophyllineAn oral bronchodilator for asthma and COPD with a narrow therapeutic range and many interactions; levels are checked…Adenosine A2A receptor (and phosphodiesterases PDE3, PDE4)
- AminophyllineTheophylline combined with ethylenediamine so it dissolves for intravenous use; same narrow range and interactions as…Adenosine A2A receptor (and phosphodiesterases PDE3, PDE4)
- Caffeine citrateThe treatment of choice for apnea of prematurity: it stimulates breathing in preterm babies and lasts days because…Adenosine A1 and A2A receptors
Others in the class
- Doxofylline
- Theobromine (in cocoa)
Test yourself
Think of the answer, then tap the question to see it.
What are two molecular actions of theophylline?
Phosphodiesterase inhibition (higher cyclic AMP) and adenosine receptor blockade.
A patient on theophylline starts ciprofloxacin and develops vomiting and palpitations. Why?
Ciprofloxacin inhibits CYP1A2, which slows theophylline metabolism and raises its levels into the toxic range.
Why may a smoker who quits need closer theophylline monitoring?
Smoking induces CYP1A2; after quitting, metabolism slows and levels rise.
Which methylxanthine is used for apnea of prematurity?
Caffeine citrate.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - THEOPHYLLINE tablet, extended release (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - CAFFEINE CITRATE- caffeine citrate injection, solution (DailyMed (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.