Theophylline

Class Adenosine receptor antagonist
Chemistry

Methylxanthine

Routes of administration

Oral

Absorption

Rapidly and completely absorbed (99-96% bioavailability)

Solubility

pKa = 8.77, slightly soluble in water

Distribution

VOD= 0.45L/kg, 58-82% protein-bound

Metabolism

90% of theophylline is metabolised by CYP 450 enzymes which have significant polymorphism, with about fourfold interindividual variation, and which are susceptible to indiuction or inhibition by other agents, which means theophylline interacts with everything (erythromycin, rifampicin, nicotine, etc)

Elimination

Minimal free drug is eliminated in the urine

Time course of action

Half-life is 8 hours, or 4-5 hours in smokers

Target receptor

Adenosine A1 and A2 receptors, which inhibit neurotransmitter releease by regulating presynaptic potassium and calcium traffic

Mechanism of action

Increases neurotransmitter (dopamine and noradrenaline) release from presynaptic nerve terminals. Adenosine is a regulatory neurotransmitter that is normally responsible for hyperpolarising presynaptic terminals, mainly through its activity on potassium channel and voltage-gated calcium channel activity. Neurotransmitter release from these terminals is therefore inhibited by adenosine; and to reverse this inhibition allows increased neurotransmitter release.

Clinical effects

Bronchodilation, pulmonary arterial vasodilation, increased diaphragmatic contractility, tachycardia, increased cardiac output, arrhythmias, diuresis, increased gastric acid secretion, and rhabdomyolysis and seizures in overdose

Literature reference

Weinberger, 1984

CICM details of understanding Level 2
Mentioned around Deranged Physiology
Related SAQs

Question 11 from the second paper of 2023 (as aminophylline)

Question 29 from the first paper of 2017 (Second Part Exam)

Question 11(p.2) from the second paper of 2007