Aminophylline

Class	Adenosine receptor antagonist
Chemistry	Methylxanthine
Routes of administration	IV or oral
Absorption	Well absorbed after oral administration, about 90% bioavailability
Solubility	pKa = 5.0, good water solubility (much better than theophylline, which is why this is the IV alternative to it)
Distribution	VOD=0.3-0.7L/kg, 60% protein-bound
Metabolism	A pro-drug - really just an ethylenediamine salt of theophylline, and so it immediately dissociates into theophylline, which is the main pharmacologically active agent.
Elimination	Minimal free drug is eliminated in the urine
Time course of action	Half-lie of aminophylline itself is minuscule, whereas the half-life of theophylline is 8 hours.
Target receptor	Adenosine A1 and A2 receptors, which inhibit neurotransmitter releease by regulating presynaptic potassium and calcium traffic. Also phospodiesterase type III and IV
Mechanism of action	Multiple effects: - Adenosine receptor inhibiition leads to the ihibition of leukotriene release by mast cells - A1 and A2 receptior inhibition also has the undesirable cardiovascular effects by increasing the release of catecholamines - Phosphodiesterase inhibition leads to increased cAMP and cGMP, leading to the relaxation of smooth muscles in bronchi and pulmonary vessels, but also to diuresis and cardiovascular stimulation - increases the action and recruitment of histone deacetylases to the site of active inflammation - Increased calcium uptake through the adenosine-mediated calcium channels in the diaphragm leads to increased contraction and reversal of diaphragm fatigue
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	Stirt & Sullivan, 1981
CICM details of understanding	Level 2
Mentioned around Deranged Physiology	Pharmacology of drugs used to treat asthma Also see Theophylline toxicity because they are basically the same drug
Related SAQs	Question 11 from the second paper of 2023

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