Aminophylline

Systematic (IUPAC) name
1,3-dimethyl-7H-purine-2,6-dione; ethane-1,2-diamine
Clinical data
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a601015
Pregnancy cat.	?
Legal status	P (UK)
Routes	oral, i.v.
Pharmacokinetic data
Protein binding	60%
Half-life	7-9 hours
Identifiers
CAS number	317-34-0 Y
ATC code	R03DA05
PubChem	CID 9433
DrugBank	DB01223
ChemSpider	9062 Y
UNII	27Y3KJK423 Y
KEGG	D00227 Y
ChEMBL	CHEMBL1210 N
Chemical data
Formula	C16H24N10O4
Mol. mass	420.427 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/2C7H8N4O2.C2H8N2/c2*1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;3-1-2-4/h2*3H,1-2H3,(H,8,9);1-4H2 Y Key:FQPFAHBPWDRTLU-UHFFFAOYSA-N Y
N (what is this?)  (verify)

Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate^[1]

Aminophylline is a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor capable of reversing ischemia-induced bradyasystole^[2] . It does this by improving the rate of return of spontaneous circulation (ROSC). During atropine-resistant out-of-hospital cardiac arrest, all aspects of attempted resuscitation must proceed in accordance with standard Advanced Cardiac Life Support (ACLS) guidelines^[3] . After exhaustive conventional therapy, aminophylline is administered early in resuscitation efforts to re-establish cardiac rhythm^[4] . With aminophylline administration, the patient may have immediate resumption of cardiac electrical activity^[5] . Aminophylline should be an intervention with the ACLS treatment of atropine-resistant asystolic out-of-hospital cardiac arrest^[6] .

Properties[link]

It is more soluble in water than theophylline. White or slightly yellowish granules or powder, having a slight ammoniacal odor and a bitter taste. Upon exposure to air, it gradually loses ethylenediamine and absorbs carbon dioxide with the liberation of free theophylline. Its solutions are alkaline. One g dissolves in 25 mL of water to give a clear solution; 1 g dissolved in 5 mL of water crystallizes upon standing, but redissolves when a small amount of ethylenediamine is added. Insoluble in alcohol and in ether.

Mechanism of action[link]

Like other methylated xanthine derivatives, aminophylline is both a

1. competitive nonselective phosphodiesterase inhibitor ^[7] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha ^[8][9] and leukotriene ^[10] synthesis, and reduces inflammation and innate immunity ^[10] and
2. nonselective adenosine receptor antagonist.^[11]

Aminophylline is less potent and shorter-acting than theophylline. Its most common use is in the treatment of bronchial asthma.

Causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenine monophosphate (cAMP) which in turn promotes catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis and induces release of epinephrine from adrenal medulla cells

Adenosine is an endogenous extracellular messenger that can regulate myocardial oxygen needs^{[12] [13]} . It acts through cellular surface receptors which effect intracellular signalling pathways to increase coronary artery blood flow, slow heart rate, block atrioventricular node conduction, suppress cardiac automaticity, and decrease β-adrenergic effects on contractility^{[14] [15]} . Adenosine also antagonizes chronotropic and ionotropic effects of circulating catecholamines^[16] . Overall, adenosine decreases the heart’s rate and force of contraction, which increases blood supply to the cardiac muscle. Given specific circumstances this mechanism (which is intended to protect the heart) may cause atropine-resistant refractory bradyasystole^[17] . Adenosine’s effects are concentration-dependent. Adenosine’s receptors are competitively antagonized by methylxanthines such as aminophylline^{[18] [19] [20]}. Aminophylline competitively antagonizes the cardiac actions of adenosine at the cell surface receptors ^[21] . Thus, it increases heart rate and contractility.

Pharmacokinetics[link]

Patients who remain in asystole two minutes after receiving initial doses of epinephrine and atropine are then administered aminophylline^[22] . Doses range from 50mg to 7mg/kg with no reported adverse effects; an optimal dose remains unclear^[23] . Additional doses of aminophylline or a weight-based dosage regimen may be necessary and result in improved cardiac outcomes when compared to a single-dosage pharmacological intervention. However ideal dosage administrations remain unclear^[24] .

Precautions, contraindications and interactions[link]

Aminophylline has only been tested in cardiac arrest that does not result secondary to trauma or hypothermia^{[25] [26]} .

Aminophylline has been found to decrease the sedative effects of propofol^[27] and decrease topiramate antiseizure action^[28] .

Other uses[link]

Aminophylline is used to reverse dipyridamole or adenosine based infusions during nuclear cardiology stress testing.

Aminophylline has shown some promise as a bodyfat reducer when used as a topical cream (sometimes referred to as "cutting gel").^[29] Aminophylline is also a treatment option for anaphylactic shock.^[30]

Brand names[link]

• Phyllocontin
• Truphylline
• Minomal R 175 mg tab
• Minomal R 350 mg tab
• Minomal SR 600 mg tab

References[link]