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Aminophylline

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Aminophylline
Clinical data
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa601015
Pregnancy
category
  • AU: A
Routes of
administration		oral, i.v.
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding60%
Elimination half-life7-9 hours
Identifiers
  • 1,3-dimethyl-7H-purine-2,6-dione; ethane-1,2-diamine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.696 Edit this at Wikidata
Chemical and physical data
FormulaC16H24N10O4
Molar mass420.427 g/mol g·mol−1
3D model (JSmol)
  • O=C2N(c1ncnc1C(=O)N2C)C.O=C2N(c1ncnc1C(=O)N2C)C.NCCN
  • 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 checkY
  • Key:FQPFAHBPWDRTLU-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Aminophylline 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 less potent and shorter-acting than theophylline. Its most common use is in the treatment of airway obstruction from asthma or COPD. It is used off-label as a reversal agent during nuclear stress testing. Aminophylline is a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor.[2]

Medical uses

Aminophylline is used to reverse regadenoson, 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.[3] Aminophylline is also a treatment option for anaphylactic shock.[4]

While it has been suggested for use in cardiac arrest evidence does not support a benefit.[5][6]

Side effects

Aminophylline can lead to theophylline toxicity. Aminophylline has been found to decrease the sedative effects of propofol[7] and decrease topiramate antiseizure action.[8]

Properties

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. 1 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

Like other methylated xanthine derivatives, aminophylline is both a

  1. competitive nonselective phosphodiesterase inhibitor[9] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha[10][11] and leukotriene[12] synthesis, and reduces inflammation and innate immunity[12] and
  2. nonselective adenosine receptor antagonist.[13]

Aminophylline causes bronchodilation, diuresis*, central nervous system and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenosine monophosphate (cAMP) which in turn promotes catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis, and induces release of epinephrine from adrenal medulla cells.

  • Note that diuresis is caused by an increase in cAMP which acts in the CNS to inhibit the release of Anti-diuretic hormone (Arginine-Vasopressin).

Adenosine is an endogenous extracellular messenger that can regulate myocardial oxygen needs.[2][14] 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.[2][14] Adenosine also antagonizes chronotropic and ionotropic effects of circulating catecholamines.[15] 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.[2] Adenosine’s effects are concentration-dependent. Adenosine’s receptors are competitively antagonized by methylxanthines such as aminophylline.[2][14][15] Aminophylline competitively antagonizes the cardiac actions of adenosine at the cell surface receptors.[14] Thus, it increases heart rate and contractility.

Brand names

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

References

  1. ^ "Aminophylline Professional Monograph".
  2. ^ a b c d e Mader, TJ; Smithline HA; Durkin L; Scriver G (March 2003). "A randomized control trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest". Academic Emergency Medicine. 10 (3): 192–197. doi:10.1197/aemj.10.3.192. PMID 12615581. Retrieved Feb 10, 2012.
  3. ^ Caruso MK, Pekarovic S, Raum WJ, Greenway F (May 2007). "Topical fat reduction from the waist". Diabetes, obesity & metabolism. 9 (3): 300–3. doi:10.1111/j.1463-1326.2006.00600.x. PMID 17391155.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Blackbourne LH. Surgical Recall. Lippincott Williams and Wilkins, 2009. pp169
  5. ^ "Aminophylline in bradyasystolic cardiac arrest", Emerg Med J., 24 (8): 582–3, 2007, doi:10.1136/emj.2007.051342, PMC 2660094, PMID 17652689
  6. ^ Hurley, KF; Magee, K; Green, R (23 November 2015). "Aminophylline for bradyasystolic cardiac arrest in adults". The Cochrane database of systematic reviews. 11: CD006781. PMID 26593309.
  7. ^ Turan, A; Kasuya Y; Govinda R; Obal D; Rauch S; Dalton J; et al. (February 2010). content/110/2/449 "The effect of aminophylline on loss of consciousness, bispectral index, propofol requirement, and minimum alveolar concentration of desflurane in volunteers". Anesthesia and Analgesia. 110 (2): 449–454. doi:10.1213/ane.0b013e3181c6be7e. Retrieved Feb 17, 2012. {{cite journal}}: Check |url= value (help)
  8. ^ Luszczki, JJ; Jankiewicz K; Jankiewicz M; Czuczwar SJ (May 2007). portal.info.sub zero.lib.uoguelph.ca/detailssfx.xqy?uri=/0014299 9/v562i12/53_papio atmmesm.xml "Pharmacokinetic and pharmacodynamic interactions of aminophylline and topiramate in the mouse maximal electroshock-induced seizure model". European Journal of Pharmacology. 562 (1–2): 53–59. doi:10.1016/j.ejphar.2007.01.038. Retrieved Feb 17, 2012. {{cite journal}}: Check |url= value (help)
  9. ^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087.
  10. ^ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R. (2008). "Insights into the Regulation of TNF-α Production in Human Mononuclear Cells: The Effects of Non-Specific Phosphodiesterase Inhibition". Clinics (Sao Paulo). 63 (3): 321–8. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". Am. J. Respir. Crit. Care Med. 159 (2): 508–11. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ a b Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. (2005). "Leukotrienes: underappreciated mediators of innate immune responses". J Immunol. 174 (2): 589–94. doi:10.4049/jimmunol.174.2.589. PMID 15634873.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Daly JW, Jacobson KA, Ukena D. (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol Res. 230 (1): 41–632. PMID 3588607.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ a b c d Mader, TJ; Gibson, P (7 January 1997). cws_home/505959/description#description "Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study". Elsevier Resuscitation. 35: 3–7. doi:10.1016/s0300-9572(97)01097-6. Retrieved Feb 10, 2012. {{cite journal}}: Check |url= value (help)
  15. ^ a b Perouansky, M; Shamir M; Hershkowitz E; Donchin Y (12 June 1998). portal.info.subzero.lib.uoguelph.ca/tmp/5676621964383762041.pdf "Successful resuscitation using aminophylline in refrectory cardiac arrest with asystole" (PDF). Elsevier Resuscitation. 38: 39–41. doi:10.1016/s0300-9572(98)00079-3. Retrieved Feb 16, 2012. {{cite journal}}: Check |url= value (help)
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