Pentoxifylline

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Pentoxifylline
Pentoxifylline2DACS.svg
Pentoxifylline3Dan2.gif
Systematic (IUPAC) name
3,7-Dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione
Clinical data
Trade names Trental
AHFS/Drugs.com monograph
MedlinePlus a685027
Licence data US FDA:link
Pregnancy cat. B1 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 10-30%[1]
Metabolism Hepatic and via erythrocytes
Half-life 0.4-0.8 hours (1-1.6 hours for active metabolite)[1]
Excretion Urine (95%), faeces (<4%)[1]
Identifiers
CAS number 6493-05-6 YesY
ATC code C04AD03
PubChem CID 4740
DrugBank DB00806
ChemSpider 4578 YesY
UNII SD6QCT3TSU YesY
KEGG D00501 YesY
ChEMBL CHEMBL628 YesY
Chemical data
Formula C13H18N4O3 
Mol. mass 278.31 g/mol
 YesY (what is this?)  (verify)

Pentoxifylline (INN, BAN, USAN) or oxpentifylline (AAN)[2][3] is a drug commonly sold by Sanofi under the brand name Trental. Its chemical name is 1-(5-oxohexyl)-3, 7-dimethylxanthine. Pentoxifylline is a xanthine derivative. Other brand names include Pentox, Pentoxil and Flexital.

Medical uses[edit]

Its primary use in medicine is in treating the symptoms of intermittent claudication resulting from peripheral artery disease.[4] This is its only FDA, MHRA and TGA-labelled indication.[3][5][6]

Other indications for which the literature supports its use in include:

  • Pentoxyphylline is also used to prevent renal toxicity in cases of alcoholic hepatitis. [17]

Adverse effects[edit]

Adverse effects by frequency:[1][2][3][5][6]
Common (1-10% frequency):

  • Dizziness
  • Headache
  • Nausea
  • Vomiting
  • Indigestion
  • Flushing

Uncommon (0.1-1% frequency):

  • Angina
  • Palpitations

Rare (<0.1% frequency):

Contraindications[edit]

Contraindications include:[1]

  • Intolerance to pentoxifylline or other xanthine derivatives
  • Recent retinal or cerebral haemorrhage
  • Risk factors for haemorrhage

Interactions[edit]

Co-administration of pentoxifylline and sodium thiopental may cause death by acute pulmonary edema in rats.[18]

This drug is passed into the breast milk. Animal studies have shown no evidence of teratogenicity at high doses.

Mechanism[edit]

Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor[19] which raises intracellular cAMP, activates PKA, inhibits TNF[20][21] and leukotriene [22] synthesis, and reduces inflammation and innate immunity.[22] In addition, pentoxifylline improves red blood cell deformability (known as a haemorrheologic effect), reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation.[23] Pentoxifylline is also an antagonist at adenosine 2 receptors.[24]

See also[edit]

References[edit]

  1. ^ a b c d e "Trental, Pentoxil (pentoxifylline) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 3 February 2014. 
  2. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  3. ^ a b c "PRODUCT INFORMATION TRENTAL® 400" (PDF). TGA eBusiness Services. sanofi-aventis australia pty limited. 25 March 2010. Retrieved 3 February 2014. 
  4. ^ Salhiyyah, Kareem; Senanayake, Eshan; Abdel-Hadi, Mohammed; Booth, Andrew; Michaels, Jonathan A (Jan 18, 2012). "Pentoxifylline for intermittent claudication". In Salhiyyah, Kareem. Cochrane Database Syst Rev 1 (1): CD005262. doi:10.1002/14651858.CD005262.pub2. PMID 22258961. 
  5. ^ a b "PENTOXIFYLLINE tablet, extended release [Apotex Corp.]". DailyMed. Apotex Corp. February 2013. Retrieved 3 February 2014. 
  6. ^ a b "Trental 400 - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sanofi. 10 October 2013. Retrieved 3 February 2014. 
  7. ^ "European Pentoxifylline Multi-Infarct Dementia Study". European neurology 36 (5): 315–21. 1996. doi:10.1159/000117279. PMID 8864715. 
  8. ^ Brant, WO; Dean, RC; Lue, TF (February 2006). "Treatment of Peyronie's disease with oral pentoxifylline". Nature Clinical Practice Urology 3 (2): 111–115. doi:10.1038/ncpuro0409. PMID 16470210. 
  9. ^ Beegle, SH; Barba, K; Gobunsuy, R; Judson, MA (2013). "Current and emerging pharmacological treatments for sarcoidosis: a review." (PDF). Drug Design, Development and Therapy 7: 325–38. doi:10.2147/DDDT.S31064. PMC 3627473. PMID 23596348. 
  10. ^ Laczy, B; Cseh, J; Mohás, M; Markó, L; Tamaskó, M; Koszegi, T; Molnár, GA; Wagner, Z; Wagner, L; Wittmann, I (Jun 2009). "Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.". Acta diabetologica 46 (2): 105–11. doi:10.1007/s00592-008-0064-5. PMID 18839054. 
  11. ^ Sherer, JT; Glover, PH (Sep 2000). "Pentoxifylline for sickle-cell disease.". The Annals of pharmacotherapy 34 (9): 1070–4. doi:10.1345/aph.19397. PMID 10981255. 
  12. ^ Akriviadis, E; Botla, R; Briggs, W; Han, S; Reynolds, T; Shakil, O (December 2000). "Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial". Gastroenterology 119 (6): 1637–1648. doi:10.1053/gast.2000.20189. PMID 11113085. 
  13. ^ Li, W; Zheng, L; Sheng, C; Cheng, X; Qing, L; Qu, S (April 2011). "Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease.". Lipids in health and disease 10: 49. doi:10.1186/1476-511X-10-49. PMC 3088890. PMID 21477300. 
  14. ^ Alborzi, S; Ghotbi, S; Parsanezhad, ME; Dehbashi, S; Alborzi, S; Alborzi, M (Jan–Feb 2007). "Pentoxifylline therapy after laparoscopic surgery for different stages of endometriosis: a prospective, double-blind, randomized, placebo-controlled study.". Journal of minimally invasive gynecology 14 (1): 54–8. doi:10.1016/j.jmig.2006.06.024. PMID 17218230. 
  15. ^ Okunieff, P; Augustine, E; Hicks, JE; Cornelison, TL; Altemus, RM; Naydich, BG; Ding, I; Huser, AK; Abraham, EH; Smith, JJ; Coleman, N; Gerber, LH (Jun 1, 2004). "Pentoxifylline in the treatment of radiation-induced fibrosis.". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22 (11): 2207–13. doi:10.1200/JCO.2004.09.101. PMID 15169810. 
  16. ^ Delanian, S; Porcher, R; Rudant, J; Lefaix, JL (2005). "Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis,". J Clin Oncol 23 (34): 8570–8579. doi:10.1200/JCO.2005.02.4729. PMID 16260695. 
  17. ^ [1]
  18. ^ Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-De-La-Asunción, J; Viña, J; Sastre, J (2006). "Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats". British Journal of Pharmacology 149 (4): 450–5. doi:10.1038/sj.bjp.0706871. PMC 1978439. PMID 16953192. 
  19. ^ Essayan DM. (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. 108 (5): 671–80. doi:10.1067/mai.2001.119555. PMID 11692087. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ Ward, A; Clissold, SP (1987). "Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy". Drugs 34 (1): 50–97. doi:10.2165/00003495-198734010-00003. PMID 3308412. 
  24. ^ Rodríguez-Morán M, Guerrero-Romero F (February 2008). "Efficacy of pentoxifylline in the management of microalbuminuria in patients with diabetes". Curr Diabetes Rev 4 (1): 55–62. doi:10.2174/157339908783502343. PMID 18220696. 

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