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Deferoxamine

January 01, 1970

Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium.[1] It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an underlying genetic condition, and aluminium toxicity in people on dialysis.[1][2] It is used by injection into a muscle, vein, or under the skin.[1]

Deferoxamine
Skeletal formula and spacefill model of deferoxamine
Clinical data
Trade namesDesferal
Other namesdesferrioxamine B, desferoxamine B, DFO-B, DFB ,N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
AHFS/Drugs.comMonograph
Routes of
administration
  • intramuscular
  • intravenous
  • subcutaneous
ATC code
Pharmacokinetic data
Elimination half-life6 hours
Identifiers
  • N'-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide
CAS Number
  • 70-51-9  Y
PubChem CID
  • 2973
DrugBank
  • DB00746
ChemSpider
  • 2867
UNII
  • J06Y7MXW4D
KEGG
  • D03670
ChEBI
  • CHEBI:4356
ChEMBL
  • ChEMBL556
CompTox Dashboard (EPA)
  • DTXSID7022887
ECHA InfoCard100.000.671
Chemical and physical data
FormulaC25H48N6O8
Molar mass560.693 g·mol−1
3D model (JSmol)
  • Interactive image
  • CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN
  • InChI=1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)
     Y
  • Key:UBQYURCVBFRUQT-UHFFFAOYSA-N

Common side effects include pain at the site of injection, diarrhea, vomiting, fever, hearing loss, and eye problems.[1] Severe allergic reactions including anaphylaxis and low blood pressure may occur.[1] It is unclear if use during pregnancy or breastfeeding is safe for the baby.[3] Deferoxamine is a siderophore from the bacteria Streptomyces pilosus.[4][5]

Deferoxamine was approved for medical use in the United States in 1968.[1] It is on the World Health Organization's List of Essential Medicines.[6]

Medical uses edit

Deferoxamine is used to treat acute iron poisoning, especially in small children.[7] This agent is also frequently used to treat hemochromatosis, a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic anemia (e.g. thalassemia and myelodysplastic syndrome) who require many blood transfusions, which can greatly increase the amount of iron in the body. Treatment with iron-chelating drugs such as deferoxamine reduces mortality in persons with sickle cell disease or β‐thalassemia who are transfusion dependent.[8]

Administration for chronic conditions is generally accomplished by subcutaneous injection over a period of 8–12 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "vin rosé urine". Apart from iron toxicity, deferoxamine can be used to treat aluminium toxicity (an excess of aluminium in the body) in selected patients. In US, the drug is not FDA-approved for this use. Deferoxamine is also used to minimize doxorubicin's cardiotoxic side effects and in the treatment of patients with aceruloplasminemia.[9] Deferoxamine may be effective for improving neurologic outcomes in persons with intracranial hemorrhage, although the evidence supporting the efficacy and safety for this indication was weak.[10]

Some published manuscripts suggesting the use of deferoxamine for patients diagnosed with COVID-19 because of the high level of ferritin among them.[11][12]

Adverse effects edit

It is unclear if use during pregnancy is safe for the baby.[3]

Chronic use of deferoxamine may increase the risk of hearing loss in patients with thalassemia major.[13]

Chronic use of deferoxamine may cause ocular symptoms, growth retardation, local reactions and allergy.[14]

Mechanism edit

Deferoxamine is produced by removal of the trivalent iron moiety from ferrioxamine B, an iron-bearing sideramine produced by the actinomycetes, Streptomyces pilosus. Its discovery was a serendipitous result of research conducted by scientists at Ciba in collaboration with scientists at the Swiss Federal Institute of Technology in Zurich and the University Hospital in Freiburg, Germany[15][4] Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron from persons with hemochromatosis, the agent reduces the damage done to various organs and tissues, such as the liver. Also, it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma).[citation needed] Deferoxamine may modulate expression[16] and release of inflammatory mediators by specific cell types.[17]

Research edit

Deferoxamine is being studied as a treatment for spinal cord injury[18] and intracerebral hemorrhage.[19][20] It is also used to induce hypoxia-like environment in mesenchymal stem cells.[21][22]

Since the terminal amine group of Deferoxamine does not participate in metal chelation, it has been used to immobilize Deferoxamine to surfaces and substrates for various industrial and biomedical applications.[23]

See also edit

References edit

  1. ^ a b c d e f "Deferoxamine Mesylate". The American Society of Health-System Pharmacists. from the original on 21 December 2016. Retrieved 8 December 2016.
  2. ^ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 61–62. hdl:10665/44053. ISBN 9789241547659.
  3. ^ a b "Deferoxamine (Desferal) Use During Pregnancy". www.drugs.com. from the original on 21 December 2016. Retrieved 13 December 2016.
  4. ^ a b Giardina PJ, Rivella S (2012). "Thalassemia Syndromes". In Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J (eds.). Hematology: Diagnosis and Treatment (6th ed.). Elsevier Health Sciences. p. 515. ISBN 978-1-4557-4041-3. from the original on 2016-12-20.
  5. ^ Keberle H (October 1964). "The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism". Annals of the New York Academy of Sciences. 119 (2): 758–768. doi:10.1111/j.1749-6632.1965.tb54077.x. PMID 14219455. S2CID 37277528.
  6. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ^ Merlot AM, Kalinowski DS, Richardson DR (March 2013). "Novel chelators for cancer treatment: where are we now?". Antioxidants & Redox Signaling. 18 (8): 973–1006. doi:10.1089/ars.2012.4540. PMID 22424293.
  8. ^ Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM (July 2018). "The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review". American Journal of Hematology. 93 (7): 943–952. doi:10.1002/ajh.25103. PMID 29635754.
  9. ^ Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD (March 1997). "Use of desferrioxamine in the treatment of aceruloplasminemia". Annals of Neurology. 41 (3): 404–407. doi:10.1002/ana.410410318. PMID 9066364. S2CID 22425032.
  10. ^ Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J (2018). "Deferoxamine therapy for intracerebral hemorrhage: A systematic review". PLOS ONE. 13 (3): e0193615. Bibcode:2018PLoSO..1393615Z. doi:10.1371/journal.pone.0193615. PMC 5863956. PMID 29566000.
  11. ^ Abobaker A (November 2020). "Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?". European Journal of Clinical Pharmacology. 76 (11): 1619–1620. doi:10.1007/s00228-020-02942-9. PMC 7325475. PMID 32607779.
  12. ^ Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E (January 2021). "Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients". Alexandria Journal of Medicine. 57 (1): 21–27. doi:10.1080/20905068.2020.1870788. PMC 8108185.
  13. ^ Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, et al. (2017). "Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis". Caspian Journal of Internal Medicine. 8 (4): 239–249. doi:10.22088/cjim.8.4.239. PMC 5686301. PMID 29201313.
  14. ^ Taher AT, Musallam KM, Cappellini MD (February 2021). "β-Thalassemias". The New England Journal of Medicine. 384 (8): 727–743. doi:10.1056/NEJMra2021838. PMID 33626255. S2CID 232049825.
  15. ^ Yawalkar SJ (1993). "Milestones in the research and development of desferrioxamine". Nephrology, Dialysis, Transplantation. 8 (Suppl 1): 40–42. doi:10.1093/ndt/8.supp1.40. PMID 8389019.
  16. ^ Lee HJ, Lee J, Lee SK, Lee SK, Kim EC (September 2007). "Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes". BMC Cancer. 7: 176. doi:10.1186/1471-2407-7-176. PMC 2078595. PMID 17850672.
  17. ^ Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, et al. (June 2004). "Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways". Journal of Immunology. 172 (11): 7069–7077. doi:10.4049/jimmunol.172.11.7069. PMID 15153529.
  18. ^ . Committee for Orphan Medicinal Products. European Medicines Agency. 3 October 2013. Archived from the original on 2013-07-17.
  19. ^ Wu H, Wu T, Xu X, Wang J, Wang J (May 2011). "Iron toxicity in mice with collagenase-induced intracerebral hemorrhage". Journal of Cerebral Blood Flow and Metabolism. 31 (5): 1243–1250. doi:10.1038/jcbfm.2010.209. PMC 3099628. PMID 21102602.
  20. ^ Ren H, Han R, Chen X, Liu X, Wan J, Wang L, et al. (September 2020). "Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update". Journal of Cerebral Blood Flow and Metabolism. 40 (9): 1752–1768. doi:10.1177/0271678X20923551. PMC 7446569. PMID 32423330.
  21. ^ Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, et al. (August 2006). "Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions". Biochemical and Biophysical Research Communications. 347 (1): 12–21. doi:10.1016/j.bbrc.2006.05.169. PMID 16814746.
  22. ^ Woo KJ, Lee TJ, Park JW, Kwon TK (April 2006). "Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway". Biochemical and Biophysical Research Communications. 343 (1): 8–14. doi:10.1016/j.bbrc.2006.02.116. PMID 16527254.
  23. ^ Touma, J. G.; Kelly, C.; Coblyn, M.; Jovanovic, G. N.; Schilke, K. (2023). "Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate". Industrial & Engineering Chemistry Research. 62 (37): 15109–15119. doi:10.1021/acs.iecr.3c00812.

January 01, 1970
deferoxamine, dfoa, also, known, desferrioxamine, sold, under, brand, name, desferal, medication, that, binds, iron, aluminium, specifically, used, iron, overdose, hemochromatosis, either, multiple, blood, transfusions, underlying, genetic, condition, aluminiu. Deferoxamine DFOA also known as desferrioxamine and sold under the brand name Desferal is a medication that binds iron and aluminium 1 It is specifically used in iron overdose hemochromatosis either due to multiple blood transfusions or an underlying genetic condition and aluminium toxicity in people on dialysis 1 2 It is used by injection into a muscle vein or under the skin 1 DeferoxamineSkeletal formula and spacefill model of deferoxamineClinical dataTrade namesDesferalOther namesdesferrioxamine B desferoxamine B DFO B DFB N 5 Acetyl hydroxy amino pentyl N 5 3 5 aminopentyl hydroxy carbamoyl propanoylamino pentyl N hydroxy butane diamideAHFS Drugs comMonographRoutes ofadministrationintramuscularintravenoussubcutaneousATC codeV03AC01 WHO Pharmacokinetic dataElimination half life6 hoursIdentifiersIUPAC name N 5 Acetyl hydroxy amino pentyl N 5 4 5 aminopentyl hydroxy amino 4 oxobutanoyl amino pentyl N hydroxysuccinamideCAS Number70 51 9 YPubChem CID2973DrugBankDB00746ChemSpider2867UNIIJ06Y7MXW4DKEGGD03670ChEBICHEBI 4356ChEMBLChEMBL556CompTox Dashboard EPA DTXSID7022887ECHA InfoCard100 000 671Chemical and physical dataFormulaC 25H 48N 6O 8Molar mass560 693 g mol 13D model JSmol Interactive imageSMILES CC O N O CCCCCNC O CCC O N O CCCCCNC O CCC O N O CCCCCNInChI InChI 1S C25H48N6O8 c1 21 32 29 37 18 9 3 6 16 27 22 33 12 14 25 36 31 39 20 10 4 7 17 28 23 34 11 13 24 35 30 38 19 8 2 5 15 26 h37 39H 2 20 26H2 1H3 H 27 33 H 28 34 YKey UBQYURCVBFRUQT UHFFFAOYSA N Common side effects include pain at the site of injection diarrhea vomiting fever hearing loss and eye problems 1 Severe allergic reactions including anaphylaxis and low blood pressure may occur 1 It is unclear if use during pregnancy or breastfeeding is safe for the baby 3 Deferoxamine is a siderophore from the bacteria Streptomyces pilosus 4 5 Deferoxamine was approved for medical use in the United States in 1968 1 It is on the World Health Organization s List of Essential Medicines 6 Contents 1 Medical uses 2 Adverse effects 3 Mechanism 4 Research 5 See also 6 ReferencesMedical uses editDeferoxamine is used to treat acute iron poisoning especially in small children 7 This agent is also frequently used to treat hemochromatosis a disease of iron accumulation that can be either genetic or acquired Acquired hemochromatosis is common in patients with certain types of chronic anemia e g thalassemia and myelodysplastic syndrome who require many blood transfusions which can greatly increase the amount of iron in the body Treatment with iron chelating drugs such as deferoxamine reduces mortality in persons with sickle cell disease or b thalassemia who are transfusion dependent 8 Administration for chronic conditions is generally accomplished by subcutaneous injection over a period of 8 12 hours each day Administration of deferoxamine after acute intoxication may color the urine a pinkish red a phenomenon termed vin rose urine Apart from iron toxicity deferoxamine can be used to treat aluminium toxicity an excess of aluminium in the body in selected patients In US the drug is not FDA approved for this use Deferoxamine is also used to minimize doxorubicin s cardiotoxic side effects and in the treatment of patients with aceruloplasminemia 9 Deferoxamine may be effective for improving neurologic outcomes in persons with intracranial hemorrhage although the evidence supporting the efficacy and safety for this indication was weak 10 Some published manuscripts suggesting the use of deferoxamine for patients diagnosed with COVID 19 because of the high level of ferritin among them 11 12 Adverse effects editIt is unclear if use during pregnancy is safe for the baby 3 Chronic use of deferoxamine may increase the risk of hearing loss in patients with thalassemia major 13 Chronic use of deferoxamine may cause ocular symptoms growth retardation local reactions and allergy 14 Mechanism editDeferoxamine is produced by removal of the trivalent iron moiety from ferrioxamine B an iron bearing sideramine produced by the actinomycetes Streptomyces pilosus Its discovery was a serendipitous result of research conducted by scientists at Ciba in collaboration with scientists at the Swiss Federal Institute of Technology in Zurich and the University Hospital in Freiburg Germany 15 4 Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine By removing excess iron from persons with hemochromatosis the agent reduces the damage done to various organs and tissues such as the liver Also it speeds healing of nerve damage and minimizes the extent of recent nerve trauma citation needed Deferoxamine may modulate expression 16 and release of inflammatory mediators by specific cell types 17 Research editDeferoxamine is being studied as a treatment for spinal cord injury 18 and intracerebral hemorrhage 19 20 It is also used to induce hypoxia like environment in mesenchymal stem cells 21 22 Since the terminal amine group of Deferoxamine does not participate in metal chelation it has been used to immobilize Deferoxamine to surfaces and substrates for various industrial and biomedical applications 23 See also editChelation therapyReferences edit a b c d e f Deferoxamine Mesylate The American Society of Health System Pharmacists Archived from the original on 21 December 2016 Retrieved 8 December 2016 World Health Organization 2009 Stuart MC Kouimtzi M Hill SR eds WHO Model Formulary 2008 World Health Organization pp 61 62 hdl 10665 44053 ISBN 9789241547659 a b Deferoxamine Desferal Use During Pregnancy www drugs com Archived from the original on 21 December 2016 Retrieved 13 December 2016 a b Giardina PJ Rivella S 2012 Thalassemia Syndromes In Hoffman R Benz Jr EJ Silberstein LE Heslop H Weitz J Anastasi J eds Hematology Diagnosis and Treatment 6th ed Elsevier Health Sciences p 515 ISBN 978 1 4557 4041 3 Archived from the original on 2016 12 20 Keberle H October 1964 The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism Annals of the New York Academy of Sciences 119 2 758 768 doi 10 1111 j 1749 6632 1965 tb54077 x PMID 14219455 S2CID 37277528 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO Merlot AM Kalinowski DS Richardson DR March 2013 Novel chelators for cancer treatment where are we now Antioxidants amp Redox Signaling 18 8 973 1006 doi 10 1089 ars 2012 4540 PMID 22424293 Ballas SK Zeidan AM Duong VH DeVeaux M Heeney MM July 2018 The effect of iron chelation therapy on overall survival in sickle cell disease and b thalassemia A systematic review American Journal of Hematology 93 7 943 952 doi 10 1002 ajh 25103 PMID 29635754 Miyajima H Takahashi Y Kamata T Shimizu H Sakai N Gitlin JD March 1997 Use of desferrioxamine in the treatment of aceruloplasminemia Annals of Neurology 41 3 404 407 doi 10 1002 ana 410410318 PMID 9066364 S2CID 22425032 Zeng L Tan L Li H Zhang Q Li Y Guo J 2018 Deferoxamine therapy for intracerebral hemorrhage A systematic review PLOS ONE 13 3 e0193615 Bibcode 2018PLoSO 1393615Z doi 10 1371 journal pone 0193615 PMC 5863956 PMID 29566000 Abobaker A November 2020 Can iron chelation as an adjunct treatment of COVID 19 improve the clinical outcome European Journal of Clinical Pharmacology 76 11 1619 1620 doi 10 1007 s00228 020 02942 9 PMC 7325475 PMID 32607779 Alkattan A Alabdulkareem K Kamel A Abdelseed H Almutairi Y Alsalameen E January 2021 Correlation between Micronutrient plasma concentration and disease severity in COVID 19 patients Alexandria Journal of Medicine 57 1 21 27 doi 10 1080 20905068 2020 1870788 PMC 8108185 Badfar G Mansouri A Shohani M Karimi H Khalighi Z Rahmati S et al 2017 Hearing loss in Iranian thalassemia major patients treated with deferoxamine A systematic review and meta analysis Caspian Journal of Internal Medicine 8 4 239 249 doi 10 22088 cjim 8 4 239 PMC 5686301 PMID 29201313 Taher AT Musallam KM Cappellini MD February 2021 b Thalassemias The New England Journal of Medicine 384 8 727 743 doi 10 1056 NEJMra2021838 PMID 33626255 S2CID 232049825 Yawalkar SJ 1993 Milestones in the research and development of desferrioxamine Nephrology Dialysis Transplantation 8 Suppl 1 40 42 doi 10 1093 ndt 8 supp1 40 PMID 8389019 Lee HJ Lee J Lee SK Lee SK Kim EC September 2007 Differential regulation of iron chelator induced IL 8 synthesis via MAP kinase and NF kappaB in immortalized and malignant oral keratinocytes BMC Cancer 7 176 doi 10 1186 1471 2407 7 176 PMC 2078595 PMID 17850672 Choi EY Kim EC Oh HM Kim S Lee HJ Cho EY et al June 2004 Iron chelator triggers inflammatory signals in human intestinal epithelial cells involvement of p38 and extracellular signal regulated kinase signaling pathways Journal of Immunology 172 11 7069 7077 doi 10 4049 jimmunol 172 11 7069 PMID 15153529 Public summary of opinion on orphan designation Deferoxamine mesylate for the treatment of traumatic spinal cord injury Committee for Orphan Medicinal Products European Medicines Agency 3 October 2013 Archived from the original on 2013 07 17 Wu H Wu T Xu X Wang J Wang J May 2011 Iron toxicity in mice with collagenase induced intracerebral hemorrhage Journal of Cerebral Blood Flow and Metabolism 31 5 1243 1250 doi 10 1038 jcbfm 2010 209 PMC 3099628 PMID 21102602 Ren H Han R Chen X Liu X Wan J Wang L et al September 2020 Potential therapeutic targets for intracerebral hemorrhage associated inflammation An update Journal of Cerebral Blood Flow and Metabolism 40 9 1752 1768 doi 10 1177 0271678X20923551 PMC 7446569 PMID 32423330 Ren H Cao Y Zhao Q Li J Zhou C Liao L et al August 2006 Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions Biochemical and Biophysical Research Communications 347 1 12 21 doi 10 1016 j bbrc 2006 05 169 PMID 16814746 Woo KJ Lee TJ Park JW Kwon TK April 2006 Desferrioxamine an iron chelator enhances HIF 1alpha accumulation via cyclooxygenase 2 signaling pathway Biochemical and Biophysical Research Communications 343 1 8 14 doi 10 1016 j bbrc 2006 02 116 PMID 16527254 Touma J G Kelly C Coblyn M Jovanovic G N Schilke K 2023 Reversible Covalent Binding of Desferrioxamine B DFOB to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate Industrial amp Engineering Chemistry Research 62 37 15109 15119 doi 10 1021 acs iecr 3c00812 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Deferoxamine amp oldid 1208850384, wikipedia, wiki, book, books, library,

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