Chemistry:Deferoxamine

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Short description: Medication that binds iron and aluminium
Deferoxamine
Deferoxamine-2D-skeletal.png
Deferoxamine-3D-vdW.png
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
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
  • intramuscular
  • intravenous
  • subcutaneous
ATC code
Pharmacokinetic data
Elimination half-life6 hours
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC25H48N6O8
Molar mass560.693 g·mol−1
3D model (JSmol)

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]

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

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

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

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

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]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Deferoxamine Mesylate". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/deferoxamine-mesylate.html. 
  2. ↑ WHO Model Formulary 2008. World Health Organization. 2009. pp. 61–62. ISBN 9789241547659. 
  3. ↑ 3.0 3.1 "Deferoxamine (Desferal) Use During Pregnancy". https://www.drugs.com/pregnancy/deferoxamine.html. 
  4. ↑ 4.0 4.1 "Thalassemia Syndromes" (in en). Hematology: Diagnosis and Treatment (6th ed.). Elsevier Health Sciences. 2012. p. 515. ISBN 978-1-4557-4041-3. https://books.google.com/books?id=M5fD7gZSDYMC&pg=PA515. 
  5. ↑ "The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism". Annals of the New York Academy of Sciences 119 (2): 758–768. October 1964. doi:10.1111/j.1749-6632.1965.tb54077.x. PMID 14219455. 
  6. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  7. ↑ "Novel chelators for cancer treatment: where are we now?". Antioxidants & Redox Signaling 18 (8): 973–1006. March 2013. doi:10.1089/ars.2012.4540. PMID 22424293. 
  8. ↑ "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. July 2018. doi:10.1002/ajh.25103. PMID 29635754. 
  9. ↑ "Use of desferrioxamine in the treatment of aceruloplasminemia". Annals of Neurology 41 (3): 404–407. March 1997. doi:10.1002/ana.410410318. PMID 9066364. 
  10. ↑ "Deferoxamine therapy for intracerebral hemorrhage: A systematic review". PLOS ONE 13 (3): e0193615. 2018. doi:10.1371/journal.pone.0193615. PMID 29566000. Bibcode: 2018PLoSO..1393615Z. 
  11. ↑ "Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?". European Journal of Clinical Pharmacology 76 (11): 1619–1620. November 2020. doi:10.1007/s00228-020-02942-9. PMID 32607779. 
  12. ↑ "Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients.". Alexandria Journal of Medicine 57 (1): 21–27. January 2021. doi:10.1080/20905068.2020.1870788. 
  13. ↑ "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. 2017. doi:10.22088/cjim.8.4.239. PMID 29201313. 
  14. ↑ "β-Thalassemias". The New England Journal of Medicine 384 (8): 727–743. February 2021. doi:10.1056/NEJMra2021838. PMID 33626255. 
  15. ↑ "Milestones in the research and development of desferrioxamine". Nephrology, Dialysis, Transplantation 8 (Suppl 1): 40–42. 1993. doi:10.1093/ndt/8.supp1.40. PMID 8389019. 
  16. ↑ "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. September 2007. doi:10.1186/1471-2407-7-176. PMID 17850672. 
  17. ↑ "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. June 2004. doi:10.4049/jimmunol.172.11.7069. PMID 15153529. 
  18. ↑ "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. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b. 
  19. ↑ "Iron toxicity in mice with collagenase-induced intracerebral hemorrhage". Journal of Cerebral Blood Flow and Metabolism 31 (5): 1243–1250. May 2011. doi:10.1038/jcbfm.2010.209. PMID 21102602. 
  20. ↑ "Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update". Journal of Cerebral Blood Flow and Metabolism 40 (9): 1752–1768. September 2020. doi:10.1177/0271678X20923551. PMID 32423330. 
  21. ↑ "Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions". Biochemical and Biophysical Research Communications 347 (1): 12–21. August 2006. doi:10.1016/j.bbrc.2006.05.169. PMID 16814746. 
  22. ↑ "Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway". Biochemical and Biophysical Research Communications 343 (1): 8–14. April 2006. doi:10.1016/j.bbrc.2006.02.116. PMID 16527254. 



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