دفروكسامين

دفروكسامين
Deferoxamine-2D-skeletal.png
Deferoxamine-3D-vdW.png
Skeletal formula and spacefill model of deferoxamine
البيانات السريرية
الأسماء التجاريةDesferal
أسماء أخرىdesferrioxamine 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
مسارات
الدواء
  • intramuscular
  • intravenous
  • subcutaneous
رمز ATC
بيانات الحركية الدوائية
Elimination half-life6 hours
المعرفات
رقم CAS
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.671 Edit this at Wikidata
Chemical and physical data
التركيبC25H48N6O8
الكتلة المولية560٫69 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]

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الاستخدامات الطبية

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 a patients with aceruloplasminemia.[9] Deferoxamine maybe 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]


الآثار الجانبية

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]

الآلية

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).[بحاجة لمصدر] Deferoxamine may modulate expression[16] and release of inflammatory mediators by specific cell types.[17]

الأبحاث

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]

انظر أيضاً

المراجع

  1. ^ أ ب ت ث ج ح "Deferoxamine Mesylate". The American Society of Health-System Pharmacists. Archived 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. ^ أ ب "Deferoxamine (Desferal) Use During Pregnancy". www.drugs.com. Archived from the original on 21 December 2016. Retrieved 13 December 2016.
  4. ^ أ ب 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 (in الإنجليزية) (6th ed.). Elsevier Health Sciences. p. 515. ISBN 978-1-4557-4041-3. Archived 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. ^ "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.
  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.
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