Deferoxamine

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Deferoxamine
Deferoxamine-2D-skeletal.png
Deferoxamine-3D-vdW.png
Skeletal formula and spacefill model of deferoxamine
Clinical data
Trade names Desferal
AHFS/Drugs.com Monograph
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
  • intramuscular
  • intravenous
  • subcutaneous
ATC code V03AC01 (WHO)
Pharmacokinetic data
Biological half-life 6 hours
Identifiers
Synonyms desferrioxamine 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
CAS Number 70-51-9  YesY
PubChem (CID) 2973
DrugBank DB00746
ChemSpider 2867
UNII J06Y7MXW4D
KEGG D03670
ChEBI CHEBI:4356
ChEMBL CHEMBL556
ECHA InfoCard 100.000.671
Chemical and physical data
Formula C25H48N6O8
Molar mass 560.69 g·mol−1
3D model (Jmol) Interactive image

Deferoxamine (DFOA), 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 it of injection, diarrhea, vomiting, fever, hearing loss, and eye problems. 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]

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, the most effective and safe medicines needed in a health system.[5] The wholesale cost in the developing world is about 6.76 to 13.52 USD per dose.[6] In the United States a course of treatment costs more than 200 USD.[7]

Medical uses[edit]

Deferoxamine is used to treat acute iron poisoning, especially in small children. 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. 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 select 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 patient with aceruloplasminemia.[8]

Mechanism[edit]

Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron, 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[9] and release of inflammatory mediators by specific cell types.[10]

Research[edit]

Deferoxamine is being studied as a treatment for spinal cord injury[11] and intracerebral hemorrhage.[12] It is also used to induce hypoxia-like environment in mesenchymal stem cells.[13][14]

See also[edit]

References[edit]

  1. ^ a b c d e "Deferoxamine Mesylate". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 61-62. ISBN 978-92-4-154765-9. Retrieved 8 December 2016. 
  3. ^ "Deferoxamine (Desferal) Use During Pregnancy". www.drugs.com. Retrieved 13 December 2016. 
  4. ^ Hoffman, Ronald; Jr, Edward J. Benz; Silberstein, Leslie E.; Heslop, Helen; Weitz, Jeffrey; Anastasi, John (2012). Hematology: Diagnosis and Treatment (6 ed.). Elsevier Health Sciences. p. 515. ISBN 1-4557-4041-1. 
  5. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  6. ^ "Deferoxamine". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  7. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 470. ISBN 978-1-284-05756-0. 
  8. ^ Miyajima, Hiroaki; Takahashi, Yoshitomo; Kamata, Tadashi; Shimizu, Hideaki; Sakai, Naoki; Gitlin, Jonathan D. (1997). "Use of desferrioxamine in the treatment of aceruloplasminemia". Annals of Neurology. 41 (3): 404–7. doi:10.1002/ana.410410318. PMID 9066364. 
  9. ^ Lee, Hwa-Jeong; Lee, Jun; Lee, Sun-Kyung; Lee, Suk-Keun; Kim, Eun-Cheol (2007). "Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes". BMC Cancer. 7: 176. doi:10.1186/1471-2407-7-176. PMC 2078595Freely accessible. PMID 17850672. 
  10. ^ Choi, E. Y.; Kim, E. C.; Oh, H. M.; Kim, S; Lee, H. J.; Cho, E. Y.; Yoon, K. H.; Kim, E. A.; Han, W. C.; Choi, S. C.; Hwang, J. Y.; Park, C; Oh, B. S.; Kim, Y; Kimm, K. C.; Park, K. I.; Chung, H. T.; Jun, C. D. (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): 7069–77. PMID 15153529. 
  11. ^ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b[full citation needed]
  12. ^ Wu, He; Wu, Tao; Xu, Xueying; Wang, Jessica; Wang, Jian (2010). "Iron toxicity in mice with collagenase-induced intracerebral hemorrhage". Journal of Cerebral Blood Flow & Metabolism. 31 (5): 1243–50. doi:10.1038/jcbfm.2010.209. PMC 3099628Freely accessible. PMID 21102602. 
  13. ^ Ren, Hongying; Cao, Ying; Zhao, Qinjun; Li, Jing; Zhou, Cixiang; Liao, Lianming; Jia, Mingyue; Zhao, Qian; Cai, Huiguo; Han, Zhong Chao; Yang, Renchi; Chen, Guoqiang; Zhao, Robert Chunhua (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. 
  14. ^ Woo, Kyung Jin; Lee, Tae-Jin; Park, Jong-Wook; Kwon, Taeg Kyu (2006). "Desferrioxamine, an iron chelator, enhances HIF-1α 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.