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{{Short description|Form of vitamin B12}} |
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{{Citation style|date=November 2009}} |
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{{Use dmy dates|date=March 2024}} |
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{{Drugbox |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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| verifiedrevid = 457640474 |
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| Watchedfields = changed |
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| verifiedrevid = 396493901 |
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| IUPAC_name = Coα--<br>Coβ-hydroxocobamide |
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| image = Hydroxocobalamin.svg |
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| image = Hydroxocobalamin.svg |
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| width = 250 |
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| width = 250 |
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| alt = |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = |
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| tradename = |
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| Drugs.com = {{drugs.com|CDI|hydroxocobalamin}} |
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| Drugs.com = {{drugs.com|monograph|vitamin-b12}} |
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| MedlinePlus = a605007 |
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| MedlinePlus = a605007 |
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| pregnancy_AU = |
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| pregnancy_AU = |
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| pregnancy_category = |
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| pregnancy_US = |
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| routes_of_administration = ], ], ] |
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| pregnancy_category = |
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| ATC_prefix = B03 |
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| ATC_suffix = BA03 |
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| ATC_supplemental = {{ATC|V03|AB33}} |
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| legal_AU = |
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| legal_AU = |
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| legal_NZ= Prescription only (IM ampule) |
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| legal_UK = |
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| legal_UK = |
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| legal_US = |
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| legal_US = OTC |
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| legal_status = Prescription injectable in U.S. Not DEA-controlled |
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| legal_US_comment = (by prescription when injectable), not DEA-controlled |
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| legal_status = |
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| routes_of_administration = Injectable (], ], or ]) |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = Very high (90%) |
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| protein_bound = Very high (90%) |
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| metabolism = Primarily hepatic. Cobalamins are absorbed in the ileum and stored in the liver. |
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| metabolism = Primarily liver, cobalamins are absorbed in the ileum and stored in the liver. |
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| elimination_half-life = ~6 days |
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| elimination_half-life = ~6 days |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 13422-51-0 |
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| CAS_number = 13422-51-0 |
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| ATC_prefix = B03 |
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| ATC_suffix = BA03 |
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| ATC_supplemental = {{ATC|V03|AB33}} |
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| PubChem = 6433575 |
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| PubChem = 6433575 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00200 |
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| DrugBank = DB00200 |
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| ChemSpiderID = 28534326 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChEBI = 27786 |
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| ChemSpiderID = 21160115 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = Q40X8H422O |
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| UNII = Q40X8H422O |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D01027 |
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| KEGG = D01027 |
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| ChEMBL = 1237097 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| synonyms = vitamin B<sub>12</sub>, vitamin B<sub>12a</sub>, hydroxycobalamin |
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| ChEMBL = <!-- blanked - oldvalue: 1200742 --> |
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| C=62 | H=89 | Co=1 | N=13 | O=15 | P=1 |
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<!-- Chemical data --> |
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| molecular_weight = 1346.37 g/mol |
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| IUPAC_name = Coα--<br/>Coβ-hydroxocobamide |
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| C=62 | H=89 | Co=1 | N=13 | O=15 | P=1 |
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| smiles = Cc1cc2ncn(c2cc1C)C9OC(CO)C(OP3(=O)OC(C)CNC(=O)CCC5C4=C(C)C8=NC(=CC7=NC(=C(C)C6=NC(C)(C(N4(O)O3)C5(C)CC(N)=O)C(C)(CC(N)=O)C6CCC(N)=O)C(C)(CC(N)=O)C7CCC(N)=O)C(CCC(N)=O)C8(C)C)C9O |
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| smiles = Cc1cc2ncn(c2cc1C)C9OC(CO)C(OP3(=O)OC(C)CNC(=O)CCC5C4=C(C)C8=NC(=CC7=NC(=C(C)C6=NC(C)(C(N4(O)O3)C5(C)CC(N)=O)C(C)(CC(N)=O)C6CCC(N)=O)C(C)(CC(N)=O)C7CCC(N)=O)C(CCC(N)=O)C8(C)C)C9O |
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| InChI = 1/C62H90N13O14P.Co.H2O/c1-29-20-40-41(21-30(29)2)75(28-70-40)56-52(84)53(42(27-76)87-56)89-90(85,86)88-31(3)26-69-49(83)19-15-36-50-32(4)54-58(6,7)34(12-16-43(63)77)38(71-54)22-39-35(13-17-44(64)78)59(8,23-46(66)80)55(72-39)33(5)51-37(14-18-45(65)79)61(10,25-48(68)82)62(11,74-51)57(73-50)60(36,9)24-47(67)81;;/h20-22,28,31,34-37,42,52-53,56-57,76,84H,12-19,23-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;1H2/q;+3;/p-3/rC62H89CoN13O15P/c1-29-20-40-41(21-30(29)2)75(28-71-40)56-52(85)53(42(27-77)88-56)90-92(87)89-31(3)26-70-49(84)19-15-37-51-33(5)54-58(6,7)34(12-16-43(64)78)38(72-54)22-39-35(13-17-44(65)79)59(8,23-46(67)81)55(73-39)32(4)50-36(14-18-45(66)80)61(10,25-48(69)83)62(11,74-50)57(76(51)63(86)91-92)60(37,9)24-47(68)82/h20-22,28,31,34-37,42,52-53,56-57,77,85-86H,12-19,23-27H2,1-11H3,(H2,64,78)(H2,65,79)(H2,66,80)(H2,67,81)(H2,68,82)(H2,69,83)(H,70,84) |
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| InChIKey = GTSMWDDKWYUXGH-JJXMDWIBAB |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C62H90N13O14P.Co.H2O/c1-29-20-40-41(21-30(29)2)75(28-70-40)56-52(84)53(42(27-76)87-56)89-90(85,86)88-31(3)26-69-49(83)19-15-36-50-32(4)54-58(6,7)34(12-16-43(63)77)38(71-54)22-39-35(13-17-44(64)78)59(8,23-46(66)80)55(72-39)33(5)51-37(14-18-45(65)79)61(10,25-48(68)82)62(11,74-51)57(73-50)60(36,9)24-47(67)81;;/h20-22,28,31,34-37,42,52-53,56-57,76,84H,12-19,23-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;1H2/q;+3;/p-3 |
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| StdInChI = 1S/C62H90N13O14P.Co.H2O/c1-29-20-40-41(21-30(29)2)75(28-70-40)56-52(84)53(42(27-76)87-56)89-90(85,86)88-31(3)26-69-49(83)19-15-36-50-32(4)54-58(6,7)34(12-16-43(63)77)38(71-54)22-39-35(13-17-44(64)78)59(8,23-46(66)80)55(72-39)33(5)51-37(14-18-45(65)79)61(10,25-48(68)82)62(11,74-51)57(73-50)60(36,9)24-47(67)81;;/h20-22,28,31,34-37,42,52-53,56-57,76,84H,12-19,23-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;1H2/q;+3;/p-3 |
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| StdInChIKey = GTSMWDDKWYUXGH-UHFFFAOYSA-K |
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| StdInChIKey = GTSMWDDKWYUXGH-UHFFFAOYSA-K |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Hydroxocobalamin''' (OHCbl, or B<sub>12a</sub>) is a natural form, or ], of ], a basic member of the cobalamin family of compounds. Hydroxocobalamin is the form of vitamin B<sub>12</sub> produced by many bacteria which are used to produce the vitamin commercially. Like other forms of vitamin B<sub>12</sub>, hydroxocobalamin has an intense red color. It is not a form normally found in the human body, but is easily converted in the body to usable coenzyme forms of vitamin B<sub>12</sub>. Pharmaceutically, hydroxycobalamin is usually produced as a sterile injectable solution, and is used for treatment of the vitamin deficiency, and also (because of its afinity for cyanide ion) as a treatment for ].<ref>Dart, Richard C., , ''Clinical Toxicology, 2006, Vol. 44, No. s1, Pages 1-3'', Retrieved (2010-02-14)</ref> Experimentally, it has been tested as a scavenger of ]. |
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'''Hydroxocobalamin''', also known as '''vitamin B<sub>12a</sub>''' and '''hydroxycobalamin''', is a ] found in food and used as a ].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | page=251 }}</ref> As a supplement it is used to treat ] including ].<ref name=WHO2008/><ref name=AHFS2016/> Other uses include treatment for ], ], and ].<ref>{{cite journal | vauthors = MacLennan L, Moiemen N | title = Management of cyanide toxicity in patients with burns | journal = Burns | volume = 41 | issue = 1 | pages = 18–24 | date = February 2015 | pmid = 24994676 | doi = 10.1016/j.burns.2014.06.001 }}</ref><ref name=UK2016>{{cite web|title=Hydroxocobalamin 1mg in 1ml solution for injection - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/31182|website=www.medicines.org.uk|access-date=30 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161230231442/https://www.medicines.org.uk/emc/medicine/31182|archive-date=30 December 2016}}</ref> It is given by ] or ],<ref name=AHFS2016>{{cite web|title=Vitamin B12|url=https://www.drugs.com/monograph/vitamin-b12.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161230232154/https://www.drugs.com/monograph/vitamin-b12.html|archive-date=30 December 2016}}</ref> by pill or sublingually. |
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<!-- Side effects and mechanism --> |
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Vitamin B<sub>12</sub> is a term that refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with folic acid, cobalamins are essential cofactors required for ] synthesis in cells where ] replication and division are occurring—most notably the ] and ] cells. As a ], cobalamins are essential for two cellular reactions: (1) the mitochondrial methylmalonylcoenzyme A mutase conversion of ] (MMA) to succinate, which links lipid and carbohydrate metabolism, and (2) activation of methionine synthase, which is the rate limiting step in the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate. |
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Side effects are generally few.<ref name=AHFS2016/> They may include ], ], hot flushes, itchiness, ], ], and ].<ref name=AHFS2016/> Normal doses are considered safe in ].<ref name=Preg2016>{{cite web|title=Hydroxocobalamin Use During Pregnancy | work = Drugs.com |url= https://www.drugs.com/pregnancy/hydroxocobalamin.html |access-date=30 December 2016|url-status=live|archive-url=https://web.archive.org/web/20170101001316/https://www.drugs.com/pregnancy/hydroxocobalamin.html|archive-date=1 January 2017}}</ref> No overdosage or toxicity has been reported with this drug.<ref name="AHFS2016" /> Hydroxocobalamin is the natural form of ] and a member of the ] family of compounds.<ref>{{cite book| vauthors = Bullock S, Manias E |title=Fundamentals of Pharmacology|date=2013|publisher=Pearson Higher Education AU|isbn=9781442564411|page=862|url=https://books.google.com/books?id=ODjiBAAAQBAJ&pg=PA862|language=en|url-status=live|archive-url=https://web.archive.org/web/20161231074729/https://books.google.ca/books?id=ODjiBAAAQBAJ&pg=PA862|archive-date=31 December 2016}}</ref><ref name=NIH2016>{{cite web|title=Office of Dietary Supplements - Dietary Supplement Fact Sheet: Vitamin B12|url=https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/|website=ods.od.nih.gov|access-date=30 December 2016|date=11 February 2016|url-status=live|archive-url=https://web.archive.org/web/20161231073715/https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/|archive-date=31 December 2016}}</ref> It is found in both raw and cooked beef, together with other cobalamins.<ref>{{cite journal | vauthors = Czerwonka M, Szterk A, Waszkiewicz-Robak B | title = Vitamin B12 content in raw and cooked beef | journal = Meat Science | volume = 96 | issue = 3 | pages = 1371–1375 | date = March 2014 | pmid = 24361556 | doi = 10.1016/j.meatsci.2013.11.022 }}</ref> Hydroxocobalamin, or another form of vitamin B<sub>12</sub>, are required for the body to make ].<ref name=NIH2016/> |
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<!-- History, society and culture --> |
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==Chemical characteristics== |
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Hydroxocobalamin was first isolated in 1949.<ref>{{cite book| vauthors = Eitenmiller RR, Landen WO |title=Vitamin Analysis for the Health and Food Sciences|date=2010|publisher=CRC Press|isbn=9781420050165|page=467|url=https://books.google.com/books?id=gZTsb_CelS8C&pg=PA467|language=en|url-status=live|archive-url=https://web.archive.org/web/20161231074447/https://books.google.ca/books?id=gZTsb_CelS8C&pg=PA467|archive-date=31 December 2016}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Hydroxocobalamin is available as a ].<ref name=AHFS2016/> Commercially it is made using one of a number of types of ].<ref>{{cite book|title=Ullmann's encyclopedia of industrial chemistry.|date=2011|publisher=Wiley-VCH|location=Weinheim|isbn=9783527303854|chapter=Vitamins, 6. B Vitamins}}</ref> |
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Description: OHCbl acetate occurs as an odorless, dark-red ] needles. The injection formulations appear as a clear, dark-red solution. |
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Distribution Coefficient: 1.133 × 10-5 (octanol:acetate buffer pH 7.4) pKa: 7.65 |
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Systematic Name: Cobinamide, Co-hydroxy-, dihydrogen phosphate (ester), inner salt, 3'- ester with (5,6-dimethyl-1-alpha-D-ribofuranosyl-1H-benzimidazole- kappaN3) |
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==Medical uses== |
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==Causes of deficiency== |
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] |
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] |
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Hydroxocobalamin Injection USP, are used to rectify the following causes of vitamin B<sub>12</sub> deficiency (list taken from the drug prescription label published by the ] (FDA): |
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* Pernicious anemia, whether uncomplicated or accompanied by nervous system involvement |
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* Dietary deficiency of vitamin B<sub>12</sub> occurring in strict vegetarians and in their ] infants. (Isolated vitamin B<sub>12</sub> deficiency is very rare.) |
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* Malabsorption of vitamin B<sub>12</sub> resulting from structural or functional damage to the stomach where ] is secreted or to the ileum where intrinsic factor facilitates vitamin B<sub>12</sub> absorption (These conditions include tropical sprue and nontropical sprue . Folate deficiency in these patients is usually more severe than vitamin B<sub>12</sub> deficiency.) |
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* Inadequate secretion of intrinsic factor, resulting from lesions that destroy the ] (ingestion of corrosives, extensive ], and a number of conditions associated with a variable degree of gastric atrophy, such as ], certain ], ], and subtotal ]). (Total gastrectomy always produces vitamin B<sub>12</sub> deficiency.) |
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* Structural lesions leading to vitamin B<sub>12</sub> deficiency include regional ], ileal reactions, malignancies, etc. |
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* Competition for vitamin B<sub>12</sub> by ] or ] |
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* The fish ] (''Diphyllobothrium latum'') absorbs huge quantities of vitamin B<sub>12</sub> and infested patients often have associated gastric atrophy. The ] may produce deficiency of vitamin B<sub>12</sub> or ]. |
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* Inadequate utilization of vitamin B<sub>12</sub> (This may occur if ] for the vitamin are employed in the treatment of ].) |
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==Indications== |
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===Vitamin B<sub>12</sub> deficiency=== |
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===Vitamin B<sub>12</sub> deficiency=== |
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Standard therapy for treatment of vitamin B<sub>12</sub> deficiency has been intramuscular (IM) or intravenous (IV) injections of hydroxocobalamin (OHCbl), since the majority of cases are due to malabsorption by the enteral route (gut).<ref>{{cite journal | vauthors = Thakkar K, Billa G | title = Treatment of vitamin B12 deficiency – Methylcobalamine? Cyancobalamine? Hydroxocobalamin? – clearing the confusion | journal = European Journal of Clinical Nutrition | volume = 69 | issue = 1 | pages = 1–2 | date = January 2015 | pmid = 25117994 | doi = 10.1038/ejcn.2014.165 | doi-access = free }}</ref> It is used ] patients with intrinsic cobalamin ], vitamin B<sub>12</sub>-deficient patients with tobacco amblyopia due to cyanide poisoning, and patients with pernicious anemia who have optic neuropathy.<ref name="Carethers_1988">{{cite journal | vauthors = Carethers M | title = Diagnosing vitamin B12 deficiency, a common geriatric disorder | journal = Geriatrics | volume = 43 | issue = 3 | pages = 89–94, 105–107, 111–112 | date = March 1988 | pmid = 3277892 }}</ref> |
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Vitamin B<sub>12</sub> compounds are used as prescription medicine (injection) for ] replacement therapy, usually at 100 mcg/dose. In the UK 1,000mcg (1 mg) per dose is generally used. Damage that results from vitamin B<sub>12</sub> deficiency can be prevented with early diagnosis and adequate treatment. |
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In a newly diagnosed vitamin B<sub>12</sub>-deficient patient, normally defined as when serum levels are less than 200 pg/ml, daily IM injections of hydroxocobalamin up to 1,000 μg (1 mg) per day are given to replenish the body's depleted cobalamin stores. In the presence of neurological symptoms, following daily treatment, injections up to weekly or biweekly are indicated for six months before initiating monthly IM injections. Once clinical improvement is confirmed, maintenance supplementation of B<sub>12</sub> will generally be needed for life.{{citation needed|date=April 2020}} |
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For most, the standard therapy for treatment of vitamin B<sub>12</sub> deficiency has been intramuscular (IM) injections of vitamin B<sub>12</sub> in the form of ] (CNCbl) or hydroxocobalamin (OHCbl). CNCbl is traditionally prescribed in the ]. Outside of the United States, OHCbl is most generally used for vitamin B<sub>12</sub> replacement therapy and is considered the “drug of choice” for vitamin B<sub>12</sub> deficiency by the Martindale Extra Pharmacopoeia (Sweetman, 2002) and the ] (WHO) Model List of Essential Drugs. This preference for OHCbl in many countries is due to its long retention in the body and the need for less frequent IM injections in restoring vitamin B<sub>12</sub> (cobalamin) serum levels. Furthermore, IM administration of OHCbl is also the preferred treatment for ] patients with intrinsic cobalamin ]; vitamin B<sub>12</sub> deficient patients with tobacco amblyopia due to cyanide poisoning; and patients with pernicious anemia who have optic neuropathy (Carethers, 1988; Chisholm et al., 1967; Freeman, 1992; Markle, 1996). |
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Although less common in this form than cyanocobalamine and methylcobalamine, hydroxocobalamine is also available as pills for oral or ] administration. However, one study on the treatment of children with ] and ] found oral hydroxocobalamine at 1 mg daily to be ineffective in reducing levels of ]. In a trial on adult volunteers, this dose did not lead to a significant increase in serum vitamin B<sub>12</sub> levels when given thrice daily for one week. In addition, once-daily administration of 1 mg oral hydroxocobalamine caused the studied children's levels of homocysteine to increase and their levels of ] to decrease, while the reverse happened when hydroxocobalamine was given intramuscularly.<ref name="e629">{{cite journal | vauthors = Bartholomew DW, Batshaw ML, Allen RH, Roe CR, Rosenblatt D, Valle DL, Francomano CA | title = Therapeutic approaches to cobalamin-C methylmalonic acidemia and homocystinuria | journal = The Journal of Pediatrics | volume = 112 | issue = 1 | pages = 32–39 | date = January 1988 | pmid = 3257264 | doi = 10.1016/s0022-3476(88)80114-8 | publisher = Elsevier BV }}</ref> |
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In a newly-diagnosed vitamin B<sub>12</sub>-deficient patient, normally defined as when serum cobalamin (vitamin B<sub>12</sub>) levels are less than 200 pg/mL, daily IM injections of OHCbl up to 1,000 μg (1 mg) per day are given to replenish the body’s depleted cobalamin stores. In the presence of neurological symptoms, following daily treatment, injections up to weekly or biweekly are indicated for 6 months before initiating monthly IM injections. Once clinical improvement is confirmed, maintenance supplementation of B<sub>12</sub> will generally be needed for life. |
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===Cyanide poisoning=== |
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===Cyanide poisoning=== |
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In 2006 the ] approved hydroxocobalamin for treating smoke inhalation, which can cause cyanide poisoning.<ref>{{cite web |title=Bronx Firefighter Who Collapsed in Burning Home Likely Saved by Smoke Inhalation Drug | date = 20 May 2024 |url=https://www.insurancejournal.com/news/east/2024/05/20/775014.htm |website=Insurance Journal |access-date=20 May 2024}}</ref> Hydroxocobalamin is first line therapy for people with ].<ref name="AHFS2016" /> Hydroxocobalamin converts cyanide to the much less toxic ]. Cyanocobalamin is renally cleared. The use of hydroxocobalamin became first line due to its low adverse risk profile, rapid onset of action, and ease of use in the prehospital setting.<ref name="pmid18397973">{{cite journal | vauthors = Shepherd G, Velez LI | title = Role of hydroxocobalamin in acute cyanide poisoning | journal = The Annals of Pharmacotherapy | volume = 42 | issue = 5 | pages = 661–669 | date = May 2008 | pmid = 18397973 | doi = 10.1345/aph.1K559 | s2cid = 24097516 | url = https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_hydroxycobalamin-acute-cyanide-poisoning_removed.pdf | access-date = 23 July 2021 | archive-date = 7 November 2022 | archive-url = https://web.archive.org/web/20221107064416/https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_hydroxycobalamin-acute-cyanide-poisoning_removed.pdf | url-status = dead }}</ref> |
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Hydroxocobalamin has also been used in the treatment of ].<ref name="pmid17098327">{{cite journal |author=Hall AH, Dart R, Bogdan G |title=Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning? |journal=Ann Emerg Med |volume=49 |issue=6 |pages=806–13 |year=2007 |month=June |pmid=17098327 |doi=10.1016/j.annemergmed.2006.09.021 |url=http://linkinghub.elsevier.com/retrieve/pii/S0196-0644(06)02276-1}}</ref><ref name="pmid18397973">{{cite journal |author=Shepherd G, Velez LI |title=Role of hydroxocobalamin in acute cyanide poisoning |journal=Ann Pharmacother |volume=42 |issue=5 |pages=661–9 |year=2008 |month=May |pmid=18397973 |doi=10.1345/aph.1K559 |url=http://www.theannals.com/cgi/pmidlookup?view=long&pmid=18397973}}</ref><ref name="pmid17543660">{{cite journal |author=Borron SW, Baud FJ, Mégarbane B, Bismuth C |title=Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation |journal=Am J Emerg Med |volume=25 |issue=5 |pages=551–8 |year=2007 |month=June |pmid=17543660 |doi=10.1016/j.ajem.2006.10.010 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-6757(06)00436-0}}</ref> |
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===Injectable hydroxocobalamin=== |
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Hydoxyocobalamin is marketed under the trade name Cyanokit for cyanide toxicity.<ref></ref> The standard dose is 5 gm IV infused over 15 minutes. A second 5 gm dose can be given in patients with severe toxicity. Hydroxocobalamin will bind circulating and cellular cyanide molecules to form ] which is excreted in the urine.<ref name="pmid18397973" /> |
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Injection of hydroxocobalamin is used to rectify the following causes of vitamin B<sub>12</sub> deficiency (list taken from the drug prescription label published by the ]) |
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* Dietary deficiency of vitamin B<sub>12</sub> occurring in strict vegetarians and in their ] infants (isolated vitamin B<sub>12</sub> deficiency is very rare) |
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* Malabsorption of vitamin B<sub>12</sub> resulting from damage to the stomach, where ] is secreted, or damage to the ], where intrinsic factor facilitates vitamin B<sub>12</sub> absorption. These conditions include ] and ] (celiac disease). |
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* Inadequate secretion of intrinsic factor, resulting from lesions that destroy the ] (which can be caused by ingestion of corrosives, extensive ], and conditions associated with gastric atrophy, such as ], certain ], ], and subtotal ]) |
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* Structural lesions leading to vitamin B<sub>12</sub> deficiency, including regional ], ileal reactions, and malignancies |
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* Competition for vitamin B<sub>12</sub> by ] or bacteria. The ] from undercooked fish ('']'') absorbs huge quantities of vitamin B<sub>12</sub>, and infested patients often have associated gastric atrophy. The ] may produce deficiency of vitamin B<sub>12</sub> or ]. |
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* Inadequate use of vitamin B<sub>12</sub>, which may occur if ] for the vitamin are employed in the treatment of ] |
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] is the most common cause of vitamin B<sub>12</sub> deficiency.<ref name="Qudsiya">{{cite book | vauthors = Qudsiya Z, De Jesus O | chapter = Subacute Combined Degeneration of the Spinal Cord | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK559316/ | title = StatPearls |publisher=StatPearls Publishing |date=2022|pmid=32644742 }}</ref> While it technically refers to anemia caused specifically by autoimmune deficiency of intrinsic factor, it is commonly used to refer to B<sub>12</sub>-deficient anemia as a whole, regardless of cause. |
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==Side effects== |
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===Experimental uses as nitric oxide scavenger and antiinflammatory=== |
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The literature data on the acute toxicity profile of hydroxocobalamin show it is generally regarded as safe with local and systemic exposure. The ability of hydroxocobalamin to rapidly scavenge and detoxify cyanide by chelation has resulted in several acute animal and human studies using systemic hydroxocobalamin doses at suprapharmacological doses as high as 140 mg/kg to support its use as an ] (IV) treatment for cyanide exposure.<ref name="Forsyth_1993">{{cite journal | vauthors = Forsyth JC, Mueller PD, Becker CE, Osterloh J, Benowitz NL, Rumack BH, Hall AH | title = Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers | journal = Journal of Toxicology. Clinical Toxicology | volume = 31 | issue = 2 | pages = 277–294 | date = 1993 | pmid = 8492341 | doi = 10.3109/15563659309000395}}</ref><ref name="Riou_1993">{{cite journal | vauthors = Riou B, Berdeaux A, Pussard E, Giudicelli JF | title = Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs | journal = Intensive Care Medicine | volume = 19 | issue = 1 | pages = 26–32 | date = 1993 | pmid = 8440794 | doi = 10.1007/BF01709274| s2cid = 19462753 }}</ref> The US FDA at the end of 2006 approved the use hydroxocobalamin as an injection for the treatment of cyanide poisoning. |
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Hydroxycobalamin is a scavenger of ] as well as cyanide, and has been used experimentally to modifify ] mediated inflammation. For example, a hydoxocobalamin skin creme was found to reduce chronic skin inflammation.<ref> Topical vitamin B12—a new therapeutic approach in atopic dermatitis—evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial.British Journal of Dermatology Volume 150, Issue 5, pages 977–983, May 2004</ref> |
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The drug causes a reddish discoloration of the urine (]), which can look like ].<ref>{{cite journal | vauthors = Koratala A, Chamarthi G, Segal MS | title = Not all that is red is blood: a curious case of chromaturia | journal = Clinical Case Reports | volume = 6 | issue = 6 | pages = 1179–1180 | date = June 2018 | pmid = 29881591 | pmc = 5986001 | doi = 10.1002/ccr3.1514 }}</ref> |
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Hydroxycobalamin has also been used in a pilot-study treatment of migraines, as an inhibitor of nitric oxide induced vasodilation.<ref> An open study of hydroxocobalamin in migraine.</ref> |
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==Toxicity== |
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==Properties== |
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Hydroxocobalamin acetate occurs as odorless, dark-red ] crystals. The injection formulations appear as clear, dark-red solutions. It has a ] of {{gaps|1.133|e=-5}} and a ] of 7.65.{{citation needed|date=October 2023}} |
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The literature data on the acute toxicity profile of OHCbl show that it is generally regarded as safe with local and systemic exposure. The ability of OHCbl to rapidly scavenge and detoxify cyanide by chelation has resulted in several acute animal and human studies using systemic OHCbl doses at suprapharmacological doses as high as 140 mg/kg to support its use as an ] (IV) treatment for cyanide exposure (Forsyth et al., 1993; Riou et al., 1993). The US FDA at the end of 2006 approved the use OHCbl as an injection for the treatment of cyanide poisoning. |
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==Mechanism of action== |
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==Vitamin B<sub>12</sub> group== |
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Vitamin B<sub>12</sub> refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with ], cobalamins are essential cofactors required for ] synthesis in cells where ] replication and division are occurring—most notably the ] and ] cells. As a ], cobalamins are essential for two cellular reactions: |
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Vitamin B<sub>12</sub> is a term that refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with ], cobalamins are essential cofactors required for DNA synthesis in cells where chromosomal replication and division are occurring—most notably the ] and ]. As a cofactor, cobalamins are essential for two cellular reactions: (1) the mitochondrial ] conversion of ] (MMA) to ], which links lipid and carbohydrate metabolism, and (2) activation of ], which is the rate limiting step in the synthesis of methionine from ] and ] (Katzung, 1989). Cobalamins are characterized by a ]-like ] nucleus that contains a single ] atom bound to a ] nucleotide and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: ], ], ], and ]. In the serum, OHCbl and CNCbl are believed to function as storage or transport forms of the molecule; whereas, methylcobalamin and 5¢ deoxyadenosylcobalamin are the active forms of the coenzyme required for cell growth and replication (Katzung, 1989). CNCbl is usually converted to OHCbl in the serum, whereas OHCbl is converted to either methylcobalamin or 5¢ deoxyadenosyl cobalamin. Cobalamins circulate bound to serum proteins called ] (TC) and ]. OHCbl has a higher affinity to the TC II transport protein than CNCbl, or 5- deoxyadenosylcobalamin. From a ] point of view, two essential enzymatic reactions require vitamin B<sub>12</sub> (cobalamin) (Katzung, 1989, Hardman, 2001). ] vitamin B<sub>12</sub> is maintained in two active coenzymes, methylcobalamin and 5¢ deoxyadenosylcobalamin, which are both involved in specific enzymatic reactions. In the face of vitamin B<sub>12</sub> deficiency, conversion of methylmalonyl-CoA to ] cannot take place, which results in accumulation of methylmalonyl CoA and aberrant fatty acid synthesis. In the other enzymatic reaction, methylcobalamin supports the methionine synthase reaction, which is essential for normal metabolism of folate. The folate-cobalamin interaction is pivotal for normal synthesis of ] and ] and the transfer of the methyl group to cobalamin is essential for the adequate supply of ], the substrate for metabolic steps that require folate. In a state of vitamin B<sub>12</sub> deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of ]. The resulting elevated concentrations of ] and MMA are often found in patients with low serum vitamin B<sub>12</sub> and can usually be lowered with successful vitamin B<sub>12</sub> replacement therapy. However, elevated MMA and homocysteine concentrations may persist in patients with cobalamin concentrations between 200 to 350 pg/mL (Lindenbaum et al. 1994). Supplementation with vitamin B<sub>12</sub> during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and deoxyadenosylcobalamin. |
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*the mitochondrial ] conversion of ] (MMA) to ], which links lipid and carbohydrate metabolism, and |
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*the activation of ], which is the rate-limiting step in the synthesis of ] from ] and ].<ref name="Katzung_1989">{{cite book | vauthors = Katzung BG |title=Clinical Pharmacology |date=1989 |publisher=Appleton & Lange |location=Connecticut |isbn=978-0-8385-1301-9}}</ref> |
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Cobalamins are characterized by a ]-like ] nucleus that contains a single ] atom bound to a ] ] and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: ] (CNCbl), ] (MeCbl), ] (AdCbl, also known as cobamamide or 5-deoxyadenosylcobalamin), and hydroxocobalamin (OHCbl). In the serum, hydroxocobalamin and cyanocobalamin are believed to function as storage or transport forms of the molecule, whereas methylcobalamin and adenosylcobalamin are the active forms of the coenzyme required for cell growth and replication.<ref name="Katzung_1989" /> Cyanocobalamin is usually converted to hydroxocobalamin in the serum, whereas hydroxocobalamin is converted to either methylcobalamin or adenosylcobalamin. Cobalamins circulate bound to serum proteins called ] (TC) and ]s. Hydroxocobalamin has a higher affinity to the TC II transport protein than cyanocobalamin, or adenosylcobalamin. From a ] point of view, two essential enzymatic reactions require vitamin B<sub>12</sub> (cobalamin).<ref name="Katzung_1989"/><ref>{{cite book | vauthors = Hardman JG, Limbird LE, Gilman AG |title=Goodman & Gilman's The pharmacological basis of therapeutics |date=2001 |publisher=McGraw-Hill Medical Publications |location=New York, NY |isbn=978-0-07-135469-1 |edition=10th}}</ref> |
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== See also == |
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*] |
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*] |
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] vitamin B<sub>12</sub> is maintained in two active coenzymes, methylcobalamin and adenosylcobalamin. In the face of vitamin B<sub>12</sub> deficiency, conversion of methylmalonyl-CoA to ] cannot take place, which results in accumulation of methylmalonyl-CoA and aberrant fatty acid synthesis. In the other enzymatic reaction, methylcobalamin supports the methionine synthase reaction, which is essential for normal metabolism of folate. The folate-cobalamin interaction is pivotal for normal synthesis of ] and ] and the transfer of the methyl group to cobalamin is essential for the adequate supply of ], the substrate for metabolic steps that require folate. In a state of vitamin B<sub>12</sub> deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of ]. The resulting elevated concentrations of ] and ] are often found in patients with low serum vitamin B<sub>12</sub> and can usually be lowered with successful vitamin B<sub>12</sub> replacement therapy. However, elevated ] and ] concentrations may persist in patients with cobalamin concentrations between 200 and 350 pg/mL.<ref name="pmid8154512">{{cite journal | vauthors = Savage DG, Lindenbaum J, Stabler SP, Allen RH | title = Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies | journal = The American Journal of Medicine | volume = 96 | issue = 3 | pages = 239–46 | date = March 1994 | pmid = 8154512 | doi = 10.1016/0002-9343(94)90149-x }}</ref> Supplementation with vitamin B<sub>12</sub> during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and adenosylcobalamin. |
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==References== |
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{{Refimprove|date=January 2007}} |
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{{reflist}} |
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==External links== |
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== References == |
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{{reflist}} |
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* in the ] database |
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