Hydroxocobalamin: Difference between revisions

{{Short description|Form of vitamin B12}}

{{Drugbox

| alt =  

<!-- Clinical data -->

| tradename =   

| ATC_supplemental = {{ATC|V03|AB33}}

| legal_AU =   

| legal_UK =   

| legal_status =  

<!-- Pharmacokinetic data -->

| bioavailability =   

| excretion =

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| synonyms = vitamin B₁₂, vitamin B_12a, hydroxycobalamin

<!-- Chemical data -->

| IUPAC_name = Coα-[α-(5,6-dimethylbenzimidazolyl)]-<br/>Coβ-hydroxocobamide

'''Hydroxocobalamin''', also known as '''vitamin B_12a''' and '''hydroxycobalamin''', is a [[vitamin]] found in food and used as a [[dietary supplement]]. As a supplement it is used to treat [[vitamin B12 deficiency]] including [[pernicious anemia]]. Other uses include treatment for [[cyanide poisoning]], [[Leber's optic atrophy]], and [[toxic amblyopia]]. It is given by [[intramuscular|injection into a muscle]] or [[intravenous|vein]].

<!-- Side effects and mechanism -->

<!-- History, society and culture -->

Hydroxocobalamin was first isolated in 1949. It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]]. Hydroxocobalamin is available as a [[generic medication]].

[[File:HydroxycobalaminSolid.JPG|thumb|left|Hydroxocobalamin at standard conditions is a solid composed of dark red crystals.]]

[[File:Hydroxocobalamin Injection.jpg|thumb|upright|Hydroxocobalamin injection USP (1000 μg/mL) is a clear red liquid solution. Shown is 500 μg B-12 prepared for subcutaneous injection.]]

Standard therapy for treatment of vitamin B₁₂ 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). It is used [[pediatric]] patients with intrinsic cobalamin [[metabolic diseases]], vitamin B₁₂-deficient patients with tobacco amblyopia due to cyanide poisoning, and patients with pernicious anemia who have optic neuropathy.

In a newly diagnosed vitamin B₁₂-deficient patient, normally defined as when serum levels are less than 200&nbsp;pg/ml, daily IM injections of hydroxocobalamin up to 1,000&nbsp;μg (1&nbsp;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 B₁₂ will generally be needed for life.

Hydroxocobalamin is first line therapy for people with [[cyanide poisoning]]. Hydroxocobalamin converts cyanide to the much less toxic [[cyanocobalamin]]. 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.

Injection of hydroxocobalamin is used to rectify the following causes of vitamin B₁₂ deficiency (list taken from the drug prescription label published by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]])

* Dietary deficiency of vitamin B₁₂ occurring in strict vegetarians and in their [[breastfed]] infants (isolated vitamin B₁₂ deficiency is very rare)

[[Pernicious anemia]] is the most common cause of vitamin B₁₂ deficiency. While it technically refers to anemia caused specifically by autoimmune deficiency of intrinsic factor, it is commonly used to refer to B₁₂-deficient anemia as a whole, regardless of cause.

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&nbsp;mg/kg to support its use as an [[intravenous]] (IV) treatment for cyanide exposure. The US FDA at the end of 2006 approved the use hydroxocobalamin as an injection for the treatment of cyanide poisoning.

The drug causes a reddish discoloration of the urine ([[chromaturia]]), which can look like [[hematuria|blood in the urine]].

Hydroxocobalamin acetate occurs as odorless, dark-red [[orthorhombic]] crystals. The injection formulations appear as clear, dark-red solutions. It has a [[distribution coefficient]] of {{gaps|1.133|e=-5}} and a [[pKa]] of 7.65.

Vitamin B₁₂ refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with [[folate]], cobalamins are essential cofactors required for [[DNA]] synthesis in cells where [[chromosomal]] replication and division are occurring—most notably the [[bone marrow]] and [[myeloid]] cells. As a [[Cofactor (biochemistry)|cofactor]], cobalamins are essential for two cellular reactions:

*the mitochondrial [[methylmalonyl-CoA mutase]] conversion of [[methylmalonic acid]] (MMA) to [[succinate]], which links lipid and carbohydrate metabolism, and

*the activation of [[methionine synthase]], which is the rate-limiting step in the synthesis of [[methionine]] from [[homocysteine]] and [[5-methyltetrahydrofolate]].

Cobalamins are characterized by a [[porphyrin]]-like [[corrin]] nucleus that contains a single [[cobalt]] atom bound to a [[benzimidazole|benzimidazolyl]] [[nucleotide]] and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: [[cyanocobalamin|CNCbl]], [[methylcobalamin]], [[cobamamide|5-deoxyadenosylcobalamin]], and OHCbl. In the serum, hydroxocobalamin and cyanocobalamin 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. Cyanocobalamin is usually converted to hydroxocobalamin in the serum, whereas hydroxocobalamin is converted to either methylcobalamin or 5-deoxyadenosyl cobalamin. Cobalamins circulate bound to serum proteins called [[transcobalamins]] (TC) and [[haptocorrin]]s. Hydroxocobalamin has a higher affinity to the TC II transport protein than cyanocobalamin, or 5-deoxyadenosylcobalamin. From a [[biochemical]] point of view, two essential enzymatic reactions require vitamin B₁₂ (cobalamin).

[[Intracellular]] vitamin B₁₂ is maintained in two active coenzymes, methylcobalamin and 5-deoxyadenosylcobalamin. In the face of vitamin B₁₂ deficiency, conversion of methylmalonyl-CoA to [[succinyl-CoA]] 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 [[purines]] and [[pyrimidines]] and the transfer of the methyl group to cobalamin is essential for the adequate supply of [[tetrahydrofolate]], the substrate for metabolic steps that require folate. In a state of vitamin B₁₂ deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of [[levomefolic acid|methyltetrahydrofolate]]. The resulting elevated concentrations of [[homocysteine]] and [[methylmalonic acid|MMA]] are often found in patients with low serum vitamin B₁₂ and can usually be lowered with successful vitamin B₁₂ replacement therapy. However, elevated [[methylmalonic acid|MMA]] and [[homocysteine]] concentrations may persist in patients with cobalamin concentrations between 200 and 350&nbsp;pg/mL. Supplementation with vitamin B₁₂ during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and deoxyadenosylcobalamin.

{{Vitamin}}

{{Antidotes}}

{{Portal bar | Medicine}}

{{二次利用|date=18 March 2024}}

[[Category:Antidotes]]

[[Category:Vitamin B12]]

[[Category:World Health Organization essential medicines]]