Cyancobalamin

Cyanocobalamin is a form of vitamin used to treat vitamin deficiency except in the presence of cyanide toxicity. The deficiency may occur in pernicious anemia, following surgical removal of the stomach, with fish tapeworm, or due to bowel cancer. It is less preferred than hydroxocobalamin for treating vitamin deficiency. It is used by mouth, by injection into a muscle, or as a nasal spray.

Cyanocobalamin is generally well tolerated. Minor side effects may include diarrhea and itchiness. Serious side effects may include anaphylaxis, low blood potassium, and heart failure. Use is not recommended in those who are allergic to cobalt or have Leber's disease. Vitamin is an essential nutrient meaning that it cannot be made by the body but is required for life.

Cyanocobalamin was first manufactured in the 1940s. It is available as a generic medication and over the counter. In 2020, it was the 105th most commonly prescribed medication in the United States, with more than 6million prescriptions.

Medical use

Cyanocobalamin is usually prescribed after surgical removal of part or all of the stomach or intestine to ensure adequate serum levels of vitamin . It is also used to treat pernicious anemia, vitamin deficiency (due to low intake from food or inability to absorb due to genetic or other factors), thyrotoxicosis, hemorrhage, malignancy, liver disease and kidney disease. Cyanocobalamin injections are often prescribed to gastric bypass patients who have had part of their small intestine bypassed, making it difficult for to be acquired via food or vitamins. Cyanocobalamin is also used to perform the Schilling test to check ability to absorb vitamin .

Cyanocobalamin is also produced in the body (and then excreted via urine) after intravenous hydroxycobalamin is used to treat cyanide poisoning.

Side effects

Possible side effects of cyanocobalamin injection include allergic reactions such as hives, difficult breathing; redness of the face; swelling of the arms, hands, feet, ankles or lower legs; extreme thirst; and diarrhea. Less-serious side effects may include headache, dizziness, leg pain, itching, or rash.

Treatment of megaloblastic anemia with concurrent vitamin deficiency using vitamers (including cyanocobalamin), creates the possibility of hypokalemia due to increased erythropoiesis (red blood cell production) and consequent cellular uptake of potassium upon anemia resolution. When treated with cyanocobalamin, patients with Leber's disease may develop serious optic atrophy, possibly leading to blindness.

Chemistry

Vitamin is the "generic descriptor" name for any vitamers of vitamin . Animals, including humans, can convert cyanocobalamin to any one of the active vitamin compounds.

Cyanocobalamin is one of the most widely manufactured vitamers in the vitamin family (the family of chemicals that function as when put into the body), because cyanocobalamin is the most air-stable of the forms. It is the easiest to crystallize and therefore easiest to purify after it is produced by bacterial fermentation. It can be obtained as dark red crystals or as an amorphous red powder. Cyanocobalamin is hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at . The vitamin coenzymes are unstable in light. After consumption the cyanide ligand is replaced by other groups (adenosyl, methyl) to produce the biologically active forms. The cyanide is converted to thiocyanate and excreted by the kidney.

Chemical reactions

In the cobalamins, cobalt normally exists in the trivalent state, Co(III). However, under reducing conditions, the cobalt center is reduced to Co(II) or even Co(I), which are usually denoted as and , for reduced and super reduced, respectively.

and can be prepared from cyanocobalamin by controlled potential reduction, or chemical reduction using sodium borohydride in alkaline solution, zinc in acetic acid, or by the action of thiols. Both and are stable indefinitely under oxygen-free conditions. appears orange-brown in solution, while appears bluish-green under natural daylight, and purple under artificial light.

is one of the most nucleophilic species known in aqueous solution. This property allows the convenient preparation of cobalamin analogs with different substituents, via nucleophilic attack on alkyl halides and vinyl halides.

For example, cyanocobalamin can be converted to its analog cobalamins via reduction to , followed by the addition of the corresponding alkyl halides, acyl halides, alkene or alkyne. Steric hindrance is the major limiting factor in the synthesis of the coenzyme analogs. For example, no reaction occurs between neopentyl chloride and , whereas the secondary alkyl halide analogs are too unstable to be isolated. This effect may be due to the strong coordination between benzimidazole and the central cobalt atom, pulling it down into the plane of the corrin ring. The trans effect determines the polarizability of the Co–C bond so formed. However, once the benzimidazole is detached from cobalt by quaternization with methyl iodide, it is replaced by or hydroxyl ions. Various secondary alkyl halides are then readily attacked by the modified to give the corresponding stable cobalamin analogs. The products are usually extracted and purified by phenol-methylene chloride extraction or by column chromatography.

Cobalamin analogs prepared by this method include the naturally occurring coenzymes methylcobalamin and cobamamide, and other cobalamins that do not occur naturally, such as vinylcobalamin, carboxymethylcobalamin and cyclohexylcobalamin. This reaction is under review for use as a catalyst for chemical dehalogenation, organic reagent and photosensitized catalyst systems.

Production

Cyanocobalamin is commercially prepared by bacterial fermentation. Fermentation by a variety of microorganisms yields a mixture of methylcobalamin, hydroxocobalamin and adenosylcobal