Medication Summary
Pharmacotherapy involves the administration of vitamin B12, folate, or both, as indicated. The goals of pharmacotherapy are to correct vitamin deficiencies, to prevent complications, and to reduce morbidity. For information on iron supplements, see Iron Deficiency Anemia.
Vitamins
Class Summary
Cyanocobalamin (vitamin B12) is used to correct vitamin B12 deficiency and folic acid is used to treat folic acid deficiencies. Cyanocobalamin does not naturally occur. It is an in vitro artifact that is readily converted to active forms of cobalamin in humans and mammals.
There are several forms of cyanocobalamin available for treatment of B12 deficiencies. Only intramuscular and oral cyanocobalamin are recommended. However, the effectiveness of oral cyanocobalamin in managing cobalamin-related neurological disorders has not been proven. Hence, oral cyanocobalamin is not recommended for subacute combined system degeneration and other cobalamin-related neurological disorders. [22]
Intravenous cobalamin is not recommended because (1) it does not accumulate since most of a dose is excreted in urine and (2) intravenous cobalamin can raise blood pressure. Intranasal cobalamin is not recommended because (1) absorption is inconsistent and not predictable and (2) it is expensive. [30, 31]
Cobalamin has been associated with allergic reactions. It is not clear whether the reactions are due to preservatives in intramuscular preparations or whether it is due to cobalamin in both parenteral and oral preparations. [31]
Cobalamin therapy for patients with Leber hereditary neuropathy, especially during early phases of the disorder, may cause blindness and is contraindicated. [31]
Cyanocobalamin (Calo-Mist, Ener-B, Nascobal)
Cyanocobalamin is most commonly given to patients. It is an in vitro artifact and is not an active form of the vitamin. However, it is converted to active forms.
Folic acid (Folvite)
Folic acid is an essential cofactor for enzymes used in DNA synthesis.
Electrolyte Supplements
Class Summary
Serum potassium levels can fall during therapy for severe cobalamin or folate deficiency and can lead to sudden death. Therefore, potassium supplements may be indicated.
Potassium chloride (K-Tab, Klor-Con, microK, Epiklor)
Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss, or because of low intake.
Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss of about 100-200 mEq of potassium from body stores.
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Megaloblastic anemia. View of red blood cells
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Megaloblastic anemia. The structure of cyanocobalamin is depicted. The cyanide (Cn) is in green. Other forms of cobalamin (Cbl) include hydroxocobalamin (OHCbl), methylcobalamin (MeCbl), and deoxyadenosylcobalamin (AdoCbl). In these forms, the beta-group is substituted for Cn. The corrin ring with a central cobalt atom is shown in red and the benzimidazole unit in blue. The corrin ring has 4 pyrroles, which bind to the cobalt atom. The fifth substituent is a derivative of dimethylbenzimidazole. The sixth substituent can be Cn, CC3, hydroxycorticosteroid (OH), or deoxyadenosyl. The cobalt atom can be in a +1, +2, or +3 oxidation state. In hydroxocobalamin, it is in the +3 state. The cobalt atom is reduced in a nicotinamide adenine dinucleotide (NADH)–dependent reaction to yield the active coenzyme. It catalyzes 2 types of reactions, which involve either rearrangements (conversion of l methylmalonyl coenzyme A [CoA] to succinyl CoA) or methylation (synthesis of methionine).
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Megaloblastic anemia. Inherited disorders of cobalamin (Cbl) metabolism are depicted. The numbers and letters correspond to the sites at which abnormalities have been identified, as follows: (1) absence of intrinsic factor (IF); (2) abnormal Cbl intestinal adsorption; and (3) abnormal transcobalamin II (TC II), (a) mitochondrial Cbl reduction (Cbl A), (b) cobalamin adenosyl transferase (Cbl B), (c and d) cytosolic Cbl metabolism (Cbl C and D), (e and g) methyl transferase Cbl utilization (Cbl E and G), and (f) lysosomal Cbl efflux (Cbl F).
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Megaloblastic anemia. Cobalamin (Cbl) is freed from meat in the acidic milieu of the stomach where it binds R factors in competition with intrinsic factor (IF). Cbl is freed from R factors in the duodenum by proteolytic digestion of the R factors by pancreatic enzymes. The IF-Cbl complex transits to the ileum where it is bound to ileal receptors. The IF-Cbl enters the ileal absorptive cell, and the Cbl is released and enters the plasma. In the plasma, the Cbl is bound to transcobalamin II (TC II), which delivers the complex to nonintestinal cells. In these cells, Cbl is freed from the transport protein.
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Peripheral smear of blood from a patient with pernicious anemia. Macrocytes are observed, and some of the red blood cells show ovalocytosis. A 6-lobed polymorphonuclear leukocyte is present.
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Bone marrow aspirate from a patient with untreated pernicious anemia. Megaloblastic maturation of erythroid precursors is shown. Two megaloblasts occupy the center of the slide with a megaloblastic normoblast above.
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Response to therapy with cobalamin (Cbl) in a previously untreated patient with pernicious anemia. A reticulocytosis occurs within 5 days after an injection of 1000 mcg of Cbl and lasts for about 2 weeks. The hemoglobin (Hgb) concentration increases at a slower rate because many of the reticulocytes are abnormal and do not survive as mature erythrocytes. After 1 or 2 weeks, the Hgb concentration increases about 1 g/dL per week.
