Drugs Megaloblastic Anemia (FETT)

FOLIC ACID

HYDROXOCOBALAMIN

• Synonyms: folic acid, folate

• Substance class: pteridines

• Inactive precursor (provitamin): none

• Active form: tetrahydrofolic acid (THF)

• Sources

  • Leafy green vegetables, fortified foods (e.g., bread, flour, and cereal)

  • Small amounts are synthesized in intestinal flora

• Resorption: jejunum via specific transporters

• Transport in blood: via folate-binding transport proteins

• Storage: small reserve in the liver (enough for approx. 3–4 months)

• Anemia

• Dietary requirements

• Prevention of neuroal tube defects

  
  

Administration of phenytoin, primidone, barbiturates, methotrexate, nitrofurantoin, alcohol, or pyrimethamine may result in folate deficiency. 

Phenytoin

Possible increase in seizure frequency. 

Chloramphenicol

Possible delayed response to folic acid 

• Folic acid is prepared synthetically.  Naturally occurring conjugates of folic acid (food folate; pteroylpolyglutamates) are present in a wide variety of foods, particularly liver, kidneys, yeast, leafy green vegetables, other vegetables, citrus fruits and juice, and legumes. 

• An exogenous source of folate is required for nucleoprotein synthesis and the maintenance of normal erythropoiesis. 

• Folic acid is not metabolically active as such, but is the precursor of tetrahydrofolic acid which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purines and thymidylates of nucleic acids. Folate supplementation before and during pregnancy associated with a reduction in risk for fetal neural tube defects. 

• Hydroxocobalamin (precursor of vitamin B12): binds cyanide directly and forms cyanocobalamin, which is excreted in urine (first-line antidote)

• Synonyms: cobalamin

• Substance class: cobalamin

• Inactive precursor (provitamin): none

• Active forms: methylcobalamin and adenosylcobalamin (activation occurs in the liver)

• Sources

  • Synthesis: Only microorganisms can produce vitamin B12.

    • The colonic flora produces vitamin B12.

    • However, vitamin B12 produced by colonic flora cannot be absorbed by the body because the terminal ileum (absorption site) lies prior to the colon.

• Found almost exclusively in animal products (except yeast extract)

  1. Some dried and fermented plant foods (e.g., tempeh, nori)

• Absorption

  • Stomach: Cobalamin is released from ingested proteins by pepsin and binds to the glycoprotein haptocorrin (R-protein), which protects it from gastric acid. [19]

  • Duodenum: Cobalamin is released from haptocorrin by trypsin and binds to intrinsic factor (IF), a protein produced by the parietal cells of the stomach that facilitates cobalamin absorption in the ileum.

  • Terminal ileum: cubilin receptor‐mediated endocytosis of the intrinsic factor-cobalamin complex → breakdown of IF in enterocytes, release of cobalamin, followed by binding to carrier protein transcobalamin II and then enters the plasma → cobalamin is either delivered to metabolically active tissues or stored in the liver

• Transport in blood: via transcobalamin

• Storage: large reserve pool

  • 60% in the liver (enough for approx. 3–4 years)

  • 30% in muscle tissue