Dr Sadia Batool Shahid PGTMPhil Pharmacology It is

Dr. Sadia Batool Shahid PGT-M-Phil, Pharmacology

It is also called cobalamin It is a cobalt containing molecule Along with folic acid is required in one carbon units transfers These steps are necessary for DNA synthesis Vitamin B 12 is produced by bacteria only.

Essential in two reactions: 1. Conversion of methylmalonyl-coenzyme A to Succinyl-Co. A 2. Conversion of Homocysteine to Methionine The second reaction is linked to folic acid metabolism and synthesis of deoxythymidylate (d. TMP) d. TMP is a precursor for DNA synthesis

In Vitamin B 12 deficiency, folate accumulates as N-Methyltetrahydrofolate The supply of tetrahydrofolate is depleted This slows production of RBCs Folic acid replacement can correct B 12 deficiency anemia, but not the neurological manifestation of B 12 deficiency.

VITAMIN B 12 DEFICIENCY LEADS TO: Synthesis of DNA in RBC hampered RNA goes on forming, defective DNA Increased Haemoglobin formation Erythroblasts become large and odd shaped (megaloblasts) These mature into macrocytes rather than erythrocytes Have fragile membranes, therefore rupture easily

Folic acid (H 4 folate) is a precursor of several folate cofactors These are essential for one carbon transfer reactions These steps are important for DNA synthesis e. g Synthesis of thymidylate acid from deoxyuridylate Synthesis of purine

Absorption: Vitamin B 12 binds to Intrinsic factor (secreted by gastric parietal cells) It prevents digestion of B 12 In bound state , it binds to receptors on brush border of mucosa These receptors are located in ileum Bound intrinsic factor and B 12 are absorbed with pinocytosis

DISTRIBUTION: Vitamin B 12 is distributed to various cells bound to a plasma glycoprotein, Transcobalamin II STORAGE: Excess vitamin B 12 (upto 300 -500 microgram) is stored in liver

ELIMINATION : Trace amounts of vitamin B 12 are normally lost in urine and stool. Significant amount of vitamin B 12 are excreted in urine (when large amounts are given parenterally)

ABOSRPTION: Form: Dietary folates in polyglutamate forms; first undergo hydrolysis by conjugase (present in brush border of intestinal mucosa) and form monoglutamate Site: Proximal jejunum Only modest amounts of folic acid are stored in body, therefore a decrease in diet will lead to anemia in few months

Distribution: Widely distributed through out the body via blood stream Storage: Normally, 5 -20 mg is stored in liver and other tissues Elimination: Excreted in urine and stool, and also destroyed by catabolism

These are used in anemia (megaloblastic , macrocytic anemia) Pernicious anemia ( Vitamin B 12) Prophylaxis for neural tube defects (folic acid before conception) Neuropathy (Vitamin B 12) Cancer chemotherapy Certain drug therapies lead to deficiency of folic acid so replacement is required

Tablet Folic acid 5 mg: One tablet daily is sufficient It has excellent absorption Syrup Form Combined with iron and multivitamins There is no parenteral preparation available for Folic acid.

Tablet and syrup forms: Cyanocobalamin, Hydroxycobalamin Parenteral: I/M, I/V. Use: Ø To corrects major depletion of B 12 quickly Ø If patient is unbale to take orally Ø Required in patients with pernicious anemia(IF deficiency) Parenteral therapy can lead to pain at injection site

Both are very well tolerated There are no remarkable adverse effects of therapy