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

Vitamin b12... 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 B12 is produced by bacteria only.

VITAMIN B12.... Essential in two reactions: Conversion of methylmalonyl-coenzyme A to Succinyl-CoA Conversion of Homocysteine to Methionine The second reaction is linked to folic acid metabolism and synthesis of deoxythymidylate (dTMP) dTMP is a precursor for DNA synthesis

VITAMIN B12..... In Vitamin B12 deficiency, folate accumulates as N-Methyltetrahydrofolate The supply of tetrahydrofolate is depleted This slows production of RBCs Folic acid replacement can correct B12 deficiency anemia, but not the neurological manifestation of B12 deficiency.

Role of Vitamin B12 In rbc production VITAMIN B12 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

ROLE OF FOLIC ACID IN RBC PRODUCTION Folic acid (H4 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

VITAMIN b12... Absorption: Vitamin B12 binds to Intrinsic factor (secreted by gastric parietal cells) It prevents digestion of B12 In bound state ,it binds to receptors on brush border of mucosa These receptors are located in ileum Bound intrinsic factor and B12 are absorbed with pinocytosis

VITAMIN B12.... DISTRIBUTION: Vitamin B12 is distributed to various cells bound to a plasma glycoprotein,Transcobalamin II STORAGE: Excess vitamin B12 (upto 300-500 microgram) is stored in liver

VITAMIN B12 ELIMINATION : Trace amounts of vitamin B12 are normally lost in urine and stool. Significant amount of vitamin B12 are excreted in urine (when large amounts are given parenterally)

FOLIC ACID..... 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

Folic acid 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

CLINICAL USES OF VIT B12 AND FOLIC ACID These are used in anemia (megaloblastic ,macrocytic anemia) Pernicious anemia ( Vitamin B12) Prophylaxis for neural tube defects (folic acid before conception) Neuropathy (Vitamin B12) Cancer chemotherapy Certain drug therapies lead to deficiency of folic acid so replacement is required

FOLIC ACID PREPARATIONS: 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.

VITAMIN B12 PREPARATIONS Tablet and syrup forms: Cyanocobalamin, Hydroxycobalamin Parenteral: I/M, I/V. Use: To corrects major depletion of B12 quickly If patient is unbale to take orally Required in patients with pernicious anemia(IF deficiency) Parenteral therapy can lead to pain at injection site

VITAMin B12 and folic acid Both are very well tolerated There are no remarkable adverse effects of therapy