In this presentation we will briefly discuss Megaloblastic anemia, Vit B12 and Folic acid , Its brief pharmacology and its uses.

1. MEGALOBLASTIC ANEMIA
TREATMENT
Folic acid and Vitamin B12 Deficiency

2. MEGALOBLASTIC ANEMIA
 Is a condition in which the bone marrow produces
unusually large, structurally abnormal, immature red
blood cells (megaloblasts).
 Is caused by impaired DNA synthesis due to
Hypovitaminosis (Folate and Vit. B12 deficiency).
 It is characterised by:
1. dec. RBC
2. Inc. MCV (> 110fl)
3. Hypersegmented
neutrophils
4. inc. Homocysteine

3. VITAMIN B12
A. Role of Vitamin B12:- Vitamin B12
(cobalamin), a cobalt-containing molecule.
 act as cofactor in DNA synthesis and in
both fatty acid and amino acid metabolism.
 Sources: It is naturally found in animal
foods, including meats, fish, poultry, eggs
and dairy.
 Vitamin B12 is produced only by bacteria;
this vitamin cannot be synthesized by
multicellular organisms.

4. B. PHARMACOKINETICS
 Bioavailability :Readily absorbed in distal
half of the ileum in the presence of intrinsic
factor, product of the parietal cells of the
stomach.
 Vitamin B12 deficiency anemia is almost
always caused by inadequate absorption.
 Absorption of Vit.B12 decreases in the
presence of drugs like PPIs and Antacids
and in conditions such as Pernicious
Anemia and Crohn’s disease.

5. B. PHARMACOKINETICS. (CONTD)
 Protein binding: Very high to
specific transcobalamins plasma proteins.
Binding of hydroxocobalamin is slightly
higher than cyanocobalamin.
 Metabolism :Liver
 Storage: Liver ;a normal individual has
enough to last 5 yr.
 Elimination half-life: Approximately 6 days
(400 days in the liver)
 Excretion: kidney

6. C. PHARMACODYNAMICS
essential in 2 reactions:
a. Conversion of methylmalonyl-coenzyme A (CoA)
to succinyl-CoA and
b. conversion of homocysteine to methionine.
second reaction is linked to folic acid
metabolism and synthesis of
Thymidine ( deoxythymidylate dTMP;
a precursor required for DNA
synthesis)

9. C. PHARMACODYNAMICS (CONTD)
 In vitamin B12 deficiency, folates accumulate
as N 5-methyltetrahydrofolate;
 the supply of tetrahydrofolate is depleted; and
the production of red blood cells slows.
 Administration of folic acid to patients with
vitamin B12 deficiency helps refill the
tetrahydrofolate pool;
 Partially or fully corrects anemia BUT
 the exogenous folic acid does not correct the
neurologic defects of vitamin B12 deficiency.

10. D. CLINICAL USE AND TOXICITY
 Two available forms of Vit. B12
1. Cyanocobalamin
2. Hydroxocobalamin
 Indications : naturally occuring Pernicious
Anemia OR dec. absorbtion due to gastric
resecton.
 Main route of Administration: Parentral
 No Significant Toxicity

11. FOLIC ACID
A.Role of Folic Acid: Same as that of
Vit. B12
 Used as a precursor in DNA
synthesis
 Deficiency lead to :
1. Megaloblastic anemia
2. Neural Tube Defects in fetus during
pregnancy

12. A. ROLE OF FOLIC ACID (CONTD)
 deficiency from decreased intake of Folate
alone is not very common.
 Usually a deficiency is caused by an
increased demand for folate:
1. in pregnancy
2. in Hemolytic anemias such as Sickle cell disease
OR
 In addition deficiency can also be caused by drugs
that inhibit the pathways that involve folate such as
trimethoprim (antibiotic) and Methotrexate
(chemotherapy).

13. B. SOURCES AND PHARMACOKINETICS
 Main Source of Folic acid:
1. Leafy Vegetables such spinach , lettuces
etc.
2. Fortified grains
 In addition liver is the richest source of
folate
 Bioavailability: 50–100%; readily absorb
from GI tract.
 Metabolism: Liver
 Excretion :Urine

14. C. PHARMACODYNAMICS
 converted to tetrahydrofolate by the action
of dihydrofolate reductase.
 tetrahydrofolate and dihydrofolate involved
in the reaction cycles that supplies the
dTMP required for DNA synthesis.
 As rapidly dividing cells require more Folic
acid;
 Antifolate drugs are useful in the treatment
of various infections and cancers

15. D. CLINICAL USE AND TOXICITY
Indications : 1.Megaloblastic anemia
2. maternal folic acid deficiency to avoid
NTDs(like anencephaly etc) in Fetus ;
recommended before and during
pregnancy.
 Does not correct the neurologic deficits of
Vitamin B12
 Folic acid has no recognized toxicity.

16. THE END