megaloblastic anaemia (pharmacology)

1. Dr. Jyoti Prabha Bharati
For the lecture of this topic, visit BISHAL CHAUHAN channel on youtube

2.  Defined as a reduced concentration of hemoglobin (Hb)
in blood.
 Anaemia occurs when the balance between production
and destruction of RBCs is disturbed
 Normal Hb level
Adult male : >15g/dl
Adult female:>14g/dl

3. (a) Blood loss (acute or chronic)
(b) Impaired red cell formation due to:
• Deficiency of essential factors, i.e. iron,
vitamin B12, folic acid.
• Bone marrow depression (hypoplastic anaemia),
erythropoietin deficiency.
(c) Increased destruction of RBCs (haemolytic
anaemia

4.  Megaloblastic anemia is characterized by red blood
cells that are larger than normal. known as vitamin B-
12 or folate deficiency anemia, or macrocytic anemia
 number of red blood cells is lower than normal and are
large immature and dysfunctional.

6.  Vitamin B₁₂ deficiency or defective metabolism
 Folate deficiency or defective metabolism
 Others:
 Pernicious anaemia
 Surgeries
 Aplastic anemia
 Alcohol excess

7. Common symptoms include:
 Fatigue
 Shortness of breath
 Muscle weakness
 Abnormal paleness of the skin
 Glossitis (swollen tongue)
 Loss of appetite/weight loss
 Diarrhea
 Nausea
 Fast heartbeat
 Tingling in hands and feet

8.  PERIPHERAL BLOOD FINDINGS
1. Hemoglobin – decreased
2. Hematocrit – decreased
3. RBC count – decreased/normal
.4 MCV –increased
5. MCHC – NORMAL
6. Reticulocytopenia.(marrow failure)
7. Total WBC count – normal / low
8. Platelet count – normal/ low
9. Pancytopenia, especially if anaemia is severe.

9.  Vitamin B-12 is a nutrient found in some foods like
meat, fish, eggs, and milk. Some people can’t absorb
enough vitamin B-12 from their food, leading to
megaloblastic anemia.
 Megaloblastic anemia caused by vitamin B-12
deficiency is referred to as pernicious anemia.

10.  Vitamin B-12 deficiency is most often caused by the
lack of a protein in the stomach called “intrinsic
factor.”
 Without intrinsic factor, vitamin B-12 can’t be
absorbed
 Daily requirement 1–3 μg,
 pregnancy and lactation 3–5 μg.

11.  Insufficient dietary intake (very rare)
 Strict vegetarians
 Deficient absorption
 Pernicious anaemia
 Total or partial gastrectomy
 Prolonged use of PPI or H2 blockers
 Diseases of small intestine
 Fish tapeworm infestation

12. PATHOGENESIS
 Immunologically mediated, autoimmune destruction of
gastric mucosa
 CHRONIC ATROPHIC GASTRITIS – marked loss of
parietal cells

13. 2 mechanism
Active (75%) – requires the presence of intrinsic factor (
a glycoprotein produced by gastric mucosa)
Passive – absorption occurs by diffusion and works when
pharmacological doses of vitamin B12 are ingested

14.  Vitamin B12 in food + R-Binder(glycoprotein)
 B12-R-Binder complex
Intrinsic Factor (IF)
 IF-B12 complex + Freed R-Binder
(Degradation IF)
B12 Circulation

16.  Following absorption by the ileal mucosal cells,
vitamin B12 is carried in the plasma by various
transporting proteins:
 Transcobalamin I
 Transcobalamin II
 Transcobalamin III

19.  Cyanocobalamin and hydroxocobalamin are
complex cobalt containing compounds present in the diet
and referred to as vit B12.
 Vit B12 occurs as water soluble, thermostable
red crystals. It is synthesized in nature only by
microorganisms; plants and animals acquire it
from them.

20.  Cyanocobalamin: 35 μg/5 ml liq.
 Hydroxocobalamin: 500 μg, 1000 μg inj.
 Because of higher protein binding and better
retention in blood, hydroxocobalamin is preferred for
parenteral administration to treat vit B12 deficiency.

21.  Folate is another nutrient that’s important for the
development of healthy red blood cells.
 Folate is found in foods like beef liver, spinach

22.  Folate deficiency can also be caused by chronic alcohol
abuse, since alcohol interferes with the body’s ability to
absorb folic acid.
 Pregnant women are more likely to have folate
deficiency, because of the high amounts of folate
needed by the developing fetus.
 Spina bifida-most common neural defect

23. Folate Deficiency
 lack of folate may be treated with oral or intravenous
folic acid supplements.
Dietary changes also help boost folate levels.
 oranges
 leafy green vegetables
 peanuts
 lentils

24. (a) Megaloblastic anaemia (generally the first
manifestation), neutrophils with hypersegmented
nuclei, giant platelets.
(b) Glossitis, g.i. disturbances: damage to epithelial
structures.

25. (c) Neurological: subacute combined degeneration of
spinal cord
 peripheral neuritis—diminished vibration and position
sense, paresthesias, depressed stretch reflexes
 mental changes—poor memory, mood changes,
hallucinations, etc. are late effects.

26.  Methylcobalamin: (methyl B12) is the active
coenzyme form of vit B12 for synthesis of
methionine and S-adenosylmethionine that is
needed for integrity of myelin.
 This preparation of vit B12 in a dose of 1.5 mg/day has
been especially promoted for correcting the
neurological defects in diabetic, alcoholic and other
forms of peripheral neuropathy

27.  Treatment of vit B12 deficiency:
 vit B12 is used as outlined above. It is wise to add 1–5
mg of oral folic acid and an iron preparation.
 Mega doses of vit B12 have been used in
neuropathies, psychiatric disorders, cutaneous
sarcoid and as a general tonic to allay fatigue,
improve growth.

28.  Even large doses of vit B12 are quite safe. Allergic
reactions have occurred on injection, probably due to
contaminants.
 Anaphylactoid reactions (probably to sulfite contained
in the formulation) have occurred on i.v. injection: this
route should never be employed.

29.  Note:
If the cause of megaloblastic anemia is not known, folic
acid alone should not be given because it will correct
blood picture of anemia but neurological deficts due to
vitamin B12 deficiency may be aggravated( due to
diversion of small amount of vit B12 lelf in correcting
anemia instead of utilization in myelin formation).

30. THANK YOU