Mechanism, Treatment and Factors

1. MGV’S COLLEGE OF PHARMACY
Department Of Pharmacology
By:- Sagar Bagul
SAGAR BAGUL 1

2. INTRODUCTION
HEMATINICS
 These are the agent that tends to stimulate blood cell formation or
to increase the hemoglobin in the blood.
 Or used for the prevention & treatment of anemia.
HEMOGLOBIN
• Formed in red bone marrow.
• It is a conjugated protein, consisting of an iron containing
pigment combined with histone (protein) is known as Globin.
• The iron containing protein is a porphyrin consisting of 4 pyrrole
rings.
• This porphyrin is designated as Heam.
• Folic acid & vitamin B12 are capable of increasing the rate of
Heam synthesis in the red cells.
SAGAR BAGUL 2

3. ANEMIA
 A condition in which the blood is deficient in the RBC
(erythrocytes), in hemoglobin.
 Or deficiency in quality or in the quantity of blood.
 Erythrocytes are mainly responsible for the delivering
oxygen to the tissues, less RBC means less oxygen to tissues.
 4 types
I. Microcytic anemia – Deficiency of iron (Fe)
II. Macrocytic Anemia- Deficiency of folic acid and B12
III. Hemolytic anemia – Abnormal breakdown of RBCs
IV. Aplastic anemia – Body stops producing new blood
cells.
SAGAR BAGUL 3

4. HIMATINICS
1. IRON
2. FOLIC ACID (pteroylglutamic acid)
3. VITAMIN B12 (cyanocobalamin)
SAGAR BAGUL 4

5. IRON
 The human body contains about 3.5gm
of iron of which about 2/3 is contained
in the blood.
 5 - 10% of ingested iron is absorbed
 Once ingested the acid in the
stomach:
 1. Aids in ionization of iron
 2. Splits chelated food iron from
chelator
 3. Maintains iron in soluble form
 4. Allows iron to remain in the
absorbable form Fe3+
SAGAR BAGUL 5

6. Mechanism of Iron Absorption
SAGAR BAGUL 6

7. Therapeutic uses of Iron
 Iron Deficient Anemia
 Pregnancy
 Premature Babies
 Blood loss
 Hookworn infestation
 Malabsorption
Syndrome
 GI Bleeding due to:
 Ulcers
 Aspirin
 Excess consumption of
coffee
SAGAR BAGUL 7

8. Iron Preparations
 Oral Iron
 Ferrous Sulfate (Feosol) – 300 mg tid
 Side Effects are extremely mild:
 Nausea, upper abdominal pain, constipation or diarrhea.
 Cheapest form of Iron and one of the most widely used
 Parenteral
 Iron Dextran (Imferon) – IM or IV
 Indicated for patients who cannot tolerate or absorb oral
iron or where oral iron is insufficient to treat the
condition ie. Malabsorption syndrome, prolonged
salicylate therapy, dialysis patients
SAGAR BAGUL 8

9. Toxicity of iron Toxic levels
 ALD – 200-300mgkg, plasma iron > 300ug/dl
 Treatment of acute poisoning.
 Bicarbonate for acidosis
 Fluids for blood loss
 Ipecac or lavage
 Chelation with Deferoxamine
SAGAR BAGUL 9

10. Folic Acid
 Source in food – yeast, egg yolk, liver and leafy vegetables
 Folic Acid (F.A.) is absorbed in the small intestines.
 F.A. is converted to tetrahydrofolate by dihydrofolate
reductase.
 Folic Acid deficiency (F.A. Deficiency) is also called Will’s
Disease.
 Deficiency may produce megaloblastic anemia; neural tube
defect in fetus.
SAGAR BAGUL 10

11. Therapeutic Uses of Folic Acid
 1. Megaloblastic Anemia due to inadequate dietary
intake of folic acid
 Can be due to chronic alcoholism, pregnancy, infancy,
impaired utilization: uremia, cancer or hepatic disease.
 2. To alleviate anemia that is associated with
dihydrofolate reductase inhibitors.
 i.e. Methotrexate (Cancer chemotherapy), Pyrimethamine
(Antimalarial)
 Administration of citrovorum factor (methylated folic acid)
alleviates the anemia.
SAGAR BAGUL 11

12. Therapeutic Uses of Folic Acid
 3. Ingestion of drugs that interfere with intestinal
absorption and storage of folic acid.
 Mechanism- inhibition of the conjugases that break off folic
acid from its food chelators.
 Ex. – phenytoin, progestin/estrogens (oral contraceptives)
 4. Malabsorption – Sprue, Celiac disease, partial
gastrectomy.
 5. Rheumatoid arthritis – increased folic acid demand
or utilization.
SAGAR BAGUL 12

13. Folic acid
Dose
Synthetic folic acid daily 10-30mg orally is given.
Toxicity
Non toxic to man.
SAGAR BAGUL 13

14. Vitamin B12 Source: In food, especially in liver and kidneys. GI
Microorganism synthesis, Vitamin Supplements
(Cyanocobalamin)
 Necessary for normal DNA synthesis
 Absorption of B12
 1. Intrinsic Factor (low dose): a protein made by stomach parietal
cells that binds to B12 and delivers it from the ileum via a calcium
mediated event.
 2. Mass Action (High dose): 1000mg/day, absorbed via passive
diffusion
SAGAR BAGUL 14

15. Distribution of B12
Vitamin B12 is distributed to various cells
bound to a plasma glycoprotein, Transcobalamin II
Storage of B12
Excess vitamin B12 (upto 300-500 microgram) is
stored in liver.
SAGAR BAGUL 15

16. Therapeutic Uses of B12
 Daily Requirements - 0.6-1.0mh/day; T1/2 ~ 1 year
 Pernicious Anemia
 Impaired GI absorption of B12
 Gastrectomy
 Corrosive Injury of GI mucosa
 Fish tape worm: worm siphons off B12
 Placebo abuse with B12, especially in elderly patients.
 Malabsorption syndrom
SAGAR BAGUL 16

17. HAEMOPOIETIC GROWTH
FACTORS
17

18. ERYTHROPOITIN (Epogen)
 Is a glycoprotein hormone
 It stimulates the production of erythrocytes
(erythropoiesis) in the bone marrow
 In adults, 85% of circulating erythropoietin is
synthesized in the endothelial cells of the peritubular
capillaries in the renal cortex; the remainder is
synthesized in the liver
SAGAR BAGUL 18

19. ERYTHROPOITIN (Epogen)
 The erythropoietin deficiency may result from
chronic renal failure and can result in the
development of a normocytic, hypochromic
anaemia (though this may sometimes be
complicated by other factors as iron and folate
deficiency)
 This may be corrected by epoetin (recombinant
erythropoietin
SAGAR BAGUL 19

20. Clinical Uses of Epoietin
(i) Anaemia of chronic renal failure, treated by s.c or i.v
injection. Response is fastest after i/v injection
(ii) Anaemia during chemotherapy for cancer
(iii) Prevention of the anaemia that occurs in premature
infants
(iv) Anaemia of AIDS (exacerbated by zidovudine
treatment)
SAGAR BAGUL 20

21. Colony-stimulating Factors
 CSFs are called so because they were found to stimulate the
formation of maturing colonies of leucocytes in semi-solid
medium in vitro
 Are classified as cytokines
 They stimulate particular committed progenitor cells to
proliferate and also cause irreversible differentiation
 Granulocyte colony-stimulating factors (G-CSF)
-produced mainly by monocytes, fibroblasts and
endothelial cells,
-controls primarily the development of neutrophils
(stimulates neutrophil progenitor)
-is available as filgrastim; it is given i/v or s/c
SAGAR BAGUL 21

22. Colony- Stimulating Factors
 Granulocyte-macrophage colony stimulating factors
(GM-CSF)
• Stimulates development of many types of progenitor cell.
• Is available as molgramostin and is given i/v, s/c.
• Can cause fever, rashes, bone pain, hypotension,
gastrointestinal symptoms and arterial oxygen desaturation.
SAGAR BAGUL 22

23. Clinical uses of CSFs
 To reduce the severity and duration of the neutropenia
induced by cytotoxic drug during anticancer
chemotherapy and following bone marrow transplant
 For persistent neutropenia in advanced HIV infection
 May have a role in treatment of aplastic anaemia
SAGAR BAGUL 23

24. THANK YOU
SAGAR BAGUL 24