This explains drugs used in management of anemia

1. ANTIANEMIC DRUGS -
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2. At the end of the session ,
student should be able to
• Identify types of anemia.
• Describe manifestations of megaloblastic
anemia.
• describe physiological functions of
Vitamin B 12.
• Identify clinical conditions where Vitamin
B12 is uses , and mentions Folate trap
• Enumerate the indications of Folic acid.
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3. Anemia is a condition in which blood will
have too few red blood cells
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4. TYPES OF ANEMIAS
Classified based on the size of red blood
cells i.e. mean corpuscular volume (MCV)
Microcytic: smaller than normal (under
80 fl)
Normocytic:normal size (80-100 fl)
Macrocytic: larger than normal (over
100 fl)
femtoliters
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5. MICROCYTIC ANEMIA
Iron deficiency anemia: most common
Paler & smaller than usual
Normocytic anemia
Overall Hb levels decreased
red blood cell size (MCV) remains
normal
Causes: Acute blood loss, chronic
disease, Aplastic anemia (bone marrow
failure), Hemolytic anemia
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6. MACROCYTIC ANEMIA
Megaloblastic anemia: deficiency of
either Vitamin B12 or folic acid or both
Folate deficiency: No neurological
symptoms
B12 deficiency : neurological symptoms
present
Pernicious anemia : autoimmune
condition leading to poor absorption of
vitamin B12
Alcoholism
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7. Vitamine B12 (cyanocobalamine)
Source
Animals/plants do not synthesize, Microbes
synthesize
Animal source: liver, kidneys, sea fish, egg
yolk, meat, cheese
Vegetable source: Legumes
Colonic microflora synthesize insufficient
Streptomyces griseus: commercial source
Daily requirement
1-3 μg; pregnancy & lactation: 3-5 μg.
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8. Dietary and
storage folate
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9. Utilization of B12
Parietal cells Intrinsic factor B12 + Intrinsic
factor
Absorption
(ileum)
Total body storage: 4 mg
Surgery and antibodies
Liver (stored)
Intrinsic
factor
Transcob
alamine
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10. INDICATIONS OF B12
Pernicious anemia
Malabsorption
Gastric mucosal damage
Schilling test: diminished absorption of
radioactively labelled vitamin B12. This
is corrected with intrinsic factor +
radioactive B12
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11. Manifestations of B12
Symptoms of megaloblastic anemia
Hematologic – macrocytic anemia
Neurological – peripheral neuritis, poor
memory etc.
Psychiatric illness
Neuropathies
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12. Therapeutic use of B12
Due to lack of intrinsic factor
Orally B-12 can not be given
B-12 should be given parenterally
(im/sc)
Not given iv due to anaphylaxis
Treatment is life long
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13. TREATMENT REGIMEN
1-10 days = 30-100 μg
Weekly = 100 μg
Monthly = 100 μg
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14. 04/17/19 14patki

15. FOLIC ACID (B-9)
Dietary source: liver, green leafy
vegetables, egg, meat, milk
Absorbed from upper intestine.
Folic acid DHFA CH3THFA
Liver traps large amount of Ch3THFA
and releases into the bile and again
absorbed by enterohepatic circulation.
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16. Folate Deficiency
Malabsorption
Chronic alcoholism
Pregnancy and lactation
Drug induced deficiency: Phenytoin,
phenobarbitone, primidone, oral
contraceptives etc.
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17. Manifestations
Epithelial damage, glossitis, enteritis,
diarrhea, steatorrhoea, weight loss,
sterility etc.
Dietary source: Liver, green leafy
vegetables, egg, meat, milk etc
Daily requirement: 400 μg
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18. Therapeutic Uses
Megaloblastic anemia
Prophylaxis: pregnancy, lactation,
antiepileptic therapy, malabsoption etc.
Folinic acid (leucovorin/citrovorum
factor/5-formyl-THFA) readily converted
to folic acid derivatives.
Dihydrofolate reductase is not
required.
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19. ERYTHROPOIETIN
Essential for normal erythropoiesis
Produced by peritubular cells of the
kidney during anemia and hypoxia
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20. USES OF ERYTHROPOIETIN
Anemia in chronic renal failure(sc/iv)
Cancer chemotherapy induced anemia
AIDS induced anemia
Prophylaxis – anemia in premature
infants
Anemia – inflammatory conditions
(Rheumatoid)
Adverse effects: flu-like symptoms, mild
hypertension, encephalopathy, occasionally
convulsions, risk of thrombosis due to
hematocrit rises.
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21. ADVERSE EFFECTS OF ERYTHROPOIETIN
Increased clot formation
Hypertensive episodes
Flu like symptoms lasting 2-4 hr
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22. Granulocyte colony-stimulating factor (G-
CSF)
Stimulates neutrophil progenitors.
intravenously or subcutaneously.
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23. Granulocyte-macrophage colony-stimulating
factor (GM-CSF)
Stimulates many types of progenitor cell.
intravenously, subcutaneously.
Side effects: fever, rashes, bone pain,
hypotension, git symptoms, arterial
oxygen desaturation.
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24. 04/17/19 24patki

25. 04/17/19 25patki

26. Which of the following defects is
associated with megaloblastic anemia?
– Defective RNA synthesis
– Defective immunoglobulin synthesis
– Defective globin synthesis
– Defective DNA synthesis
– Defective hemopoitic pathway.
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27. What is a leading cause of anemia in a
patient who is alcoholic?
– Folate deficiency
– Iron deficiency
– Vitamin B 12 deficiency
– Uridine triphosphate deficiency
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28. – Most common disorder in clinical practice.
– Charectarized by a decrease in the O2 carrying
capacity of the blood due to reduced
concentration of Hb or RBCS
Iron deficiency anemia
Pink of your
health

29.  IRON DEF ANAEMIA CHARACTERISED BY-
• MICROCYTOSIS (presence of small
erythrocytes).
• HYPO CHROMIA ( poorly filled with
haemoglobin).
• POIKILOCYTOSIS (bizzare shaped cells).
• ANISOCYTIOSIS (different shapes).
•

30. DISTRIBUTION OF IRON IN THE BODY
– Iron(Fe) is the essential body constituent .
– Total body iron in an adult –
2.5 – 5 g (average 3.5g).
– It is more in men - (50mg/kg)
Than in women (38mg/kg)
– It is distributed as follows :
•Hemoglobin (Hb) – 66%
•Iron stores ferritin and Haemosiderin – 25%
•Myoglobin ( in muscles) – 3%
•Parenchymal iron (in enzymes etc) – 6%

31. Loss of 100ml of blood (containing 15g Hb) means loss of
50mg elemental iron.
To raise Hb level of blood by 1g/dl about 200mg of iron is
needed.
Daily requirement of iron
 Adult male – 0.5 – 1 mg (13mg/kg)
 Adult female – 1 – 2 mg (21mg/kg)
(Menstruating)
 Infants – 60mg/kg
 Children – 25 mg/kg
 Pregnancy – 3.5 mg (80mg/kg)
(Last 2 trimesters)

32. DIETARY SOURCES OF IRON
 Rich → liver, egg yolk, oyster, drybeans, dry fruits, wheat germ,
yeast.
 Medium → meat, chicken, fish, spinach, banana, apple.
 Poor → milk and its products, root vegetables.

33. Iron absorption
 Average daily diet contains- 10-20mg of iron.
 Absorption occurs all over the intestine, but more in the
upper part.
 There are two major forms of dietary iron.
 Heme iron, found primarily in red meats, is the most easily
absorbed form.
 Majority of dietary iron is in ferric form.
 It is reduced to ferrous form before absorption.
 Absorption occurs through 2 separate iron transporters in
the intestinal mucosal cells.
•Divalent metal transporter – 1 (DMT 1)
•Ferroportin

34.  FACTORS FACILITATING FE ABSORPTION
– Acid: By favouring dissolution and reduction of ferric form.
– Reducing substances – Ascorbic acid.
– Meat – By increasing Hcl secretionand providing heme iron.
FACTORS IMPEDING FE ABS
– Alkalies – (Antacids) Renders iron insoluble, oppose its
reduction.
– Phosphates (rich in egg yolk)
– Phytates (maize, wheat) by complexing iron
– Tetracyclines
– Prescence of other foods in stomach.

35. MUCOSAL BLOCK
• It is a mechanism to prevent entry of excess iron in the body
• Iron reaching inside mucosal cell is eigther transported to
plasma or oxidised to ferric form and complexed with
apoferritin to form ferritin.
• The ferritin stored on the mucosal cells is lost when they are
shed (life span 2-4 days).
• This is called ferritin curtain.
• Thus the amount of iron entering into the body is governed
by the iron status of the body and the erythropoietic activity.

36. Transport, utilization, storage and excretion.
• Free iron is highly toxic.
• It is converted to ferric form and complexed with a
glycoprotein - transferrin (TF).
• Iron is transported in to erythropoietic and other cells by
attachment of transferrin to transferrin receptors (TFRS)
which is engulfed by endocytosis.
• Iron dissociates from complex and is utilised for Hb
synsthesis while TF and TFR return to cell surface to carry
fresh loads.

37. Cont…
• Iron is stored in reticulo endothelial cells in liver, spleen
bone morrow, also in hepatocytes & myocytes as ferritin
and haemosiderin.
• Daily excretion – 0.5mg daily (adult male) mainly as
exfoliated G.I mucosal cells some RBC’s and in bile,
desquamated skin.
• In menstruating women – monthly menstrual loss may be
averaged to 0.5-1 mg/day.
• Excess iron is required during pregnancy for expansion of
RBC mass, transfer to foetus and loss during delivery
totaling about 700mg .

39. PREPARATIONS AND DOSAGE
Oral iron
This is the preferred route of iron administration.
– Because
• Dissociable Ferrous salts are inexpensive.
•Have high iron content
•Better absorbed than ferric salts.
Some oral iron preparations
•Ferrous sulphate – cheapest
•Ferrous gluconate
•Ferrous fumarate.
•Colloidal ferric hydroxide
•Ferric hydroxy poly maltose

40. • Sustained release preperations – not rational.
• Most of iron absorbed in upper intestine – but
these preperations release iron lower down.
• Liquid formulations – may stain teeth.
– Hence should be put back on tongue.
DOSE
 A total of 200mg of elemental iron given daily in 3
divided doses – produce maximal haematopoietic
response.
 Absorption of iron is much better when it is taken on
empty stomach – side effects are also more on empty
stomach.
 Prophylactic dose – 30 mg iron daily.

41. INDICATIONS OF IRON
THERAPY
PROPHYLATIC
pregnancy ,menstruation ,blood donors .
• THERAPEUTIC
- to treat existing iron deficiency.
• Nutritional deficiency.
• Anaemia of infancy and pregnancy.
• Anaemia due to acute or chronic blood loss.
menorrhagia ,peptic ulcer, hookworm
infestation.

42. ADVERSE EFFECTS OF ORAL IRON
– Adverse effects are related to elemental iron
content.
1. Epigastric pain
2. Heart burn
3. Nausea & vomiting
4. Staining of teeth
5. Metallic taste
6. Bloating, colic
7. Constipation

43. PARENTERAL IRON
 INDICATIONS
1. Oral iron is not tolerated - bowel upset is more.
2. Failure to absorb iron – mal absorption,
Inflammatory bowel disease.
3. Non compliance to oral iron.
4. In prescence of severe deficiency with chronic
bleeding.
• Parenteral iron therapy needs calculation of the
total iron requirement of the pt.
• Iron requirement (mg) = 4.4 X body wt (kg) X Hb
deficit (g/dl)

44. PARENTERAL IRON THERAPY
 PREPARATIONS:
• IRON DEXTRAN for IMIV use {imferon} contra
indicated in early pregnancy.
• IRON SORBITOL CITRIC ACID
COMPLEX{JECTOFER} for IM injection
(urine turns black –iron sulfide formation).

45. • IRON CARBOHYDRATE COMPLEX
{UNIFERON}
- iron ,dextran sorbitol citric acid .
- Given IM , each ml contains 50 mg of
elemental iron.
• Injection made by Z technique.
• Test dose of 25 mg is given followed by 100
mg .
• IV infusion is given at the rate of 10 drops
per minute.

46. IV Route
• Iron dextran
• Ferrous –sucrose
• Sodium ferric gluconate
After a test dose with 0.5ml, 2ml to be given
over 10min.
Alternatively dose diluted in 500ml
glucose/saline –to be infused over 6-8hrs.
• Should be stopped if pt complains of
giddiness, paraesthesias and tightness in the
chest.

47. ADVERSE EFFECTS OF PARENTERAL IRON
LOCAL –
pain at injection site
pigmentation of skin,
sterile abscess.
SYSTEMIC –
fever,
head ache,
joint pains,
flushing,
palpitation,
chest pain,
dyspnoea,
lymphnode enlargement.

48. USES
IRON DEFICIENCY ANEMIA
 Most imp indication for medicinal iron.
CAUSES:
1.Nutritional deficiency
2.Chronic bleeding from G.I tract (common cause)
(ulcers, hook worm infestation)
3.Repeated attacks of malaria.
4.Chr. inflammatary diseases.

49. 04/17/19 patki 49
BE HAPPY
BE INTELLIGENT
One tab of Fersolate per
day