Pharmacology PPT

1. Hematinics
Dr Chintan Doshi

2. Introduction
• These are the substances required in the formation of
blood, and are used in the treatment of anaemias
• Anaemia: a condition in which there is a deficiency of
red cells or of haemoglobin in the blood, resulting in
pallor
a. Blood Loss (acute or chronic)
b. Impaired cell formation due to
a. Deficiency of essential factors – Iron, Vit. B12 and Folic
acid
b. Bone marrow depression (hypoplastic), erythropoietin
deficiency
c. Increased cell destruction (haemolytic)

3. Iron
• Total Body Iron content – 3.5 gm
• Hemoglobin – 66% - Protoporphyrin – 4 Iron
containing haeme residues
• Loss of 100 ml of blood – 50 mg elemental Iron
• To raise 1 gm/dl – 200 mg elemental Iron
required
• Stored only in Ferric form (Fe3+) – in combination
with apoferritin – mainly in RE Cells

4. Contd.
Many cellular enzymes –
Cytochromes,
Peroxidases,
Catalases,
Xanthine oxidases
Some mitochondrial enzymes

5. Iron Absorption
• absorbed from all over the Intestine
• Factors increasing absorption
– Acid
– Reducing substances – ascorbic acid
– Amino acid
– Meat
• Factors impending absorption
– alkali (antacids)
– Phosphates
– phytates,
– tetracycline
– presence of other food

6. Iron – Transport, storage etc.
• In plasma immediately converted to Fe3+
form – complexed with transferrin (Tf)
• Transported to RBCs by transferrin receptors
(TfRs) – endocytosis
• Iron utilized for Hb synthesis – TfRs return to
surface
• Storage – RE cells in Liver, spleen, bone and
muscles as ferritin and haemsiderin

7. Iron Preparations - Oral
• Preferred route – ferrous salts
– High Iron content
– Inexpensive
– Better absorbed than ferric salts
• Gastric irritation and constipation limits use
• Ferrous sulfate
• Ferrous gluconate
• Ferrous fumerate
• Colloidal ferric hydroxide

8. • Other preparations
– Ferrous succinate,
– Iron choline citrate,
– Iron calcium complex
• Low Iron content (less GI upset) and expensive
• Dosage: 200 mg daily in 3 divided doses (3 – 5
mg/kg for children)

9. ADR
• Epigastric pain
• heartburn
• Nausea
• Vomiting
• Staining of teeth, metallic taste, bloating
• CONSTIPATION
• Diarrhoea

10. Iron Preparations - Parenteral
• Indications
– Failure to absorb oral Iron – malabsorption,
inflammatory bowel disease
– Post gastrectomy conditions
– Severe deficiency with chronic bleeding
– Either intolerance and non-compliance to oral
Iron
– With erythropoietin

11. • Calculation: 4.4 X body weight (kg) X Hb
deficit (g/dl)
• Preparations
– Iron-dextran (I.v., I.M.)
– Iron-sorbitol-citric acid complex(IM)

12. Newer preparations
• Ferrous-sucrose
• high molecular weight complex of iron
hydroxide with sucrose
• safer than the older formulations
• Dose:100 mg i.v
• hypersensitivity reaction is very low
• Indicated for anaemia in kidney disease
patients

13. • Ferric carboxymaltose
• Latest formulation of iron in which a ferric
hydroxide core is stabilized by a carbohydrate
shell
• macromolecule is rapidly taken up by the RE cells,
primarily in bone marrow (upto 80%)
• Iron is released and delivered subsequently to the
target cells
• rapid increase in haemoglobin level in anaemia
patients and replenished stores
• Incidence of acute reaction is very low

14. ADRs:
• Local: Pain in IM injection, pigmentation of skin,
sterile abscess
• – Systemic:
– Fever,
– headache,
– joint pain,
– flushing,
– palpitation,
– chest pain
– lymph node enlargement

15. Contd.
• Anaphylactoid reaction

16. Uses:
Iron deficiency anaemia
• Nutritional deficiency
• chronic blood loss
• Oral Iron preferred
• Target – 0.5 to 1 g/dl per week
• 1 to 3 months therapy plus 2 to 3 months
afterwards

17. Contd.
• Prophylaxis
– Later half of pregnancy and infancy
– Chronic illness, menorrhagia, after acute blood
loss
• Megaloblastic anaemia

18. ACUTE IRON POISONING
Infants and children – 10 to 20 tablets (60 mg/kg Iron)
Symptoms
Vomiting, abdominal pain,
Haematemesis, diarrhoea,
lethargy, cyanosis, dehydration, acidosis,
Convulsion, CVS collapse
Death

19. Contd.
• Haemorrhage and inflammation of gut, hepatic
necrosis and brain damage
• Treatment:
– Prevent further absorption
a. Induce vomiting or gastric lavage with NaHCO3
b. Egg yolk and Milk orally
• Antidote: Desferrioxamine
• 0.5 to 1.00 gm IM repeated 4 – 12 Hourly
• DTPA and Calcium edetate
• Supportive: Fluid and electrolyte, correction of
acidosis and Diazepam

20. Introduction
• Complex cobalt containing compounds
Cyanocobalamin and hydroxocobalamin
• Physical: Water soluble, red crystals
• Sources: Liver, Kidney, sea fish, egg
yolk,Cheese
• Daily Requirement: 1 – 3 mcg

21. Function
• Conversion of homocysteine to methionine:B12
deficiency THFA gets trapped in the methyl form
and a number of one carbon transfer reactions
suffer
• essential for cell growth and multiplication
DAB12
• Methionine S-adenosyl methionine
• Purine and pyrimidine synthesis is affected
primarily due to defective ‘one carbon’ transfer
because of ‘folate trap

22. Deficiency - Vit. B12
• Pernicious anaemia
• Gastric mucosal damage
• Damaged intestinal mucosa
• Consumption by abnormal flora
• Nutritional deficiency
• Increased demand

23. Manifestations
• Megaloblastic anaemia
• Glossitis
• GI disturbance
• Degeneration of spinal cord &Peripheral
neuritis: diminished vibration and position
sense, paresthesias, depressed stretch
reflexes; mental changes

24. Preparations
• Cyanocobalamin Injection
• Hydroxocobalamin Injection
• Methylcobalamin Tablets
• higher protein binding and better retention in
blood, hydroxocobalamin is preferred

25. Dose
• Prophylactic dose: 3–10 μg/day orally in those
at risk of developing deficiency
Therapeutic dose:
• Injected vit B12 is a must when deficiency is
due to lack of intrinsic factor
• Cyanocobalamin 100 μg i.m./ s.c. daily for 1
week, then weekly for 1 month, and then
monthly for maintenance indefinitely

26. Vit. B12 – Uses and ADRs
• Prophylactic: in diabetics and alcoholics
• Treatment of deficiency states: Add Folic acid
and Iron
• Mega doses:
– Neuropathies
– Psychiatric disorders
– Cutaneous sarcoid
• Tobacco amblyopia – cyanide to
cyanocobalamin

27. • ADRs: Safe
• – allergic reactions due to contaminants

28. FOLIC ACID

29. Metabolic function
Conversion of homocysteine
to methionine
Generation of thymidylate
Conversion of serine to
glycine
Purine synthesis de novo
Histidine metabolism

30. Deficiency
• Inadequate dietary intake
• Malabsorption
• biliary fistula
• Chronic alcoholism
• Increased demand
• Drug induced:Phenytoin, barbiturates

31. Manifestations:
• Megaloblastic anaemia
• Epithelial damage
– glossitis, enteritis, diarrhoea
• Neural tube defects
• General debility

32. Preparations
• Folic acid tablets and Folinic acid Injections

33. Uses
• Megaloblastic anaemia
– Nutritional deficiency
– Pernicious anaemia
– Malabsorption syndromes
– Antiepileptic therapy
• Prophylaxis: 1 mg per day routinly in pregnancy
• Methotrexate toxicity: Folinic acid
• Citrovorum factor rescue:high dose of
methotrexate is injected i.v followed by i.v folinic
acid

34. • To enhance anticancer efficacy of 5-
fluorouracil:Folinic acid is given

35. • Folic acid should never be given alone to
patients with vit B12 deficiency, because
haematological response may occur, but
neurological defect may worsen due to
diversion of meagre amount of vit B12 present
in body to haemopoiesis

36. ADR
• Non toxic orally
• Sensitivity by injections rarely

37. Erythropoietin
(EPO)

38. Introduction
• Sialoglycoprotein hormone – produced by
peritubular cells of Kidney
• Recombinant human erythropoietin (Epoetin
α, β) – administerd IV or SC
• Half life: 6 – 10 Hours
• Required for erythropoiesis

39. Functions
• Stimulates proliferation of colony forming cells
of erythroid series
• Induces Hb formation and erythroblast
maturation
• Release of reticulocytes

40. MOA:
• Binds to specific EPO receptor (JAK-STAT-
kinase)
• Alters phosphorylation of intracellular
proteins
• Activates transcription factors to regulate
gene expression
• Erythropoiesis

41. Uses
• Anaemia of chronic renal failure
– 25 – 100 U/kg SC or IV 3 times a day
– concomitant Iron therapy
• Anaemia with AIDS patients treated with
zidovudine
• Cancer chemotherapy induced anaemia
• Preoperative increased blood production –
autologous transfusion

42. ADRs:
• Increased clot formation in AV- shunts
• hypertensive episodes
• Seizure
• flu like symptoms

44. MCQ
• 1) A patient has subclinical folate deficiency.
All of the following drugs can precipitate
megaloblastic anemia in this patient except
• (a) Alcohol
• (b) Phenytoin
• (c) Chloroquine
• (d) Sulfasalzine

45. Granulocyte colony stimulating factor
• Filgrastim
• Pegfilgrastim
• Lenograstim

46. GM-CSF
• Sargramostim
• Molgramostim

47. • 2) Iron is most commonly absorbed from:
• (a) Duodenum and upper jejunum
• (b) Lower jejunum
• (c) Stomach
• (d) Ileum

48. • Pre-conceptional intake of which of the
following results in decrease in incidence of
neural tube defects?
• (a) Vitamin A
• (b) Folate
• (c) Vitamin E
• (d) Vitamin C

49. • Posterior column sensations in lower limbs
are lost in:
• (a) Vitamin A deficiency
• (b) Vitamin B12 deficiency
• (c) Vitamin C deficiency
• (d) Vitamin D deficiency

50. • Erythropoietin is mainly produced in
• (a) Liver
• (b) Kidney
• (c) Intestine
• (d) Bone

51. • Methotrexate should be given with which of
the following to decrease its side effects?
• (a) Folic acid
• (b) Cyanocobalamin
• (c) Thiamine
• (d) Folinic acid

52. • Deficiency of this haemophilic factor during
early pregnancy will result in neural tube
defect:
• (a) Folic acid
• (b) Iron
• (c) Cyanocobalamine
• (d) Antioxidants

53. • All of the following changes seen in
megaloblastic anemia can be corrected by
administration of folic acid except:
• (a) Megaloblastic hyperplasia of bone marrow
• (b) Macrocytic normochromic canges in RBC
• (c) Neurological changes
• (d) Loss of appetite and easy fatigue

54. • Cyanide poisoning can be treated by:
• (a) Pyridoxine
• (b) Vitamin B12
• (c) Hyperbaric oxygen
• (d) Flumazenil

55. THANK
YOU