Haematinics

HAEMATINICS
Haematinics are the agents required in the formation of blood
and used for the treatment of anaemia.
• Essential Haematinics: Iron, Vitamin B12, Folic acid

Etiology: Anaemia occurs when:

• Blood loss (acute or chronic)
• Impaired RBC formation due to:
a) Deficiency of iron, vit B12, folic acid.
b) Bone marrow depression.
• Increased destruction of RBCs
 Haematinics : IRON

IRON: Essential for haemoglobin production.

• Each molecule of haemoglobin has 4 iron containing residues.
• Total body Iron : 2.5 – 5 g
• Loss of 100 ml of blood (containing 15 g Hb) means loss of 50
mg elemental iron. To raise the Hb level of blood by 1 g/dl—
about 200 mg of iron is needed.
• Stored in ferric form with apoferritin.
Apoferritin + Fe 3+ Ferritin
aggregates
Ferritin Haemosiderin
 Haematinics : IRON

Distribution of Iron in the body Daily Iron requirement

Haemoglobin 66% Adult male : 0.5–1 mg
Ferritin, haemosiderin 25%
Adult female : 1–2 mg (menstruating)
Myoglobin (in muscles) 03%
Enzymes (cytochromes etc) 06% Children : 25 µg/kg
Pregnancy : 3–5 mg
Dietary sources of iron rich
Liver, egg yolk, dry fruits,
wheat germ, spinach,
Meat, chicken, fish,
banana, apple.
 Iron absorption
Dietary iron

Haeme Inorganic iron (Fe3+)

Meat grains & vegetables
Absorbed faster Slowly absorbed
As such needs to be dissociated
ferro from organic compounds
Fe3+ reductase
Fe2+(absorbed)
• Two separate iron transporters in the intestinal mucosal cells function to effect iron absorption:
1. divalent metal transporter 1 (DMT1)
carries ferrous iron into the mucosal cell.
2. ferroportin are bound with ferrous iron
& pass through mucosal cell
directly into the blood steam.
Iron absorption, transportation, utilization & storage

Average daily diet contains 10–20

mg of iron, of which 10% is
absorbed from all over the
intestine (majority upper part)
 Iron : Storage and Excretion
• Iron is stored in RE cells (in liver, spleen, bonemarrow), as well as
in hepatocytes and myocytes as ferritin and haemosiderin.
• Daily excretion of iron in adult male is 0.5–1 mg, mainly as
exfoliated g.i. mucosal cells, some RBCs and in bile (lost in
faeces).
• Other routes :skin, little in urine and sweat.
• In menstruating women,
monthly menstrual loss is 0.5-1 mg/day.
Oral Iron Adverse effects
• Epigastric pain, nausea, vomiting
• Staining of teeth, blackening of stool
• Metallic taste
• Constipation (astringent effect)/ diarrhoea (irritant effect)

Oral Preparations
•Ferrous sulphate 200mg- 3-4 tablets/day
•Ferrous succinate
•Iron choline citrate
•Ferric ammonium citrate
•Ferric gluconate
Parenteral iron
Given parenterally as deep IM injection or intravenously, only in following
indications: Parentral Preparations
•Oral iron is not tolerated: bowel upset • Iron- dextran
•Failure to absorb oral iron: malabsorption. • Iron-sorbitol-citric acid
•Non-compliance to oral iron. • Iron sucrose and sodium ferric
gluconate
•In severe deficiency with chronic bleeding.
•Along with erythropoietin
Adverse effects :
pain at the site of injection
pigmentation of skin
Headache, joint pain, palpitation,
urticaria, nausea, rarely anaphylaxis
 Acute Iron Poisoning
• More common in infants and children Uses of Iron:
• 1-2g can be lethal Iron deficiency anaemia: prophylaxis
Symptoms: and treatment
Vomiting, abdominal pain, haematemesis, Increased Iron requirement:
Bloody diarrhoea, shock, drowsiness, pregnancy, infancy, professional
acidosis, dehydration, cardiovascular blood donors.
collapse
• Immediate treatment is important
Treatment
 Gastric lavage with sodium bicarbonate
Give egg yolk and milk orally: to complex
iron. Activated charcoal does not adsorb iron.
 Antidote : Desferrioxamine IV/IM :
prevents Iron absorption.
 Correction of acidosis and shock
 Maturation Factors: Vitamin B12 & Folic Acid
Water soluble, B-complex Group Vitamins. Daily requirement of Vitamin B12 &
folic acid
Essential for Normal DNA synthesis
Adults Pregnancy
Deficiency: Megaloblastic anaemia Vit B12 1-3µg 3-5µg
•Impaired DNA synthesis Folic acid 50-100µg 200-400µg
•Abnormal maturation of RBCs
•Other manifestations: Glossitis, stomatitis
•Neurological manifestations-
subacute degeneration of spinal cord
peripheral neuritis
 VITAMIN-B12 (Cyanocobalamin)
• Complex cobalt containing compounds Cyanocobalamin and hydroxocobalamin 
• synthesized by microorganisms; plants and animals acquire it from them.
Dietary sources : Liver, kidney, sea fish, egg yolk, meat, cheese.
• Two active coenzyme forms of B12 are deoxyadenosyl-cobalamin (DAB12) and
methyl-cobalamin (methyl B12).

Vit B12 deficiency occurs due to:

1. Addisonian pernicious anaemia:
autoimmune disorder → deficiency of
intrinsic factor due to destruction of gastric
parietal cells → inability to absorb vit B12.
2. Other causes :chronic gastritis,
gastrectomy, malabsorption, infestation of fish
tape worm.
Vit B12 is absorbed in the intestine with the help of Intrinsic factor. It is transported
in the blood by Transcobalmin II to the liver for storage or to erythropoietic cells to
facilitate conversion of methyltetrahydrofolic acid to Tetrahydrofolic acid, important
in DNA synthesis. Vit B12 is not degraded in the body, excreted mainly in bile

Vit B12 and Folate metabolism

 Functions: Vitamin B12
Vit. B12 act as cofactor in following rxn-
• conversion of homocysteine to methionine – methionine is methyl
group donor in metabolic reactions .
• Purine and pyrymidine synthesis – needed for DNA synthesis
• Malonic acid DAB12 Succinic acid –
important for propionic acid metabolism
(Carbohydrate and lipid metabolism)

• for cell growth and multiplication

 Preparations and Uses of Vitamin B12
• Vit B12 is directly and completely absorbed after i.m. or deep s.c. injection.
• Cyanocobalamin: 35 μg/5 ml liq., Hydroxocobalamin: 500 μg, 1000 μg inj.
• Mostly available as combination preparation along with other vitamins
Uses:  Treatment of Vitamin B12 deficiency
Megaloblastic anaemia : defects in the metabolism of vitamin B12 or folic acid.
Pernicious anaemia : body isn't able to absorb orally vitamin B12 due to a lack of
intrinsic factor so given parentrally IM orSC
• Prophylaxis : 3-10 μg daily
• Neurological condition
Neuropathies, trigeminal neuralgia,
Multiple sclerosis, psychiatric disorders
 Folic Acid
• Pteroyl glutamic acid (PGA) (pteridine + paraaminobenzoic acid (PABA) +
glutamic acid.)
• Dietary sources: Liver, green leafy vegetables (spinach), Yeast , egg, milk.
• Present in food as poly-glutamates
• Absorption :in the duodenum and jejunum
• Transported in the blood as methyl-THFA  by active and passive transport.
• Stored in cells as polyglutamate, Liver takes up a large part
and secretes methyl-THFA in bile

Functions:
folate
DHFRa se
FA reductase DHFA THFA
THFA- essential for the biosynthesis of purines.
Deficiency & manifestation:
• Megaloblastic anaemia.
• Dietary deficiency.
• Malabsorption.
• Epithelial damage.
• Weight loss
• • Folic acid: -liquid oral, Injectable
Few drugs e.g. phenytoin,
phenobarbitone, methotrexate,
oral- contraceptives can induce
folate deficiency.
Therapeutic use:
• Megaloblastic anaemia
• Folic acid deficiency
• Protect epithelial cell
• Growth in infants
• in pregnancy
Preparations and dose:
• Folinic acid:-CALCIUM LEUCOVORIN 3
mg/ml inj.
 Erythropoietin (EPO)
• Hormone secreted by peritubular cells of kidney, essential for normal
erythropoiesis.
• Kidney cells release EPO in response to anaemia and hypoxia
• Binds to EPO receptors on red cell progenitors and stimulates red cell production:
Induces haemoglobin formation and erythroblast maturation.
Releases reticulocytes in the circulation.
Recombinant human erythropoietin
1. Epoetin α: given thrice weekly
2. Epoetin ß: once in 2-4 weeks
3. Darbopoetin α: longer half-life
given once a week
• administered by i.v. or s.c.
 Erythropoietin (EPO)
Therapeutic Uses:
In treatment of anaemia due to:
• Chronic renal failure if Hb < 8 mg/dl
• Zidovudine therapy in AIDS patients
• Cancer chemotherapy
• Multiple myeloma and cancer of bone marrow
Adverse Effects: with sudden rise in hematocrit.
Hb level should not exceed 12g/dl.
• Increased clot formation in the A-V shunts
• Hypertensive episodes
• Serious thromboembolic events
• Flu like symptoms
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