These are the substances required in the formation of blood, and are used in the treatment of anaemias

1. Heamatinics
Presented by:
Shivam Kumar Pandey
M.Pharm (1st Semester)2018-20
Department of Pharmacology
INDO-SOVIET FRIENDSHIP COLLEGE OF PHARMACY MOGA, (PUNJAB)
EMAIL: shivamkumarpandey067@gmail.con
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2. Contents
• Introduction
• Types of Anaemia
• classification of Haematinics
• Iron
• Maturation factors
• Erythropoietin
• References
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3. Haematinics
These are the substances required in the formation of blood, and are used in
treatment of Anaemias
Anaemia : a condition in which there is a deficiency of red cells or of
Haemoglobin in the blood or reduce concentration of Haemoglobin in the
Balance between production and destruction of RBCs are disturbed:
-Blood Loss (acute or chronic)
-Impaired cell formation due to
.Deficiency of essential factors – Iron, Vit. B12 and Folic acid
.Bone marrow depression
.erythropoietin deficiency Increased red blood cell destruction
(haemolytic )
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5. Types of Anaemia
1. Microcytic Anaemia : deficiency of iron
2. Macrocytic Anaemia: deficiency of folic acid and vitamin B₁₂
3. Pernicious anaemia: lack of intrinsic factor INF
4. Aplastic Anaemia : due to Bone marrow dysfunction
5. Haemolytic Anaemia : Excessive haemolysis
6. Sickle cell Anaemia : sickle shaped RBCꜱ
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6. Symptoms of Anaemia
The main symptoms of anaemia is fatigue but ,especially if it is
chronic-
Other symptoms include-
•Weakness
• Pale skin
• Rapid heartbeat
• Shortness of breath
• Dizziness
• Irritability in children with anaemia
• Coldness in hand and feet
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7. Classification of Haematinics
A. Iron
1. Oral preparation of iron 2. Parentral preparation of iron
Ferrous sulfate iron Dextran
ferrous succinate iron sorbital
ferrous aminoate iron sucrose
ferrous fumarate ferric coboxy maltose
ferrous gluconate
B. Maturation factor
Vitamin B12: Cynocobalamin ,hydroxycobalamin ,methylcobalamin
Folic acid: Folinic acid ( Leucovorine , festovorine )
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8. Iron
All body cells need iron . its crucial for oxygen transport energy production
and cellular growth and proliferation
. The human body contains an average 3.5gm (Male 4gm, female 3gm)
. Daily requirement of iron is
Adult male -1gm
Menstruating female -2mg
Pregnant female-5mg
Distribution
. About 65% of iron circulate in blood as Hb
. 25% store in liver, spleen and bone marrow as ferratin and haemosidrin
available for
haemoglobin synthesis
. Rest present in myoglobin , cytochrome and various enzyme
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9. Iron: Absorption
. Site of absorption –duodenum and upper jejunum
. In stomach iron dissolve and bind to mucoprotein(Carrier)
Dietary iron in ferric form (Fe3+) is low soluble in neutral pH and not absorb
Ascorbic acid
Reduce to ferrous form + Vitamin C
Soluble iron- ascorbate chelate
Absorption occurs
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10. Iron: transport
Iron enters in plasma in ferrous form
oxidise
Immediately into ferric form
complex with transferrin a carrier (glycoprotein)
storage in the mucosal to the plasma
as ferritin
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11. Iron : storage & Excretion
•In plasma immediately converted to Fe3+ form – complexed with transferrin (
Tfr) Total Plasma Iron – 3 mg - recycled
• In two forms: Ferritin & Haemosiderin
Apoferritn + Fe3+ Ferritin Haemosiderin
Excretions by:
• 0.5 to 1 mg/day – GI mucosal cells, RBCs and in Bile , Also in skin, urine and
sweat
Aggregates
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12. Iron Preparations – Oral
• Preferred route – ferrous salts – high Iron content, inexpensive,
better absorbed than ferric salts Gastric irritation and constipation limits use
– Ferrous sulfate (20% hydrated salt and dried salt 32% or 65 mg)
Ferrous gluconate (12% Iron or 28-36 mg)
Ferrous fumerate (33% or 106 mg)
Colloidal ferric hydroxide (50%) 150 to 200 mg per day
• Dosage: 200 mg daily in 3 divided doses (3 – 5 mg for children)
• ADRs: Epigastric pain, heart burn, nausea, vomiting, staining of teeth, metallic
taste, constipation
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13. Iron Preparations - Parenteral
 Indications: –
 Failure to absorb oral Iron – malabsorption, inflammatory bowel
disease
 Post gastrectomy conditions – Severe deficiency with chronic bleeding
 Calculation: 4.4 X body weight (kg) X Hb deficit (g/dl)
 Not faster absorption than oral but stores replenish faster
 Preparations: Iron-dextran (colloidal solution) 50 mg/ml Iron and Iron-
sorbitol-citric acid complex and Sodium ferric gluconate complex in
sucrose
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14. ADRs: –
 Local: Pain in IM injection, pigmentation of skin,
 Systemic: Fever, headache, joint pain, flushing, palpitation, chest
pain, dyspnoea, Metallic taste
 Anaphylactoid reaction – Kidney diseases (no sorbitol)
 Uses: – Iron deficiency anaemia: Nutritional deficiency, chronic
blood loss (GIT ulcers and hook worm)
 Oral Iron preferred : Target – 0.5 to 1 g/dl per week – 1 to 3
months therapy.
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15. Acute Iron Poisoning
• Symptoms: Vomiting, abdominal pain, diarrhoea, lethargy,
dehydration, acidosis.
.Haemorrhage and inflammation of gut, hepatic necrosis
Antidote: Desferrioxamine - an iron chelator 0.5 to 1.00 gm IM
repeated
4 – 12 Hourly or IV 10 – 15 mg/kg/Hour (max 75 mg/day) till serum
levels fall
- It bound with ferric & unbound iron, not absorbed from the gut &
prevent its absorption.
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16. Maturation factors :
Vitamin B₁₂
 Complex cobalt containing compounds Cyanocobalamin and
hydroxocobalamin
 Physical: Water soluble, red crystals synthesized only by
 Sources: Liver, Kidney, sea fish, egg yolk
 Daily Requirement: 1 – 3 mcg (Pregnancy and Lactation3 – 5 mcg)
 Vit. B12 – Kinetics
 Absorption: Present in food as protein conjugates – released by
cooking/proteolysis – IF forms a complex with Vit. B12 – attaches to
specific receptor in mucosa – absorbed by active transport
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17.  Transport: after absorption it is transported in the blood in
combination with transcobalamin ɪɪ
 Storage: In liver
 Degradation: Not degraded in body – excreted mainly in Bile
enterohepatic circulation
Deficiency: Addisonian pernicious anaemia (destruction of
parietal cells – IF absent), gastric mucosal damage, damaged
intestinal mucosa, c, nutritional deficiency.
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18.  Manifestations: Megaloblastic anaemia, GI disturbance, degeneration
peripheral neuritis , paresthesia
 Preparations: Cyanocobalamin Injection, Hydroxocobalamin Injection and
Methylcobalamin Tablets
 Vit. B12 – Uses and ADRs
 Prophylactically in diabetics and alcoholics – to prevent peripheral neuritis – 1.5
mg/day
 Treatment of deficiency states: Add Folic acid and Iron – Very quick response –
appetite increases, patient feel better, mucosal lesions heal, neurological
parameters improve – If due to IF factor lacking – IM or SC (not IV) Mega doses:
in neuropathies, psychiatric disorders
 Tobacco amblyopia – cyanide to cyanocobalamin
 ADRs: allergic reactions are may be occur
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19. Folic acid
 Introduction
 Physical: Yellow crystals, insoluble in water, Pteroyl glutamic acid (PGA) –
pteridine + paraminobenzoic acids + glutamic acid
 Daily requirement: 0.2 mg per day (0.8 mg in pregnancy and lactation)
 Kinetics: – Absorption: As polyglutamates in food – glutamates split off and
absorbed in upper intestine ….. Reduction to DHFA and methylation also
occurs at same site –
 Transport: as methyl-THFA – partly bound to plasma protein
 Store: tissues extract FA rapidly and store as polyglutamates in cells.
 Liver takes up major portion – releases methyl-THFA – enterohepatic
circulation (alcohol interferes) –
 Excretion: Pharmacological doses – excreted in Urine
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20. Folic acid – Metabolic function
 Conversion of homocysteine to methionine
 Generation of thymidylate
 Conversion of serine to glycine
 Purine synthesis de novo
 Histidine metabolism
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21. Deficiency - Folic acid
 Deficiency: Inadequate dietary intake, Malabsorption (upper GIT –
coeliac disease)
 biliary fistula, chronic alcoholism, increased demand (pregnancy),
drug induced (phenytoin, phenobarbitone etc.)
 Manifestations: Megaloblastic anaemia (body store lasts for 2-3
months), epithelial damage (glossitis, diarrhoea), neural tube defects
(spina bifida), general debility (weakness, loss weight, sterility)
 Preparations: Folic acid tablets and Folinic acid Injections (Calcium
leucovorin)
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22. Folic acid – Uses and ADRs
 Megaloblastic anaemia: due to nutritional deficiency,
 pregnancy, pernicious anaemia (adjuvant role with Vit.
B12),
 malabsorption syndromes, antiepileptic therapy
 Prophylaxis: 1 mg per day routinly in pregnancy
 Methotrexate toxicity: Folinic acid, citrovorum factor
 ADRs: Non toxic orally, sensitivity by injections rarely
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23. Erythropoietin
 Sialoglycoprotein hormone – produced by peritubular cells
Kidney
 • Recombinant human erythropoietin (Epoetin α, β) –
administerd IV or SC
 • Half life: 6 – 10 Hours • Required for erythropoiesis:
and hypoxia sensed by kidney cells – EPO secretes and acts
marrow: – Stimulates proliferation of colony forming cells of
erythroid series – Induces Hb formation and erythroblast
maturation – Release of reticulocytes
 • MOA: Binds to specific EPO receptor (JAK-STAT-kinase) –
alters phosphorylation of intracellular proteins and activates
transcription factors to regulate gene expression –
erythropoiesis
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24. Erythropoietin – Uses and ADRs
 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
 ADRs: Nonimmunogenic, ----- ADRs occur due to increase in
haematocrit, viscosity and peripheral resistance – increased clot
formation in AV- shunts, hypertensive episodes, seizure, flu like
symptoms
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25. References:
1. Tripathi KD. Essentials of Medical pharmacology. 7th ed. New Delhi : Jaypee
Brothers Medical Publisher (p) ltd ; 2013. pp.599-612
2. Rang & Dale’s pharmacology 6th edition ;2007. pp.329-392
3. Gobind Rai Garg & Sparsh Gupta Review of pharmacology.11th ed. New Delhi:
jaypee
Brothers Medical Publisher (p) ltd; 2017. pp.309-312
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