2. HEMATINICS
• Substances or essential nutrients that are required by the
body( Stem Cells) to the proper formation of components
of blood— iron, Vitamin B12, and Folic acid as well as
hematopoietic growth factors, proteins.
3. Hematopoiesis
• Formation of blood components— RBCs, Leukocytes & Platelets by
stem cells present in bone marrow.
• 200 billion new blood cells are produced each day & greater in
conditions that cause destruction or loss of blood cells.
• Inadequate supply of essential nutrients or growth factors result in
deficiency of functional blood cells can lead to Anemia,
Thrombocytopenia or neutropenia
• Iron, VIT. B12, and folic acid along with hematopoietic growth
factors play a key role in hematopoiesis
4. Types of Anemia
• Anemia is the decrease in the oxygen carrying capacity of blood due to reduced
concentration of hemoglobin or RBCs, due to a. dietary deficiency, b. faulty
absorption, transportation and storage, c. Blood loss, d. Excessive demand-
pregnancy, lactation, growth e. Infections
• Microcytic Anemia: —small cell RBCs—deficiency of Iron
• Macrocytic anemia:— large nucleated RBCs—low capacity of oxygen carrying—
VitB12 or Folic acid deficiency
• Pernicious anemia— megoloblastic anemia—failure of secretion of intrinsic factor by
stomach
• Haemolytic. Anemia— bone marrow destruction— premature RBCs— immune
disorder
• Aplastic anemia— hypo-plasia of bone marrow— bone marrow disease or cytotoxic
drugs
• Sickle cell anemia— altered amino acid structure of hemoglobin— presence of
hemoglobin-S— deshape the RBCs—increase viscosity of bloods— thrombosis &
infarcts
• Sideroblastic anemia— inadequate utilization of iron by bone marrow
5.
6.
7.
8.
9. AGENTS USED IN THE TREATMENT OF ANEMIA
• IRON
• VITAMIN B12
• FOLIC ACID
• ERYTHROPOIETIN GROWTH FACTORS
• OTHER MEASURES
10. IRON (FERROUS)
• Total body content of Iron- 3.5-4g M & 2.5g F— 70% in circulation as
hemoglobin, 15-18% stored in liver, spleen and bone marrow as
ferritin & hemosiderin
• Daily requirement of iron- 0.5-1mg about 5-10% of 10-15mg of daily
intake of elemental iron. 1-2/day for menstruation, and 3-5mg/d for
lactating and pregnant women & 25mg/kg/day for children
• Iron deficiency anemia— most common cause of chronic anemia
• Features— pallor, fatigue, dizziness, exertional Dyspnoea and tissue
hypoxia with tachycardia, inc. cardiac output, vasodilation
11. • Iron forms the nucleus of the iron-porphyrin heme ring, which
together with globin chains forms hemoglobin.
• Hemoglobin reversibly binds oxygen and provides the critical
mechanism for oxygen delivery from the lungs to other tissues.
• In the absence of adequate iron, small erythrocytes with insufficient
hemoglobin are formed, giving rise to microcytic hypochromic anemia
• Iron- containing heme is also an essential component of myoglobin,
cytochromes, and other proteins with diverse biologic functions.
12. IRON— Pharmacokinetics
• Absorption— by. Active transport of ferrous iron in duodenum and
proximal jejunum by divalent metal transporter(DMT1)
• Heme iron ( myoglobin in dietary meat and other. Sources ) is readily
absorbed than non heme iron which is absorbed as ferrous(Fe++)
• VIT. C, Succinic acid, and cysteine facilitate conversion of Fe3+ to Fe2+ for
absorption.
• Absorbed iron is transported by ferroportin
• Hepcidin inhibit the release of intestinal release of iron
• Excess iron is stored in intestinal cells as Ferritin(water soluble) in a shell of
Apoferritin
• Tea, coffee, antacids, Ca, Al, Mg— decreases iron absorption in GI system.
13. • Transportation: in plasma—Beta globulin, Transferrin—binds two
molecules of ferric iron—transferrin-iron—enters in erythroid cell(maturing
RBCs)
• In endosomes— dissociation of transferrin from iron — returns to plasma
and iron is ferrous is stored as ferritin or with synthesis of hemoglobin.
• Storage: mucosal cells macrophages in the liver, spleen bones and liver
cells- as ferritin,
• Mobilisation of iron from these cells is carried out by Hepcidin
• Ferritin is detectable in serum—estimation of total body iron stores.
• Elimination: no mechanism for excretion of iron, but little amounts in
feces due to exfoliation
14. Treatment of iron deficiency/ microcytic
anemia(hypo-chromic Anemia)
Oral Iron Therapy
• Available in elemental Iron tablets and suspensions &
sustained release granules
• Ferrous Sulphate/ fumerate/ lactate/ succinate/
gluconate
• Containing approximately 12%-33% Iron
• 200mg bd/tid after meals
• Children 3-5mg/kg/d
• Lactating mothers 30mg/d
• Also available in 100% iron content
• E.g ferric hydroxide polymaltose complex
• Side Effects
• Metallic taste, Staining of teeth, Epigastric Pain, N/V &
heart burn
Parenteral Iron Therapy
• Iron dextran 50mg/ml I/v I/M (0.8-2g of iron daily)
• Iron Sucrose IV, IM
• Iron Sodium Glonate IV, IM
• Iron Sorbitol citric acid IM only
• Sensitive test before administration
• Dosage
• DOSE in mg = [(14.8-Hb g/dl)^150]+600mg
• DOSE in ml = [(14.8-Hb g/dl)^150]+600mg / 50 of iron- dextran
• Side Effects
• Local-Pain at injection site, pigmentation, sterile abscess
• Systemic – fever, headache, lymphadenopathy, urticaria,
Anaphalactoid reaction- (palpitations, chest pain, dyspepsia, CV
collapse) & iron toxicity
• Antidote- Desferoxamine & deferasirox ( chelating Agents)
15. Treatment of megaloblastic/ Macrocytic
anemia(Hyper-chromic Anemia)
Vitamin B12( Cyanocobalamin,
Methylcobalamin, hydroxocobalmin)
• Source: meat, Fish, Liver, eggs, Yeast and
Milk & Microbial- streptomyces griseus
• Daily requirement: 2-3mcg/d
• Cyanocobolamin: 100-100mcg/d IM
• Methylcobalamin 1000-1500mcg/d
IM,PO
• Water soluble, in GIT—liberates from
food—binds R protiens—Pancreatic
proteases degrade—free cobalamin—a
absorbed onto Intrinsic factor(IF)—
transported across ilium cells—converted
into methylcobalamin— binds
transcobalmin II—portal circulation.
Folic Acid/ Vit B9(Pteroyglutamic Acid)
• Source: green leafy Vvegetables, fruits,
Mushrooms, milk and Yeast
• Absorption: proximal jejunum
• Daily Requirements: 50mcg/d
• Pregnancy :200-300mcg/d
• Also Used to treat folate deficiency due to
anti cancer agents, Phenytoin,
phenobarbital drugs.
• Dificiency due to: diet, Malabsorption,
excessive demand like pregnancy, liver
disease, drug induced
16. HEMATOPOIETIC GROWTH FACTORS
• Responsible to maintain balance between proliferation and differentiation
of blood cells.
• HGFs direct the division and maturation of : RBCs, Platelets, Monocytes,
Neutrophils, Eosinophils, Basophils, B-lymphocytes, T-lymphocytes
• HFGs also known a Cytokine Growth Factors, about 100 cytokines are
present but important among them are:
• Erythropoietin,
• Colony Stimulating factors(CSFs) such as:
• Granulocyte Colony Stimulating Factors
• Granulocyte Macrophage colony stimulating factors &
• Interleukins-II
17. ERYTHROPOIETIN
• In Human Body, a Cytokine Produced by
Juxutatubular(JXT) cells in kidneys and macrophages
and DNA recombinant Technology.
• Used in anemia/ myeosupression
• Stimulates bone marrow stimulation by acting on
receptors on red cell proginators and promote
release of reitculocytes from bone marrow
• Available as epoietin alpha and epoietin beta,& long
acting Darbepoietin
• Dosage 25-100IU/kg SC,IV, 3 times weekly
• Averse effects: Flu like symptoms, mild HT,
encephalopathy, increases blood viscosity due o
increase in HCT, risk of thrombosis
COLONY STIMULATING FACTORS(
MYELOID GROWTH FACTORS)(CSFs)
• Accelerate the formation of matured colonies of various bone
marrow progenator cells in Vitro include:
• 1. G-CSFs & GM-CSF
• Molgramostim
• Sargramostim
• Uses: Neutropenia related to Cytotoxic drugs, HIV, Congenital
neutropenia, Chemotheraphy,
• 2. Megakaryocyte Growth factors-
• Interleukin-II Alison known as thromobpoietin
• Ex. Oprelvekin
• Stimulates growth of myeloid and lymphoid cells— increase
peripheral platelets and neutrophils
• Uses: throbocytopenia in chemotherapy,
• Adverse effects: dizziness, headache, fatigue and Dyspnoea.
Anemia and production of auto antibody against
thrombopoietin
18. Other measures to control Anemia
• 1. Diet: iron rich foods , meat, fish, organ meat, eggs, green leafy
vegetables, mushrooms
• 2. Blood transfusion, blood components administration
• 3. Bone marrow transplantation
• Genetic counseling