Hematinics

Hematinics

• 1.
  HEMATINICS IRON VITAMIN B9 FOLICACID VITAMIN B12 COBALAMIN ERYTHROPOETIN
• 2.
  HAEMATINICS are substancesrequired in the formation of blood, and are used for treatment of anaemias. • Anaemia occurs when the balance between production and destruction of RBCs is disturbed by: (a) Blood loss (acute or chronic) (b) Impaired red cell formation due to: • Deficiency of essential factors, i.e. iron, vitamin B12 & folic acid. • Bone marrow depression (hypoplastic anaemia), erythropoietin deficiency. (c) Increased destruction of RBCs (haemolytic anaemia)
• 3.
  ANAEMIA Types: Normocytic, normochromicanaemia  Acute blood loss Microcytic, hypochromic anaemia  Iron deficiency anaemia, thalessimia Macrocytic anaemia  Vit B12 deficiency, folic acid deficiency Pernicious anaemia  Vit B12 deficiency Hemolytic anaemia  Destruction of RBC Sickle cell anaemia  Sickle shaped RBC Aplastic anaemia  Bone marrow disorder
• 4.
  • IRON isan essential body constituent. It is an essential constituent of hemoglobin, cytochrome, and other components of respiratory enzyme systems. Its chief functions are in the transport of oxygen to tissue (hemoglobin) and in cellular oxidation mechanisms. Depletion of iron stores may result in iron-deficiency anemia. Iron is used to build up the blood in anemia.Total body iron in an adult is 2.5–5 g. It is more in men (50 mg/kg) than in women (38 mg/kg). It is distributed into: • Haemoglobin (Hb) : 66% • Iron stores as ferritin and haemosiderin: 25% • Myoglobin (in muscles) : 3% • Parenchymal iron (in enzymes, etc.) : 6%
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  • Daily requirement •Adult male : 0.5–1 mg (13 μg/kg) • Adult female : 1–2 mg (21 μg/kg)(menstruating) • Infants : 60 μg/kg • Children : 25 μg/kg • Pregnancy : 3–5 mg (80 μg/kg)(last 2 trimesters) • Dietary sources of iron • Rich : Liver, egg yolk, oyster, dry beans, dry fruits, wheat germ, yeast. • Medium : Meat, chicken, fish, spinach, banana, apple. • Poor : Milk and its products, root vegetables.
• 6.
  • Haemoglobin isa protoporphyrin; each molecule having 4 iron containing haeme residues. It has 0.33% iron; thus 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. Iron is stored only in ferric form, in combination with a large protein apoferritin.
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  Iron is foundin two forms: • Heme Iron: Meat, Myoglobin • Non-Heme Iron: Cereals, Fruits, Legumes Vitamin C increases absorption of Non-Heme Iron Iron is absorbed via two mechanisms: i) active transport of ferrous iron and ii) absorption of iron complexed with heme
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  Absorption of IRON
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  • MOA: Ironis important component of hemoglobin that carries oxygenated blood from lungs to different body parts. It also acts as catalyst for many metabolic reactions essential for cell growth. It maintains a healthy immune system & aids in energy production. It is transported inside mucosal cell by DMT1 & across basolateral membrane BY FP1 transporter protein . Iron released into plasma binds to transferrin & transported to different cells. • Indication: • Dietary Iron deficiency • Pregnancy • Premature babies • Malabsorption • Haemodialysis • Anaemia
• 10.
  Oral iron • Thepreferred route of iron administration is oral. • Ferrous sulfate: (hydrated salt 20% iron, dried salt 32% iron) • Ferrous gluconate (12% iron) • Ferrous fumarate (33% iron) Dose: 200 mg elemental iron (infants and children 3–5 mg/kg) TDS Absorption is much better in empty stomach. A/E: Gastric Irritaion, Constipation, Staining of teeth, Metallic taste Parenteral iron • Iron therapy by injection is indicated only when: 1. Oral iron is not tolerated: bowel upset is too much. 2. Failure to absorb oral iron: inflammatory bowel disease. 3. Non-compliance to oral iron. 4. In presence of severe deficiency with chronic bleeding. 5. Along with erythropoietin. • IRON DEXTRAN • IRON SUCROSE, DOSE: 75mg i.m (Max 100mg i.m.)
• 11.
  ACUTE IRON POISONING •It occurs mostly in infants and children: 10–20 iron tablets or equivalent of the liquid preparation (> 60 mg/kg iron) may cause serious toxicity in them. • Manifestations are vomiting, abdominal pain, haematemesis, diarrhoea, lethargy, cyanosis, dehydration, acidosis, convulsions; finally shock, cardiovascular collapse and death. • Treatment It should be prompt. To prevent further absorption of iron from gut (a) Induce vomiting or perform gastric lavage with sodium bicarbonate solution (b) Give egg yolk and milk orally: to complex iron. To bind and remove iron already absorbed Desferrioxamine (an iron chelating agent) is the drug of choice. It should be injected i.m. (preferably) 0.5–1 g (50 mg/kg) repeated 4–12 hourly as required, or i.v. (if shock is present) 10–15 mg/kg/hour; max 75 mg/kg in a day till serum iron falls below 300 μg/dl.
• 12.
  VITAMIN B12 (Cobalamin, Antiperniciousanemia factor)
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  VITAMIN B12 (COBALAMIN) •It occurs as red crystals synthesized in nature only by microorganisms; plants and animals acquire it from them. • MOA: Vitamin B12 is essential constituents of the human diet, being necessary for DNA synthesis and consequently for cell proliferation. • Vitamin B12 is important in the normal functioning of the nervous system due to its role in the synthesis of myelin and in the maturation of developing red blood cells in the bone marrow. • Dietary sources Liver, kidney, sea fish, egg yolk, meat, cheese, legumes, etc. • Daily requirement 1–3 μg, pregnancy and lactation 3–5 μg.
• 14.
  Vitamin B12 isa family of related compounds containing a cobalt atom (cobalamins). The two dietary forms of vitamin B12 are available and they are known as methylcobalamin (methyl-B12) and 5- deoxyadenosylcobalamin (coenzyme-B12). Synthetic forms of vitamin B12 are known as hydroxy-cobalamin and cyanocobalamin (not occur naturally in foods).
• 16.
  Vitamin B12 isrequired for: A. Conversion of methyl-FH4 to active formyl-FH4, which is a co-factor in the synthesis of purines and pyrimidines. B. Isomerisation of methylmalonyl-CoA to succinyl-CoA.
• 17.
  • METHYLCOBALAMIN isthe active coenzyme form of vit B12 for synthesis of methionine and S- adenosylmethionine that is needed for integrity of myelin. • This preparation of vit B12 in a dose of 1.5 mg/day has been especially promoted for correcting the neurological defects in diabetic, alcoholic and other forms of peripheral neuropathy. • Indications: a) Megaloblastic anemia b) Neurologic syndrome associated with cobalamin deficiency c) Pernicious anemia d) Treatment of vit B12 deficiency
• 18.
  VITAMIN B9 (FOLIC ACID)
• 19.
  VITAMIN B9 (FOLICACID) • It occurs as yellow crystals which are insoluble in water, but its sodium salt is freely water soluble. • Chemically it is Pteroyl glutamic acid (PGA) consisting of pteridine + paraaminobenzoic acid (PABA) + glutamic acid. • MOA: Folic acid is a precursor needed to make, repair, and methylate DNA; a cofactor in cell division and growth, such as in infancy and pregnancy. • Folate is itself inactive. After absorption it is converted into the active coenzyme, tetrahydrofolic acid, essential for amino acid and DNA biosynthesis and cell division.
• 21.
  Folate deficiency occursdue to: (a) Inadequate dietary intake (b) Malabsorption: especially involving upper intestine—coeliac disease, tropical sprue, regional ileitis, etc. (c) Biliary fistula; bile containing folate for recirculation is drained. (d) Chronic alcoholism: intake of folate is generally poor. (e) Increased demand: pregnancy, lactation, rapid growth periods, haemolytic anaemia and other diseases. (f) Drug induced: prolonged therapy with anticonvulsants (phenytoin, phenobarbitone, primidone) and oralcontraceptives— interfere with absorption and storage of folate. Manifestations of deficiency are: (i) Megaloblastic anaemia, indistinguishable from that due to vit B12 deficiency. (ii) Epithelial damage: glossitis, enteritis, diarrhoea, steatorrhoea. (iii) Neural tube defects, including spina bifida in the offspring, due to maternal folate deficiency.
• 22.
  Sources : yeast, liver , green vegetables, fruits , nuts and cereals Daily requirements : Adult: 50 mcg / day Pregnant women : 100-200 mcg / day Lactating women : 100-200 mcg / day Dose: Therapeutic 2 to 5 mg/day, prophylactic 0.5 mg/day. Indications: 1) Treat magaloblastic anemia due to folate deficiency 2) Pregnant women 3) Premature infants 4) Patients with hemolytic anemia 5) Methotrexate toxicity 6) Citrovorum factor rescue 7) Enhance anticancer efficacy of 5-fluorouracil 8) With anticonvulsant drugs
• 23.
  ERYTHROPOIETIN is aglycoprotein, normally made by the kidneys, that regulates red blood cell proliferation and differentiation in bone marrow. (a)Stimulates proliferation of colony forming cells. (b)Induces haemoglobin formation & erythroblast maturation. (c)Releases reticulocytes in the circulation. The recombinant human erythropoietin (Epoetin α, β) is administered 25–100 U/kg by i.v. or s.c. injection 3 times a week.
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  Indication: • Anaemia • ChronicRenal failure (patients with Hb ≤ 8 g/dl should be considered for EPO) • Anaemia in AIDS patients treated with zidovudine. • Cancer chemotherapy induced anaemia. • Preoperative increased blood production for autologous transfusion during surgery. • A/E: Increased clot formation in the A-V shunts (most patients are on dialysis), hypertensive episodes, serious thromboembolic events, occasionally seizures & Flu like symptoms.
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  White blood cells Platelets Redblood cells Artery
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  Stem cell Hemocytoblast Proerythro- blast Early erythroblast Late erythroblast Normoblast Phase1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus Reticulo- cyte Erythro- cyte Committed cell Developmental pathway
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