What is anaemia ?• Definition:• Erythropoeisis :• Causes: Anemia occurs when balance between production and destruction of RBC`S is disturbed by – Blood loss ( acute or chronic) – Impaired red cell formation due to • Deficiency of essential factors (iron, vitamin B12 ) • Bone marrow depression • Erythropoietin deficiency – Destruction of RBC`S ( hemolytic anemia)• Types of Anemia
Iron deficiency anemia – Hemoglobin = Haem + Globin – Haem = Ferrous Iron (Fe2+) chelated between porphyrin rings and globin chain – When iron is inadequate small erythrocytes with insufficient hemoglobin are formed giving rise to microcytic hypochromic anemia• Clinical features Pallor, fatigue, dizziness, exertional dyspnoea• Total body content of iron 3.5 to 4 gm in adult male , 2.5 gm female
• Daily requirement of iron – Adult male 0.5 to 1 mg – Menstruating female 1-2 mg/ day – Pregnancy 3-5 mg/day – Infant 60 µg/Kg – Children 25 µg/Kg• 5- 10 % of the dietary iron is absorbed• 1 molecule of hemoglobin = 33% iron• 1ml blood loss= 0.5 mg iron loss• Dietary sources of iron
Dietary sources of iron• Rich :liver,egg yolk,dry beans,dry fruits,wheat germ,yeast• Medium:meat,chicken,fish, spinach, banana, apple• Poor:milk and its products,root vegetables
• Haeme iron is better absorbed, but forms a smaller fraction of the dietary iron(6%).• Dietary iron :Haeme or non haeme /Inorganic iron• Non haeme iron and iron in inorganic form is present as ferric iron must be first reduced to ferrous iron .
• Pharmacokinetics • Dietary iron mostly in the ferric form (Fe3+)In the stomach Fe3+ Fe2+In the mucosal cells Fe2+ Fe3+ Apoferritin Ferritin ( Stored) Iron slowly released In the plasma Fe2+ Fe3+ + Transferrin Iron bound transferrin Transfers iron to bone marrow , Liver , Spleen ( Stored)
• Iron excretion – Tenaciously conserved in body 0.5 to 1 mg excreted – Intestine , Bile and sweat – Menstrual blood loss 0.5 to 1 mg/ day – Milk 1.5 mg appears in milk daily during lactation
Factors affecting iron absorption– Facilitated by • Acidic pH of stomach , • Ascorbic acid • Cysteine by reducing ferric to ferrous form– Inhibited by • Excess phosphates, oxalates, Phytates • Milk, antacids, tetracycline ↓ iron absorption by forming insoluble complexes.
Iron preparations can be given in 2 routes – Orally – Parenterally
ORAL IRON THERAPY These preparation are mostly available as ferrous(Fe+2) and some in ferric(Fe+3)form Ferrous salt are better absorbed than ferric salts
– Oral 1. Ferrous sulphate: 200 mg tab contains 20 – 32% iron 2. Ferrous gluconate : 300 mg tab contains 12% elemental iron 3. Ferrous fumarate: 200 mg tab ( 33%) 4. Colloidal ferric hydroxide: 200 mg tab (50%) • Other oral preparations are ferrous choline citrate , ferric ammonium citrate , iron calcium complex, iron hydroxy polymatose.
Iron is poorly absorbed in the form ofcarbonate, citrate and pyrophosphate, colloidaliron and iron carbohydrate complexFORMS •Tablets, capsules •Sugar coated & uncoated tablets •Slow release tabs & chewable tabs •Drops &syrups—used by childrens
• Dosage : – 200 mg of elemental iron in three divided doses produces maximal haemopoietic response –Prophylactic dose is 30 mg daily –Absorption better on empty stomach but side effects more
• Important points to remember oElemental iron content and not quantity of iron compound per unit dose to be considered oSustained released preparations expensive and irrational oLiquid formulations should be put on back of tongue and swallowed
• Indications for iron therapy – Prophylactic • Pregnancy: 100 mg elemental iron 4 month onward • Infancy and rapidly growing children • Professional blood donors: 300 mg FeSo4 daily 1 month • Menstruating women and following partial gastrectomy – Therapeutic • Nutritional deficiency anemia (↓ Intake, ↓absorption) • Anemia of infancy and pregnancy • Anemia due to acute or chronic blood loss
• Response to oral therapy is considered as satisfactory if Hb ↑ by 1 % per day (0.15 g %) , with atleast 10 % (1.5 g % ) within 3 weeks• Following oral iron normal Hb attained in 1- 3 months depending on initial Hb level but therapy should be continued for 12 to 20 weeks after Hb levels return to normal in order to replenish depleted stores
Causes of failure of oral iron therapy• Incorrect Diagnosis• Non compliance• Continued blood loss• Defective iron absorption• Superimposed infection/Inflammation• Underlying uremia or malignancy
Adverse reactions to oral iron• Constipation is common than diarrhea• Epigastric pain• Vomiting• Heart burn• Metallic taste• Nausea• Staining of teeth.
Indications of parenteral therapy• Oral iron is not tolerated• Failure to absorb oral iron• Non compliance to oral iron• In presence of severe deficiency with chronic bleeding• Along with erythropoietin
Calculation for parenteral iron• Parenteral iron therapy needs calculation of total iron requirement of the patient – Iron requirement (mg) = 4.4 X Body wt (Kg) X Hb deficit g/dL
Parenteral iron preparations1. Iron dextran (Imferon): I.V/ I.M2. Iron sorbitol citric acid complex: Only I.M3. Iron carbohydrate complex : I.M4. Sodium ferric gluconate: Recently approved preparation for I.V use has much lower risk of anaphylactic reaction than iron dextran
I.M therapy• Iron dextran and iron sorbitol both contain 50 mg/mL recommended dose is 100 mg daily 2 mL on alternate days untill total required dose is administered or maximum 2 g . To prevent staining to skin given deep I.M in buttock using z track technique
I.V Therapy• Iron dextran after test dose 0.5 mL iron dextran injected I.V over 5 to 10 min• Total dose required diluted in 500 mL NS & infused slowly over 6 to 8 hours under supervision• If required amount greater than 50 mL given on two consecutive days
Comparative properties of iron dextran and iron sorbitolIron dextran Iron sorbitol1. High molecular weight 1. Low molecular weight2. I.M / I.V 2. I.M3. I.M , 10 -30 % locally bound not 3. Not locally boundavailable for immediate utilisation4. Not excreted 4. 30 % excreted in urine5. I.M absorbed through lymphatics 5. Absorbed directly in circulation6. Not bound to transferrin 6. Bound to transferrin may saturate it so very high free levels of iron in blood will be attained so not suitable for I.V administration7. Taken up by macrophages and 7. Directly availablemade slowly available to erythron
Adverse effects• Intramuscular: – Local pain at site , pigmentation of skin , sterile abcess – Systemic: headache, fever, arthralgia, backache, tachycardia, flushing hemolysis and collapse these effects are probably due to excessive amount of free iron in plasma – Iron sorbitol may cause disorientation and temporary loss of taste, urine turns black on standing
Adverse effects• Intravenous – Systemic reaction of more severe form – Anaphylactoid reaction can occur within minutes – Severe chest pain , resp distress circulatory collapse
Treatment of Acute iron poisoning1. Stomach wash with 1% NaHCO3 to render it insoluble and remove undissolved iron tablets2. Desferrioxamine Mesylate 5 to 10 g in 100 mL isotonic saline or calcium sodium edetate 35 to 40 mg/Kg to retard the absorption from GIT3. Early replacement of fluids and electrolytes, correction of metabolic acidosis and hypotension by using RL and vasopressors4. I.v desferrioxamine infusion5. Diazepam and other anticonvulsants if epileptic
Desferrioxamine Mesylate• Obtained from streptomyces pilosus• Potent specific chelator of iron binds ferric iron to form ferrioxamine a stable water soluble chelate• Ferrioxamine is excreted 2/3 in urine and 1/3 in bile colors urine reddish brown• Removes iron from hemosiderin except that in bone marrow• Well tolerated rapid I.V may cause hypotension, anaphylactic reactions and tachycardia• Allergic reactions and cataract known with chronic administration• Contraindicated in renal disease anuria and pregnancy
• Uses of desferrioxamine – Acute iron intoxication DOC • I.M : 0.5 TO 1 g( 50 mg / kg repeat 4 to 12 hourly as required • I.V in shock: 10- 15 mg / Kg/ Hr Maximum 75 mg/ Kg in a day till serum iron falls less than 300 µg/dL