ANTIANAEMIC DRUGS Anaemia - Lconcentration of hemoglobin (Hb) > \L oxygen carrying capacity of the blood = normal haemoglobin: 13-18 g% (male); 11.5-16.5 g% (female) Causes: 1. Diminished production = deficiency of iron, By2& folic acid (most common in Myanmar) ~ depressed haemopoiesis (bone marrow depression, decrease erythropoietin) 2. Excessive red cell destruction: haemolytic anaemia : uraemia, widespread malignant diseases Types: Based on mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (mcHc) 1. Normocytic (within normal range} 2, Microcytic hypochromic (e.g,, iron deficiency anaemia } 3. Normochromic (e.g., sepsis) 4. Macrocytic (e.g,, vitamin B2 & Folic acid deficiency) Diagnosi = _ blood film - hypochromic microcytic in iron deficiency anaemia - _ megaloblastic macrocytic in vit. By» & folic acid deficiency anaemia The goal of anemia therapy = to increase Hb to levels that improve red cell oxygen-carrying capacity, alleviate symptoms, and prevent complications from anemia IRON DEFICIENCY ANAEMIA. Iron physiology - total body iron = 3-5 g ( 50 mg/kg (male) ; 38 mg/kg (female) - Hb contains 2/3 of total body iron requirement =1 mg (low) - 13 pg/kg for male, 21 g/kg for female, 60 g/kg for infants, 25 yg/kg for children, 80 pg/kg for pregnancy - dietary sources - meat and vegetable ~ iron released by R&C destruction is reused for Hb synthesis - absorbed as Fe2+, more in duodenum, carried along in blood as ferritinnorrnal lass fram desquamated epithelia storage asfemitin and haemosiderin (liver, spleen, bone marrow) no excretory mechanism regulation of iron balance must be achieved by changing intestinal absorption & storage of iron in respanse to bady’ need Ducdenum — Dietary iron (average, 1-2 mg LS) per dey) Uiilization pall \F Muscle (myoglobin) (300 mg) 6 Liver Reticulo- parenchyma endothelial (1000 mg) eee (600 ma) ‘Sloughed mucosal cells, Desquamation Menstruation Other blood loss, (average, 1-2 molday) Iron loss FIGURE 66-2. The distribution of iron use in adults. (From Andrews NC. Disorders of iron metabolism. N Eng! J Med. 1999;341:1 986-1995) bution of iron in the bodyDeficiency states 3 major factors, {@) chronic blood loss - piles, Gl ulcers, heavy menstruation {0) increased physiological demand = pregnancy ane lactation = growth sourt in children and adolescence = premature infants {ch inadequate intake or assorption - life-long vegetarian diet = subtotal gastrectomy = hook worm infestation Iron therapy Indication: - for iron deficiency states ‘Types: oral and parenteral {a) Oral iron therapy - preferred route of iron administration + safe, efficient, inexpensive = wide variety of preparations 1) Ferrous sulphate 2}. Ferrous gluconate 3). Ferrous fumarate (Furamin BC) (ferrous furarate, riboflavin, folic acié, ascorbic acia) = 50-100 mg of iron can be incorporated into haemoglobin daily and about 25% of oral iron given as Fe™ salt can be absorbed = thus, 200 - 400 mg of elemental iron should be given daily to correct iron deficiency anaemia rapidly = oraliron should be continued for 3 - 6 month after correction of iran loss to replenish iron stares ‘Toke Preparation Sie Fercueate, 325 ma hyraed Feoussuifte, 200mg deceit’ Fert 325 m9 gluconate Faroe 250) fumarate emental onper ma asm soma 4 ‘Some commonly used oral iron preparationDose - 200 - 400 mg/day (25 mg iron per day increases 1% of Hb (0.15g%Hb) per day; a reticulocyte response occurs between 4 ~ 12 days) Side effects = Glupset - constipation, nausea, epigastric pain, abdominal cramps, diarrhea - dose related black coloured stool (can be mistaken for malena stool) ~ staining of teeth, metallic taste (b) Parenteral iron therapy Indication: 1. Intolerance to oral iron therapy 2. Impaired iron absorption from GIT Various post gastrectomy conditions Previous small bowel resection Inflammatory bowel disease involving proximal small bowel Malabsorption syndrome Severe anaemi in late pregnancy or before surgery Extensive blood loss which cannot be maintained with oral iron alone Inj iron dextran (inferon) - 50mg of elemental iron / mL of the solution - deep IM, IV injection or infusion - IV daily doses of 2 ml (undiluted) until the total dose is reached or given as a single total dose infusion, diluted in 250-1000 mL of 0.9% saline infused over 1-2 hour = _ advantages - eliminate the local pain and tissue staining - _ to prevent anaphylaxis - small test dose should always be given caution for IM admi stration - each day's dose should not exceed 0.5 ml (25 mg iron) for infants< 2.5 kg - 1 mL (50 mg iron) for children <9 kg = 2 mL (100 mg iron) for other patients until the calculated total amount required has been reached = should be injected only into the muscle mass of upper outer quadrant of the buttock using a Z- track technique (displacement of skin laterally prior to injection) Inj iron sorbitol citric acid complex (Jectofer) - deep IM (should not be given IV)IV sodium ferric gluconate complex (Ferrlecit) Side effects: ~ local pain and tissue staining (brownish discolouration of tissue overlying the injection site), long-continued discomfort and concerned about malignant change at site of injection (which make IM inappropriate except when IV route is inaccessible) ~ headache, back pain, fever, arthralgia, nausea, vomiting ~ allergic reaction (flushing, urticaria, bronchospasm, rarely anaphylaxis and death) Caution: - _ should perform a small test dose (0.5 ml = 25 mg of iron) ~ _anti-shock measure to be kept ready Acute iron intoxication - with oral preparation ~ adult can tolerate large dose (50 g) without toxicity but 1- 2 g of iron but may be lethal in young children ~ signs and symptoms are necrotizing gastroenteritis, with vomiting, abdominal pain, and bloody diarrhea followed by shock, lethargy, and dyspnoea ~ may be followed by severe metabolic acidosis, coma, and death Treatment: - gastric aspiration followed by lavage with bisodium carbonate solution to form insoluble iron salt (Activated charcoal does NOT bind iron, ineffective) ~ intragastric desferioxamine to prevent further absorption - intermittent IM injection or continuous IV infusion of desferioximine to promote its excretion from body ~ appropriate supportive therapy (shock, acidosis, coma) Chronic iron overload (Hemochromatosis) - excess iron deposition in the heart, liver, pancreas, and other organs that can lead to organ failure and death - most commonly occurs in patients with inherited hemochromatosis, a disorder characterized by excessive iron absorption, and in patients who receive many red cell transfusions over a long, period of time (e.g, individuals with B-thalassemia) Treatment: - Chronic iron overload in the absence of anemia is most efficiently treated by intermittent phlebotomy (One unit of blood can be removed every week until all of the excess iron is removed) - Other options: Parentral desferioximine (1-2 g/day, infusion) ; Oral iron chelator deferasirox or deferiproneVITAMIN B.2 AND FOLIC ACID - both are essential for normal DNA synthesis ~ deficiency leads to impaired DNA synthesis, inhibition of normal mitosis, and abnormal maturation and fun n of the cells produced ~ Byzalso essential for maintenance of myelin sheath Vitamin B,, (active form - cyanocobalamin, hydroxocobalamin) Source: diet: yeast, cheese, liver, kidney, sea fish, egg yolk, meat and legumes (pulses) Daily requirement: - 1-3 g/day, pregnancy and lactation —3-5 pg Absorption: = terminal ileum, as intrinsic factor-B;» complex ~ binds to protein (glycoprotein, transcobalamin Il) ~ transported to tissue, storage in liver - not significantly metabolised, excreted via bile, Deficiency state: megaloblastic anaemia Causes: = impaired absorption due to = lack of intrinsic factor in total or partial gastrectomy - lack of absorptive capacity - malabsorption ~ drugs (e.g, phenformin, metformin, PAS, cimetidine, neomycin) Clinical feature: ~ plossitis, weakness, palpitation, tinnitus ~ subacute combined degeneration of spinal cord (SACD) Indication: Prevention and treatment of Vit. B,> deficiency due to = pernicious anaemia (Intrinsic Factor deficiency) - total gastrectomy = malabsorption syndrome ~ diagnostic use (Schilling test) Dose: For Vit Bra deficiency of dietary origin, Or 0-150 pg or more daily taken between meals IM: initially 1000 pg repeated 10 times at interval of 2 - 3 days, maintenance 1000 ug every 3 months For pernicious anaemia, other macrocytic anaemias = without neurological involvement, initially 1000 j4g 3 times a week for 2 weeks then 1000 ng every 3 months.~ with neurological involvement, initially 1000 ig on alternate days until no further improvement, then 1000p every 2 months Folic acid deficiency (water soluble vitamin) = common in Myanmar Active form: - tetrahydrofolic acid Source: - fresh green leafy vegetable, animal protein (heat labile) Daily requirement: = 50 meg/day (100 - 200 meg in pregnancy, lactation and in patients with increase cell turnover) Absorption: - duodenum, upper jejunum Pharmacokinetics: - orally absorbed, widely distributed, excreted in stool and urine = low body store and high daily requirement = intake of folic acid stopped within 1-6 month, anaemia can occur Deficiency state - megaloblastic anaemia a ical features - glossitis, irritability, forgetfulness, sleeplessness Causes: - decrease intake - poverty, ignorance, cooking method ~ impaired absorption ~ increase demand - pregnancy, haematological disorder - drugs (e.g., phenytoin, oral contraceptive, isoniazid, methotrexate) Indication: Prevention and treatment of folic acid deficiency due to ~ dietary deficiency ~ malabsorption syndrome = pregnancy ~ patient with haemolytic anaemia - alcoholic ~ patient with liver disease - patient who requi Preparation - tablet form (5 mg/tab) Dose: s renal dialysis + oral tially 5 mg daily for 4 months i maintenance 5 mg every 1-7 days depending on underlying disease = therapy should be continued until the underlying cause of the deficiency is removed or correctedPrecaution: should never be given alone or in conjunction with inadequate amount of vitamin By» for the treatment of undiagnosed megaloblastic anaemia (it may mask the vitamin B,, deficiency state; precipitate SACD) folate dependent tumor Drug Interaction Vitamin C+ Iron = Increase iron absorption Alcohol + Iron = Increase iron absorption Tetracycline + Iron = Chelation = Reduced absorption of both Iron + Haemopoietic vitamins/minerals = Better haemopoiesis, more effective treatment of