Section 6/ Drug Acting on Blood 248 of which 66% is in haemoglobin and 25% is stored as ferritin and hemosiderin and rest is in muscles and enzyme Iron absorption occurs predominantly in the duodenum and upper jejunum The physical state of iron entering the duodenum greatly influences its absorption At physiological pH, ferrous iron is rapidly oxidized to the insoluble ferric form Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron When gastric acid production is impaired, iron absorption is reduced substantially Ascorbic acid enhances iron absorption Ascorbic acid mobilizes iron from iron-binding proteins in vivo, which in turn could catalyze lipid peroxidation Iron absorption is inhibited by antacids, phytates, phosphates and tetracyclines The iron is transferred by the mucosal epithelium to the body and is bound to plasma transferrin in the ferric state In the plasma, iron takes part in a dynamic transferrin-iron equilibrium and is distributed into vascular and interstitial extravascular compartment 50 to 60% of transferrin is extravascular The plasma iron pool in adults is about mg and has an estimated turnover of 20 to 30 mg per 24 hours Daily and obligatory losses of iron in healthy men are about mg; in healthy menstruating women these average mg and in either case are compensated by a net absorption of to mg from the intestine, which enters the mobile pool of transferrin iron Pharmacokinetics After oral administration iron is absorbed in ferrous form The conversion of ferric iron to ferrous iron is aided by hydrochloric acid Iron is transported via transferrin When body stores of iron are high, ferric iron combines with apoferritin to form ferritin Ferritin is the protein of iron storage About 80 percent iron in plasma goes to erythroid marrow The excretion of iron is minimal Only little amount of iron is lost by exfoliation of intestinal mucosal cells and trace amount is excreted in urine, sweat and bile After confirmation of iron deficiency iron therapy can be given by oral or parenteral route Generally oral iron therapy is given unless the patient is suffering from severe anaemia, malabsorption syndrome, gastrectomy or patient is showing adverse effects to oral iron therapy Uses Nutritional iron deficiency anaemia; other causes in which iron deficiency can occur are pregnancy, lactation, infants, children In patients with malabsorption syndrome, patients who are taking NSAIDs for long period, patients with chronic inflammatory disease and in patients of gastrectomy Preparations of iron alone or in combination with vitamin B12, folic acid or other vitamins are available (see table 6.2.1) Most of the oral formulations contain one of the iron compound with many vitamins, amino acids, liver extract, minerals, folic acid, appetite stimulants (cyproheptadine like compound) Adverse Effects Oral administration can cause nausea, vomiting, epigastric pain, metallic taste, staining of teeth, constipation and diarrhoea both can occur, but constipation is more common Haematinincs (Drugs Used in Anaemia) 249 Table 6.2.1: Classification for iron preparations Ferrous sulphate (Hydrated salt 20% iron, exsiccated salt 30% iron; FERSOLATE) Ferrous gluconate (12% iron; FERRONICUM) Ferrous fumarate (33% iron; AUTRIN) Colloidal ferric hydroxide (50% iron; NEOFERUM) 200-600 mg/day 300-1200 mg/day 100-300 mg/day 200-800 mg/day Other forms of iron which are present in different pharmaceutical preparations are ferric ammonium citrate, ferrous succinate, iron choline citrate, ferrous amionate, iron calcium complex, carbonyl iron, ferric glycerophosphate, haemoglobin, elemental iron, ferrous glycine sulphate, glycerinated haemoglobin, and iron (III) hydroxide polymaltose complex (equivalent to elemental iron) Parenteral preparations: Iron dextran (IMFERON) & Iron-sorbitol citric acid complex (JECTOFER) The parenteral administration can cause local pain at the site of injection The other adverse effects include headache, fever, flushing, palpitation, dyspnoea, chest pain, metallic taste and even disorientation and temporary loss of taste IV administration can cause anaphylactic reaction characterized by circulatory collapse and even deaths have been reported Treatment of Acute Iron Poisoning Gastric lavage with 1% sodium bicarbonate solution to remove any undissolved iron tablets Administration of milk or egg yolk to complex iron Specific iron binding chelating agent like desferrioxamine mesylate (5-10 g in 100 ml isotonic saline) or calcium diethylene triamine pentaacetate (DTPA) 35-40 mg/kg or calcium disodium acetate (35-40 mg/kg) Electrolytes and other fluids to correct metabolic acidosis and hypotension Supportive administration of various agents e.g anticonvulsants drugs to control convulsions ERYTHROPOIETIN It is produced primarily by peritubular cells in the proximal tubule of the kidney In anaemia renal secretion of erythropoietin increases rapidly manifold Erythropoietin levels are always detectable in plasma It exerts its action by binding to receptor on surface of erythroid precursor cells There is increase in intracellular concentration of calcium and arachidonate and changes in intracellular phosphorylation It stimulates proliferation, maturation and haemoglobin formation by committed erythroid progenitors Recombinant human erythropoietin is available It is given by parenteral route (IV or SC) It is used in the treatment of anaemia of chronic renal failure, in anaemia of patients with AIDS who are being treated with zidovudine and anaemia associated with cancer chemotherapy Adverse effects include exacerbation of or new onset of hypertension and seizures in patients with renal disease This page intentionally left blank Section Drugs Acting On GIT This page intentionally left blank ...Haematinincs (Drugs Used in Anaemia) 249 Table 6.2.1: Classification for iron preparations Ferrous sulphate (Hydrated salt 20% iron, exsiccated salt 30% iron; FERSOLATE)... hydroxide (50% iron; NEOFERUM) 200-600 mg/day 300-1200 mg/day 100-300 mg/day 200-800 mg/day Other forms of iron which are present in different pharmaceutical preparations are ferric ammonium citrate,... changes in intracellular phosphorylation It stimulates proliferation, maturation and haemoglobin formation by committed erythroid progenitors Recombinant human erythropoietin is available It is