Antianemeic drugs - PowerPoint PPT Presentation

antianemeic drugs n.
Skip this Video
Loading SlideShow in 5 Seconds..
Antianemeic drugs PowerPoint Presentation
Download Presentation
Antianemeic drugs

play fullscreen
1 / 38
Download Presentation
Antianemeic drugs
Download Presentation

Antianemeic drugs

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Antianemeic drugs Agents to Tr anemia Dr Alia Alshanawani

  2. Hematopoiesis: production of erythrocytes, platelets, & leukocytes from stem cells in ! Bone marrow. • Require a constant supply of 3 essential nutrients: - Iron - Vitamin B12 - Folic acid + hematopoietic growth factors. Anemia: deficiency in O2-carrying erythrocytes.

  3. Anti-anemic drugs In iron deficiency & other hypochromic anemia: • Iron • Pyridoxine, Riboflavin, Copper In megaloblastic anemia: • Vit B12 • Folic acid Hematopoietic GFs • Erythropoietin (in chronic renal failure).

  4. Agents used to Tr anemia 1- Iron: Iron deficiency is ! most common cause of chronic anemia. Total Body Iron 4 g in ! adult male 2.5 g in ! adult female Source: meat & green vegetables.

  5. Iron forms ! nucleus of ! iron-porphyrin heme ring, which together with globin chains forms Hg. • Hg reversibly binds O2 (delivery). • Iron deficiency causes: small erythrocytes with insufficient Hg are formed: microcytic hypochromic anemia. PK: • All of ! iron used to support hematopoiesis is reclaimed from catalysis of ! Hg in aged / damaged erythrocytes.

  6. Dietary requirements are small & easily available in food. Iron absorption: Actively absorbed in duodenum & proximal jejunum. In ! ferric (+++) form & is complexed to other organic & inorganic molecules. ! acids in ! stomach & hydrolytic enzs in small intestine release ! iron from these complexes. It is then reduced to ! ferrous (++) form (more readily absorbed). Absorption is increased by: glucose, amino acids & ascorbic acid. & decreased by : phosphate bicarbonate bile acids, antacids & tetracycline. Heme iron in meat Hg & myoglobin can be absorbed intact. Iron in vegetables & grains, tightly bound to organic compounds; < available for absorption.

  7. Excess iron: stored in mucosal cell as ferritin, a water-soluble complex. Distribution: Iron is transported in ! plasma bound to transferrin, a β globulin binds 2 molecules of ferrous iron. ! iron is transported to ! marrow for use /storage. ! transferrin-iron complex enters maturing erythroid cells by a specific R mechanism.

  8. Storage: When free iron levels are high, apoferritin is produced to sequester iron & protect organs from toxic effect of excess free iron. Iron is stored in intestinal mucosal cells & as ferritin, in macrophages in liver, spleen, & bone.

  9. A- Uses of iron: • Treatment of iron deficiency anemia • Prevent anemia in increased iron requirement: - premature infants, - children during rapid growth periods, - pregnant & lactating women, - increased blood losses & iron (heavy menstruation), - patients with chronic kidney disease & treatment with GF erythropoietin (parenteral iron is preferred). - Malabsorption, inadequate iron absorption, GIT bleeding, gastrectomy & severe small bowel disease.

  10. B- Treatment Iron deficiency anemia is treated with po/ parenteral iron. po iron if GIT is normal. 1- Po iron: 200 – 400 mg for 3-6 months. Forms: FERROUS sulfate, gluconate, fumarate or succinate. All are effective & inexpensive.

  11. SE: N, epigastric discomfort, abdominal cramps, constipation/ diarrhea & black stools. Treatment: lower ! dose/ taking ! tablet immediately after/ with meal.

  12. 2- Parenteral iron; used in ! Following cases: (postgasrectomy, small bowel section, inflammatory bowel disease, noncompliance of po, malabsorption syndrome, marked blood loss & advanced chronic renal disease). • Iron dextran: stable complex of ferric hydroxide & low molecular weight dextran (IM/ IV infusion). Advantage of IV: eliminates local pain & tissue staining (SE: IM). + allow delivery of entire iron dose. • Also Iron sorbitol (IM)

  13. SE: headache, light-headness, fever, arthralgia, N, V, back pain, flushing, urticaria, Bronchospasm. Rare: anaphylaxis & death. Also dextran can cause hypersensitivity reactions. • Alternative preparations: Iron-sucrose complex & iron Na+ gluconate complex. ONLY (IV) less hypersensitivity than dextran.

  14. A- Acute iron tox: (multiple blood transfusions /acute child iron poisoning) Signs & symptoms: Necrotizing gastroenteritis, V, abdominal pain, bloody diarrhea, followed by shock, lethargy, & dyspnea. + severe metabolic acidosis, coma & death. Treatment: • Whole bowel irrigation/ gastric lavage: 1% NaHCO3. • Antidote: Deferoxamine (Desferroxamine), potent iron-chelating agent, bind absorbed iron & promote its excretion in urine & feces (intragastric, IM, SC, IV infusion).

  15. B- Chronic iron tox: Overload / hemochromatosis, result when excess iron is deposited in ! heart, liver, pancreas, & other organs. It can lead to organ failure & death. Causes: patients with inherited hemochromatosis (excessive iron abs;; tissue damage), & iron overload in patients who receive many RBCs transfusions over a long period of time as chronic hemolytic, microcytic anemia (thalassemias).

  16. Treatment tox: intermittent phlebotomy: Removing one unit of blood every week until all excess iron is removed. Or parenteral deferoxamine (less efficient, more complicated, expensive, & hazardous). • Recent oral iron chelator: deferasirox. Effective as deferoxamine at reducing liver iron conc & more convenient.

  17. 2- Cyanocobalamin = Vitamin B 12 (extrinsic F) CoFactor for several essential biochemical reactions. Its Deficiency;; anemia, GI symptoms, & neurological abnormalities. Chemistry: porphyrin-like ring with a central cobalt atom & nucleotide. Source: Meat (liver), eggs, & dairy products. For therapeutic use: Cyanocobalamin & hydroxycobolamin.

  18. PK: Stored mainly in liver Normal daily requirement: 2 -3 mcg. For its absorption, it makes a complex with intrinsic Factor, a glycoprotein secreted by ! parietal cells of ! gastric mucosa + R mediated transport system in ! lumen. Must be converted to active forms b4 absorption: Deoxy-adenosyl-cobalamin & methyl-cobalamin. Vit B12 deficiency results from malabsorption due to lack/loss/ malfunction of intrinsic F. This intrinsic F may be absent in gastrectomy & pernicious (megaloblastic) anemia. Nutritional deficiency (rare). Route of administration: mainly: parenteral,, IM Or po/ aerosol. Excretion: kidney.

  19. Pharmacodynamics: essential enzymatic rxs require Vit B12: Methylcobalamin: as intermediate in ! transfer of methyl gp from N-methylTHF to homocysterine, forming methionine & tetrahydrofolate (THFA). Required for purines & DNA synthesis. Depletion of THFA prevent ! synthesis of DNA. Treatment: Vit B12 + folic acid.

  20. Clinical pharm: Features of Vit B12 deficiency: • Impaired DNA synthesis; mainly RBCs • Megaloblastic anemia (macrocytic anemia + leukopenia &/ thrombocytopenia) • Hematologic abnormalities • GI symptoms • Neurological syndrome: paresthesia & weakness in peripheral nerves, spasticity, & ataxia.

  21. Causes of vit B12 deficiency: • Pernicious anemia (Defective secretion of intrinsic F by ! gastric mucosal cells). • Partial/ total gastrectomy • Malabsorption syndrome, inflammatory bowel syndrome or small bowel resection. • Damage of distal ileum that absorb vitB12-intrinsic F complex, • Surgical resection of ! ileum. TR: Vit B12.

  22. Tr: parenteral inj of vit B12. Available as: 1-Cyanocobalamin 2-Hydroxycobolamin is preferred (more highly protein bound: longer duration). Uses: 1- Pernicious (Addison) anemia 2- Neurologic abnormalities 3- Gastrectomy 4- Cyanide poisoning; Hydroxyocobalamin will bind circulating & cellular cyanide molecules to form cyanocobalamin which is excreted in ! urine .

  23. Initial therapy: 100-1000 mcg of vit B12 IM daily or every other day for 1-2 wks • Maintenance: 100-1000 mcg IM once a month for life. • Oral dose of 1000 mcg of vit B12 in pernicious anemia who refuse or cannot tolerate ! inj. • After parenteral, ! vit can also administered as a spray/ gel.

  24. Adverse effect of Vit B12 1- Allergic hypersensitivity reactions 2- Arrhythmia secondary to hypokalemia.

  25. 3- Folic acid (FA): Function: synthesis of amino acids, purines, pyrimidines, DNA & therefore cell division. Its deficiency is uncommon. deficiency of THFA causes anemia, congenital malformations in newborns & occlusive vascular D. Chemistry: FA is pteroglutamic acid, composed of pteridine, P-aminobenzoic acid + glutamic acid.

  26. FA can undergo reduction, catalyzed by DHFRase>> dihydroFA >>HFA (active form). • Vit B12 is required for activation of FA (demethylation). • PK: Source (as polyglutamate form): yeast, liver, kidney, & green vegetables. 5-20 mg of folates are stored in liver. Route: po Converted to mono-glutamyl form then absorbed in ! proximal jejunum . Excreted in urine & stool.

  27. Preparations: 1- Synthetic FA (tablets/ parenteral) 2- Folinic acid (5-formyl derivative of THFA, active form).

  28. FA Deficiency is caused by • Malabsorption & inadequate dietary intake of folate. • Alcohol dependence • Liver Disease. Clinical Pharm: • Folate deficiency; megaloblastic anemia. (1 mg po daily): reverse megaloblastic anemia, restore normal serum folate, & replenish body store of folate. • Prophylactically: Pregnant women & patients with hemolytic anemia have increase folate requirements & may become FA-deficient, esp if their diets are marginal. • Maternal FA deficiency: fetal neural tube defect as spina bifida.

  29. Patients who require renal dialysis. • Drugs: Methotrexate, trimethoprim & pyrimethamine inhibit DHFRase: deficiency of folate CoFs;; megaloblastic anemia. • Long term use of phenytoin • H risk patients (FA supplementation): pregnancy, premature infants, hemolytic anemia, liver D, & renal dialysis.

  30. 4- Hematopoietic Growth Factors: Glycoprotein hormones regulate ! proliferation & differentiation of hematopoietic progenitor cells in Bone marrow. Produced by recombinant DNA technology.

  31. Erythropietin : Produced in ! Kidney 1- Epotein: PK: • IV/ SC • T1/2: 4-13 hr • Not cleared by dialysis. • Given 2-3 times weekly. 2- Darbepoetin (α): glycosylate form, longer t1/2.

  32. Pharmacodynamics: 1- Stimulate erythroid proliferation & differentiation by interacting with specific erythropoietin Rs on RBC progenitors. 2- Induces release of reticulocytes from bone marrow (BM) 3- Tissue hypoxia stimulate erythropoietin synthesis.

  33. Clinical Pharm/ Uses: 1- Anemia + chronic renal failure Erythropoietin 50-150 IU/kg, IV/SC: improve ! hematocrit (in 10 days) & Hg level (in 2-6 wk) & eliminate ! need for transfusion + Iron & FA. 2- Anemia in HIV patients & zidovudine (anti HIV). 3- Anemia in cancer patients. 4- Anemia due to BM disorders. As in patients with aplastic anemia & other BM failure states, & multiple myeloma. 5- Anemia associated with chronic inflammation (RA) 7- Anemia of prematurity 8- To accelerate erythropoiesis after phlebotomies. 9- Misused by athletes to increase O2 delivery & performance.

  34. Adverse effects &Toxicity: 1- Rapid increase of hematocrit & Hg: HTN & thrombosis. 2- Seizure, headache 3- Transient influenza-like syndrome 4- Mild allergic reactions.