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Chapter 55

Chapter 55. Drugs for Deficiency Anemias. Anemias. Decrease in erythrocytes (RBCs) Number Size Hemoglobin content Causes Blood loss Hemolysis Bone marrow dysfunction Deficiency of substances essential for RBC formation and maturation. Red Blood Cell Development.

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Chapter 55

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  1. Chapter 55 Drugs for Deficiency Anemias

  2. Anemias • Decrease in erythrocytes (RBCs) • Number • Size • Hemoglobin content • Causes • Blood loss • Hemolysis • Bone marrow dysfunction • Deficiency of substances essential for RBC formation and maturation

  3. Red Blood Cell Development • Development begins in the bone marrow • Matures in the blood • Evolves through four stages • Healthy development requires: • Healthy bone marrow erythropoietin, iron, and other factors to support DNS synthesis

  4. Biochemistry and Physiology of Iron • Metabolic functions • Fate in the body • Uptake and distribution • Uptake into mucosal cells in small intestine • Undergoes storage within mucosal cells • Undergoes binding to transferrin • Utilization and storage • Taken up by cells of the bone marrow • Taken up by the liver and other tissues • Taken up by muscle

  5. Iron in the Body • Fate in the body (cont’d) • Recycling:undergoes continuous recycling • Elimination:1 mg of iron excreted each day • Regulated through control of intestinal absorption

  6. Iron Deficiency • Most common nutritional deficiency and cause of nutrition-related anemia • Causes • Consequences • Diagnosis

  7. Iron • Daily requirements • Determined by rate of erythrocyte production • Increased requirement during pregnancy • Dietary sources • Available in foods of plant and animal origin

  8. Iron Deficiency: Causes, Consequences, and Diagnosis • Results from an imbalance in iron uptake and iron demand • Causes • Pregnancy (blood volume expansion) • Infancy and early childhood • Chronic blood loss • Consequences • Microcytic, hypochromic anemia

  9. Iron Deficiency: Causes, Consequences, and Diagnosis • Diagnosis • Presence of microcytic, hypochromic erythrocytes • Absence of hemosiderin in bone marrow • Other laboratory work • RBC count • Reticulocyte count • Hemoglobin • Hematocrit • Serum iron • Increased serum iron-binding capacity (IBC)

  10. Oral Iron Preparations I: Iron Salts • Ferrous sulfate • Indications—drug of choice • Prophylactic therapy • Adverse effects • GI disturbances • Staining of teeth • Toxicity

  11. Oral Iron Preparations I: Iron Salts • Drug interactions • Antacids • Tetracycline • Ascorbic acid • Other oral iron salts • Ferrous gluconate, ferrous fumarate, and ferrous aspartate • Carbonyl iron

  12. Parenteral Iron Preparations I: Iron Dextran • Iron dextran (INFeD, DexFerrum) • Used for patients who have experienced intolerable or ineffective oral dosing • Adverse effects • Anaphylactic reactions • Hypotension • Persistent pain with IM injection

  13. Parenteral Iron Preparations II: Sodium Ferric Gluconate Complex and Iron Sucrose • Alternatives to iron dextran • Sodium ferric gluconate (SFGC) (Ferrlecit) • Low risk of anaphylaxis • Iron sucrose (Venofer) • Limited to patients undergoing chronic hemodialysis • All patients must also receive erythropoietin • Most common side effects • Hypotension • Cramps • Ferumoxytol • Approved in 2009 • Iron deficiency anemia, chronic kidney disease (CKD)

  14. Iron Deficiency Treatment Guidelines • Assessment • Routes of administration • Duration of therapy • Therapeutic combinations

  15. Vitamin B12 (Cobalamin) • Essential for synthesis of DNA • Absorption requires intrinsic factor • Elimination takes place very slowly • Daily requirement • Dietary sources • Limited to microorganisms • Animal products (liver, dairy products) • Fortified foods

  16. Vitamin B12 (Cobalamin) Fate in the body • Absorption • Distribution and storage • Elimination

  17. Vitamin B12 Deficiencies: Causes, Consequences, and Diagnosis • Causes • Usually result of impaired absorption • Regional enteritis • Celiac disease • Absence of intrinsic factor

  18. Vitamin B12 Deficiencies: Causes, Consequences, and Diagnosis • Consequences • Megaloblastic anemia • Neurologic damage • Demyelination of neurons • GI disturbances • Diagnosis • Measurement of plasma B12 • Schilling test

  19. Vitamin B12 Preparations: Cyanocobalamin • Administration • Oral, parenteral, intranasal • Adverse effects • Hypokalemia • Long-term treatment • With lack of intrinsic factor, vitamin B12 therapy lifelong • Potential hazards of folic acid

  20. Guidelines for Treating Vitamin B12Deficiency • Route of B12 administration • Treatment of moderate B12 deficiency • Treatment of severe B12 deficiency • Long-term treatment • Potential hazard of folic acid

  21. Folic Acid Deficiency • Folic acid • Essential factor for DNA synthesis • DNA replication • Cell division cannot proceed • Absorbed in the early segment of the small intestine • Significant amounts excreted daily • Daily requirements • Dietary sources: all foods

  22. Folic Acid Anemia: Causes and Consequences • Causes • Poor diet (malnutrition and alcoholism) • Malabsorption syndrome (sprue) • Consequences for developing fetus • Neural tube defects (eg, spina bifida, anencephaly) • Adequate intake before conception is critical • The USPSTF now recommends that women of child-bearing age consume 400 to 800 mcg of supplemental folate each day, in addition to the folate they get in food

  23. Folic Acid Anemia:Causes and Consequences • Consequences for anyone • Megaloblastic anemia • Leukopenia, thrombocytopenia, injury to the oral and GI mucosa • May increase risk of colorectal cancer and atherosclerosis

  24. Folic Acid Preparations • Nomenclature • Folic acid (pteroylglutamic acid)

  25. Guidelines for Treating Folic Acid Deficiency • Choice of treatment modality • Route of administration • Prophylactic use of folic acid • Treatment of severe deficiency

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