1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 55 Drugs for Deficiency Anemias

2. 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 Deficiency of substances essential for RBC formation and maturation

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Biochemistry and Physiology of Iron  Metabolic functions  Fate in the body  Uptake and distribution Uptake into mucosal cells in small intestine Uptake into mucosal cells in small intestine Undergoes storage within mucosal cells Undergoes storage within mucosal cells Undergoes binding to transferrin Undergoes binding to transferrin  Utilization and storage Taken up by cells of the bone marrow Taken up by cells of the bone marrow Taken up by the liver and other tissues Taken up by the liver and other tissues Taken up by muscle Taken up by muscle

5. 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Iron Deficiency  Most common nutritional deficiency and cause of nutrition-related anemia  Causes  Consequences  Diagnosis

7. 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Iron  Daily requirements  Determined by rate of erythrocyte production  Increased requirement during pregnancy  Dietary sources  Available in foods of plant and animal origin

8. 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Iron Deficiency: Causes, Consequences, and Diagnosis  Diagnosis  Presence of microcytic, hypochromic erythrocytes  Absence of hemosiderin in bone marrow  Other laboratory work RBC count RBC count Reticulocyte count Reticulocyte count Hemoglobin Hemoglobin Hematocrit Hematocrit Serum iron Serum iron Increased serum iron-binding capacity (IBC) Increased serum iron-binding capacity (IBC)

10. 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Oral Iron Preparations I: Iron Salts  Ferrous sulfate  Indications—drug of choice  Prophylactic therapy  Adverse effects  GI disturbances  Staining of teeth  Toxicity

11. 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Parenteral Iron Preparations II: Sodium Ferric Gluconate Complex and Iron Sucrose  Alternatives to iron dextran  Sodium ferric gluconate (SFGC) (Ferrlecit) Low risk of anaphylaxis Low risk of anaphylaxis  Iron sucrose (Venofer) Limited to patients undergoing chronic hemodialysis Limited to patients undergoing chronic hemodialysis All patients must also receive erythropoietin All patients must also receive erythropoietin  Most common side effects  Hypotension  Cramps  Ferumoxytol  Approved in 2009  Iron deficiency anemia, chronic kidney disease (CKD)

14. 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Iron Deficiency Treatment Guidelines  Assessment  Routes of administration  Duration of therapy  Therapeutic combinations

15. 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vitamin B 12 (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. 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vitamin B 12 (Cobalamin) Fate in the body  Absorption  Distribution and storage  Elimination

17. 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vitamin B 12 Deficiencies: Causes, Consequences, and Diagnosis  Causes  Usually result of impaired absorption  Regional enteritis  Celiac disease  Absence of intrinsic factor

18. 18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vitamin B 12 Deficiencies: Causes, Consequences, and Diagnosis  Consequences  Megaloblastic anemia  Neurologic damage Demyelination of neurons Demyelination of neurons  GI disturbances  Diagnosis  Measurement of plasma B 12  Schilling test

19. 19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vitamin B 12 Preparations: Cyanocobalamin  Administration Oral, parenteral, intranasal Oral, parenteral, intranasal  Adverse effects Hypokalemia Hypokalemia  Long-term treatment With lack of intrinsic factor, vitamin B 12 therapy lifelong With lack of intrinsic factor, vitamin B 12 therapy lifelong Potential hazards of folic acid Potential hazards of folic acid

20. 20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Guidelines for Treating Vitamin B 12 Deficiency  Route of B 12 administration  Treatment of moderate B 12 deficiency  Treatment of severe B 12 deficiency  Long-term treatment  Potential hazard of folic acid

21. 21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Folic Acid Deficiency  Folic acid  Essential factor for DNA synthesis DNA replication DNA replication Cell division cannot proceed Cell division cannot proceed  Absorbed in the early segment of the small intestine  Significant amounts excreted daily  Daily requirements  Dietary sources: all foods

22. 22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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. 24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Folic Acid Preparations  Nomenclature  Folic acid (pteroylglutamic acid)

25. 25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Guidelines for Treating Folic Acid Deficiency  Choice of treatment modality  Route of administration  Prophylactic use of folic acid  Treatment of severe deficiency