Chapter 55

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 55

Drugs for Deficiency Anemias

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

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 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


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


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


Iron Deficiency Most common nutritional deficiency and

cause of nutrition-related anemia Causes Consequences Diagnosis


Iron Daily requirements

Determined by rate of erythrocyte production Increased requirement during pregnancy

Dietary sources Available in foods of plant and animal origin


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


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)


Oral Iron Preparations I: Iron Salts Ferrous sulfate

Indications—drug of choice Prophylactic therapy

Adverse effects GI disturbances Staining of teeth Toxicity


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


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


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)


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


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


Vitamin B12 (Cobalamin)

Fate in the body Absorption Distribution and storage Elimination


Vitamin B12 Deficiencies: Causes, Consequences, and Diagnosis

Causes Usually result of impaired absorption Regional enteritis Celiac disease Absence of intrinsic factor


Vitamin B12 Deficiencies: Causes, Consequences, and Diagnosis

Consequences Megaloblastic anemia Neurologic damage

• Demyelination of neurons GI disturbances

Diagnosis Measurement of plasma B12

Schilling test


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


Guidelines for Treating Vitamin B12 Deficiency

Route of B12 administration Treatment of moderate B12 deficiency Treatment of severe B12 deficiency Long-term treatment Potential hazard of folic acid


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


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


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


Folic Acid Preparations Nomenclature Folic acid (pteroylglutamic acid)


Guidelines for Treating Folic Acid Deficiency

Choice of treatment modality Route of administration Prophylactic use of folic acid Treatment of severe deficiency

Documents

Chapter 55