Practical Clinical Pharmacy II – Lab.

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Drugs for Anemia
Dr. Heba Muwafak Attash

Introduction
 Hematopoiesis is the production (from undifferentiated stem cells) of circulating
erythrocytes, platelets, and leukocytes.
 The hematopoietic machinery resides in the bone marrow and requires a constant
supply of three essential nutrients (Iron, vitamin B12, and folic acid) as well as
hematopoietic growth factors.
 Inadequate supplies of either the essential nutrients or the growth factors result in
deficiency of functional blood cells.
Agents used in Anemia
Iron
 Iron deficiency is the most common cause of chronic anemia.
 Iron deficiency anemia leads to pallor, fatigue, dizziness and exertional dyspnea.
 Iron forms the nucleus of the iron-porphyrin heme ring which together with globin
chains forms hemoglobin.
 Hemoglobin reversibly binds oxygen and provides the critical mechanism for
oxygen delivery from the lungs to other tissues.
 In the absence of adequate iron, small erythrocytes with insufficient hemoglobin are
formed, giving rise to microcytic hypochromic anemia.
Indications for the use of Iron
 The only clinical indication for the use of iron preparations is the treatment or
prevention of iron deficiency anemia.
 Iron deficiency is commonly seen in populations with increased iron requirements.
These include:
1. infants
2. children during rapid growth period
3. pregnant and lactating women and
4. patients with chronic kidney disease.
 Inadequate iron absorption can also cause iron deficiency. This is seen after
gastrectomy and in generalized malabsorption

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Treatment
 Iron deficiency anemia is treated with oral or parenteral iron preparations.
 Oral iron corrects anemia as rapidly and completely as parenteral iron if iron
absorption from the gastrointestinal tract is normal.
Oral iron therapy
 Because ferrous iron is more efficiently absorbed, ferrous salts should be used.
Ferrous gluconate, and ferrous fumarate are all effective.
 In an iron deficient individual, about 50-100 mg of iron can be incorporated into
hemoglobin daily, and about 25% of oral iron given as ferrous salt can be absorbed.
 Therefore, 200 - 400 mg of elemental iron should be given daily to correct iron
deficiency most rapidly.
 Treatment with oral iron should be continued for 3-6 months after correction of the
cause of the iron loss.
 Common adverse effects of oral iron therapy include nausea, abdominal cramps,
constipation, and diarrhea.
 These effects are usually dose-related and can be overcome by lowering the daily
dose of iron or by taking the tablets immediately after or with meals.
Parenteral iron therapy
 Parenteral therapy should be reserved for patients with documented iron deficiency
who are unable to tolerate or absorb oral iron and for patients with extensive chronic
anemia who cannot be maintained with oral iron alone.
 Iron dextran is a stable complex of ferric oxyhydroxide and dextran polymers
containing 50 mg of elemental iron per milliliter of solution.
 It can be given by deep intramuscular injection or by intravenous infusion, although
the intravenous route is used most commonly.
 Intravenous administration eliminates the local pain and tissue staining that often
occur with the IM route.
 Adverse effects of intravenous iron dextran therapy include: headache, fever,
arthralgia, flushing, bronchospasm, and rarely, anaphylaxis and death.
Vitamin B12
 Vitamin B12 (cobalamin) serves as a cofactor for several essential biochemical
reactions in humans.
 Deficiency of vitamin B12 leads to megaloblastic anemia, gastrointestinal
symptoms, and neurologic abnormalities.
 Vitamin B12 is used to treat or prevent deficiency.

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 Once a diagnosis of megaloblastic anemia is made, it must be determined whether
vitamin B12 or folic acid deficiency is the cause.
 The most common causes of vitamin B12 deficiency are pernicious anemia,
gastrectomy, malabsorption syndromes, and inflammatory bowel disease.
 Pernicious anemia results from defective secretion of intrinsic factor by the gastric
mucosal cells. Patients with pernicious anemia have gastric atrophy and fail to
secrete intrinsic factor (as well as hydrochloric acid).
 Almost all cases of vitamin B12 deficiency are caused by malabsorption of the
vitamin; therefore, parenteral injections of vitamin B12 are required for therapy.
 Vitamin B12 for parenteral injection is available as cyanocobalamin or
hydroxocobalamin.
 Hydroxocobalamin is preferred because it is more highly protein-bound and
therefore remains longer in the circulation.
Folic acid
 Reduced forms of folic acid are required for essential biochemical reactions that
provide precursors for the synthesis of amino acids, purines, and DNA.
 Folate deficiency is relatively common, even though the deficiency is easily
corrected by administration of folic acid.
 The consequences of folate deficiency go beyond the problem of anemia because
folate deficiency is implicated as a cause of congenital malformations in newborns.
 Folate deficiency results in a megaloblastic anemia that is microscopically
indistinguishable from the anemia caused by vitamin B12 deficiency.
 Folate deficiency does not cause the neurologic syndrome seen in vitamin B12
deficiency.
Causes of folic acid deficiency
 Folic acid deficiency is often caused by inadequate dietary intake of folates.
 Patients with alcohol dependence and patients with liver disease can develop folic
acid deficiency because of poor diet and diminished hepatic storage of folates.
 Pregnant women and patients with hemolytic anemia have increased folate
requirements and may become folic acid deficient. Evidence implicates maternal
folic acid deficiency in the occurrence of neural tube defects.
 Patients with malabsorption syndromes also frequently develop folic acid
deficiency.
 Patients who required renal dialysis are at risk of folic acid deficiency because
folates are removed from the plasma during the dialysis procedure.

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 Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent,
trimethoprime and pyrimethamine, inhibit dihydrofolate reductase and may result in
megaloblastic anemia.

o Parenteral administration of folic acid is rarely necessary, since oral folic acid is well
absorbed even in patients with malabsorption syndromes.
o A dose of 1 mg of folic acid orally daily is sufficient to reverse megaloblastic anemia.
o Therapy should be continued until the underlying cause of the deficiency is removed
or corrected.
o Therapy may be required indefinitely for patients with malabsorption or dietary
inadequacy.
o Folic acid supplementation to prevent folic acid deficiency should be considered in
high- risk patients, including pregnant women, patients with alcohol dependence,
hemolytic anemia, liver disease, and patients on renal dialysis.