Anemia is a decrease in the number of red blood cells (RBCs), a decrease in the amount of hemoglobin in RBCs,or both a decrease in the number of RBCs and hemoglo-
bin. When there is an insufficient amount of hemoglobin to deliver oxygen to the tissues, anemia exists. There are various types and causes of anemia. For example, anemia can be the result of blood loss, excessive destruction of
RBCs, inadequate production of RBCs, and deficits in var-ious nutrients, such as in iron deficiency anemia. Once the type and cause have been identified, the primary
health care provider selects a method of treatment.
The anemias discussed in this chapter include iron deficiency anemia, anemia in patients with chronic renal disease, pernicious anemia, and anemia resulting
from a folic acid deficiency. Drugs used in treatment of anemia are sum-
marized in the Summary Drug Table: Drugs Used in the Treatment of Anemia.
DRUGS USED IN THE TREATMENT
OF IRON DEFICIENCY ANEMIA
Iron deficiency anemia is by far the most common type of anemia. Iron is a component of hemoglobin, which is in RBCs. It is the iron in the hemoglobin of RBCs that picks up oxygen from the lungs and carries it to all body tissues. Iron is stored in the body and is found mainly in the reticuloendothelial cells of the liver, spleen, and bone marrow. When the body does not have enough iron to supply the body’s needs, the resulting condition is iron deficiency anemia.
ACTIONS AND USES
Iron salts, such as ferrous sulfate or ferrous gluconate,are used in the treatment of iron deficiency anemia,which occurs when there is a loss of iron that is greater than the available iron stored in the body. Iron prepa-rations act by elevating the serum iron concentration,which replenishes hemoglobin and depleted iron
stores.Iron dextran is a parenteral iron that is also used for the treatment of iron deficiency anemia. It is primarily used when the patient cannot take oral drugs or when the patient experiences gastrointestinal intolerance to oral iron administration. Other iron preparations, both oral and parenteral, used in the treatment of iron defi-ciency anemia
ADVERSE REACTIONS
Iron salts occasionally cause gastrointestinal irritation,nausea, vomiting, constipation, diarrhea, headache,
backache, and allergic reactions. The stools usually appear darker (black). Iron dextran is given by the parenteral route. Hypersensitivity reactions, including fatal anaphylactic reactions, have been reported with the use of this form of iron. Additional adverse reactions include soreness, inflammation, and sterile abscesses at the intramuscular (IM) injection site. Intravenous (IV) administration may result in phlebitis at the injection site. When iron is administered via the IM route, a brownish discoloration of the skin may occur. Patients with rheumatoid arthritis may experience an acute exacerbation of joint pain, and swelling may occur when iron dextran is administered
CONTRAINDICATIONS, PRECAUTIONS,
AND INTERACTIONS
Drugs used to treat anemia are contraindicated in patients with known hypersensitivity to the drug or any compo-nent of the drug. Iron compounds are contraindicated in patients with any anemia except iron deficiency anemia.
Iron compounds are used cautiously in patients with tar-trazine or sulfite sensitivity because some iron compounds contain these substances. Oral iron preparations are Pregnancy Category B drugs; iron
dextran is a Pregnancy Category C drug. The iron preparations are used cautiously during pregnancy and lactation. Iron dosages of 15 to 30 mg/d are sufficient to meet the needs of pregnancy. Iron dextran is used cautiously in patients with cardiovascular disease, a history of asthma or allergies, and rheumatoid
arthritis (may exacerbate joint pain).The absorption of oral iron is decreased when the agent is administered with antacids, tetracyclines, penicillamine, and the fluoroquinolones. When iron is administered with levothyroxine, there may be a decrease in the effectiveness of levothyroxine. When administered orally, iron deceases the absorption of lev-odopa. Ascorbic acid increases the absorption of oral iron. Iron dextran administered concurrently with chlor-amphenicol increases serum iron levels.
DRUGS USED IN THE TREATMENT OF ANEMIA ASSOCIATED WITH
CHRONIC RENAL FAILURE
Anemia may occur in patients with chronic renal failure as the result of the inability of the kidney to produce ery-thropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate
and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia. Two examples of drugs used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp).
ACTIONS AND USES
Epoetin alfa is a drug that is produced using recombinant DNA technology. The drug acts in a manner similar to that of natural erythropoietin. Epoetin alfa is used to treat anemia associated with chronic renal failure, ane-mia in patients with cancer who are receiving chemother-apy, and in patients with anemia who are undergoing elective nonvascular surgery. Darbepoetin alfa (Aranesp)is an erythropoiesis-stimulating protein produced in Chinese hamster ovary cells by recombinant DNA technology. Darbepoetin stimulates erythropoiesis by the same manner as natural erythropoietin. The drug is used to treat anemia associated with chronic renal failure in patients receiving dialysis as well as for patients who are not receiving dialysis. These drugs elevate or maintain RBC levels and decrease the need for transfusions.
ADVERSE REACTIONS
Epoetin alfa (erythropoietin; EPO) and darbepoetin alfa are usually well tolerated. The most common adverse reactions include hypertension, headache, tachycardia,nausea, vomiting, diarrhea, skin rashes, fever, myalgia,and skin reaction at the injection site.
CONTRAINDICATIONS, PRECAUTIONS,AND
INTERACTIONS
Epoetin alfa is contraindicated in patients with uncon-trolled hypertension, those needing an emergency trans-fusion, or those with a hypersensitivity to human albumin. Darbepoetin alfa (Aranesp) is contraindicated in patients with uncontrolled hypertension or in those allergic to the drug.Epoetin alfa and darbepoetin alfa are used with cau-tion in patients with hypertension, heart disease, congestive heart failure, or a history of seizures. Both of these drugs are Pregnancy Category C drugs and are used cautiously during pregnancy and lactation.
DRUGS USED IN THE TREATMENT OF FOLIC ACID DEFICIENCY ANEMIA
Folic acid is required for the manufacture of RBCs in the bone marrow. Folic acid is found in leafy green vegetables, fish, meat, poultry, and whole grains. A deficiency of folic acid results in megaloblastic anemia.Megaloblastic ane- mia is characterized by the presence of large, abnormal,immature erythrocytes circulating in the blood.
ACTION AND USES
Folic acid is used in the treatment of megaloblastic ane-mias that are caused by a deficiency of folic acid.Although not related to anemia, studies indicate there is a decreased risk for neural tube defects if folic acid is taken before conception and during early pregnancy.Neural tube defects occur during early pregnancy,
when the embryonic folds forming the spinal cord and brain join together. Defects of this type include anen-cephaly (congenital absence of brain and spinal cord),spina bifida (defect of the spinal cord), and meningo-cele (a saclike protrusion of the meninges in the spinal cord or skull). The United States Public Health Service recommends the use of folic acid for all women of childbearing age to decrease the incidence of neural tube defects. Dosages during pregnancy and lactation are as great as 0.8 mg/d.
Leucovorin is a derivative (and active reduced form) of folic acid. The oral and parenteral forms of this drug are used in the treatment of megaloblastic anemia.
Leucovorin may also be used to diminish the hematologic effects of (intentional) massive doses of methotrexate, a drug used in the treatment of certain types of cancer. Leucovorin “rescues” normal cells from the destruction caused by methotrexate and allows them to survive. This technique of administering leucovorin after a large dose of methotrexate is called folinic acid rescue or leucovorin rescue. Occasionally, high doses of methotrexate are administered to select patients.Leucovorin is then used either at the time methotrexate is
administered or a specific number of hours after the methotrexate has been given to decrease the toxic effects of the methotrexate. Leucovorin may be ordered to be given via the IV, IM, or oral route.
ADVERSE REACTIONS
Few adverse reactions are associated with the adminis-tration of folic acid and leucovorin. Rarely, parenteral administration may result in allergic hypersensitivity.
CONTRAINDICATIONS, PRECAUTIONS,AND INTERACTIONS
Folic acid and leucovorin are contraindicated for the treatment of pernicious anemia or for other anemias for which vitamin B12 is deficient. Folic acid is a Pregnancy Category A drug and is generally considered safe for use during pregnancy. Pregnant women are more likely to experience folate acid deficiency because folic acid
requirements are increased during pregnancy. Pregnant women with a folate deficiency are at increased risk for complications of pregnancy and fetal abnormalities.The recommended daily allowance (RDA) of folate dur- ing pregnancy is 0.4 mg/d and during lactation, 0.26 to 0.28 mg/d. Although fetal harm appears remote, the drug should be used cautiously and only within the RDAs. Use of aminosalicylic with folic acid may decrease serum folate levels. Folic acid utilization is decreased when folate is administered with methotrexate. Signs of folic acid deficiency may occur when sul-fasalazine is administered concurrently. An increase in seizure activity may occur when folic acid is adminis- tered with the hydantoins.Leucovorin is a Pregnancy Category C drug and is used cautiously during pregnancy.Leucovorin decreases the effectiveness of the anti-convulsants. There is an increased risk of 5-fluorouracil toxicity when the drug is administered with leucovorin.
DRUGS USED IN THE TREATMENT OF PERNICIOUS ANEMIA
Vitamin B12 is essential to growth, cell reproduction, the manufacture of myelin (which surrounds some nerve fibers), and blood cell manufacture. The intrinsic factor,which is produced by cells in the stomach, is necessary for the absorption of vitamin B12 in the intestine. A deficiency of the intrinsic factor results in abnormal formation of erythrocytes because of the body’s failure to absorb vita-min B12, a necessary component for blood cell formation.The resulting anemia is a type of megaloblastic anemia called pernicious anemia.
ACTIONS AND USES
Vitamin B12 (cyanocobalamin) is used to treat a vitamin B12 deficiency. A vitamin B12 deficiency may be seen in:
• Strict vegetarians
• Persons who have had a total gastrectomy or sub total gastric resection (when the cells producing the
intrinsic factor are totally or partially removed)
• Persons who have intestinal diseases, such as ulcerative colitis or sprue
• Persons who have gastric carcinoma
• Persons who have a congenital decrease in the
number of gastric cells secreting intrinsic factorVitamin B12 is also used to perform the Schilling test,
which is used to diagnose pernicious anemia.
A deficiency of this vitamin caused by a low dietary intake of vitamin B12 is rare because the vitamin is
found in meats, milk, eggs, and cheese. The body is alsoable to store this vitamin; a deficiency, for any reason,
will not occur for 5 to 6 years.
ADVERSE REACTIONS
Mild diarrhea and itching have been reported with the administration of vitamin B12. Other adverse reactions that may be seen include a marked increase in RBC
production, acne, peripheral vascular thrombosis, con-gestive heart failure, and pulmonary edema.
CONTRAINDICATIONS, PRECAUTIONS,AND INTERACTIONS
Vitamin B12 is contraindicated in patients allergic to cobalt. Vitamin B12 is a Pregnancy Category A drug if administered orally and a Pregnancy Category C drug if given parenterally. Vitamin B12 is administered cau-tiously during pregnancy and in patients with pul-monary disease and anemia. Alcohol, aminosalicylic
acid, neomycin, and colchicine may decrease the absorp-tion of oral vitamin B12.
If iron dextran is administered, the nurse informs the patient that soreness at the injection site may occur. Injection sites are checked daily for signs of inflammation, swelling, or abscess formation.The nurse assesses the patient for relief of the symp-toms of anemia (fatigue, shortness of breath, sore tongue,headache, pallor). Some patients may note a relief of symptoms after a few days of therapy. Periodic labora-tory tests are necessary to monitor the results of therapy.
bin. When there is an insufficient amount of hemoglobin to deliver oxygen to the tissues, anemia exists. There are various types and causes of anemia. For example, anemia can be the result of blood loss, excessive destruction of
RBCs, inadequate production of RBCs, and deficits in var-ious nutrients, such as in iron deficiency anemia. Once the type and cause have been identified, the primary
health care provider selects a method of treatment.
The anemias discussed in this chapter include iron deficiency anemia, anemia in patients with chronic renal disease, pernicious anemia, and anemia resulting
from a folic acid deficiency. Drugs used in treatment of anemia are sum-
marized in the Summary Drug Table: Drugs Used in the Treatment of Anemia.
DRUGS USED IN THE TREATMENT
OF IRON DEFICIENCY ANEMIA
Iron deficiency anemia is by far the most common type of anemia. Iron is a component of hemoglobin, which is in RBCs. It is the iron in the hemoglobin of RBCs that picks up oxygen from the lungs and carries it to all body tissues. Iron is stored in the body and is found mainly in the reticuloendothelial cells of the liver, spleen, and bone marrow. When the body does not have enough iron to supply the body’s needs, the resulting condition is iron deficiency anemia.
ACTIONS AND USES
Iron salts, such as ferrous sulfate or ferrous gluconate,are used in the treatment of iron deficiency anemia,which occurs when there is a loss of iron that is greater than the available iron stored in the body. Iron prepa-rations act by elevating the serum iron concentration,which replenishes hemoglobin and depleted iron
stores.Iron dextran is a parenteral iron that is also used for the treatment of iron deficiency anemia. It is primarily used when the patient cannot take oral drugs or when the patient experiences gastrointestinal intolerance to oral iron administration. Other iron preparations, both oral and parenteral, used in the treatment of iron defi-ciency anemia
ADVERSE REACTIONS
Iron salts occasionally cause gastrointestinal irritation,nausea, vomiting, constipation, diarrhea, headache,
backache, and allergic reactions. The stools usually appear darker (black). Iron dextran is given by the parenteral route. Hypersensitivity reactions, including fatal anaphylactic reactions, have been reported with the use of this form of iron. Additional adverse reactions include soreness, inflammation, and sterile abscesses at the intramuscular (IM) injection site. Intravenous (IV) administration may result in phlebitis at the injection site. When iron is administered via the IM route, a brownish discoloration of the skin may occur. Patients with rheumatoid arthritis may experience an acute exacerbation of joint pain, and swelling may occur when iron dextran is administered
CONTRAINDICATIONS, PRECAUTIONS,
AND INTERACTIONS
Drugs used to treat anemia are contraindicated in patients with known hypersensitivity to the drug or any compo-nent of the drug. Iron compounds are contraindicated in patients with any anemia except iron deficiency anemia.
Iron compounds are used cautiously in patients with tar-trazine or sulfite sensitivity because some iron compounds contain these substances. Oral iron preparations are Pregnancy Category B drugs; iron
dextran is a Pregnancy Category C drug. The iron preparations are used cautiously during pregnancy and lactation. Iron dosages of 15 to 30 mg/d are sufficient to meet the needs of pregnancy. Iron dextran is used cautiously in patients with cardiovascular disease, a history of asthma or allergies, and rheumatoid
arthritis (may exacerbate joint pain).The absorption of oral iron is decreased when the agent is administered with antacids, tetracyclines, penicillamine, and the fluoroquinolones. When iron is administered with levothyroxine, there may be a decrease in the effectiveness of levothyroxine. When administered orally, iron deceases the absorption of lev-odopa. Ascorbic acid increases the absorption of oral iron. Iron dextran administered concurrently with chlor-amphenicol increases serum iron levels.
DRUGS USED IN THE TREATMENT OF ANEMIA ASSOCIATED WITH
CHRONIC RENAL FAILURE
Anemia may occur in patients with chronic renal failure as the result of the inability of the kidney to produce ery-thropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate
and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia. Two examples of drugs used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp).
ACTIONS AND USES
Epoetin alfa is a drug that is produced using recombinant DNA technology. The drug acts in a manner similar to that of natural erythropoietin. Epoetin alfa is used to treat anemia associated with chronic renal failure, ane-mia in patients with cancer who are receiving chemother-apy, and in patients with anemia who are undergoing elective nonvascular surgery. Darbepoetin alfa (Aranesp)is an erythropoiesis-stimulating protein produced in Chinese hamster ovary cells by recombinant DNA technology. Darbepoetin stimulates erythropoiesis by the same manner as natural erythropoietin. The drug is used to treat anemia associated with chronic renal failure in patients receiving dialysis as well as for patients who are not receiving dialysis. These drugs elevate or maintain RBC levels and decrease the need for transfusions.
ADVERSE REACTIONS
Epoetin alfa (erythropoietin; EPO) and darbepoetin alfa are usually well tolerated. The most common adverse reactions include hypertension, headache, tachycardia,nausea, vomiting, diarrhea, skin rashes, fever, myalgia,and skin reaction at the injection site.
CONTRAINDICATIONS, PRECAUTIONS,AND
INTERACTIONS
Epoetin alfa is contraindicated in patients with uncon-trolled hypertension, those needing an emergency trans-fusion, or those with a hypersensitivity to human albumin. Darbepoetin alfa (Aranesp) is contraindicated in patients with uncontrolled hypertension or in those allergic to the drug.Epoetin alfa and darbepoetin alfa are used with cau-tion in patients with hypertension, heart disease, congestive heart failure, or a history of seizures. Both of these drugs are Pregnancy Category C drugs and are used cautiously during pregnancy and lactation.
DRUGS USED IN THE TREATMENT OF FOLIC ACID DEFICIENCY ANEMIA
Folic acid is required for the manufacture of RBCs in the bone marrow. Folic acid is found in leafy green vegetables, fish, meat, poultry, and whole grains. A deficiency of folic acid results in megaloblastic anemia.Megaloblastic ane- mia is characterized by the presence of large, abnormal,immature erythrocytes circulating in the blood.
ACTION AND USES
Folic acid is used in the treatment of megaloblastic ane-mias that are caused by a deficiency of folic acid.Although not related to anemia, studies indicate there is a decreased risk for neural tube defects if folic acid is taken before conception and during early pregnancy.Neural tube defects occur during early pregnancy,
when the embryonic folds forming the spinal cord and brain join together. Defects of this type include anen-cephaly (congenital absence of brain and spinal cord),spina bifida (defect of the spinal cord), and meningo-cele (a saclike protrusion of the meninges in the spinal cord or skull). The United States Public Health Service recommends the use of folic acid for all women of childbearing age to decrease the incidence of neural tube defects. Dosages during pregnancy and lactation are as great as 0.8 mg/d.
Leucovorin is a derivative (and active reduced form) of folic acid. The oral and parenteral forms of this drug are used in the treatment of megaloblastic anemia.
Leucovorin may also be used to diminish the hematologic effects of (intentional) massive doses of methotrexate, a drug used in the treatment of certain types of cancer. Leucovorin “rescues” normal cells from the destruction caused by methotrexate and allows them to survive. This technique of administering leucovorin after a large dose of methotrexate is called folinic acid rescue or leucovorin rescue. Occasionally, high doses of methotrexate are administered to select patients.Leucovorin is then used either at the time methotrexate is
administered or a specific number of hours after the methotrexate has been given to decrease the toxic effects of the methotrexate. Leucovorin may be ordered to be given via the IV, IM, or oral route.
ADVERSE REACTIONS
Few adverse reactions are associated with the adminis-tration of folic acid and leucovorin. Rarely, parenteral administration may result in allergic hypersensitivity.
CONTRAINDICATIONS, PRECAUTIONS,AND INTERACTIONS
Folic acid and leucovorin are contraindicated for the treatment of pernicious anemia or for other anemias for which vitamin B12 is deficient. Folic acid is a Pregnancy Category A drug and is generally considered safe for use during pregnancy. Pregnant women are more likely to experience folate acid deficiency because folic acid
requirements are increased during pregnancy. Pregnant women with a folate deficiency are at increased risk for complications of pregnancy and fetal abnormalities.The recommended daily allowance (RDA) of folate dur- ing pregnancy is 0.4 mg/d and during lactation, 0.26 to 0.28 mg/d. Although fetal harm appears remote, the drug should be used cautiously and only within the RDAs. Use of aminosalicylic with folic acid may decrease serum folate levels. Folic acid utilization is decreased when folate is administered with methotrexate. Signs of folic acid deficiency may occur when sul-fasalazine is administered concurrently. An increase in seizure activity may occur when folic acid is adminis- tered with the hydantoins.Leucovorin is a Pregnancy Category C drug and is used cautiously during pregnancy.Leucovorin decreases the effectiveness of the anti-convulsants. There is an increased risk of 5-fluorouracil toxicity when the drug is administered with leucovorin.
DRUGS USED IN THE TREATMENT OF PERNICIOUS ANEMIA
Vitamin B12 is essential to growth, cell reproduction, the manufacture of myelin (which surrounds some nerve fibers), and blood cell manufacture. The intrinsic factor,which is produced by cells in the stomach, is necessary for the absorption of vitamin B12 in the intestine. A deficiency of the intrinsic factor results in abnormal formation of erythrocytes because of the body’s failure to absorb vita-min B12, a necessary component for blood cell formation.The resulting anemia is a type of megaloblastic anemia called pernicious anemia.
ACTIONS AND USES
Vitamin B12 (cyanocobalamin) is used to treat a vitamin B12 deficiency. A vitamin B12 deficiency may be seen in:
• Strict vegetarians
• Persons who have had a total gastrectomy or sub total gastric resection (when the cells producing the
intrinsic factor are totally or partially removed)
• Persons who have intestinal diseases, such as ulcerative colitis or sprue
• Persons who have gastric carcinoma
• Persons who have a congenital decrease in the
number of gastric cells secreting intrinsic factorVitamin B12 is also used to perform the Schilling test,
which is used to diagnose pernicious anemia.
A deficiency of this vitamin caused by a low dietary intake of vitamin B12 is rare because the vitamin is
found in meats, milk, eggs, and cheese. The body is alsoable to store this vitamin; a deficiency, for any reason,
will not occur for 5 to 6 years.
ADVERSE REACTIONS
Mild diarrhea and itching have been reported with the administration of vitamin B12. Other adverse reactions that may be seen include a marked increase in RBC
production, acne, peripheral vascular thrombosis, con-gestive heart failure, and pulmonary edema.
CONTRAINDICATIONS, PRECAUTIONS,AND INTERACTIONS
Vitamin B12 is contraindicated in patients allergic to cobalt. Vitamin B12 is a Pregnancy Category A drug if administered orally and a Pregnancy Category C drug if given parenterally. Vitamin B12 is administered cau-tiously during pregnancy and in patients with pul-monary disease and anemia. Alcohol, aminosalicylic
acid, neomycin, and colchicine may decrease the absorp-tion of oral vitamin B12.
If iron dextran is administered, the nurse informs the patient that soreness at the injection site may occur. Injection sites are checked daily for signs of inflammation, swelling, or abscess formation.The nurse assesses the patient for relief of the symp-toms of anemia (fatigue, shortness of breath, sore tongue,headache, pallor). Some patients may note a relief of symptoms after a few days of therapy. Periodic labora-tory tests are necessary to monitor the results of therapy.
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