Drugs Used in Anemias Flashcards
Name the 3 Oral and 3 Parenteral Agents Used in Iron Deficiency Anemia and their Adverse Effects
ORAL IRON THERAPY
A wide variety of oral iron preparations is available. Ferrous iron is most efficiently absorbed, therefore only ferrous salts should be used. Ferrous sulfate, ferrous gluconate, and ferrous fumarate are all effective.
Treatment with oral iron should be continued for 3–6 months after correction of the cause of the iron loss.
ADVERSE EFFECTS
Common adverse effects of oral iron therapy include nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea.
Patients taking oral iron develop black stools; this has no clinical significance in itself but may obscure the diagnosis of continued gastrointestinal blood loss.
PARENTERAL IRON THERAPY
Parenteral therapy should be reserved for patients with 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.
In the USA, the three available forms of parenteral iron are iron dextran, sodium ferric gluconate complex, and iron sucrose.
Deferoxamine and Deferasirox
ACUTE IRON TOXICITY
Acute iron toxicity is seen almost exclusively in young children who accidentally ingest iron tablets. Children who are poisoned with oral iron experience necrotizing gastroenteritis, with vomiting, abdominal pain, and bloody diarrhea which may be followed by shock, metabolic acidosis, coma, and death.
Urgent treatment is necessary. Whole bowel irrigation should be performed to flush out unabsorbed pills. Deferoxamine, an iron-chelator, can be given systemically to bind iron that has already been absorbed and to promote its excretion in urine and feces. Activated charcoal, a highly effective adsorbent for most toxins, does not bind iron and thus is ineffective.
CHRONIC IRON TOXICITY
Chronic iron toxicity, also known as hemochromatosis, results when excess iron is deposited in the heart, liver, pancreas, and other organs. It can lead to organ failure and death.
It most commonly occurs in patients with inherited hemochromatosis, a genetic disorder characterized by excessive iron absorption, and in patients who receive many red cell transfusions over a long period of time (eg, patients with thalassemia major).
Chronic iron overload in the absence of anemia is most efficiently treated by phlebotomy.
Iron chelation therapy using parenteral deferoxamine or deferasirox may be needed in patients with thalassemia major to retard the accumulation of iron.
Agents of Choice for Vitamin B12 Deficieny
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.
Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia.
There are no known adverse effects of vitamin B12.
Drugs that cause Folic Acid Deficiency
Patients with malabsorption syndromes also frequently develop folic acid deficiency.
Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia.
Long-term therapy with phenytoin can also cause folate deficiency, but only rarely causes megaloblastic anemia.
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, or certain skin diseases, and patients on renal dialysis.
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, especially if their diets are marginal.
Erythropoietin and Darbepoetin
The erythropoietin receptor is a member of the JAK/STAT superfamily of cytokine receptors.
Erythropoietin stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors. Erythropoietin also induces release of reticulocytes from the bone marrow.
Endogenous erythropoietin is primarily produced in the kidney. In response to tissue hypoxia, more erythropoietin is produced through an increased rate of transcription of the erythropoietin gene. This results in correction of the anemia.
Normally, an inverse relationship exists between the hematocrit or hemoglobin level and the serum erythropoietin level. As the hematocrit and hemoglobin levels fall and anemia becomes more severe, the serum erythropoietin level rises.
The most important exception to this inverse relationship is in the anemia of chronic renal failure. In patients with renal disease, erythropoietin levels are usually low because the kidneys cannot produce the growth factor. These are the patients most likely to respond to treatment with exogenous erythropoietin.
Erythropoietin is used for the anemia associated with renal failure and is sometimes effective for patients with other forms of anemia (eg primary bone marrow disorders, or anemias secondary to cancer chemotherapy or HIV treatment, bone marrow transplantation, AIDS or cancer).
Darbepoetin is a long-acting version of erythropoietin that differs from erythropoietin by the addition of two carbohydrate chains, which improves its biologic activity. Therefore, darbepoetin has decreased clearance and has a half life about three times that of erythropoietin.
Erythropoietin is one of the drugs banned by the International Olympic Committee. The use of erythropoietin by athletes is based on their hope that increased red blood cell concentration will increase oxygen delivery to muscles and improve performance.
ADVERSE EFFECTS
The most common adverse effects of erythropoietin are hypertension and thrombotic complications.
FILGRASTIM AND SARGRAMOSTIN
MYELOID GROWTH FACTORS
FILGRASTIM AND SARGRAMOSTIN
Filgrastim (granulocyte colony-stimulating factor; G-CSF) and sargramostin (granulocyte-macrophage colony-stimulating factor; GM-CSF) stimulate the production and function of neutrophils. GM-CSF also stimulates production of other myeloid and megakaryocyte progenitors.
PHARMACODYNAMICS
The myeloid growth factors stimulate proliferation and differentiation by interacting with specific receptors found on various myeloid progenitor cells. Like the erythropoietin receptor, these receptors are members of the JAK/STAT superfamily.
Both growth factors are used to accelerate recovery of neutrophils after cancer chemotherapy and to treat other forms of secondary and primary neutropenia.
The toxicity of G-CSF is minimal; sometimes it causes bone pain. GM-CSF can cause fever, arthralgias and capillary damage with edema. Allergic reactions are rare.
INTERLEUKIN-11
MEGAKARYOCYTE GROWTH FACTORS
INTERLEUKIN-11
Interleukin-11 stimulates growth of primitive megakaryocytic progenitors and increases the number of peripheral platelets. IL-11 is used for the treatment of patients who have had a prior episode of thrombocytopenia after a cycle of cancer chemotherapy. In such patients it reduces the need for platelet transfusions.
HYDROXYUREA
AGENTS USED TO TREAT SICKLE-CELL DISEASE
HYDROXYUREA
Hydroxyurea can relieve the painful clinical course of sickle-cell disease.
In sickle-cell disease, the drug apparently increases fetal hemoglobin levels, thus diluting the abnormal hemoglobin S (HbS). This process takes several months. Polymerization of HbS is delayed in the treated patients so that painful crises are not caused by sickled cells blocking capillaries and causing tissue anoxia.
Important side effects of hydroxyurea include bone marrow suppression and cutaneous vasculitis.
Hydroxyurea is currently also being used to treat chronic myelogenous leukemia and polycythemia vera.
