1
AGENTS USED IN CYTOPENIAS; HEMATOPOIETIC GROWTH FACTORS
AGENTS USED IN ANEMIA
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
● The absence of adequate iron, small erythrocytes with insufficient hemoglobin are formed, giving rise to microcytic hypochromic anemia
● Absorbed in the duodenum and proximal jejunum
● Absorption increases in response to low iron stores or increased iron requirements
ABSORPTION ● Total iron absorption increases to 1-2 mg/d in menstruating women and may be as high as 3-4 mg/d in pregnant woman
● Nonheme iron in foods and iron in inorganic iron salts and complexes must be reduced by a ferrireductase to ferrous iron (Fe2+) before it can be absorbed by intestinal
mucosal cells
● transported in the plasma bound to transferrin, a beta globin that can bind two molecules of ferric iron
TRANSPORT
● Transferrin-iron complex enters maturing erythroid cells by a specific receptor mechanism
● Iron also stored, primarily as ferritin , in macrophages in the liver, spleen, and bone, and in parenchymal liver cells
STORAGE
● Mobilization of iron from macrophages and hepatocytes is primarily controlled by hepcidin regulation of ferroportin activity
● No mechanism for excretion of iron
ELIMINATION
● Small amounts are lost in the feces by exfoliation of intestinal mucosal cells, and trace amounts are excreted in bile, urine, and sweat
CLINICAL PHARMACOLOGY
● Indications for the use of iron
○ Only clinical indication for use of iron preparations is the B treatment or prevention of iron deficiency anemia
○ Manifests as hypochromic, microcytic anemia in which the erythrocyte mean volume (MCV) and the mean cell hemoglobin concentration are low
○ Most common cause of iron deficiency anemia in adults is blood loss
● 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
ORAL IRON THERAPY ● 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, epigastric discomfort, abdominal cramps, constipation, and diarrhea, black stools
● Reserved for patients with documented iron deficiency who are unable to tolerate or absorb oral iron and for patients with extensive chronic anemia
PARENTERAL IRON THERAPY who cannot be maintained with oral iron alone
● Parenteral administration of inorganic free ferric iron produces serious dose-dependent toxicity, which severely limits the dose that can be administered
AJA
, 2
● Stable complex of ferric oxyhydroxide and dextran polymers containing 50 mg of elemental iron per milliliter of solution
● Can be given by deep intramuscular injection or by intravenous infusion
IRON DEXTRAN ● Adverse effects include headache, light-headedness, fever, arthralgias, nausea and vomiting, back pain, flushing, urticaria, bronchospasm, and, rarely,
anaphylaxis and death
● Sodium ferric gluconate complex and iron-sucrose complex are alternative parenteral iron preparations
TOXICITY
ACUTE CHRONIC
● necrotizing gastroenteritis with vomiting, abdominal pain, and bloody diarrhea ● iron overload
followed by shock, lethargy, and dyspnea ● also known as hemochromatosis, results when excess iron is deposited in the
● improvement is often noted, but this may be followed by severe metabolic heart, liver, pancreas, and other organs
acidosis, coma, and death ● most commonly occurs in patients with inherited hemochromatosis, a disorder
● Whole bowel irrigation should be performed to flush out unabsorbed pills characterized by excessive iron absorption, and in patients who receive many
● Deferoxamine, a potent iron-chelating compound, can be given intravenously red cell transfusions over a long period of time (eg, individuals with
to bind iron that has already been absorbed and to promote its excretion in urine β-thalassemia)
and feces ● most efficiently treated by intermittent phlebotomy
● One unit of blood can be removed every week or so until all of the excess iron
is removed
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
● Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans
● Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms
● 1–5 mcg of which is usually absorbed
● Avidly stored, primarily in the liver, with an average adult having a total vitamin B12 storage pool of 3000–5000 mcg
PHARMACOKINETICS
● Only trace amounts of vitamin B12 are normally lost in urine and stool
● Absorbed after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa
AJA
AGENTS USED IN CYTOPENIAS; HEMATOPOIETIC GROWTH FACTORS
AGENTS USED IN ANEMIA
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
● The absence of adequate iron, small erythrocytes with insufficient hemoglobin are formed, giving rise to microcytic hypochromic anemia
● Absorbed in the duodenum and proximal jejunum
● Absorption increases in response to low iron stores or increased iron requirements
ABSORPTION ● Total iron absorption increases to 1-2 mg/d in menstruating women and may be as high as 3-4 mg/d in pregnant woman
● Nonheme iron in foods and iron in inorganic iron salts and complexes must be reduced by a ferrireductase to ferrous iron (Fe2+) before it can be absorbed by intestinal
mucosal cells
● transported in the plasma bound to transferrin, a beta globin that can bind two molecules of ferric iron
TRANSPORT
● Transferrin-iron complex enters maturing erythroid cells by a specific receptor mechanism
● Iron also stored, primarily as ferritin , in macrophages in the liver, spleen, and bone, and in parenchymal liver cells
STORAGE
● Mobilization of iron from macrophages and hepatocytes is primarily controlled by hepcidin regulation of ferroportin activity
● No mechanism for excretion of iron
ELIMINATION
● Small amounts are lost in the feces by exfoliation of intestinal mucosal cells, and trace amounts are excreted in bile, urine, and sweat
CLINICAL PHARMACOLOGY
● Indications for the use of iron
○ Only clinical indication for use of iron preparations is the B treatment or prevention of iron deficiency anemia
○ Manifests as hypochromic, microcytic anemia in which the erythrocyte mean volume (MCV) and the mean cell hemoglobin concentration are low
○ Most common cause of iron deficiency anemia in adults is blood loss
● 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
ORAL IRON THERAPY ● 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, epigastric discomfort, abdominal cramps, constipation, and diarrhea, black stools
● Reserved for patients with documented iron deficiency who are unable to tolerate or absorb oral iron and for patients with extensive chronic anemia
PARENTERAL IRON THERAPY who cannot be maintained with oral iron alone
● Parenteral administration of inorganic free ferric iron produces serious dose-dependent toxicity, which severely limits the dose that can be administered
AJA
, 2
● Stable complex of ferric oxyhydroxide and dextran polymers containing 50 mg of elemental iron per milliliter of solution
● Can be given by deep intramuscular injection or by intravenous infusion
IRON DEXTRAN ● Adverse effects include headache, light-headedness, fever, arthralgias, nausea and vomiting, back pain, flushing, urticaria, bronchospasm, and, rarely,
anaphylaxis and death
● Sodium ferric gluconate complex and iron-sucrose complex are alternative parenteral iron preparations
TOXICITY
ACUTE CHRONIC
● necrotizing gastroenteritis with vomiting, abdominal pain, and bloody diarrhea ● iron overload
followed by shock, lethargy, and dyspnea ● also known as hemochromatosis, results when excess iron is deposited in the
● improvement is often noted, but this may be followed by severe metabolic heart, liver, pancreas, and other organs
acidosis, coma, and death ● most commonly occurs in patients with inherited hemochromatosis, a disorder
● Whole bowel irrigation should be performed to flush out unabsorbed pills characterized by excessive iron absorption, and in patients who receive many
● Deferoxamine, a potent iron-chelating compound, can be given intravenously red cell transfusions over a long period of time (eg, individuals with
to bind iron that has already been absorbed and to promote its excretion in urine β-thalassemia)
and feces ● most efficiently treated by intermittent phlebotomy
● One unit of blood can be removed every week or so until all of the excess iron
is removed
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
● Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans
● Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms
● 1–5 mcg of which is usually absorbed
● Avidly stored, primarily in the liver, with an average adult having a total vitamin B12 storage pool of 3000–5000 mcg
PHARMACOKINETICS
● Only trace amounts of vitamin B12 are normally lost in urine and stool
● Absorbed after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa
AJA
