Hematopoietic Drugs



Hematopoietic Drugs



Classification of Hematopoietic Drugs





aAlso ferrous fumarate and ferrous gluconate.


bAlso iron sucrose and ferric gluconate.




Overview


Mature blood cells are continuously formed in the bone marrow and are removed from the circulation by reticuloendothelial cells in the liver and spleen. The process by which blood cells are replaced is called hematopoiesis. This process requires minerals and vitamins and is regulated by hematopoietic growth factors that promote the differentiation and maturation of marrow stem cells to form leukocytes, erythrocytes, and platelets.


Anemia, a subnormal concentration of erythrocytes or hemoglobin in the blood, can result from inadequate erythropoiesis, blood loss, or accelerated hemolysis. Erythropoiesis can be impaired by a lack of essential nutrients or by the myelosuppressive effects of certain drugs or irradiation. Infection, cancer, endocrine deficiencies, and chronic inflammation can also cause anemia. Iron, folic acid, and vitamin B12 deficiencies are the most common causes of nutritional anemia.


This chapter describes the pharmacologic properties and uses of minerals, vitamins, and hematopoietic growth factors in the treatment of anemia and other blood cell deficiencies.



Drugs


Minerals


Iron, an essential dietary mineral, serves as an important component of hemoglobin, myoglobin, and a number of enzymes. The average dietary intake of iron is 18 to 20 mg/day, but people with normal iron stores absorb only about 10% of this amount. Absorption is enhanced twofold or threefold when stored iron is depleted or when erythropoiesis occurs at an accelerated rate. The absorption of iron is regulated by the amount of iron that is stored in the intestinal mucosa.


Iron is absorbed from the intestines into the circulation, where it is bound to transferrin and transported to various tissues, including the bone marrow and liver. In these tissues, iron is stored as ferritin (Fig. 17-1). In the marrow, iron is incorporated into heme and packaged in new erythrocytes. The erythrocytes circulate in the blood for about 120 days and then are taken up and degraded by reticuloendothelial cells. These cells later return most of the iron to the plasma so that it can be used again in erythropoiesis. Iron is highly conserved by the body, and only small amounts of it are excreted via the intestinal tract.


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FIGURE 17-1 Iron metabolism. Ingested iron is absorbed from the intestinal mucosa into the circulation, where it is bound to transferrin. Iron is distributed to tissues for incorporation into hemoglobin, myoglobin, and enzymes, or it is stored as ferritin. After about 120 days, erythrocytes are degraded by reticuloendothelial cells, and the iron is returned to the plasma or stored.

The dietary iron requirement per kilogram of body weight is highest in infants and pregnant women, somewhat lower in children and nonpregnant women, and lowest in men. Pregnant women have the greatest need for routine iron supplementation because their dietary iron often cannot meet the requirements for maternal and fetal erythropoiesis. Most multivitamin supplements contain iron, and many processed foods, including bread, are supplemented with iron.


If dietary iron intake is inadequate to support sufficient erythropoiesis and maintain a normal hemoglobin concentration in the blood, the body will use stored iron to maintain erythropoiesis until the stores are depleted. When iron stores are significantly depleted, the plasma iron level begins to fall and erythropoiesis is reduced. Over time, these changes lead to hypochromic microcytic anemia, a form of anemia in which the mean corpuscular hemoglobin concentration and the mean corpuscular volume are decreased. The iron preparations described in the following paragraphs are used to prevent and treat iron deficiency anemia in affected individuals.



Oral Iron Preparations


Iron is administered orally in the form of ferrous salts, including ferrous sulfate, ferrous gluconate, and ferrous fumarate. Iron contained in these preparations is absorbed in the same manner as is dietary iron. In patients with iron deficiency, the amount of iron absorbed increases progressively with larger doses, but the percentage absorbed decreases as the dosage increases. Food can retard iron absorption by 40% to 60%, but the gastric distress caused by iron often necessitates administering iron preparations with food. The percentage of iron absorbed from sustained-release preparations is lower than that absorbed from immediate-release preparations. This is because iron is primarily absorbed from the duodenum, and some of the sustained-release iron is transported to the lower intestinal tract before it is released for absorption.


In iron deficiency states, oral iron preparations are usually administered three times a day in doses that provide a total of 100 to 200 mg of elemental iron daily. The various iron salts contain different percentages of elemental iron. Ferrous sulfate contains about 20%, so that a 300-mg tablet contains approximately 60 mg of elemental iron. The duration of iron therapy depends on the cause and severity of the iron deficiency. In general, a course of about 4 to 6 months of oral iron therapy is required to reverse uncomplicated iron deficiency anemia.


At therapeutic doses, iron salts have few adverse effects, but they sometimes cause epigastric pain, nausea, vomiting, diarrhea or constipation, and black stools. Liquid iron preparations can also stain the teeth. Bile acid–binding resins (e.g., cholestyramine) reduce the absorption of iron, whereas ascorbic acid increases iron absorption by maintaining iron in the reduced ferrous state because ferrous iron is better absorbed than is ferric iron. Iron can reduce the absorption of tetracyclines, fluoroquinolones, levothyroxine, and vitamin E. The administration of these drugs should be separated from iron administration by at least 2 hours. The ingestion of large quantities of iron can cause serious and potentially lethal toxicity. Hence, iron preparations should be kept out of the reach of children.



Parenteral Iron Preparations


Iron preparations for parenteral therapy include iron dextran, iron sucrose, and sodium ferric gluconate. Iron dextran is a mixture of ferric hydroxide and dextran. Both low-molecular-weight and high-molecular-weight iron dextran preparations have been used, but the low-molecular-weight preparations cause fewer adverse effects. Iron dextran is intended for intramuscular or intravenous treatment of iron deficiency anemia in patients who cannot tolerate oral iron preparations or fail to respond to oral iron therapy. After administration, the iron dextran complex is removed from the circulation by the reticuloendothelial system, and the iron is transferred to the plasma for distribution to the bone marrow and other tissues.


The dosage required for each patient is calculated on the basis of the observed hemoglobin concentration and body weight.


Intravenous administration of iron dextran can cause peripheral flushing and hypotensive reactions. Intramuscular administration of iron dextran can cause adverse reactions at the injection site, including pain, inflammation, sterile abscesses, and brown discoloration of skin. For this reason, the preparation must be given by deep intramuscular injection into the outer quadrant of the buttock. A Z-track technique, in which the skin is displaced laterally before injection, is used to avoid leakage into the subcutaneous tissue. Iron dextran administration has rarely caused fatal anaphylactic reactions.


Iron sucrose is a complex of iron hydroxide in sucrose for intravenous administration in the treatment of anemia in patients with chronic kidney disease. Sodium ferric gluconate has a similar indication.

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Jul 23, 2016 | Posted by in PHARMACY | Comments Off on Hematopoietic Drugs

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