Anemia Drugs



Anemia Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



Drug Profiles



Key Terms


Erythrocytes Another name for red blood cells (RBCs). (p. 878)


Erythropoiesis The process of erythrocyte production. (p. 878)


Globin The protein part of the hemoglobin molecule (see later); the four different structural globin chains most often found in adults are the alpha1, alpha2, beta1, and beta2 chains. (p. 878)


Hematopoiesis The normal formation and development of all blood cell types in the bone marrow. (p. 878)


Heme Part of the hemoglobin molecule; a nonprotein, iron-containing pigment. (p. 878)


Hemoglobin A complex protein-iron compound in the blood that carries oxygen to the cells from the lungs and carbon dioxide away from the cells to the lungs. (p. 878)


Hemolytic anemias Anemias resulting from excessive destruction of erythrocytes. (p. 879)


Hypochromic Pertaining to less than normal color. The term usually describes an RBC with decreased hemoglobin content and helps further characterize anemias associated with reduced synthesis of hemoglobin. (p. 878)


Microcytic Pertaining to or characterized by smaller than normal cells. (p. 878)


Pernicious anemia A type of megaloblastic anemia usually seen in older adults and caused by impaired intestinal absorption of vitamin B12 (cyanocobalamin) due to lack of availability of intrinsic factor. (p. 879)


Reticulocytes An immature erythrocyte characterized by a meshlike pattern of threads and particles at the former site of the nucleus. (p. 878)


Spherocytes Small, globular, completely hemoglobinated erythrocytes without the usual central concavity or pallor. (p. 879)


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Anatomy, Physiology, and Pathophysiology Overview


Erythropoiesis


The formation of new blood cells is one of the primary functions of bones. This process is known as hematopoiesis, and it includes the production of erythrocytes (red blood cells, or RBCs), as well as leukocytes (white blood cells) and thrombocytes (platelets). This process takes place in the myeloid tissue or bone marrow. This specialized tissue is located primarily in the ends, or epiphyses, of certain long bones and also in the flat bones of the skull, pelvis, sternum, scapulae, and ribs.


Erythropoiesis, the process of erythrocyte formation, is the focus of this chapter. This involves the maturation of a nucleated RBC precursor into a hemoglobin-filled, nucleus-free erythrocyte. This process is driven by the hormone erythropoietin, which is produced by the kidneys. Erythropoietin is also produced commercially and is used to treat anemia in certain specific circumstances and is discussed in detail later in the chapter.


When RBCs are manufactured in the bone marrow by myeloid tissue, they are released into the circulation as immature RBCs called reticulocytes. Once in the circulation, reticulocytes undergo a 24- to 36-hour maturation process to become mature, fully functional RBCs. After this, they have a lifespan of about 120 days.


More than one third of an RBC is composed of hemoglobin. Hemoglobin (abbreviated Hgb) is composed of two parts: heme and globin. Heme is a red pigment. Each heme group contains one atom of iron. Globin is a protein chain. The four different structural globin chains most often found in adults are the alpha1, alpha2, beta1, and beta2 chains. Together, four heme groups, each linked to one protein chain of globin, make up one hemoglobin molecule (Figure 54-1).



Types of Anemia


Anemias are classified into four main types based on the underlying causes (Figure 54-2). Anemia of chronic disease is another common type of anemia. Anemias can be caused by maturation defects, or they can be secondary to excessive RBC destruction. Two types of maturation defects lead to anemias, categorized by the location of the defect within the cell: cytoplasmic maturation defects occur in the cell cytoplasm, and nuclear maturation defects occur in the cell nucleus. Factors responsible for excessive RBC destruction can be either intrinsic or extrinsic.



Figure 54-3 summarizes the types of anemias arising from cytoplasmic maturation defects. Major examples include iron-deficiency anemia and genetic disorders such as thalassemia, which result in defective globin synthesis. For each of these anemias, the RBCs appear hypochromic (lighter red than normal) and microcytic (smaller than normal) on blood smear. Cytoplasmic maturation anemias occur as a result of reduced or abnormal hemoglobin synthesis. Because hemoglobin is synthesized from both iron and globin, a deficiency in either one can lead to a hemoglobin deficiency. Some common causes of iron-deficiency anemia are blood loss, surgery, childbirth, gastrointestinal bleeding (which can be caused by NSAID ingestion; see Chapter 44), menstrual blood loss, and hemorrhoids.



Figure 54-4 summarizes the types of anemias arising from nuclear maturation defects. These occur because of defects in deoxyribonucleic acid (DNA) or protein synthesis. Both DNA and protein synthesis require vitamin B12 and folic acid (B9) to be present in normal amounts for their proper production. If either of these two vitamins is absent or deficient, anemias secondary to nuclear maturation defects may develop. In such anemias, RBCs actually appear to be normochromic (normal in color) but are commonly macrocytic (larger than normal) on blood smear. One example is pernicious anemia. This type of anemia results from deficiency of vitamin B12, which is used in the formation of new RBCs. The usual underlying cause is the failure of the stomach lining to produce intrinsic factor. Intrinsic factor is a gastric glycoprotein that allows vitamin B12 to be absorbed in the intestine (see Chapter 53). Another example is the anemia caused by folic acid deficiency. Both pernicious anemia and folic acid deficiency anemia are also known as types of megaloblastic anemia, because they are both characterized by large, immature RBCs. Megaloblastic anemias not caused from a lack of intrinsic factor are usually related to poor dietary intake and are most commonly seen in infancy, childhood, and pregnancy.



Figure 54-5 summarizes the types of anemias arising from excessive RBC destruction, or hemolytic anemias. These can occur because of abnormalities within the RBCs themselves (intrinsic factors) or as a result of factors outside of (extrinsic to) the RBCs. In both cases, the erythrocytes appear on blood smear as spherocytes. RBC abnormalities caused by intrinsic factors are usually the result of a genetic defect. Examples include sickle cell anemia, hereditary spherocytosis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and paroxysmal nocturnal hemoglobinuria. Examples of extrinsic mechanisms for excessive RBC destruction include drug-induced antibodies that target and destroy RBCs, septic shock that produces disseminated intravascular coagulation, and mechanical forces such as those created by intraaortic balloon pumps, ventricular assist devices, and continuous veno-venous hemodialysis (CVVHD), commonly used in intensive care units.



Pharmacology Overview


ERythropoiesis Stimulating Agents


♦ epoetin alfa

Epoetin alfa (Epogen) is a biosynthetic form of the natural hormone erythropoietin, which is normally secreted by the kidneys in response to a decrease in RBCs. It promotes the synthesis of erythrocytes (RBCs) by stimulating RBC progenitor cells in the bone marrow. Epoetin alfa is used to treat anemia that is associated with end-stage renal disease, chemotherapy-induced anemia, and for anemia associated with zidovudine therapy (see Chapter 40). Epoetin causes the progenitor cells in the bone marrow to manufacture large numbers of immature RBCs and to greatly speed up their maturation. This medication is ineffective without adequate body iron stores and bone marrow function. Most patients receiving epoetin alfa need to also receive an oral iron preparation. A longer-acting form of epoetin called darbepoetin (Aranesp) is available that reduces the required number of injections, although one cost study found that there is no significant difference in overall cost between the two. Both drugs are available for injection only and can be given intravenously or subcutaneously. When the drugs are given by the subcutaneous route, the onset of action is slower, and lower dosages can be used.


Contraindications for erythropoiesis-stimulating agents (ESAs) include known drug allergy. Use of epoetin and darbepoetin is contraindicated in cases of uncontrolled hypertension and when hemoglobin levels are above 10 g/dL for cancer patients and 12 g/dL for renal patients. Use in patients with head or neck cancers or patients at risk for thrombosis is controversial as these medications increase tumor growth and risk for thrombosis. The most frequent adverse effects include hypertension, fever, headache, pruritus, rash, nausea, vomiting, arthralgia, and injection site reaction.


In 2010, the U.S. Food and Drug Administration (FDA) issued a public health advisory regarding the overzealous use of epoetin. It was found that when hemoglobin levels are above 12 g/dL and the drug is continued, patients experienced serious adverse events, including heart attack, stroke, and death. Based on these findings, the FDA now requires that any patient receiving epoetin for chemotherapy-induced anemia must be registered in a risk mitigation program called ESA Apprise Oncology. Only physicians and hospitals that are registered in this program may dispense epoetin for cancer patients. The FDA has not yet required the same for its use in chronic kidney disease; however, it is not to be given to renal patients unless their hemoglobin level is less than 12 g/dL. More information can be found at www.esa-apprise.com/ESAAppriseUI/ESAAppriseUI/default.jsp. Abuse of erythropoietin by athletes hoping to increase oxygen-carrying capacity and improve performance places the athlete at risk for diseases caused by increased blood viscosity (stroke, myocardial infarction).



Iron


Iron is a mineral that is essential for the proper function of all biologic systems in the body. It is stored in many sites throughout the body (liver, spleen, and bone marrow). Deficiency of this mineral is the principal nutritional deficiency resulting in anemia. Individuals who require the highest amount of iron are women (especially pregnant women) and children, and they are the groups most likely to develop iron-deficiency anemia. For women, this is partly due to ongoing menstrual blood losses. Most vitamin supplements for men contain little or no iron, because men are much less likely to develop iron-deficiency anemia. Nonetheless, dietary iron is usually sufficient for both men and women in developed countries.


Dietary sources of iron include meats and certain vegetables and grains. These forms of iron must be broken down by gastric juices before the iron can be absorbed. Other foods such as orange juice, veal, fish, and ascorbic acid may help with iron absorption. Conversely, eggs, corn, beans, and many cereal products containing chemicals known as phytates may impair iron absorption. Beans and eggs are common dietary sources of iron. Oral iron preparations are available as ferrous salts. See Table 54-1 for a list of the currently available oral iron salts and their respective iron content. When a patient cannot tolerate oral iron, intravenous iron may be administered. There are four injectable iron products available: iron dextran (INFeD), iron sucrose (Venofer), ferric gluconate (Ferrlecit, Nulecit), and ferumoxytol (Feraheme).



Mechanism of Action and Drug Effects


Iron is an oxygen carrier in both hemoglobin and myoglobin (oxygen-carrying molecule in muscle tissue) and is critical for tissue respiration. Iron is also a required component of a number of enzyme systems in the body and is necessary for energy transfer in the cytochrome oxidase and xanthine oxidase enzyme systems. Administration of iron corrects iron-deficiency symptoms such as anemia, dysphagia, dystrophy of the nails and skin, and fissuring of the angles of the lips, and also maintains the bodily functions described earlier.


Indications


Supplemental iron contained in multivitamins plus iron or iron supplements alone are indicated for the prevention or treatment of iron-deficiency anemia. In all cases, an underlying cause needs to be identified. After identification of the cause, treatment is aimed at attempting to correct the cause (e.g., chronic blood loss, such as from a peptic or duodenal ulcer, cancerous colon lesion, or Crohn’s disease) rather than simply alleviating the symptoms. Iron supplementation is also used in erythropoietin therapy because it is essential for the production of RBCs.


Contraindications


Contraindications to the use of iron products include known drug allergy, hemochromatosis (iron overload), hemolytic anemia, and any other anemia not associated with iron deficiency.


Adverse Effects


The most common adverse effects associated with oral iron preparations are nausea, vomiting, diarrhea, constipation, stomach cramps, and stomach pain. Excess iron intake can lead to accumulation and iron toxicity. See Table 54-2 for a more complete listing of the undesirable effects associated with iron preparations. Elderly patients tend to respond to lower doses of iron supplementation, and lower doses tend to decrease the rate of adverse effects.


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May 9, 2017 | Posted by in NURSING | Comments Off on Anemia Drugs

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