Drugs for Anemia PDF

Drugs for Anemia  Anemia Anemia can be defined as a reduction in the hemoglobin, or red blood cell number. In physiologic terms an anemia is any disorder in which the patient suffers from tissue hypoxia due to decreased oxygen carrying capacity of the blood...

Drugs for Anemia  Anemia Anemia can be defined as a reduction in the hemoglobin, or red blood cell number. In physiologic terms an anemia is any disorder in which the patient suffers from tissue hypoxia due to decreased oxygen carrying capacity of the blood 2 General signs and symptoms of anemia include: ØFatigue ØRapid heartbeat ØShortness of breath ØPale skin ØDizziness ØInsomnia 3  OVERVIEW Anemia can be caused by: Ø Chronic blood loss Ø Bone marrow abnormalities Ø Increased hemolysis Ø Infections Ø Malignancy Ø Endocrine deficiencies Ø Renal failure Ø Drug toxicity Ø Dietary deficiencies of iron, folic acid, and vitamin B12 (cyanocobalamin) Ø Genetic basis: sickle cell disease 4  Drugs of Anemia AGENTS USED TO TREAT ANEMIAS These are drugs used to treat anemia üIron üVitamin B12, Cyanocobalamin üFolic acid üErythropoietin 5  Iron Iron is stored in the intestinal mucosal cells, liver, spleen, and bone marrow as ferritin (an iron–protein complex). Iron is delivered to the marrow for hemoglobin production by a transport protein (Transferrin). Iron deficiency results from: Øacute or chronic blood loss Øinsufficient intake during periods of accelerated growth in children Øheavily menstruating or pregnant women. 6  Iron Iron deficiency causes hypochromic microcytic anemia (due to low iron and small-sized red blood cells). Iron deficiency anemia may cause Pica (hunger for ice, paper, clay, metal, chalk, soil, glass, or sand), Koilonychias (upward curvature of the finger and toe nails) Soreness and cracking at the corners of the mouth. 8  Treatment of iron deficiency anemia 150 to 180 mg/day of oral elemental iron administered in divided doses two to three times daily 9  Pharmacokinetics Iron is absorbed after oral administration. Acidic conditions in the stomach keep iron in the reduced ferrous form, which is the more soluble form. Iron is then absorbed in the duodenum. The amount absorbed depends on the current body stores of iron. Ø If iron stores are adequate, less will be absorbed. If stores are low, more iron will be absorbed 10  Pharmacokinetics The relative percentage of iron absorbed decreases with increasing doses. For this reason, it is recommended that most people take the prescribed daily iron supplement in two or three divided doses. Some extended-release formulations may be dosed once daily. 11  Pharmacokinetics Oral preparations Ø ferrous sulfate Ø ferrous fumarate Ø ferrous gluconate Ø polysaccharide– iron complex Ø carbonyl iron formulations. Ferrous sulfate is the most commonly used form of iron due to its high content of elemental iron and relatively low cost. The percentage of elemental iron varies in each oral iron preparation 12  Pharmacokinetics Parenteral formulations of iron, such as iron dextran, sodium ferric gluconate complex, and iron sucrose, are also available. Macrophages phagocytize iron dextran and release iron from the dextran molecule. Parenteral administration treats iron deficiency rapidly, while oral administration may take several weeks 13  Adverse effects of iron GI disturbances, caused by local irritation: abdominal pain, constipation, diarrhea Ø Parenteral iron formulations may be used in those who cannot tolerate oral iron. Dark stools 14  Adverse effects of iron Fatal hypersensitivity and anaphylactoid reactions can occur by parenteral iron (mainly iron dextran formulations). Ø A test dose should be administered prior to iron dextran. Excessive iron can cause toxicities that can be reversed using chelators such as deferoxamine. 15  Folic acid (folate) The primary use of folic acid is in treating deficiency states that arise from inadequate levels of the vitamin. Folate deficiency may be caused by 1) Increased demand (for example, pregnancy and lactation) 2) Poor absorption caused by pathology of the small intestine 3) Alcoholism 4) Treatment with drugs that are dihydrofolate reductase inhibitors: e.g. methotrexate, pyrimethamine, and trimethoprim 16  Folic acid (folate) Folic acid deficiency is megaloblastic anemia (large-sized red blood cells), Caused by diminished synthesis of purines and pyrimidines. This leads to an inability of erythropoietic tissue to make DNA and, thereby, proliferate Megaloblastic anemia can also be caused by Vit B12 deficiency 18  Folic acid (folate) Folic acid is well absorbed in the jejunum. If excessive amounts of the vitamin are ingested, they are excreted in the urine and feces. Oral folic acid administration is nontoxic 19  Cyanocobalamin and hydroxocobalamin (vitamin B12) Deficiencies of vitamin B12 can result from low dietary levels or, More commonly, poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (pernicious anemia) loss of activity of the receptor needed for intestinal uptake of the vitamin Nonspecific malabsorption syndromes Gastric resection 20  Cyanocobalamin and hydroxocobalamin (vitamin B12) Vitamin B12 deficiency anemia may cause Tingling (pins and needles) in the hands and feet Difficulty walking Dementia In extreme cases, hallucinations, paranoia, or schizophrenia. 21  Cyanocobalamin and hydroxocobalamin (vitamin B12) The vitamin may be administered: Orally (for dietary deficiencies) Via sublingual tablets Intramuscularly Deep subcutaneously (for pernicious anemia). 22  Cyanocobalamin and hydroxocobalamin (vitamin B12) Note: Folic acid administration alone reverses the hematologic abnormality and, thus, masks the vitamin B12 deficiency, which can then proceed to severe neurologic dysfunction and disease. The cause of megaloblastic anemia needs to be determined in order to be specific in terms of treatment. Therefore, megaloblastic anemia should not be treated with folic acid alone but, rather, with a combination of folate and vitamin B12. Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia. This vitamin is nontoxic even in large doses. 23  Erythropoietin and darbepoetin Peritubular cells in the kidneys work as sensors that respond to hypoxia and mediate synthesis and release of erythropoietin (EPO). EPO stimulates stem cells to differentiate into proerythroblasts and promotes the release of reticulocytes from the marrow and initiation of hemoglobin formation. EPO, thus, regulates red blood cell proliferation and differentiation in bone marrow 24  Erythropoietin and darbepoetin Human erythropoietin (epoetin alfa), produced by recombinant DNA technology, is effective in the treatment of anemia caused by End-stage renal disease Anemia associated with HIV infection Anemia in bone marrow disorders Anemia of prematurity Anemia in some cancer patients. 25  Erythropoietin and darbepoetin Darbepoetin is a long-acting version of erythropoietin Darbepoetin has decreased clearance and has a half-life about three times that of epoetin alfa. Due to their delayed onset of action, these agents have no value in acute treatment of anemia Supplementation with iron is required to ensure an adequate response These agents are generally well tolerated, but side effects may include elevation in blood pressure and arthralgia in some cases. 26  Erythropoietin and darbepoetin When epoetin alfa is used to target hemoglobin concentrations more than 11 g/dL, serious cardiovascular events have been observed, e.g.: Thrombosis Severe hypertension Increased risk of death 28  Erythropoietin and darbepoetin The recommendations for all patients receiving epoetin alfa or darbepoetin include: a minimum effective dose that does not exceed a hemoglobin level of 12 g/dL The hemoglobin should not rise by more than 1 g/dL over a 2-week period. If the hemoglobin level exceeds 10 g/dL, doses of epoetin alfa or darbepoetin should be reduced or treatment should be discontinued. 29 Drugs of Anemia AGENTS USED TO TREAT NEUTROPENIA 30  AGENTS USED TO TREAT NEUTROPENIA Myeloid growth factors or granulocyte colony–stimulating factors (G-CSF): Filgrastim, Tbo-filgrastim, and Pegfilgrastim Granulocyte–macrophage colony–stimulating Factors (GM-CSF): Sargramostim They stimulate granulocyte production in the marrow to increase the neutrophil counts and reduce the duration of severe neutropenia 31  AGENTS USED TO TREAT NEUTROPENIA These agents are typically used prophylactically to reduce risk of neutropenia following chemotherapy and bone marrow transplantation The main difference between the available agents lies in the frequency of dosing. There is no evidence to show superiority of one agent over another in terms of efficacy, safety, or tolerability. Bone pain is a common adverse effect with these agents. 32 Drugs of Anemia AGENTS USED TO TREAT SICKLE CELL DISEASE 33  Hydroxyurea It can reduce the frequency of painful sickle cell crises Hydroxyurea is also used off-label to treat chronic myelogenous leukemia and polycythemia vera. 34  Hydroxyurea 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 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. 35  Pentoxifylline Pentoxifylline is a methylxanthine derivative It increases the deformability of red blood cells (improves erythrocyte flexibility) and reduces the viscosity of blood. This decreases total systemic vascular resistance, improves blood flow, and enhances tissue oxygenation in patients with peripheral vascular disease. 36  Pentoxifylline It is indicated to treat intermittent claudication, where it can modestly control function and symptoms. It has been studied in diabetic angiopathies, transient ischemic attacks, sickle cell anemias, strokes, and Raynaud’s phenomenon. 37