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Ebook Basic amp; clinical pharmacology (14/E): Part 2

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Nội dung chi tiết: Ebook Basic amp; clinical pharmacology (14/E): Part 2

Ebook Basic amp; clinical pharmacology (14/E): Part 2

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2der, MD*CASE STUDYA 25-year-old woman who has been on a strict vegan diet for the past 2 years presents with increasing numbness and paresthesias in h

er extremities, generalized weakness, a sore tongue, and gastrointestinal discomfort. Physical examination reveals a pale woman with diminished vibrat Ebook Basic amp; clinical pharmacology (14/E): Part 2

ion sensation. diminished spinal reflexes, and extensor plantar reflexes (Babinski sign). Examination of her oral cavity reveals atrophic glossitis, i

Ebook Basic amp; clinical pharmacology (14/E): Part 2

n which the tongue appears deep red in color and abnormally smooth and shiny due to atrophy of the lingual papillae. Laboratory testing reveals a macr

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2 123 fl. (normal, 84-99 fL), an erythrocyte mean cell hemoglobin concentration (MCHC) of 34% (normal, 31-36%). and a low reticulocyte count. Further l

aboratory testing reveals a normal serum folate concentration and a serum vitamin B|J (cobalamin) concentration of 98 pg/mL (normal, 250-1100 pg/mL). Ebook Basic amp; clinical pharmacology (14/E): Part 2

Once megaloblastic anemia was identified, why was it important to measure serum concentrations of both folic acid and cobalamin? Should this patient b

Ebook Basic amp; clinical pharmacology (14/E): Part 2

e treated with oral or parenteral vitamin Bq?Hematopoiesis, the production from undifferentiated stem cells of circulating erythrocytes, platelets, an

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2ter. Susan B. Masters. PhD.blood cells per day in the normal person and even greater numbers of cells in persons with conditions that cause loss or de

struction of blood cells. The hematopoietic machinery resides primarily in the bone marrow in adults and requires a constant supply of three essential Ebook Basic amp; clinical pharmacology (14/E): Part 2

nutrients—iron, vitamin Bq, and folic acid—as well as the presence of hematopoietic growth factors, proteins591https://khothuvien.cori!592 SECTION VI

Ebook Basic amp; clinical pharmacology (14/E): Part 2

Drugs Used to Treat Diseases of the Blood, Inflammation, & Goutthat regulate the proliferation and differentiation of hematopoietic cells. Inadequate

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2ing erythrocytes, is the most common deficiency and several forms are easily treated. Sickle cell anemia, a condition resulting from a genetic alterat

ion in the hemoglobin molecule, is common but is not easily treated. It is discussed in the Box: Sickle Cell Disease and Hydroxyurea. Thrombocytopenia Ebook Basic amp; clinical pharmacology (14/E): Part 2

and neutropenia are not rare, and some forms are amenable to drug therapy. In this chapter, we first consider treatment of anemia due to deficiency o

Ebook Basic amp; clinical pharmacology (14/E): Part 2

f iron, vitamin B|2, or folic acid and then turn to the medical use of hematopoietic growth factors to combat anemia, thrombocytopenia, and neutropeni

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2lake other forms of chronic anemia, iron deficiency anemia leads to pallor, fatigue, dizziness, exertional dyspnea, and other generalized symptoms of

tissue hypoxia. The cardiovascular adaptations to chronic anemia—tachycardia, increased cardiac output.vasodilation—can worsen the condition of patien Ebook Basic amp; clinical pharmacology (14/E): Part 2

ts with underlying cardiovascular disease.Iron forms the nucleus of the iron-porphyrin heme ring, which together with globin chains forms hemoglobin.

Ebook Basic amp; clinical pharmacology (14/E): Part 2

Hemoglobin reversibly binds oxygen and provides the critical mechanism for oxygen delivery from the lungs to other tissues. In the absence of adequate

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2tial component of myoglobin, cytochromes, and other proteins with diverse biologic functions.PharmacokineticsFree inorganic iron is extremely toxic, b

ut iron is required for essential proteins such as hemoglobin; therefore, evolution has provided an elaborate system for regulating iron absorption, t Ebook Basic amp; clinical pharmacology (14/E): Part 2

ransport, and storage (Figure 35-1). The system uses specialized transport, storage, fcrrireducta.sc, and fcrroxida.se proteins whose concentrations a

Ebook Basic amp; clinical pharmacology (14/E): Part 2

re controlled by the body’s demand for hemoglobin synthesis and adequate iron stores (Table 33-1)- A peptide called hepcidin, produced primarily by li

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2moglobin in senescent or damaged erythrocytes. Normally, only a small amount of iron is lost from the body each day, so dietary requirements are small

and easily fulfilled by the iron available in a wide variety of foods. However, in special populations withSickle Cell Disease and HydroxyureaSickle Ebook Basic amp; clinical pharmacology (14/E): Part 2

cell disease is an important genetic cause of hemolytic anemia, a form of anemia due to increased erythrocyte destruction, instead of the reduced matu

Ebook Basic amp; clinical pharmacology (14/E): Part 2

re erythrocyte production seen with iron, folic acid, and vitamin B|J deficiency. Patients with sickle cell disease are homozygous for the aberrant ff

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2lobin gene such as hemoglobin c (Hba or p-thalassemra. sickle cell disease has an increased prevalence in individuals of African descent because the h

eterozygous trait confers resistance to malaria.In the majority of patients with sickle cell disease, anemia Is not the major problem; the anemia Is g Ebook Basic amp; clinical pharmacology (14/E): Part 2

enerally well compensated even though such individuals have a chronically low hematocrit (2ữ-309b), a low serum hemoglobin level (7-10 g/dL), and an e

Ebook Basic amp; clinical pharmacology (14/E): Part 2

levated reticulocyte count. Instead, the primary problem is that deoxygenated HbS chains form polymeric structures that dramatically change erythrocyt

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2e in the microvasculature—where oxygen tension is low and hemoglobin is deoxygenated—and cause veno-occlusive damage. In the musculoskeletal system, t

his results In characteristic.extremely severe bone and joint pain. In the cerebral vascular system, it causes ischemk stroke. Damage to the spleen in Ebook Basic amp; clinical pharmacology (14/E): Part 2

creases the risk of infection, particularly by encapsulated bacteria such as Streptococcus pneumoniae. In the pulmonary system, there Is an increased

Ebook Basic amp; clinical pharmacology (14/E): Part 2

risk of Infection and. in adults, an increase in embolism and pulmonary hypertension. Supportive treatment indudes analgesics, antibiotics, pneumococc

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2 is approved in the United States for treatment of adults with recurrent sickle cell crises and approved in Europe in adults and children with recurre

nt vaso-occlusive events. As an anticancer drug used In the treatment of chronic and acute myelogenous leukemia, hydroxyurea inhibits ribonucleotide r Ebook Basic amp; clinical pharmacology (14/E): Part 2

eductase and thereby depletes deoxynucleoside ưiphosphate and arrests cells In the $ phase of the cell cycle (see Chapter 54). In the treatment of sic

Ebook Basic amp; clinical pharmacology (14/E): Part 2

kle cell disease, hydroxyurea acts through poorly defined pathways to increase the production of fetal hemoglobin 7, which interferes with the po

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2adverse effects include hematopoietic depression, gastrointestinal effects, and teratogenicity in pregnant women.CHAPTER 33 Agents Used in Cytopenias

>1FIGURE 33-1 Absorption, transport, and storage of iron. Intestinal epithelial cells actively absorb inorganic iron via the divalentmetal transporter Ebook Basic amp; clinical pharmacology (14/E): Part 2

1 IŨMĨ1) and heme iron via the heme carrier protein 1 IHCP1). Iron that is absorbed or released from absorbed heme iron in the intestine (1) is activ

Ebook Basic amp; clinical pharmacology (14/E): Part 2

ely transported into the blood by ferroportin (fp) and stored as ferritin |F). In the blood, iron IS transported by transferrin (If) to erythroid prec

SECTION VI DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUTCHAPTERAgents Used in Cytopenias;Hematopoietic Growth33FactorsJames L. Zehnd

Ebook Basic amp; clinical pharmacology (14/E): Part 2in iron complex binds to transferrin receptors in erythroid precursors and hepatocytes and is internalized. After release of iron, the TfR Tf co

mplex is recycled to the plasma membrane and Tf is released. Macrophages that phagocytize senescent erythrocytes (RBC) reclaim the iron from the RBC h Ebook Basic amp; clinical pharmacology (14/E): Part 2

emoglobin and either export it or store it as ferritin (4). Hepatocytes use several mechanisms to take up iron and store the iron as ferritin. High he

Ebook Basic amp; clinical pharmacology (14/E): Part 2

patic iron stores increase hepcidin synthesis, and hepcidin inhibits ferroporlin; low hepatocyte iron and increased erythroferrone inhibits hepcidin a

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