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Session 3 Pharm- 4

Pharm -4- Hematology Drugs

QuestionAnswer
What is the overall process of differentiation and proliferation of blood cells from a single stem cell in the bone marrow called. hematopoiesis
What is the process of making RBCs called Erythropoiesis
What is the process of making WBCs called Leukopoiesis
What is the process of making platelets called Megakaryopoiesis
What is the stem cell that makes up .1% of all bone marrow cells and is the precursor of all blood cells. Pluripotent stem cell
How is hematopoiesis guided and controlled by local signaling molecules that signal the stem cells to differentiate into the appropriate needed cells. The signals are growth factor and cytokines such as Erythropoietin, GM-CSF, IL-11, G-CSF, Thrombopoietin, etc
Disruption to what organs or supplies can result in decreased erythrocyte balance disrupting kidneys (produce erythropoietin signal), bone marrow disease, Iron deficiency, certain vitamin deficiencies, and cancer therapy can all effect erythrocytes
What drugs can be given to replace or boost erythropoiesis recombinant erythropoietin (epoetin alfa, Epogen, Procrit, darbepoetin
which of the erythropoietin recombinant forms has the longest half life and why Darbepoetin has 4 amino acids mutated changing the carbohydrate modifications and extend the half life to 24-26 hours for darbepoetin
What is the MOA of erythropoietin and its recombinant forms they bind cell-surface erythropoietin receptors on RBC progenitor cells in bone marrow stimulation expression of specific genes increasing RBC production
What is the physiologic effect of erythropoietin and its recombinant forms increases marrow progenitor cell survival, proliferation and maturation, increases production of hemoglobin (requires iron), increases release of reticulocytes from bone marrow, increases hematocrit
What are the therapeutic uses for erythropoietin and its recombinant forms and no blood doping is not therapeutic CANCER TREATMENT (chemo and radiation therapy), blood loss, chronic kidney failure (kidney not releasing erythropoietin) anemia of chronic disease
what are the possible adverse effects of erythropoietin and its recombinant forms hypertension, thrombotic complications, polycythemia all from the rapid increase in HCT. Allergic rxn are rare, seizures (rare), N/V and Diarrhea
What type of progenitor cell do the granulocytes arise from myeloid progenitor cell that became a granulocyte monocyte progenitor
What is the stimulus for the myeloid progenitor cell to become a granulocyte monocyte progenitor cell GM-CSF
What are the following drugs for Filgrastim (G-CSF) – Neupogen; Pegfilgrastim (G-CSF) – Neulasta; Sargramostim (GM-CSF)- Leukine, Prokine Myeloid Growth Factors- these cytokine bind specific receptors to increase transcription of genes that enable granulocytes and monocytes to increase their proliferation and differentiation
What cell type does G-CSF stimulate to differentiate into stimulates progenitors committed to neutrophil lineage and prolongs neutrophil survival, increases concentration of hematopoietic stem cells in peripheral blood and allows them to be harvested for stem cell transplant
What does GM-CSF cause when administered broad actions on erythroid, granulocyte and megakaryocyte progenitors and stimulates activity of neutrophils
What are the therapeutic uses for Filgrastim (G-CSF) – Neupogen; Pegfilgrastim (G-CSF) – Neulasta; Sargramostim (GM-CSF)- Leukine, Prokine tx of Neutropenia (most common dose-limiting toxicity of chemo), drugs should be given 24hrs after chemo; Drugs used for autologous stem cell transplant by mobilizing stem cells into peripheral blood for collection used to regenerate immune system.
What are the side effects of G-CSF, GM-CSF recombinants G-CSF- bone pain, GM-CSF- fever malaise, bone and muscle pain, rash, and capillary leakage (peripheral edema, pleural and pericardial effusions
What is Oprelvekin (neumega) a recombinant for of human IL-11 produced in e. coli. This is growth factor that binds IL-11 receptors on committed progenitor cells and increases proliferation and differentiation of megakaryocytes (platelets)
What are the therapeutic uses for Oprelvekin (Neumega) (Interleukin 11) Thrombocytopenia also enhances healing of GI lesions, inhibits adipogenesis, stimulates osteoclastogenesis
What are the s/e of Oprelvekin (Neumega) (Interleukin 11) fluid retention w/ edema, rhinitis and pleural effusion, eye hemorrhage, tachycardia, vasodilation
What type of anemia does iron deficiency cause microcytic hypochromic anemia- insufficient iron means RBC can't form adequate hemoglobin so you get smaller and dulled looking cells
What are some causes of iron deficiency anemia inadequate ingestion, Decreased absorption (antacids, Crohn's, drug interactions TCN), increased requirements (pregnancy, childhood, infancy), blood loss (menstruation, GI bleed)
How is iron absorption regulated intestines regulate absorption based on amount of iron stores in mucosal cells
Which is the better source of iron red meat or plant iron red meat it is already in the necessary form of heme, Plant iron has to be converted to ferrous iron in order to be absorbed
If a pt overdoses on iron pills how does the body get rid of that excess iron if it was absorbed Body doesn't have an efficient mechanism to get rid of excess iron this can result in hemochromatosis and you may need to give chelators to the pt
What types of iron can you give to pt for iron deficiency anemia ferrous sulfate- hydrated or desiccated; Ferrous gluconate; Ferrous fumarate; carbonyl iron; polysaccharide iron complex; iron with B12 and intrinsic factor
Why do we use ferrous formulas of iron for iron deficiency anemia and not ferric iron when tx with oral iron supplementation ferric is not well absorbed.
Why do we have patient take such a high dose of Iron in iron deficiency anemia only 25% of the dose can be absorbed in the GI tract but be careful because higher doses increase s/e but too low of a dose increases time to correct anemia
What can you co administer to help aid iron absorption Vit C
What can pt do besides taking more of the Iron pill to increase absorption but it also increases likelihood of s/e take iron on an empty stomach
What are the s/e of taking oral iron supplements Nausea, Dyspepsia, abdominal cramps, constipation, black stools and dark urine (warn patient), liquid iron stains dentures
If you want to administer Ferric iron what is the appropriate route parenteral administration as ferric iron doesn’t get absorbed in the gut
Why would you give parenteral iron as opposed to oral iron supplementation corrects iron deficiency in a shorter time, can be given if pt can't tolerate oral iron.
What types of parenteral iron can you administer Sodium Ferric Gluconate Complex; Iron dextran; Iron Sucrose
If you are going to administer Iron dextran what do you need to do first give a test dose to make sure pt can tolerate it or you may kill them if you want to avoid this give sodium ferric gluconate complex
what are the s/e of parenteral iron local pain and tissue discoloration at injxn site; Headache, light headedness, fever, Hypersensitivity rxn Flushing, urticaria, bronchospasm or anaphylaxis (give test dose first); TEST IRON storage to avoid toxicity body can't eliminate excess iron
How much Iron can be fatal if overdosed 1-2 grams can be lethal but usually 2-10 grams cause death mostly affects children
what are the sx of iron overdose necrotizing gastroenteritis w/ N/V, abdominal pain, and bloody diarrhea, followed by shock, dyspnea, metabolic acidosis, coma and death if not treated
What is the tx for Iron Overdose deferoxamine and deferasirox both are iron chelators that can bind iron already absorbed into the body
What type of anemia results from Vit B12 deficiency or folate deficiency Megaloblastic anemia
What are the sx of Megaloblastic anemia paresthesias, ataxia (from effects on nervous system)
What can be causes of B12 deficiency pernicious anemia (autoimmune attack on intrinsic factor needed for B12 absorption), Crohn's disease and other GI disorders that affect absorption, there could also be inadequate utilization
What is the MOA of B12 in the body required to convert 5-methyltetrahydrofolate to tetrahydrofolate (THF), THF is involved in synthesis of DNA, fat and carbohydrate metabolism and protein and myelin synthesis (hence the neuro sx with B12 deficiency)
What is the only source of B12 only produced by bacteria and found in animal products
If you give supplemental B12 what s/e could you cause the s/e are rare so it is safe in large doses but could cause mild diarrhea, itching, urticaria, bloating, anaphylaxis (usually from the impurities that get injected with it)
What type of drug are the following (Cyanocobalamin – Redisol®, Cyanojet®, Betalin® and Nascobal® (intranasal), Hydroxocobalamin (alphaRedisol®, Hydrobexan® Supplemental B12 preparations for B12 deficiency
What is the MOA of folic acid needed for synthesis of purines and thymidylates (DNA synthesis), needed for methylation of transfer RNA, needed in amino acid synthesis of histidine to glutamic acid, serine to glycine and homocystine to methionine
What are the possible s/e of folic acid supplementation Only at high doses, Nausea, flatulence, and bitter taste. Altered sleep patterns and confusion. Anaphylaxis if used parenterally
Created by: Max Smith Max Smith on 2010-03-24



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