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What drugs interfere w folate absorption
Phenytoin, isoniazid, sulfasalazine, oral contraceptives
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What drugs interfere with folate utilization by inhibiting dihydrofolate reductase
Methotrexate and trimethoprom
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Where is folate stored
Liver
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Should folate be used to treat b12 deficiency?
No bc b12 deficiency causes neurologic damagr
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What are hematopoetic growth factors?
Glycoprotein hormones that regulate the proloferation and diff of hema progenitor cells in bone marrow
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Examples of hema growth factors
Epo and myeloid growth factors
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Hema growth factors
Recombinant human proteins, treat various forms of hema depression such as leukemia, lymphomas and end stage renal disease, treat bone marrow transplantation and chemo radiation drugs
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Epo
34kd glycoprotein in blood from proximal tubule of kidney, peritubular cells, binds to red cell progeniotrs in bone marrow to increase proliferation and differentiation
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What are the uses for EPO
Anemias w chronic renal failure, anemias w progressive renal fail, anemias AIDS zidovidune, cancer chemo anemias, preop to produce blood for autologous transfusion
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Epo adverse effects
Increase clotting during dialysis, make ppl iron deficient, seizure and htn-can be avoided by using low grad doses of drug
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Three ex of myeloid growth factors
Gc-sf, gm-csf, stem cell factor
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G-csf
Stimulates granulocyte colonies and neutrophil production promotes granulocyte release
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Gmcsf
Stimulates and proliferation of granulocytes and monocytes and macrophages
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Stem cell factor
Survival and prolif of early pluripotent cells
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Monocytes colony stimulating factor
Promotes growth of monocyte prog
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Il3
Stimulates formation of moat hemqtopoetic cell lines
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Use of myeloid growth factors
Recovery of bone marrow after disease or med therapy
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Folic acid
Essential nutrient, tetrahydro precursor needed for purine and thymidylate synthesis
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Folic acid deficiency
Leads to megaloblastic anemia, no neuro damage, impairs dna syn and rapidly dividing cells
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Vitamin b12
Cobalt containing vit 2. Rxns
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Vit b12 rxns.
Methylmalonyl co a mutase- required for conversion of methylmalonyl coa to succinyl coa.....methionine synthetaee
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Methylmalonyl coa mutase
Methylmalonyl coa accumulates incorp into cell membranes gives rise to neuro problems
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Methionine synthetaee
Megloblastic anemia tx with folate
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Pernicious anemia
Deficient intrinsic factor or defect in absorption of b12-if complex in distal ileum in malabsorption syndrome or inflammatory bowel disease
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Transcobalamin ii
Vit b12 transfer protein, stored in liver, only trace amts secreted per day therefore hard to get b12 deficiency...takes yrs to develop
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Parenteral iron inducations
Irin deficiency anemia who cannot toleratw or absorb oral iron, excessive blood loss eho cant be maintained by oral, chrnic renal fail w epo
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Iv iron dextran, na ferric gluconate complex, iron sucrose
Parenteral iv drugs for irom deficiency
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What is hereditary hemochromotosis?
Mutation in hfe gene- protein that interacts with transferrin receptor common in whites most common inherited disorder
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What is hematopoeisis?
The continuous replacement of mature red blood cells
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What are the two requirements on hematopoesis?
- 1. must be responsive to basal needs
- 2. must be responsive to situations of increased demand
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How much can RBC prodcution vary in response to anemia and hypoxia
5-10x
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What three things are reuqired for adequate hematopoesis?
- 1. iron
- 2. Vitamin B12
- 3. Folic acid
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Abscence of iron results in which type of anemia?
Microcytic hypochromic anemia
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What is iron used for?
synthesis of hemoglobin
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What is hemoglobin compopsed of?
Fe-pophyrin and globin chains (humans mostly have HbA)
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What type of anemia results from vitamin B12 or folate deficiency?
megaloblastic anemia
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What are the three major causes of anemia?
- 1. Blood loss
- 2. Disturbances in RBC production
- 3. increased destruction of RBCs
malabsorption problems such as Crohns disease and inflammatory bowel disease can cause an increased need for RBCs.
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What is the most common type of anemia?
iron deficiency
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What percentage of iron is present in hemoglobin?
60-80%
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What are the indications for therapeutic use of iron?
only for iron deficieny anemias such as in children in rapid growth periods and in adults from blood loss for example
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Why is oral iron prefered
because it works just as fast as parenteral and is less likely to cause excessive iron accumulation
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Which iron preparation is absorbed the most effieciently?
ferrous salts (ferrous sulfate and gluconate fumarate)
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What drug is used to chelate iron in acute overdose?
desforaxamine (IV)
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What is the transfer form of iron and what is the storage form?
- transfer= transferrin
- storage= ferritin
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