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What drugs interfere w folate absorption
Phenytoin, isoniazid, sulfasalazine, oral contraceptives
What drugs interfere with folate utilization by inhibiting dihydrofolate reductase
Methotrexate and trimethoprom
Where is folate stored
Should folate be used to treat b12 deficiency?
No bc b12 deficiency causes neurologic damagr
What are hematopoetic growth factors?
Glycoprotein hormones that regulate the proloferation and diff of hema progenitor cells in bone marrow
Examples of hema growth factors
Epo and myeloid growth factors
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
34kd glycoprotein in blood from proximal tubule of kidney, peritubular cells, binds to red cell progeniotrs in bone marrow to increase proliferation and differentiation
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
Epo adverse effects
Increase clotting during dialysis, make ppl iron deficient, seizure and htn-can be avoided by using low grad doses of drug
Three ex of myeloid growth factors
Gc-sf, gm-csf, stem cell factor
Stimulates granulocyte colonies and neutrophil production promotes granulocyte release
Stimulates and proliferation of granulocytes and monocytes and macrophages
Stem cell factor
Survival and prolif of early pluripotent cells
Monocytes colony stimulating factor
Promotes growth of monocyte prog
Stimulates formation of moat hemqtopoetic cell lines
Use of myeloid growth factors
Recovery of bone marrow after disease or med therapy
Essential nutrient, tetrahydro precursor needed for purine and thymidylate synthesis
Folic acid deficiency
Leads to megaloblastic anemia, no neuro damage, impairs dna syn and rapidly dividing cells
Cobalt containing vit 2. Rxns
Vit b12 rxns.
Methylmalonyl co a mutase- required for conversion of methylmalonyl coa to succinyl coa.....methionine synthetaee
Methylmalonyl coa mutase
Methylmalonyl coa accumulates incorp into cell membranes gives rise to neuro problems
Megloblastic anemia tx with folate
Deficient intrinsic factor or defect in absorption of b12-if complex in distal ileum in malabsorption syndrome or inflammatory bowel disease
Vit b12 transfer protein, stored in liver, only trace amts secreted per day therefore hard to get b12 deficiency...takes yrs to develop
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
Iv iron dextran, na ferric gluconate complex, iron sucrose
Parenteral iv drugs for irom deficiency
What is hereditary hemochromotosis?
Mutation in hfe gene- protein that interacts with transferrin receptor common in whites most common inherited disorder
What is hematopoeisis?
The continuous replacement of mature red blood cells
What are the two requirements on hematopoesis?
- 1. must be responsive to basal needs
- 2. must be responsive to situations of increased demand
How much can RBC prodcution vary in response to anemia and hypoxia
What three things are reuqired for adequate hematopoesis?
- 1. iron
- 2. Vitamin B12
- 3. Folic acid
Abscence of iron results in which type of anemia?
Microcytic hypochromic anemia
What is iron used for?
synthesis of hemoglobin
What is hemoglobin compopsed of?
Fe-pophyrin and globin chains (humans mostly have HbA)
What type of anemia results from vitamin B12 or folate deficiency?
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.
What is the most common type of anemia?
What percentage of iron is present in hemoglobin?
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
Why is oral iron prefered
because it works just as fast as parenteral and is less likely to cause excessive iron accumulation
Which iron preparation is absorbed the most effieciently?
ferrous salts (ferrous sulfate and gluconate fumarate)
What drug is used to chelate iron in acute overdose?
What is the transfer form of iron and what is the storage form?
- transfer= transferrin
- storage= ferritin
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