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This Concept Map, created with IHMC CmapTools, has information related to: Hematopoietic Drugs, Hematopoietic Drugs Normochromic, Normocytic Anemia Erythropoietin Hypoxia->EPO made in fetal liver, adult kidney Glycoprotein: stim RBC diff'n, prolif'n -binds via EPO-R on progenitors, precursors ->matures into RBC->more O2 to kidney ->less EPO, Hematopoietic Drugs Fe-Deficiency Anemia Microcytic, Hypochromic Fe Toxicity -mostly kids, 20% die -increase risk of Ca, heart dz, neuro degeneration, athero. ->lots of FREE RADICALS -hepatotoxic, pulm edema, intestinal scarring -shock, CV collapse, acidosis Tx for OD - chelation: DEFEROXAMINE, Hematopoietic Drugs Fe-Deficiency Anemia Microcytic, Hypochromic Promote Fe Absorption: Fe++, Heme Ascorbic Acid, Vitamin A-helps w/ menses Gastric Acid - convert to Fe++ Clinical states: Fe-def, inc'd epo'esis, pregnancy, anoxia REDUCING: Alkaline - panc secretions Dairy products (chelate Fe), ice cream Tea, coffee, soy, grains, cereals, rhubarb, choc, soda, red wine, candy bars, some fibers Rx: Acid-reducing, ABX (& vice-versa) -Tetracyclines, FQs Clinical states: diarrhea, plenty of Fe, decreased epo'esis, inflam (celiac, IBD), Exogenous: r-HuEPO-recombinant human Epogen-alpha (Procrit, Epogen) Epoetin-beta Darbepoetin-a (Aranesp) (hamster ovary) -2-6 wks for desired effect MIRCERA-continuous epo'esis receptor activator -recently approved -extended release-q2wks or qmonth Indications: chronic renal failure, AZT (HIV Rx) suppresses marrow CA-CTX-induced anemia ONLY Pre-elective surgery if non-bloody Anemia from chronic inflam Adequate Fe stores-monitor ADRs-generally well-tolerated -inc'd risk of CV events -NOT for uncontrolled HTN -HTN, seizures, thrombosis Blood Doping Athletes gain advantage ->inc risk for spon clot, Hematopoietic Drugs Macrocytic Anemia -1/2-1/3 NL life span -Vit B or Folate def ->increased homocysteine Vitamin B12 Deficiency-ELDERLY -stores last 5 yrs, so dz is SLOW -also prevents myelin synth->neuro d/o -paresthesias, periph neuropathy, demyelination -TONGUE lacquered, glossy -memory impairment, depression, irritable, dementia -MASKED BY FOLATE SUPPS -megaloblastic anemia in 80% def pts -advances to pancytopenia -increased METHYLMALONIC ACID -Sources: GI bac, mollusks, clams, liver, kidney, legumes, eggs, cereals, Hematopoietic Drugs Fe-Deficiency Anemia Microcytic, Hypochromic Tx: Tx underlying cause Increase dietary Fe Fe supplementation: Oral FeSO4 (ferrous sulfate) FERROUS FUMARATE FERROUS GLUCONATE +/- VITAMIN C Molasses Floradix-Fe-fed yeast-quick ADRs N/D, constipation, upper abd pain Injectable: Fe DEXTRAN-need test dose Fe SUCROSE, Fe GLUCONATE -IV-hemodialysis w/ EPO ADRs-injx site rxn, N/D, ANAPHYLAXIS ->reticulocytosis w/in 7 days Hgb increases in 3 wks, Hematopoietic Drugs For Granulocytes FILGRASTIM - SubQ admin -G-CSF-granulocytes/neutrophils -also in PEGylated form-less renal clearance -better tolerated than GM-CSF Indications: -CA pts w/ CTX-prevents febrile neutropenia due to infx -AML pts on CTX -CA pts receiving BMT ADRs: -splenic rupture, fever, malaise ARDS from PMN infiltration of lung -BONE PAIN, Hematopoietic Drugs Fe-Deficiency Anemia Microcytic, Hypochromic Dietary Iron HEME IRON: 3-5x more readily absorbed -Lamb, beef, pork, chicken -Liver NON-HEME IRON: Many processed foods, cereal Leafy, green veggies, potato skins, beets, tomatoes, buckwheat Dry beans, whole grain breads, bran Apples (green), apricots, prunes, raisins, almonds Seaweeds Absorb from duodenum, prox jejunum Transported via transferrin Stored as ferritin (liver, marrow, spleen), Hematopoietic Drugs Macrocytic Anemia -1/2-1/3 NL life span -Vit B or Folate def ->increased homocysteine Folate Deficiency -can deplete much faster than B12 -can->neural tube defects if preggers Liver: Folate-ɱ-methyltetrahydrofolate ->to tissue cells Food: OJ, oranges, green leafy veggies, rice, barley, sprouts, soy, chick peas, broc, asp, peas, fortified in grains -destroyed at cooking temps, Hematopoietic Drugs Normochromic, Normocytic Anemia Erythropoietin Exogenous: r-HuEPO-recombinant human Epogen-alpha (Procrit, Epogen) Epoetin-beta Darbepoetin-a (Aranesp) (hamster ovary) -2-6 wks for desired effect MIRCERA-continuous epo'esis receptor activator -recently approved -extended release-q2wks or qmonth Indications: chronic renal failure, AZT (HIV Rx) suppresses marrow CA-CTX-induced anemia ONLY Pre-elective surgery if non-bloody Anemia from chronic inflam Adequate Fe stores-monitor ADRs-generally well-tolerated -inc'd risk of CV events -NOT for uncontrolled HTN -HTN, seizures, thrombosis, Vitamin B12 Deficiency-ELDERLY -stores last 5 yrs, so dz is SLOW -also prevents myelin synth->neuro d/o -paresthesias, periph neuropathy, demyelination -TONGUE lacquered, glossy -memory impairment, depression, irritable, dementia -MASKED BY FOLATE SUPPS -megaloblastic anemia in 80% def pts -advances to pancytopenia -increased METHYLMALONIC ACID -Sources: GI bac, mollusks, clams, liver, kidney, legumes, eggs, cereals Tx Vit B12 Injections q1-3 mos -PAINFUL-> cold abscesses Oral-sublingual better than tabs Intranasal gel - more expensive ADRs -no toxicity, Vitamin B12 Deficiency-ELDERLY -stores last 5 yrs, so dz is SLOW -also prevents myelin synth->neuro d/o -paresthesias, periph neuropathy, demyelination -TONGUE lacquered, glossy -memory impairment, depression, irritable, dementia -MASKED BY FOLATE SUPPS -megaloblastic anemia in 80% def pts -advances to pancytopenia -increased METHYLMALONIC ACID -Sources: GI bac, mollusks, clams, liver, kidney, legumes, eggs, cereals Cause -Absent IF, pernicious anemia -tapeworm, H. pylori -ileal dz, gastric surgery -Rx: PHENYTOIN, METFORMIN, PPIs, Hematopoietic Drugs For Granulocytes SARGRAMOSTIM (LEUKINE) -yeast recommbinant GM-CSF ->gran, mac pathways -neutrophils, macs, dendritic cells Indications: after AML induction CTX in older pts, shortens recovery -accelerate myeloid recovery in BMT ADRs -bone pain, pulm cap leak syndrome -pulm edema, heart failure -fever, malaise, Folate Deficiency -can deplete much faster than B12 -can->neural tube defects if preggers Liver: Folate-ɱ-methyltetrahydrofolate ->to tissue cells Food: OJ, oranges, green leafy veggies, rice, barley, sprouts, soy, chick peas, broc, asp, peas, fortified in grains -destroyed at cooking temps Causes of Def Malnutrition -60% pts are alcoholics Increased reqs: preg, malignancy, infancy, increased hem'esis Malabsorption: celiac, int dz, no microbes -EtOH, Metformin, SMX, TMP, sulfa, OCP, Pentamidine -Anticonvulsants, methotrexate, Folate Deficiency -can deplete much faster than B12 -can->neural tube defects if preggers Liver: Folate-ɱ-methyltetrahydrofolate ->to tissue cells Food: OJ, oranges, green leafy veggies, rice, barley, sprouts, soy, chick peas, broc, asp, peas, fortified in grains -destroyed at cooking temps Tx Dietary Sources Oral Therapy: greater absorption -OTC prophylaxis for preggers -400mg/d Parenteral - for NPO pts Careful: can MASK B12 def -then can accum MTHF folate -secondary folate def, Hematopoietic Drugs Fe-Deficiency Anemia Microcytic, Hypochromic Fe-def via: BLEEDING 'TIL PROVEN O/W Pregnancy, premature babies GI bleed, infx, uterine fibroids Blood loss (10-20% menstruating FMs)