Anemias & Hematopoietic Growth Factors; L1 (11-06-15) Flashcards
Iron basic pharmacology
Approximate distribution: \_\_% in hemoglobin \_\_% in myoglobin \_\_% stored as ferritin and hemosiderin \_\_% in enzymes (e.g. cytochromes), and transferrin
Iron basic pharmacology
Approximate distribution:
70% in hemoglobin
10% in myoglobin
10-20% stored as ferritin and hemosiderin
Less than 1% in enzymes (e.g. cytochromes), and transferrin
Iron basic pharmacology
Intake:
-Average US diet contains __ mg of which __ mg is absorbed.
Iron basic pharmacology
Intake:
-Average US diet contains 10-15 mg of which 0.5-1 mg is absorbed.
Iron basic pharmacology
Absorption:
1) __ iron is absorbed intact from __ and __
2) __ iron must be reduced to __ iron (Fe2+)
3) The __ form is absorbed through DMT1 by active transport
4) Within mucosal cell, ferrous iron is converted to ____
5) Iron leaves the mucosal cell by passing through __
6) __ down-regulates __ and regulates iron absorption
Iron basic pharmacology
Absorption:
1) Heme iron is absorbed intact from duodenum and jejunum
2) Non-heme iron must be reduced to ferrous iron (Fe2+)
3) The ferrous form is absorbed through DMT1 by active transport
4) Within mucosal cell, ferrous iron is converted to ferric (Fe3+)
5) Iron leaves the mucosal cell by passing through ferroportin
6) Hepcidin down-regulates ferroportin and regulates iron absorption
Iron basic pharmacology
Fate:
1) In case of __, ferric iron is bound to __ for immediate transport via the blood to bone marrow
2) Stored as __ or __ in liver and spleen
3) __ in plasma is in equilibrium with body storage and can be used to estimate total body stores
Iron basic pharmacology
Fate:
1) In case of demand, ferric iron is bound to transferrin for immediate transport via the blood to bone marrow
2) Stored as ferritin or hemosiderin in liver and spleen
3) Ferritin in plasma is in equilibrium with body storage and can be used to estimate total body stores
Iron basic pharmacology
Balance:
1) Maintained by changes in __ regulated by the concentrations of __ and __ in mucosal cells
2) In iron deficiency, __ goes up, __ goes down
3) In iron overload, __ goes down, __ goes up
Iron basic pharmacology
Balance:
1) Maintained by changes in absorption regulated by the concentrations of transferrin and ferritin in mucosal cells
2) In iron deficiency, transferrin goes up, ferritin goes down
3) In iron overload, transferrin goes down, ferritin goes up
Indication for iron therapy: prevention or tx of iron deficiency anemia (__ __ anemia)
1) __ requirements: a) frequently present in __ infants; b) children during __ period; c) __ and __ women
2) __ absorption: post-__ or severe __ disease
3) __ loss: a) __; b) occult __
Indication for iron therapy: prevention or tx of iron deficiency anemia (microcytic hypochromic anemia)
1) Increased requirements: a) frequently present in premature infants; b) children during rapid growth period; c) pregnant and lactating women
2) Inadequate absorption: post-gastrectomy or severe bowel disease
3) Blood loss: a) menstruation; b) occult GI bleeding
Iron therapy
1) __ preparations: a) only __ (sulfate, gluconate, fumarate); b) response within __, normal in __; c) adverse effects: __ (take with or after meals); __ may obscure recognition of GI bleeding
2) __ iron therapy: a) usually iron __, deep i.m. or i.v. infusion (also iron __ and iron ____); b) indicated post-__/__ resection, __ syndromes, intolerance of __; c) adverse effects: local __ and tissue __ with i.m.; headache, fever, nausea, vomiting, __, __, __, __, __ (rare)
Iron therapy
1) Oral preparations: a) only ferrous salts (sulfate, gluconate, fumarate); b) response within a week, normal in 1-3 months; c) adverse effects: GI distress (take with or after meals); black stool may obscure recognition of GI bleeding
2) Parenteral iron therapy: a) usually iron dextran, deep i.m. or i.v. infusion (also iron sucrose and iron sodium gluconate); b) indicated post-gastrectomy/small bowel resection, malabsorption syndromes, intolerance of oral preps; c) adverse effects: local pain and tissue staining with i.m.; headache, fever, nausea, vomiting, back pain, arthralgias, urticaria, bronchospasm, anaphylaxis/death (rare)
Iron clinical toxicity
Acute (___ of iron tablets):
1) May be fatal in __
2) __ gastroenteritis
3) After short improvement, __, __, and __
3) Tx: a) gastric __, lavage with __ or __ solution; b) activated charcoal is __; c) __, a potent iron chelating substance, i.m. or i.v.
Iron clinical toxicity
Acute (accidental ingestion of iron tablets):
1) May be fatal in small children
2) Necrotizing gastroenteritis
3) After short improvement, metabolic acidosis, coma, and death
3) Tx: a) gastric aspiration, lavage with phosphate or carbonate solution; b) activated charcoal is ineffective; c) deferoxamine, a potent iron chelating substance, i.m. or i.v.
Iron clinical toxicity
Chronic (iron __):
1) Seen in an inherited disorder, __
2) Patients receiving repeated __
3) Excess iron deposited in __, __, __ -> to organ failure
4) Tx: a) intermittent __ (in the absence of anemia); b) iron chelation: __ (parenteral) or __ (oral)
Iron clinical toxicity
Chronic (iron overload):
1) Seen in an inherited disorder, hemochromotosis
2) Patients receiving repeated RBC transfusions
3) Excess iron deposited in heart, liver, pancreas -> to organ failure
4) Tx: a) intermittent phlebotomy (in the absence of anemia); b) iron chelation: deferoxamine (parenteral) or deferasirox (oral)
Vitamin B12 - basic pharmacology
Chemistry and pharmacokinetics of vitamin B12:
1) __ and __ are the active forms
2) __ and __ (therapeutic drugs) are converted to the active forms
3) Absorption: a) vitamin B12 is absorbed ONLY after complexing with __; b) absorption (__ ug/day) occurs in the __ by a specific transport system; c) deficiency often caused by lack of __ or __ (transport); d) absorbed vitamin B12 is bound to plasma __ for distribution
4) Storage: __ is the main storage site, containing __ mg of vitamin B12
Vitamin B12 - basic pharmacology
Chemistry and pharmacokinetics of vitamin B12:
1) Deoxyadenosylcobalamin and methylcobalamin are the active forms
2) Cyanocobalamin and hydroxycobalamin (therapeutic drugs) are converted to the active forms
3) Absorption: a) vitamin B12 is absorbed ONLY after complexing with intrinsic factor; b) absorption (1-5 ug/day) occurs in the distal ileum by a specific transport system; c) deficiency often caused by lack of intrinsic factor or bowel disease (transport); d) absorbed vitamin B12 is bound to plasma transcobalamin II for distribution
4) Storage: liver is the main storage site, containing 3-5 mg of vitamin B12
Vitamin B12 - basic pharmacology
Chemistry and pharmacokinetics of folic acid:
1) Richest sources are __, __, and __
2) Absorption: a) average diet contains __ ug; b) __glutamate forms must be hydrolyzed to __glutamate; c) __glutamate form enters bloodstream by __ and __ transport
3) Storage: a) __ mg of folate is stored in __ and other tissues; b) folate is excreted and destroyed by __; c) since normal daily requirements are ~__, diminished intake will result in deficiency and anemia within __
Vitamin B12 - basic pharmacology
Chemistry and pharmacokinetics of folic acid:
1) Richest sources are yeast, kidney, and green veggies
2) Absorption: a) average diet contains 500-700 ug; b) polyglutamate forms must be hydrolyzed to monoglutamate; c) monoglutamate form enters bloodstream by active and passive transport
3) Storage: a) 5-20 mg of folate is stored in liver and other tissues; b) folate is excreted and destroyed by catabolism; c) since normal daily requirements are ~50 ug, diminished intake will result in deficiency and anemia within 1-6 months
Vitamin B12 and folic acid - clinical pharmacology
Treatment of __ or __:
1) Vitamin B12 and folic acid used only for prevention or treatment of __
2) Important to determine whether vitamin B12 or folic acid deficiency is the cause since __ will NOT prevent the irreversible neurological damage
3) Vitamin B12 deficiency caused by __ usually requires lifelong parenteral injection of __ or __
4) Response is rapid and return to normal in __
5) Folic acid deficiency due to inadequate __ or diminished __ is treated with oral doses of __
Vitamin B12 and folic acid - clinical pharmacology
Treatment of macrocytic or megaloblastic anemias:
1) Vitamin B12 and folic acid used only for prevention or treatment of deficiencies
2) Important to determine whether vitamin B12 or folic acid deficiency is the cause since folic acid will NOT prevent the irreversible neurological damage
3) Vitamin B12 deficiency caused by malabsorption usually requires lifelong parenteral injection of cyanocobalamin or hydroxycobalamin
4) Response is rapid and return to normal in 1-2 months
5) Folic acid deficiency due to inadequate intake or diminished storage is treated with oral doses of folic acid
Erythropoietin - basic pharmacology
1) 34-39 kDa __
2) Functions: a) stimulates __ and __ of erythroid cells; b) promotes release of __ from __ __
3) Produced by the __
4) Usually __ relationship between __ level and serum erythropoietin level, but not in ______
5) Recombinant human erythropoietin (____) is produced in a mammalian cell expression system
Erythropoietin - basic pharmacology
1) 34-39 kDa glycoprotein
2) Functions: a) stimulates proliferation and differentiation of erythroid cells; b) promotes release of reticulocytes from bone marrow
3) Produced by the kidney
4) Usually inverse relationship between hemoglobin level and serum erythropoietin level, but not in chronic renal failure
5) Recombinant human erythropoietin (epoetin alfa) is produced in a mammalian cell expression system
Indication for erythropoietin therapy
1) _____
2) Some patients with __ anemia, __ malignancies, anemias associated with __, __ (in these patients, erythropoietin is most effective if endogenous erythropoietin levels are disproportionately __; __ doses required than in chronic renal failure, but responses are still incomplete)
3) Treatment of anemia of __
4) Post-__
Indication for erythropoietin therapy
1) Chronic renal failure
2) Some patients with aplastic anemia, hematologic malignancies, anemias associated with AIDS, cancer (in these patients, erythropoietin is most effective if endogenous erythropoietin levels are disproportionately low; higher doses required than in chronic renal failure, but responses are still incomplete)
3) Treatment of anemia of prematurity
4) Post-phlebotomy
Erythropoietin therapy
1) Given __ or __
2) Increase in __ count seen in about __ days
3) Increase in __ seen in __ weeks
Erythropoietin therapy
1) Given IV or subcutaneously
2) Increase in reticulocyte count seen in about 10 days
3) Increase in hemoglobin seen in 2-6 weeks
