2.1 Pharm Exam4: Hematology

Front 1

what three types of cells are made via hematopoiesis? what are their processes called?

Back 1

RBC- erythropoiesis
WBC- leukopoiesis
Platelet- Megakaryopoiesis

Front 2

what is the precursor of all blood cells?

Back 2

pluripotent stem cell (PSC)

Front 3

what local signaling molecule regulates erythrocytes?

which one does platelets?

which ones do neutrophils?

Back 3

eryrthrocytes- Erythropoietin
Platelet- IL-11
Neutrophils- GM-CSF & G-CSF

Front 4

what does erythropoiesis required?

Back 4

uninterrupted supply of iron

Front 5

what conditions will disrupt the erythrocyte balance?

Back 5

kidney or bone marrow dz,

iron deficiency,

certain vitamin deficiencies

cancer therapy.

Front 6

what drug is almost identical to endogenous erythropoietin?

what is the only difference between the two? what relevance does this have for blood doping?

Back 6

Epoetin alfa: Epogen, Procrit

difference: carbohydrate modifications of the protein.

D/t this difference in structure, you can give an antibody that will detect if someone has been taking erythropoietin supplements.

Front 7

which drug mimic erythropoietin, but has 4 mutated amino acids that change the carbohydrate modificatiosn?

why?

Back 7

darbopoietin alfa: Aranesp

the changed carbohydrate modifications extend the 1/2 life of the protein 24-26 hrs.

Front 8

what is the MOA of erythropoietin and recombinant forms?

Back 8

stimulates cell surface erythropoeitin receptors (JAK-STAT) on RBC progenitor cells in bone marrow-->

Stimulates/ inhibits the expression of specific genes causing-->

overall effect of increased RBC production

(inc progenitor cells, inc hemoglobin, inc reticulocyte release from marrow, inc hematocrit)

Front 9

what is the TOP therapeutic uses of erythropoietin?

Back 9

cancer tx: chemo* & radiation therapy

Front 10

what are the three adverse effects associated with and increase in hematocrit d/t erythropoietin?

Back 10

1. HTN

2. thrombotic complications

3. polycythemia

Front 11

what are the three myeloid growth factors?

what makes one of them different from the other?

Back 11

figrastim (G-CSF) ,

Pegfilgrastime (G-CSF)

Sagramostin (GM-CSF)

pegfilgrastime is different because it has polyethylene glycol (PEG) added to filgrastim to prolong its serum half-life.

Front 12

where is the recombinant human form of G-CSF generated?

Where is the recombinant human form of GM-CSF generated? (Glycosylated?)

Back 12

G-CSF: Bacteria - not glycosylated
GM-CSF: Yeast- partially glycosylated.

Front 13

what is the MOA of G-CSF targeted drugs?

GM-CSF targeted drugs?

Back 13

G-CSF: stimulate progenitors already committed to the neutrophil lineage-->

prolongs neutrophil survival & inc conc. of hematopoietic stem cells in peripheral blood

GM-CSF: Broad biologic actions on erythroid, granulocyte progenitor cells & megakaryocyte progenitors-->

stimulates activity of neutrophils.

Front 14

what is the purpose for G-CSF as far as stem cell transplantation is concerned?

Back 14

increases concentration of hematopoietic stem cells in peripheral blood.

Front 15

what is the main therapeutic use of myeloid growth factors?

which one is better tolerated G-CSF or GM-CSF?

Back 15

neutropenia- which is the most common dose-limiting toxicity of chemo

G-CSF is better tolerated (less SEs)

Front 16

which drug is a recombinant human IL-11 produced in e. coli? what is the MOA?

Back 16

Oprelvekin (neumega)

MOA: growth factors bind to IL-11 receptors on committed progenitor cells & through the JAK/STAT pathway-->

increase proliferation & differentiation of megakaryocytes (platelets)

Front 17

what is the main therapeutic use of oprelvekin (IL-11)?

Back 17

thrombocytopenia

Front 18

deficiency in what causes microcytic anemia? macrocytic anemia?

Back 18

micro- iron
macro- Vitamin B12 and Folic Acid

(tx w/ iron, Vit B12. or folic acid)

Front 19

how do you tx a pt who has anemia d/t chronic kidney dz?

what about anemia d/t cancer chemotherapy?

Back 19

epo (+iron)- chronic kidney
epo (+/- iron)- cancer chemo

Front 20

what makes up the nucleus of the porphyrin heme ring in hemoglobin?

Back 20

iron

Front 21

what does hypochromic mean?

Back 21

little or no hemoglobin (hemoglobin gives erythrocyte bright-red appearance)--> dull red

Front 22

what are the four causes of macrocytic hypochromic anemia?

Back 22

Inadequate ingestion
decreased absorption (Achlorhydria, crohn's, drug interaction)
increased requirements (infancy, childhood, pregnancy)
blood loss (menstruation and GI bleeding)

= not enough iron

Front 23

70% of the body's iron is in _____

Back 23

hemoglobin

Front 24

what is the normal dietary intake of iron?

what regulates the amount of iron absorbed by the intestine?

Back 24

dietary intake- 0.5-1 mg daily

amount of iron absorbed by the intestine is regulated by iron stores in mucosal cells.

Front 25

T/F

The body's way of getting rid of iron is through blood letting and urination.

Back 25

FALSE

The body cannot expel iron from its body via urination; it can expel iron from blood letting but that is not a body mediated mechanism to excrete iron.

Front 26

what are the three oral iron drugs that you can take if iron deficient?

Back 26

ferrous sulfate (hydrated & dessicated--> more chemically stable) = CHEAPEST
Ferrous gluconate
ferrous fumarate

(all relatively the same)

Front 27

what form of iron should be used for iron deficient individuals? why?

Back 27

ferrous because ferric is not well absorbed.

(ferrous= Fe2+ state)

Front 28

only ____ of the dose of iron can be absorbed in the GI tract.

The dose level is at _____ - _____ of elemental iron per day because of absorption and incorporation limits (50-100 mg can be incorporated daily).

Back 28

25%
200-400 mg

Front 29

what should you administer w/ iron in order to lower gastric pH?

Back 29

vitamin C- aids in absorption

Front 30

T/F

Iron is better absorbed on an empty stomach, but the side effects are worse.

Back 30

true

Front 31

what are the major side effects of oral iron?

Back 31

nausea, dyspepsia, abdominal cramps, constipation

(also causes black stool & dark urine, may stain dentures)

Front 32

what is the advantage to parental iron?

what are the drugs?

Back 32

advantage is correction of the deficiency in a shorter time period (good for Crohn's, etc that cannot tolerate GI SEs)

drugs:

sodium ferric gluconate complex (Ferrlecit)

iron dextran (INFeD & DexFerrum)

iron sucrose (Venofer)

Front 33

which parenteral iron needs to have a test dose before complete administration? why?

what sxs are usually associated w/ the test dose that would warn against severe rxn?

Back 33

iron dextran

- to avoid toxicity & anaphylaxis---> infusion related death (no elimination method**)

Sx- Hypersensitivity--> flushing, urticaria, bronchospasm

Front 34

Iron overdose mainly affects which population? what level is associated with death?

Back 34

children: 2-10 grams are associated with death

Front 35

what are the sxs of iron overdose? tx?

Back 35

sxs: necrotizing gastroenteritis w/ vomiting, abdominal pain and bloody diarrhea.

followed by shock, dyspnea, metabolic acidosis, coma & death

TX: iron cheloators: deferoxamine & deferasirox (bind iron that has already been absorbed)

Front 36

which cells are effected in megaloblastic anemia?

Back 36

erythrocytes & other rapidly dividing cells (blood cells, GI mucosal cells)

--> cells large than normal d/t inhibition of DNA synthesis (usually result of vit B12 or folate def)

Front 37

where is vitamin B12 stored?

what is necessary for absorption?

Back 37

liver;

absorption requires intrinsic factor.

Front 38

what are the 3 causes of Vitamin B12 deficiency?

Back 38

decrease absorption (pernicious anemia & crohn's dz)
inadequate uptake
inadequate utilization

Front 39

what is the initial manifestation of vitamin B12 deficiency?

later?

Back 39

initial anemia- fatigure, parasthesia, ataxia

later neurodegeneration- neuropsychiatric abnormalities (irreversible)

Front 40

17 yr old femal presents with lingering fatigue and discoordination as well as some loss of memory and slight psychosis, what might she have?

Back 40

Vitamin B12 deficiency

Front 41

what drugs are used to tx Vitamin B12 deficiency?

Back 41

cyanocobalamin (Vit B12 drugs)

(IV or nasally/orally w/ intrinsic factor)

(SEs are rare)

Front 42

what is Vitamin B12 required for?

what is the end product involved in?

Back 42

conversion of 5-methyltetrahydrofolate to THF (tetrahydrofolate)--> activating it.

(removal of methyl group)

involved in: synthesis of DNA

Front 43

Can you give your Vitamin B12 deficient pt folate? why?

Back 43

NO because Folate will just mask the neurodegenerative effects and mask the vitamin B12 deficiency.

Front 44

without vitamin B12 what cannot form?

Back 44

THF which means it can't form thymidylate (from dUMP) or purine biosythesis and can't replicate DNA.

Front 45

what is the MOA of folic acid?

Back 45

-synthesis of purines & thymidylates (DNA synthesis)

-needed for methylation of tRNA

-needed for amino acid synthesis

(SEs of def same as for B12)

Front 46

when do you start getting sxs caused by folic acid drugs?

Back 46

only at high doses.

(GI, CNS, anaphylaxis)