Drugs of hematopoiesis

Question 1

EPO ligand is produced by these cells

Answer 1

Kidney interstitial fibroblasts and perisinusoidal liver cells

Question 2

Thrombopoietin receptor is encoded by this gene, expressed in bone marrow

Answer 2

MPL gene

Question 3

ADP is a ligand for these two GPCRs, which induce platelet shape change and TxA2 production to promote aggregation

Answer 3

P2Y1 (wide expression) and P2Y12 (mostly expressed in platelets)

P2Y12 is the preferred therapeutic target because its expression is more limited, less toxic

Question 4

P2Y12 activation provides “inside out” signaling to enhance integrin affinity for this

Answer 4

Fibrinogen

Question 5

This is an integrin dimer on platelets that binds fibrinogen and vWF

Answer 5

GPIIb/IIIa

Question 6

What is the Philadelphia chromosome?

Answer 6

A mutant chromosome 22 in chronic myeloid leukemia

Chromosomes 9 and 22 exchange the ends of their q arms, resulting in a truncated chromosome 22 that creates a fusion of BCR (a RhoGEF) and ABL1 (a nonreceptor tyrosine kinase) genes
The new BCR-ABL1 gene encodes a constitutively active kinase that drives carcinogenesis

Question 7

Imatinib is a drug that can be used to treat chronic myeloid leukemia because it blocks this

Answer 7

BCR-ABL

Question 8

This drug can be used to treat chronic myeloid leukemia because it blocks BCR-ABL

Answer 8

Imatinib

Question 9

Glycoprotein that regulates RBC production by stimulating the division and differentiation of erythroid progenitor cells in bone marrow (mostly CFU-E)

Answer 9

Erythropoietin (EPO)

Question 10

In adults, the majority of erythropoietin (EPO) comes from these cells

Answer 10

Kidney interstitial cells of inner cortex near proximal tubule of nephron

10% from liver

Question 11

In children, the majority of erythropoietin (EPO) comes from these cells

Answer 11

Liver cells

is reversed from adults, which is 90% kidney and 10% liver

Question 12

Erythropoietin (EPO) expression is triggered by a low value of this

Answer 12

Hematocrit

Question 13

Epoietin alfa and Darbepoietin alfa are recombinant proteins of this

Answer 13

Erythropoietin (EPO)

Question 14

This type of drug is indicated for anemias in aphrenic patients

Answer 14

Erythropoietin (EPO) drugs:
Epoetin alfa and Darbepoietin alfa

Question 15

These are two recombinant Erythropoietin (EPO) drugs

Answer 15

Epoetin alfa and Darbepoietin alfa

Question 16

These drugs are indicated for anemia due to surgery, AIDS, or cancer chemotherapy

Answer 16

Erythropoietin (EPO) drugs:
Epoetin alfa and Darbepoietin alfa

Question 17

Before using these drugs for anemia, iron stores should be evaluated
Low ferritin or transferrin saturation should receive iron supplementation

Answer 17

Erythropoietin (EPO) drugs:
Epoetin alfa and Darbepoietin alfa

Question 18

Before using EPO drugs (Epoetin alfa and Darbepoietin alfa) this should be evaluated

Answer 18

Iron stores

Low ferritin or transferrin saturation should receive iron supplementation

Question 19

These anemia drugs are contraindicated in patients with hemoglobin concentrations >11 gm/dl

Answer 19

EPO drugs: Epoetin alfa and Darbepoietin alfa

Question 20

Epoetin alfa and Darbepoietin alfa are contraindicated in patients with hemoglobin concentrations of this

Answer 20

> 11 gm/dl

Question 21

These anemia drugs increase risk of death, MI, stroke, and venous thromboembolisms

Answer 21

EPO drugs: Epoetin alfa and Darbepoietin alfa

Question 22

Patients with chronic renal disease may have increased risk of death and seizures from use of these anemia drugs

Answer 22

EPO drugs: Epoetin alfa and Darbepoietin alfa

Question 23

These are the two black box warnings of Epoetin alfa and Darbepoietin alfa

Answer 23

Increased mortality and serious cardiovascular events
Increased thromboembolic events in surgery patients

Question 24

These are black box warnings of these drugs:
Increased mortality and serious cardiovascular events
Increased thromboembolic events in surgery patients

Answer 24

EPO drugs: Epoetin alfa and Darbepoietin alfa

Question 25

This enzyme is involved in the destruction of hypoxia inducible factor by proteosome, and inhibitors can be used to treat anemia of chronic kidney disease

Answer 25

Prolyl hydroxylase

Question 26

This drug is indicated for neutropenia due to chemo, BMT, or radiation treatment

Answer 26

G-CSF: Filgrastim

Question 27

This drug induces neutrophil progenitor proliferation and differentiation Used to boost donor peripheral blood stem cells or bone marrow

Answer 27

G-CSF: Filgrastim

Question 28

Filgrastim is this type of agent

Answer 28

G-CSF

Question 29

This is the main indication for G-CSF (Filgrastim)

Answer 29

Neutropenia (due to chemo, BMT, radiation)

Question 30

Sargramostim is this type of agent

Answer 30

GM-CSF

Question 31

This drug is indicated for aplastic anemia, mobilizing hematopoietic precursors into circulation for leukapheresis, and WBC recovery after bone marrow transplant

Answer 31

GM-CSF: Sargramostim

Question 32

These are two common adverse effects of GM-CSF (Sargramostim)

Answer 32

Fever Bone pain

Question 33

Fever and bone pain are common adverse effects of this drug for aplastic anemia

Answer 33

GM-CSF (Sargramostim)

Question 34

This anemia drug is contraindicated in yeast protein hypersensitivity

Answer 34

GM-CSF (Sargramostim)

Question 35

GM-CSF (Sargramostim) is contraindicated in patients with hypersensitivity to any ingredient, as well as to this

Answer 35

Yeast protein hypersensitivity

Question 36

Inhibitors of this may limit the efficacy of hematopoietic factor injections to treat anemia or neutropenia

Answer 36

JAK inhibitors

Question 37

Iron therapy is contraindicated for hemochromatosis and most cases of this type of anemia

Answer 37

Hemolytic anemia

Question 38

This drug is indicated for iron overdose

Answer 38

Deferoxamine

Question 39

Deferoxamine is indicated for this

Answer 39

Iron overdose

Question 40

PPI, antacids and H2 blockers may reduce oral absorption of this Time interval between or use parenteral

Answer 40

Iron

Question 41

Hydroxyurea is used to treat cancer and polycythemia because of this MOA

Answer 41

Inhibits ribonucleotide reductase to disrupt DNA synthesis

Question 42

This drug can be used to treat cancer and polycythemia because it inhibits ribonucleotide reductase

Answer 42

Hydroxyurea

Question 43

Hydroxyurea can be used to treat Sickle cell disease because of this MOA

Answer 43

Induces fetal hemoglobin synthesis

Question 44

How does Hydroxyurea induce fetal hemoglobin synthesis?

Answer 44

Donates NO group and activates NO synthase to produce NO NO activates GC to produce cGMP, activates PKG to promoted increased HbF expression

Question 45

Hydroxyurea donates a group to activate this enzyme

Answer 45

NO synthase

Question 46

After Hydroxyurea activates NO synthase, NO activates this enzyme

Answer 46

Guanylate cyclase

Question 47

In G6PD deficiency, iron is oxidized to the ferric form, to form this

Answer 47

Methemoglobin

Question 48

In G6PD deficiency, this is visualized with methylene blue stain

Answer 48

Heinz body = denatured methemoglobin

Question 49

This drug can be used for WBC recovery after autologous or allogenic bone marrow transplant

Answer 49

GM-CSF: Sargramostim

Question 50

This anemia drug is contraindicated in sickle cell disease and glomerulonephritis

Answer 50

Filgrastim

Question 51

Thrombocytopenia and splenomegaly are rare adverse effects of this drug

Answer 51

G-CSF: Filgrastim

Question 52

Upadacitinib inhibits this

Answer 52

JAK so should not be used with EPO to treat anemia, since EPO increase in RBC requires JAK activity

Question 53

These are the 3 functional effects of EPO signaling

Answer 53

Differentiation, survival and proliferation or erythroid cells

Question 54

Iron supplementation is contraindicated in these two conditions

Answer 54

Hemochromatosis and hemolytic anemias