Kruse: Pharmacology of anemia; hematopoietic growth factors

Question 1

Where is iron aborbed?

Answer 1

the duodenum

Question 2

What form of iron can be absorbed?

Answer 2

the Fe2+ kind

-ferrous

Question 3

What transfers iron in the blood?

Answer 3

transferrin

Question 4

What protein lets ferrous iron intot he cell?

Answer 4

DMT1

Question 5

What is Iron stored as?

Answer 5

ferritin

Question 6

What do we do with someone who has an iron deficiency anemia?

Answer 6

give them iron preparations

Question 7

What kind of iron should be in oral preparations?

Answer 7

the ferrous form, that is what gets absorbed!

-ferous sulfate, gluconate, or fumarate will do

Question 8

When would use parenteral iron therapy?

Answer 8

when the patient cant tolerate or absorpb the oral kind

• be careful, it bypasses the regulatory mechanisms and deliver more iron than can be stored
• gotta watch iron levels for toxicity

Question 9

What are the 3 forms of parenteral iron in the US?

Answer 9

Iron dextran: small test first because of hypersensitivity risk
Sodium ferric gluconate complex
Iron-sucrose complex
-the last 2 are less likely to cause hypersensitivity rxns

Question 10

Acute Iron toxicity

Answer 10

• exclusively in young children who accidentally ingest iron tablets
• vomiting, bloody poo, shock, lethargy

Question 11

What do we treat iron toxicity with?

Answer 11

Deferoxamine

-potent iron-chelating compound

Question 12

Chronic Iron toxicity

Answer 12

• deposits in heart, liver, pancreas, and other organs.. can lead to organ failure and death
• common in patients with inherited hemochromatosis

Question 13

What do we treat chronic iron toxicity with?

Answer 13

deferasirox

-reduces liver iron concentrations buyt data in removing iron form heart is lacking

Question 14

What does B12 deficiency give us?

Answer 14

megaloblastic anemia

Question 15

What needs to bind to B12 before we can absorb it?

Answer 15

intrinsic factor

Question 16

Where is B12 absorbed in the GI tract?

Answer 16

the distal ileum

Question 17

What 2 things does B12 do?

Answer 17

• takes a Methyl group from THF and gives it to homocystein to make METHIONINE
• helps methylmalonic acid turn into Succinyl CoA

Question 18

What is a common cause of B12 deficiency?

Answer 18

pernicious anemia

-antibodies against Intrinsic factor

Question 19

What neuro effects happen in B12 deficiency?

Answer 19

parasthesias int he peripheral nerves

-progresses to spasticity, ataxia, and other CNS dysfunctions

Question 20

What are almost all B12 deficiencies due to?

Answer 20

malabsorption

-so, we need to give parenteral B12 injections (cyanocobalamin and hydroxocobalamin)

Question 21

What is Folic Acid required for?

Answer 21

the synthesis or amino acids, purines, and DNA (dTMP)

Question 22

What are the richest sources of folic acid?

Answer 22

yeast, liver, kidney, and green veggies

Question 23

what enzyme lets folic acid reenter the cycle as dihydrofolate?

Answer 23

Folate reductase

Question 24

How does folic acid deficiency look clinically?

Answer 24

a lot like B12 defiency, but there’s no neuro symptoms because methylmalonic acid is just fine

Question 25

What are some drugs that can cause folic acid deficiency

Answer 25

methotrexate, trimethoprim, and pyrimethamine (all inhibit dihydrofolate reductase)

Question 26

What is sufficient to reverse the megaloblastic anemia caused by folic acid deficiency?

Answer 26

1 mg/day PO folic acid

Question 27

Erythropoietin

Answer 27

- JAK/STAT signaling - rises in hypoxemia - inflammatory cytokines suppress its secretion

Question 28

What is Darbepoetin alpha?

Answer 28

a modified form or EPO that is more glycosylated and has a half-life of 24-26 hours

Question 29

What gets released fromt he bone marrow into the blood stream as a result of EPO?

Answer 29

reticulocytes

Question 30

When are ESAs used (erythropoiesis-stimulating agents)

Answer 30

pts with anemia secondary to chronic kidney disease

Question 31

When else can ESAs be used?

Answer 31

for the treatment of anemia due to primary bone marrow disorders and secondary anemias

Question 32

When can ESAs NOT be used?

Answer 32

in the Olympics

Question 33

What is EPO always couple with?

Answer 33

parenteral iron supplementation | -in patients with chronic kidney disease

Question 34

What are the most common adverse effects of EPO?

Answer 34

htn | thrombotic complications

Question 35

What does EPO bind onto?

Answer 35

receptor on the surface of COMMITTED ERYTHROID PROGENITORS in the marrow after secretion -initiate JAK/STAT signal transduction pathway

Question 36

Name the Myeloid growth factors

Answer 36

- Fligrastim - Pegfilgrastim - Sargramostim - Plerixafor

Question 37

Filgrastim

Answer 37

recombinant human G-CSF produced in a | -IV or subcue administration

Question 38

Pegfilgrastim

Answer 38

- covalent conjugation product of filgrastim and polyethylene glycol (PEG) - longer serum half-life than filgrastim - can be injected once per myelosuppressive chemotherapy cyle instead of daily for several days

Question 39

What do myeloid growth factors do?

Answer 39

enhance the function of mature granulocytes and monocytes

Question 40

Sargramostim

Answer 40

- recombinant human GM-CSF produced in a yeast expression system - Iv or sub cue administration

Question 41

Plerixafor

Answer 41

MOA: reversibly inhibits binding of stromal cell-derived factor-1-alpha (SDF-1a, this is on the bone marrow stromal cells) to the CXCR4 - results in moblization of hematopoietic stem and progenitor cells from the bone marrow into peripheral blood - used in combo with filgrastim results in synergistic increase in CD34+ cell mobilization prior to autologous transplantation - used in patients who respond suboptimally to G-CSF alone

Question 42

G-CSF

Answer 42

nuetrophils | -increases the concentration of hematopoietic stem cells in the peripheral blood

Question 43

GM-CSF

Answer 43

broader biologic actions than G-CSF - primary therapeutic effect is to stimulate myelopoiesis - increases HSC's in peripheral blood to a lesser extent than G-CSF

Question 44

What is a super common use of G-CSF?

Answer 44

accelerate neutrophil recovery after myelosuppressive chemotherapy -reduce duration of neutropenia

Question 45

Which is better tolerated? Filgrastim and pegfilgrastim or GM-CSF?

Answer 45

filgrastim and pegfligrastim

Question 46

what toxicity can filgrastim and pegfilgrastim cause?

Answer 46

bone pain | -clears when discontinuied

Question 47

What toxicity does GM-CSF cause?

Answer 47

-fever, malaise, arthralgias, myalgias, and a capillary leak syndrome characterized by peripheral edema and pleural or pericardial effusions

Question 48

What do patients with thrombocytopenia has a high risk of?

Answer 48

hemorrhage

Question 49

What 2 drugs are endogenous regulators of platelet production?

Answer 49

Thrombopoietin and IL-11

Question 50

IL-11

Answer 50

- Oprelvekin - MOA: activates cell surface cytokine receptors, makes more myeloid and lymphoid cells, eventually makes more peripheral platelets and neutrophils

Question 51

Romiplostim

Answer 51

- it's just recombinant thrombopoietin - -peptibodies - MOA: activates Mpl thrombopoietin receptor to cause a dose dependent increase in platelet count - Increase in platelet count begins 5 days after SubQ injection and peaks at 12-15 days

Question 52

What is IL-11 used for?

Answer 52

secondary prevention of thrombocytopenia in patients with chronic ITP who have had insufficient response to corticosteroids, immune globulin, or splenectomy

Question 53

Toxicity of IL-11

Answer 53

- fatigue, headache, dizziness, and CV effects - Hypokalemia - all adverse effects are reversible

Question 54

Toxicity of Romiplotim

Answer 54

well tolerated except for a mild headache on the day of administration