Pharmacology of Anemia

Question 1

Where is most of the iron in the body found?

Answer 1

In hemoglobin

Question 2

What form of iron is absorbed?

Answer 2

Ferrous (Fe2+)

Question 3

Transferrin

Answer 3

Transferrin takes iron to bone marrow

Question 4

Ferritin

Answer 4

Ferritin takes iron to plasma/liver/spleen

Question 5

Ferroportin

Answer 5

Exports iron from the small intestine

Question 6

What can be used to estimate iron stores in the body?

Answer 6

Ferritin in plasma is in equilibrium with body storage and can be used to estimate total body stores

Question 7

Hepcidin

Answer 7

Downregulates ferroportin

Question 8

How does anemia of chronic disease (ACD) affect hepcidin?

Answer 8

It increases hepcidin levels which will decrease ferroportin and decrease iron uptake

Question 9

What are the transferrin and ferritin levels in iron deficiency?

Answer 9

Ferritin is low to store less iron

Transferrin is high

Question 10

What are the transferrin and ferritin levels in iron overload?

Answer 10

Ferritin is high to store more iron

Transferrin is low

Question 11

What population has increased iron requirements?

Answer 11

• premature infants
• children
• pregnant or lactating women

Question 12

What is used as oral iron therapy?

Answer 12

Ferrous sulfate, ferrous gluconate, ferrous fumarate

Question 13

When is parenteral iron therapy used?

Answer 13

Indicated when oral iron is not tolerated, post GI resection, malabsorption syndromes

Question 14

What is acute iron toxicity?

Answer 14

(1) May be fatal in small children
(2) Necrotizing gastroenteritis
(3) After short improvement, metabolic acidosis, coma and death

Question 15

What is chronic iron toxicity?

Answer 15

Seen in hemochromatosis, multiple red cell tranfusions and it leads to organ failure like heart failure

Question 16

How is acute iron toxicity treated?

Answer 16

• Gastric aspiration
• Gastric lavage-phosphate or carbonate solutions
• Iron chelation (deferoxamine)

Question 17

How is chronic iron toxicity treated?

Answer 17

• Intermittent phlebotomy (if no anemia)

- Iron chelation (deferoxamine, deferasirox)

Question 18

What atom is in all vitamin B12 forms?

Answer 18

Cobalt

Question 19

What is required for vitamin B12 absorption?

Answer 19

Intrinsic Factor

Question 20

Where is vitamin B12 absorbed?

Answer 20

In the distal ileum

Question 21

Where is folic acid stored?

Answer 21

In the liver

Question 22

What are the effects of vitamin B12 or folate deficiency?

Answer 22

• Alimentary tract: atrophic glossitis, chronic gastritis
• Blood and bone marrow: megaloblastic anemia, leukopenia with hypersegmented granulocytes, mild to moderate thrombocytopenia
• CNS: “subacute combined degeneration”: spastic paraparesis, sensory ataxia, lower limb paresthesias (not seen in folic acid deficiency)

Question 23

What is the treatment for vitamin B12 deficiency?

Answer 23

Vitamin B12 deficiency is treated by parenteral injections (IM) of cyanocobalamin or hydroxycobalamin

Question 24

What is the treatment for folic acid deficiency?

Answer 24

Oral folic acid

Question 25

Are CNS symptoms of B12 deficiency reversed with folic acid treatment?

Answer 25

NO

Question 26

Does treatment of vitamin B12 deficiency with oral vitamin B12 work even if the patient cannot make IF?

Answer 26

YES. High doses of oral B12 can bypass IF absence

Question 27

What is erythropoietin?

Answer 27

* Glycoprotein, binds to its receptor and stimulates proliferation, differentiation of erythroid cells * Stimulates release of reticulocytes from bone marrow * Produced by the kidney

Question 28

What is the usual relationship between the levels of erytrhopoietin and Hb?

Answer 28

Inverse.

Question 29

When is erythropoietin therapy necessary?

Answer 29

- Chronic renal failure - Aplastic anemia - Anemia of prematurity

Question 30

ROA of erythropoietin

Answer 30

IV or subcutaneous

Question 31

Erythropoietin SE

Answer 31

Hypertension, thrombotic complications , allergic reactions

Question 32

What is a major black box warning of erythropoietin?

Answer 32

Erythropoietin not as safe as was thought - increased | risk of tumor progression or recurrence as many tumors have an erythropoietin receptor present on them

Question 33

What are G-CSF and GM-CSF?

Answer 33

G-CSF and GM-CSF are growth factors that stimulate proliferation and differentiation of myeloid cells

Question 34

What is a unique function of G-CSF?

Answer 34

G-CSF promotes release of hematopoietic stem cells from the bone marrow into the peripheral circulation (much better than GM-CSF)

Question 35

What is a unique function of GM-CSF?

Answer 35

GM-CSF also stimulates proliferation and differentiation of erythroid and megakaryocytic cells

Question 36

What are indications for G-CSF and GM-CSF use?

Answer 36

* After intensive chemotherapy * Treatment of congenital neutropenia, cyclic neutropenia, neutropenia associated with myelodysplasia and aplastic anemia * High dose chemotherapy with autologous stem cell rescue

Question 37

Which of G-CSF or GM-CSF is better tolerated?

Answer 37

G-CSF preferred since it is better tolerated in general

Question 38

G-CSF and GM-CSF SE

Answer 38

- G-CSF can cause bone pain, splenic rupture (very rare) | - GM-CSF can cause fever, arthralgia, myalgia, peripheral edema, pleural/pericardial effusion

Question 39

IL-11 Actions

Answer 39

* Promotes proliferation of megakaryocytic progenitors | * Increases peripheral platelet counts

Question 40

IL-11 Indications

Answer 40

• Patients with thrombocytopenia after chemotherapy

Question 41

Romiplostim

Answer 41

A novel protein known as a “peptibody” with two domains; a peptide domain that binds the thrombopoietin receptor (MPL), and an antibody Fc domain that increases half-life. Romiplostim is FDA approved for the treatment of idiopathic thrombocytopenia purpura (ITP).

Question 42

Eltrombopag

Answer 42

A small molecule thrombopoietin receptor agonist of the thrombopoietin receptor, approved for the treatment of ITP and new approval for the treatment of aplastic anemia.