Pharmacology of Anemia and Hematopoietic GF's*

Question 1

Which type of iron is used for therapy for iron malabsorption, intolerance of oral therapy, or non compliance?

Answer 1

Parenteral (colloidal) iron —> iron dextran, sodium ferric gluconate complex and iron-sucrose complex

Question 2

What is the urgent treatment for iron poisoning?

Answer 2

Parenteral deferoxamine (potent iron-chelating compound)

Question 3

When would oral vs. parenteral therapy for Vit B12 supplementation be indicated to tx deficiency?

Answer 3

• Oral: generally effective, EVEN in pt’s w/ pernicious anemia
• Parenteral therapy: used if neurological sx’s are present

Question 4

What are 3 types of iron supplements that can be taken orally; what should they be taken with?

Answer 4

• Ferrous sulfate, gluconate, or fumarate that is ideally NOT enteric-coated and NOT-sustained release
• Pt should take with ONLY water/juice, not with food

Question 5

Nitrous oxide inhaled for analgesia during surgey can have what effect on B12?

Answer 5

Inactivates cyanocobalamin (common form of B12)

Question 6

What is the MOA of epoetin alfa?

Answer 6

• Stimulates erythropoiesis
• ↑ reticulocyte count ≤10 days
• ↑ RBC count, hemoglobin, and hematocrit in 2-6 weeks

Question 7

What are the clinical uses of epoetin alfa?

Answer 7

• Anemia due to: CKD; cancer chemotherapy; and zidovudine tx for HIV
• ↓ allogenic RBC transfusions in pt’s undergoing elective surgery

Question 8

There is an increased risk for what serious AE’s associated with epoetin alfa?

Answer 8

• MI
• Stroke
• Venous thrombo-embolism
• Thrombosis of vascular access and tumor progression or recurrence

Question 9

How does darbepoetin alfa differ from epoetin alfa?

Answer 9

Has 3x longer half-life

Question 10

What are the 2 MOA of Hydroxyurea?

Answer 10

• Targets ribonucleotide reductase, results in S-phase cell cycle arrest
• Somehow boosts levels of fetal hemoglobin (HbF, α2γ2)

Question 11

What is the only disease modifying therapy for sickle cell anemia?

Answer 11

Hydroxyurea

Question 12

List 4 AE’s associated with hydroxyurea used for sickle cell anemia.

Answer 12

• Cough or hoarseness
• Fever or chills
• Lower back or side pain
• Painful or difficult urination

Question 13

What is the MOA of eculizumab?

Answer 13

• Monoclonal Ab that binds complement protein C5 and inhibits cleavage to C5a and C5b
• Prevents generation of the MAC (C5b-9)

Question 14

What are the 2 effects of using eculizumab for paroxysmal nocturnal hemoglobinuria and atypical HUS?

Answer 14

• Inhibits terminal complement-mediated intravascular hemolysis in PNH
• Inhibits complement-mediated thrombotic micorangiopathy in pt’s w/ atypical HUS

Question 15

What must be given 2-weeks prior to using eculizumab?

Answer 15

Meningococcal vaccine

Question 16

List some common presenting sx’s of neutropenia?

Answer 16

• Low-grade fever
• Sore mouth
• Odynophagia
• Gingival pain and swelling
• Perirectal pain and irritation

Question 17

What is filgrastim and pegfilgrastin; how do they differ?

Answer 17

• Both are G-CSF
• Pegfilgrastim is longer lasting (PEGylated = conjugated to polyethylene glycol)

Question 18

What are some of the serious AE’s associated with Filgrastim (G-CSF)?

Answer 18

• Splenic rupture, sometimes fatal
• ARDS

Question 19

What is sargramostim?

Answer 19

GM-CSF

Question 20

What are some of the serious AE’s associated with the GM-CSF, Sargramostim?

Answer 20

• Contains benzyl alcohol, can cause fatal “grasping syndrome” in prematue infants
• Fluid retention —> edema; also pleural effusion and pericardial effusion
• Dyspnea from sequestration of granulocytes in pulmonary circulation
• Occsaional transient SVT
• May worse pre-existing renal and hepatic dysfunction

Question 21

Between Filgrastim and Sargramostim which has fewer AE’s and should be used?

Answer 21

Filgrastim (G-CSF)

Question 22

What is the MOA of Plerixafor?

Answer 22

Partial agonist at CXCR4 receptor, important for homing of hematopoietic stem cells to BM

Question 23

What is Plerixafor used for?

Answer 23

In patient who do not mobilize sufficient stem cells for autologous transplant with just G-CSF

Question 24

What is the main AE associated with Plerixafor?

Answer 24

Hypersensitivity rxn

Question 25

What is the MOA of Romiplostim?

Answer 25

• A “peptibody” of human IgG1 kappa heavy chain constant regions (an Fc fragment)
• Binds TPO receptor
• Must be given SQ because it’s a peptide!

Question 26

What is the effect and clinical use of Romiplstim?

Answer 26

• ↑ the platelet count in: healthy pt’s, pt’s with ITP and pt’s with myelodysplastic C syndrome
• Use for excess platelet destruction due to idiopathic thrombocytopenia purpura (ITP)

Question 27

What is the MOA of Eltrombopag; effects in pt’s?

Answer 27

• Potent, orally available NON-peptide TPO receptor agonist
• ↑ platelet count in: healthy pt’s, those with ITP, and thromobocytopenia due to hepatitis C

Question 28

What are the 2 clinical uses for Eltrombopag?

Answer 28

• Excess platelet destruction due to idiopathic thrombocytopenic purpura
• Cirrhosis due to hepatitis C

Question 29

What is an AE associated with Eltrombopag?

Answer 29

Hepatotoxicity when used in combo w/ interferon and ribavirin in pt’s with hepatitis C

Question 30

What is the most common drug class which causes hemolytic anemia; what is another common class?

Answer 30

• Cephalosporins, especially ceftriaxone and cefotetan = most common
• Penicillin and its derivative, especially piperacillin

Question 31

Which drugs are the most common immune and non-immune causes of drug-induced thrombocytopenia?

Answer 31

• Immune = heparin
• Non-immune = quinidine and quinine

Question 32

What are 3 major drugs/classes that may cause aplastic anemia?

Answer 32

• Cancer chemotherapeutics, especially alkylating agents, antimetabolites, and cytotoxic antibiotics
• Chloramphenicol, an Abx that is no longer used
• Benzene