Pharmacology Of Anemia & Hematopoietic Growth Factors

Question 1

Drug(s) used to treat microcytic hypochromic anemia

Answer 1

Iron (oral, parenteral)

Question 2

Drug(s) used to treat neutropenia

Answer 2

Filgrastim
Pegfilgrastim
Sargramostim
Plerixafor

Question 3

Drug(s) used to treat megaloblastic anemia

Answer 3

Vitamin B12

Folate

Question 4

Drug(s) used to treat anemia of chronic renal disease

Answer 4

Epoetin alfa
Hydroxyurea
Eculizumab

Question 5

Drug(s) used to treat thrombocytopenia

Answer 5

Oprelvekin
Romiplastin
Eltrombopag

Question 6

Formulations of oral iron therapy given for microcytic anemia

Answer 6

Ferrous sulfate
Ferrous gluconate
Ferrous fumarate

Question 7

AEs of orally administered iron

Answer 7

Nausea/vomiting
Constipation
Diarrhea
Dark stools
Anorexia
Heartburn

Question 8

Parenteral (colloidal) iron formulations used to tx microcytic anemia

Answer 8

Iron dextran, sodium ferric gluconate complex, iron-sucrose complex

Question 9

With iron replacement therapy, when can you expect reticulocytosis and increase in Hb?

Answer 9

Reticulocytosis in a few days

Hb increases in 2 weeks

Question 10

Acute vs. chronic iron toxicity

Answer 10

Acute — necrotizing gastroenteritis w/vomiting, abd pain, and bloody diarrhea —> shock, lethargy, and dyspnea —> severe metabolic acidosis, coma, and death

Chronic (hemochromatosis) — iron deposits in heart, liver, pancreas —> organ failure and death

Question 11

Tx for acute iron toxicity

Answer 11

Whole bowel irrigation and parenteral deferoxamine (iron-chelating compound)

Question 12

Oral vitamin B12 supplementation is generally effective, even in pts with pernicious anemia. When is parenteral therapy indicated?

Answer 12

If neurologic sxs are present

Question 13

T/F: adverse events are rare with vitamin B12 therapy

Answer 13

True

Question 14

Treatment of folate deficiency is oral folate. This is generally well-tolerated at recommended doses, but higher doses can cause ______ and/or ______

Answer 14

Hypotension

Hypoglycemia

Question 15

Symptomatic outcome of megaloblastic anemia treatment (w/ Vit B12 or folate)

Answer 15

Should see reticulocytosis in 3-5 days

Hct increases in <2wks w/ folate, normalizes in 2 months

Hb increases in 1 wk with B12 therapy, and should normalize in 1-2 months

Question 16

MOA and effects of epoetin alfa

Answer 16

Erythropoiesis-stimulating glycoprotein (basically EPO analog)

Stimulates erythropoeisis —> increased reticulocyte count in <10 days —> increased RBC count, Hb, and Hct in 2-6 wks

Note: iron and folate also often included in therapy

[administered IV or subQ — half life of 4-13 hrs]

Question 17

Clinical applications for epoetin alfa

Answer 17

Anemia d/t CKD, cancer chemotherapy, zidovudine tx for HIV

Reduce allogeneic RBC transfusions in pts undergoing elective surgery

Question 18

AEs of epoetin alfa

Answer 18

20-50% have DAP > 10 mm Hg despite keeping Hct in 30-35 range

Increased risk of death, MI, stroke, DVT

Minor AEs include cough, HA, myalgias, spasms, joint/bone pain, injection site pain, N/V, weight loss, insomnia, allergic rxns

Question 19

Which has a longer half life — epoetin alfa or darbepoetin alfa?

Answer 19

Darbepoetin alfa has 3x longer half life

Question 20

Only disease-modifying therapy approved for sickle cell disease

Answer 20

Hydroxyurea

Question 21

MOA and effects of hydroxyurea therapy

Answer 21

Targets ribonucleotide reductase —> S-phase cell cycle arrest

Boosts levels of HbF [mechanism unknown]

[administered orally and readily absorbed; distributed widely but concentrated in erythrocytes and leukocytes. Excreted unchanged by kidney]

Question 22

Toxicities of hydroxyurea

Answer 22

Cough or hoarseness

Fever or chills

Lower back or side pain

Painful or difficult urination

Question 23

Indications for eculizumab

Answer 23

Paroxysmal nocturnal hemoglobinuria (inhibits terminal complement-mediated intravascular hemolysis)

Atypical hemolytic uremic syndrome (inhibits complement-mediated thrombotic microangiopathy)

[only available under Risk Eval and Mitigation to which prescribers must enroll]

Question 24

MOA of eculizumab

Answer 24

Monoclonal Ab that binds to complement protein C5 w/high affinity —> inhibits cleavage to C5a and C5b —> prevents generation of MAC (C5b-C9)

Question 25

AEs of eculizumab

Answer 25

Infection (HSV, Influenza-like) Life-threatening meningococcal infections — must give vaccine prior to therapy Immunogenic, URIs, MSK pain, anemia, leukopenia, HTN, HA, insomnia, fatigue, UTIs

Question 26

The following are clinical applications for what drug: Decreases incidence of infection, as manifested by febrile neutropenia, in pts with nonmyeloid malignancies receiving myelosuppressive therapy or in those receiving bone marrow transplant Also used to mobilize HSCs into PB for collection by leukophoresis, and in those with severe chronic neutropenia

Answer 26

Filgrastim (G-CSF)

Question 27

MOA of filgrastim

Answer 27

G-CSF — regulates production of neutrophils in bone marrow and enhances some end-cell functions like phagocytic ability, respiratory burst, and Ab-dependent killing

Question 28

______ is a longer lasting version of filgrastim (G-CSF) d/t conjugation with monomethoxypolyethylene glycol

Answer 28

Pegfilgrastim

Question 29

AEs of filgrastim (G-CSF)

Answer 29

Generally well-tolerated but can cause allergic reaction Some experience mild to moderate bone pain — tx with NSAIDs Rarely splenic rupture and ARDS

Question 30

The following are clinical indications for what drug: Used to accelerate recovery of myeloid cells after autologous or allogeneic bone marrow transplant Can be used to mobilize HSCs into PB for leukophoresis Indicated for use following induction chemo in pts >55 w/ AML to shorten time to recovery/decrease incidence of infections

Answer 30

Sargramostim (GM-CSF)

Question 31

MOA of sargramostim

Answer 31

GM-CSF — acts in bone marrow to increase production of neutrophils, eosinophils, and monocytes

Question 32

AEs of sargramostim (GM-CSF)

Answer 32

Contains benzyl alcohol — can cause fatal “gasping syndrome” in premature infants Causes fluid retention —> edema, pleural effusion, pericardial effusion Sequestration of granulocytes in pulmonary circulation has caused dyspnea Occasional transient SVT Worsening pre-existing renal and hepatic dysfunction

Question 33

Drug used in the 15-20% of pts who do not mobilize sufficient HSCs for autologous transplant with just G-CSF; also approved for pts with lymphoma and multiple myeloma

Answer 33

Plerixafor

Question 34

MOA of plerixafor

Answer 34

Partial agonist of CXCR4 receptor, important for homing of HSCs to bone marrow Acts to mobilize HSCs from bone marrow to plasma

Question 35

AEs of plerixafor

Answer 35

Hypersensitivity reaction Potential to mobilize leukemia cells

Question 36

Drug that can be used to tx thrombocytopenia in pts undergoing myelosuppressive chemo for non-myeloid cancers, but does NOT have a major clinical use

Answer 36

Oprelvekin (IL-11)

Question 37

MOA and effects of oprelvekin

Answer 37

Recombinant form of IL-11; MOA unknown, but results in increases in platelets by promoting formation and maturation of megakaryocytes

Question 38

AEs of oprelvekin

Answer 38

Significant edema d/t volume expansion Cardiac dysrhythmias Severe allergic reactions “Bloodshot” eyes

Question 39

Drug used to tx excess platelet destruction d/t idiopathic thrombocytopenic purpura, as well as its counterpart which can also be used to tx cirrhosis d/t hep C

Answer 39

Romiplostim — tx ITP Eltrombopag — tx ITP and cirrhosis d/t hep C

Question 40

MOA and effects of romiplostim

Answer 40

Composed of 2 disulfide-bonded human IgG1 kappa heavy chain constant regions (an Fc fragment) that bind the TPO receptor Leads to increased platelet count in healthy individuals, ITP pts, and pts with myelodysplastic syndromes

Question 41

AEs of romiplostim

Answer 41

Generally well-tolerated; most serious AE is allergic rxn

Question 42

MOA and effects of eltrombopag

Answer 42

Potent, orally available non-peptide TPO receptor agonist Increases platelet count in healthy individuals, pts with ITP, and thrombocytopenia d/t hep C

Question 43

AEs of eltrombopag

Answer 43

May cause hepatotoxicity when used in combo with interferon and ribavirin in pts with chronic hep C

Question 44

Most common drug-related cause of hemolytic anemia

Answer 44

Cephalosporins (especially ceftriaxone and cefotetan) Other drug causes include PCN derivatives (esp. piperacillin), dapsone, levodopa, levofloxacin, methyldopa, nitrofurantoin, NSAIDs, phenazopyridine, quinidine

Question 45

most common drug-related cause of immune thrombocytopenia

Answer 45

Heparin

Question 46

Classic drug-related causes of non-immune thrombocytopenia

Answer 46

Quinidine; quinine Other causes include furosemide, NSAIDs, PCN, sulfonamides, ranitidine

Question 47

Drugs/toxins causing aplastic anemia

Answer 47

Cancer chemotherapeutics, esp alkylating agents, antimetabolites, and cytotoxic abx Chloramphenicol (no longer used) Benzene