Cancer Pharm

Question 1

mechlorethamine - how is it broken down?

Answer 1

non-enzymatic hydrolysis

Question 2

mechlorethamine SE

Answer 2

myelosupression = dose-limiting

high incidence of secondary cancers (leukemia, lymphoma, MDS)

Question 3

mechlorethamine MOA

Answer 3

alkalating agent

damages DNA in 4 ways: cross-linking, abnormal pairing w/ T residues, ring cleavage, depurination

Question 4

cyclophosphamide (MOA and PK)

Answer 4

alkalating agent

activated by CYP450

Question 5

cyclophosphamide SE

Answer 5

hemorrhagic cystitis - b/c metabolite acrolein in urine

Question 6

MESNA

Answer 6

used to tx hemorrhagic cystitis from cyclophosphamide

binds to and inactivates acrolein

Question 7

cisplatin (MOA and indication)

Answer 7

bifunctional alkating agent

used widely for lung, breast, ovarian, head & neck cancers

Question 8

cisplatin SE

Answer 8

renal insufficiency

neuropathy

Question 9

ondansetron (zofran) MOA

Answer 9

blocks 5HT stem of vagal nerve (maybe CNS too) –> prevents nausea

Question 10

aprepitant

Answer 10

neurokinin 1 agonist. blocks substance P binding –> antiemetic, can be combined w/ ondansetron

Question 11

methotrexate MOA

Answer 11

analogue of folic acid, inhibits DHFR by competitive inhibition

Question 12

methotrexate SEs

Answer 12

marrow suppression, GI tox, renal failure

prevent renal failure w/ alkalinized urine

Question 13

what do you give concurrently w/ really high dose of MTX to prevent lethal side effects?

Answer 13

leucovorin rescue

Question 14

5 Fluoroucil (MOA and indication)

Answer 14

inhibits thymidylate synthase by suicide mech

indications: breast and GI malignancy

Question 15

leucovorin action w/ 5FU

Answer 15

potentiates action of 5FU

Question 16

cytarbine (ara-C) MOA

Answer 16

drug taken into cell and metabolized –> converted into ara-CTP–> inhibits DNA polymerase alpha + some drug incorporated into DNA to slow chain elongation and inhibit ligation
S-phase specific action

Question 17

ara-C use

Answer 17

for AML and lymphoma

continuous IV in AML induction chemo w/ daunarubicin (7+3)

Question 18

7+3 regimen

Answer 18

AML tx: ara-C and daunarubicin

Question 19

HiDAC

Answer 19

high dose ara-c for 3 days

SE: acute severe cerebellar toxicity

Question 20

ara-C side effects

Answer 20

marrow aplasia, GI tox, alopecia

Question 21

antracycline antibiotics - names

Answer 21

doxorubin and daunorubicin

Question 22

anthracycline abx MOAs

Answer 22

1. inhibitor of topoisomerase II –> ds DNA breaks throughout genome
2. incorporated into DNA –> blocks replication and RNA synthesis

Question 23

major SE of anthracycline abx

Answer 23

cardiac toxicity: cumulative dose-dependant cardiomyopathy - <400mg/m2 limit
cardiomyopathy can be reversible

Question 24

epidophyllotoxins

Answer 24

etoposide, VP-16
come from may apple plant
topoisomerase II inhibitor –> ds DNA breaks

Question 25

topotecan/irinotecan

Answer 25

topoisomerase I inhibitor: ss DNA breaks --> activation of DNA damage dependant apoptosis pathway

Question 26

vinca alkaloids (MOA and metabolism)

Answer 26

vinblastine and vincristine MOA: microtubule inhibitor --> blocks cell division and induces apoptosis - both have hepatic metabolism

Question 27

vincristine use and SE

Answer 27

tox: neuropathy uses: lymphoma, sarcoma, breast, lung, cerviz

Question 28

vinblastine use and SE

Answer 28

tox: bone marrow uses: lymphoma, testicular cancer

Question 29

taxol

Answer 29

stabilizes microtubules --> prevents depolymerization and induces apoptosis

Question 30

thalidomide

Answer 30

immunomodulatory | for multiple myeloma

Question 31

lenalidomide (indications and SE)

Answer 31

immunomodulatory even better for multiple myeloma also mantle cell NHL and MDS causes peripheral neuropathy

Question 32

hematopoietic growth factors in cancer

Answer 32

to tx anemia, granulocytopenia, thrombocytopenia

Question 33

SE of G-CSF and GM-CSF

Answer 33

mild: bone pain, fever, headache

Question 34

SE of EPO

Answer 34

none, but if hgb goes to high HTN and stroke

Question 35

before stating EPO

Answer 35

check epo levels - won't help if pt already has normal response to anemia

Question 36

IL2

Answer 36

approved for renal cell carcinoma, also works for melanoma | stimulates anti-tumor immune response

Question 37

IFN

Answer 37

biologic response modulator | RCCa, NHL, melanoma, CML, MS

Question 38

rituxin

Answer 38

targeted mAb against CD20 on pre-B and B-lymphocyes 1. Fc-mediated phagocytosis (attracts macrophages) 2. complement-mediated cytotoxicity 3. apoptosis induction

Question 39

5-azacytidine

Answer 39

DNA methylation --> induces cellular differentiation | reversible!