Cancer Chemotherapy Flashcards Preview

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Flashcards in Cancer Chemotherapy Deck (70):
1

what categories of drugs make up the classical chemotherapeutic agents?

DNA damaging agents
Antimetabolites
Inhibitors of mitosis

2

DNA cross-linking drugs include:

Nitrogen mustards - cycolphosphamdie
[ - mechlorethamine, ifsofamide, chloroambucil, melphalan]

platinum analogs - cisplatin

3

DNA cleaving agents include:

bleomycin
Doxorubicin

4

Antimetabolites include which categories of drugs?

folic acid analogs
pyrimidine analogs
purine analogs

5

folic acid analogs include:

methrotrexate
leucovorin

6

pyrimidine analogs include

5-fluorouracil

7

purine analogs include

mercaptopurine

8

inhibitors of mitosis include:

pacitaxel (taxol)

9

cross linking agents work by:

covalently binding to DNA bases causing cross-linking of DNA strands
- usually at N7 guanine

prevents DNA replication and RNA synthesis

10

cyclophosphamide is what kind of drug?

DNA cross linking agent (nitrogen mustard)

11

cisplatin is what kind of drug?

DNA cross linking agent (platinum analog)

12

cyclophosphamide - activation and toxicity

P450
bone marrow suppression

13

cisplatin - toxicity

renal toxicity

14

DNA cleaving agents work by:

cleaving DNA which stalls/disrupts replication and transcription

15

bleomycin is what kind of drug?

DNA cleaving agent

16

bleomycin - activation and toxicity

activated by microsomal reduction
pulmonary toxicity

17

doxorubicin is what kind of drug?

DNA cleaving agent

18

doxorubicin - action, activation, and toxicity

freezes topoisomerase II in strand cleavage and rejoining cycles --> DNA breaks
achieved with oxygen free radicals

activated by flavin centered reductase

bone marrow suppression and cardiac toxicity

19

antimetabolites work by:

enzyme inhibitors and nucleotide analog - interfere with metabolic pathways
competitive inhibition or incorporation into DNA, RNA that causes premature chain termination and an abnormal product

20

what is the theory behind folic analog therapy?

tumor cells rapidly divide which requires a large amount of folic acid to generate nucleotides and AAs

21

methotrexate is what kind of drug?

folic acid analog

22

what is the mechanism of methotrexate?

- competitive inhibitor of dihydrofolate reductase (DHFR) which catalyzes FH2-->FH4
can't make thymine nucleotides from uracil --> pyrimidine shortage

- inhibits enzymes required for de novo purine synthesis

- impairs protein synthesis because it interferes with glycine and methionine synthesis

23

what is the major toxicity of methotrexate

bone marrow suppression
(leukopenia and thrombocytopenia)

24

leucovorin is what kind of drug?

folic acid analog (reduced)

25

what is the mechanism of leucovorin and why is it given?

used in the synthesis of purines and production of dTMP
functions to rescue normal cells by allowing them to partially recover after treatment with methotrexate

26

what is the theory behind pyrimidine and purine analogs as therapy?

become incorporated into nucleotides which results in DNA termination or an incorrect strand of DNA or RNA

27

fluorouracil is what kind of drug?

pyrimidine analog (uracil analog)

28

what is the mechanism of 5FU

uracil derivative is incorporated into RNA which prevents processing of rRNA into final product ==> 28 S ribosome
incorporation into DNA causes strand breaks
metabolite of 5FU (FdUMP) inhibits thymidylate synthase which prevents conversion of dUMP to dTMP

29

major toxicity of 5FU:

bone marrow suppression, oral and GI mucositis

30

mercaptopurine is what kind of drug

purine analog

31

what is the mechanism of mercaptopurine?

causes feedback inhibition of the first step in purine biosynthesis
results in decreased levels of purines available for nucleotide synthesis
also become incorproated in DNA causing strand breaks and inhibition of RNA synthesis

32

what is the major toxicity of mercaptopurine?

bone marrow suppression

33

Pacitaxel is what kind of drug?

mitosis inhibitor

34

what is the mechanism of pacitaxel

stabilizes microtubule formation causing arrest in G2 or mitosis

35

what is the major toxicity of pacitaxel?

neutropenia

36

what combination of drugs are frequently used to treat cervical cancer

cisplatin
bleomycin
methotrexate

37

what is the mechanism of selective estrogen receptor modulators (SERMs)

binds estrogen receptor (ER) on tumor cells that either mimics the effect of estrogen or has antiestrogenic effects

38

what are the three classes of drugs used to treat ER+ breast cancer?

SERMs
aromatase inhibitors (AIs)
Selective estrogen receptor downregulators (SERDs)

39

SERMs include:

tamoxifen
raloxifen

40

AIs include:

letrozole (femara)

41

SERDs include:

fulvestrant

42

what is the mechanism of tamoxifen

antiestrogenic effect - stops growth of tumor
in bone however, it mimics the effect of estrogen and promotes increased bone density

43

what is the effect of tamoxifen on post menopausal women

promotes cell growth of uterus and is associated with increased incidence of endometrial cancer (2/1000)

44

how can a tumor become resistant to tamoxifen

a mutation in P450 can prevent activation of tamoxifen

45

what is the mechanism of raloxifen

estrogenic effect on bone, antiestrogenic effects on uterine and breast

not effective against lobular carcinoma in situ and ductal carcinoma in situ

46

what is the mechanism of AIs

lower estrogen levels by inhibiting the aromatase that converts androstenedion to estrogen and estridiol

47

when is letrozole used?

adjuvent therapy in post menopausal patients following surgery to remove tomor

also used to treat advanced metastatic breast cancer in post menopausal patients

not associated with increased blood clot formation or endometrial cancer

48

when is letrozole NOT used?

premenopausal patients

49

the adverse reactions of letrozole include:

osteoporosis
hot flashes
joint pain
muscle pain

50

when is fulvestrant used

with ER+ post menopausal patients that no longer respond to tamoxifem or letrozole

51

what are the two approaches of endocrine therapy for prostate cancer?

block androgens from interacting with receptor
block production of androgens

52

what is the mechanism of leuprolide

GnRH superantagoinst - downregulates GnRH receptor
decreases secretion of LH and FSH and lowers androgen production by testes

53

what is the problem with leuprolide?

blocks testicular production of androgens but not adrenal androgen production ---> castration resistant tumors

54

how is the problem with leuprolide solveD?

GnRH antagonist Flutamide is given to help prevent castration resistant tumors
--> causes a complete androgen blockade (CAB)

55

how does abiraterone work?

inhibits CYP17 which inhibits androgen biosynthesis

56

how do corticosteroids and adrenocortical suppression act as tumor chemotherapy?

glucocorticoids induce cell death in lymphoid tissues --> useful for treating lympholytic anemias, Hodgkins and nonHodgkins lymphomas

57

what is the mechanism of cortiocosteroids and adrenocortical suppressants?

bind glucocorticoid receptor which initates apoptosis by caspases

58

prednisone is a:

synthetic corticosteroid

59

adverse reactions of prednisone include:

cushingoid features, sodium retension, muscle weakness, decreased glucose tolerance, acute tumor lysis syndrome

60

targeted approaches include:

monoclonal antibodies
tyrosine kinase inhibitors
proteasome inhibitors
histone deacetylase inhibitors

61

monoclonal antibodies include:

trustuzumab (herceptin)
bevacizumab (avastin)

62

the mechanism of trustuzumab is

binds to exterior surface receptor on breast cancer cells (epidermal growth factor receptor type II, tyrosine kinase activity) and blocks binding of ligand

63

the mechanism of bevacizumab is

binds to exterior surface of VEGF receptor, blocking the signal for proliferation and angiogenesis

64

tyrosine kinase inhibitors include:

imatinib (gleevec)
lapatinib

65

the mechanism of imatinib is

inhibitor of bcr-Able, KIT, PDGF
blocks catalytic activity of tyrosine kinase by binding to ATP binding domain
substrate for CYP34A cyp2c9 cyp2d6 so potential interactions can occur between drugs metabolized by these enzymes

66

the mechanism of lapatinib is

inhibitor of epidermal growth factor receptor types I and II

67

the mechanism of bortezomib (velcade) is

inhibits 26S proteosome
metabolized by 3A4

68

brotezomib is used to treat

multiple myeloma

69

the mechanism of vorinostat (zolinza) is

HDAC inhibitor
causes accumulation of acetylated histones and induces cell cycle arrest or apoptosis of cancer cells

70

vorinostat is used to treat

cuaneous t-cell lymphoma (CTCL)