Exam 9: Anti Cancer Agents Flashcards Preview

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Flashcards in Exam 9: Anti Cancer Agents Deck (60):
1

What do we need to know for each agent?

Category
Mechanism
Toxicity
Only need to know specific uses when noted explicitly (seriously, don't try to memorize a bunch of other shit)

2

Name 2 nitrogen mustards

Mechlorethamine
Cyclophosphamide

3

Name 1 nitrosourea

Carmustine

4

Name one platinum complex

Cisplatin

5

Name 1 folic acid analog

Methotrexate

6

Name 1 purine analog

Mercaptopurine

7

Name 2 pyrimidine analogs

Fluorouracil
Cytarabine

8

Name 2 anthacycline antibiotics

Daunorubicin
Doxorubicin

9

Name 4 vinca alkaloids, epipodophylotoxins, and taxanes

Vinblastine
Vincristine
Etoposide
Paclitaxel

10

Name 2 corticosteroids used in cancer treatment

Prednisone
Dexamethasone

11

Name one estrogen/antiestrogen

Tamoxifen

12

Name one Tyrosine Kinase inhibitor

Imatinib

13

Name one monoclonal antibody used for cancer treatment

Trastuzumab

14

What is a difference in general usefulness in cell cycle specific vs cell cycle non-specific agents?

CCS are better at treating tumors with lots of cells that are proliferating
CCNS are better in low-growth solid tumors

15

What are the cell cycle non specific agents?

All the alkylators and the 2 antibiotics:
Mechlorethamine, Cyclophosphamide, Carmustine, Cisplatin
and
Daunorubicin
Doxorubicin

16

What are three alkylating agents?

Mechlorethamine
Cyclophosphamide
Carmustine
Cisplatin (kind of, causes cross linking without actual alkylation)

17

What is the mechanism of alkylating agents?

Alkylation of Nitrogen 7 on Guanine

18

What are 3 consequences of alkylation of Guanine?

1. Miscoding of DNA strands (won't interact with complementary base)
2. Incomplete repair of alkylated segment (breaks/depurination)
3. Excessive cross linking of DNA and inability for strand separation

19

Are alkylating agents CCS or CCNS?

CCNS

20

What are toxicities of Alkylating agents?

Acute- Nausea, vomiting
Long Term- Bone marrow depression
These are the main toxicities seen in most cancer drugs, except when explicitly noted

21

Mechlorethamine mechanism

Alkylation of Nitrogen 7 on Guanine

22

Cyclophosphamide mechanism

Alkylation of Nitrogen 7 on Guanine

23

Cyclophosphamide pharmacokinetic consideration

Prodrug
Must be activated by p450 enzyme

24

Carmustine mechanism

Alkylation of Nitrogen 7 on Guanine
(Nirtosurea)

25

What is a pharmacodynamic feature of carmustine?

Highly lipid soluble

26

Cisplatin mechanism

Bifunctional alkylating agent
Causes cross linking

27

Cisplatin toxicity

Nephrotoxic and Ototoxic

28

Cisplatin class

Platinum complex

29

Are antimetabolites CCS or CCNS?

CCS

30

Methotrexate Mechanism

Folic acid analog
Inhibits dihydrofolate reductase, preventing creation of Tetrohydrofolate needed for DNA synthesis

31

What protects normal cells with methotrexate use?

Leucovorin (Folinic acid)
Bypasses metabolic block by methotrexate

32

What phase is affected by Methotrexate?

S phase (DNA synthesis)

33

Methotrexate toxicity

Acute- Nausea, vomiting
Long Term- Bone marrow depression

34

Methotrexate uses

Psoriasis, Rheumatoid arthritis

35

Mercaptopurine mechanism

Purine analog
Inhibits enzymes of purine interconversion, decreasing nucleotide synthesis

36

What cell cycle phase is affected by Mercaptopurine?

S phase

37

5-Fluorouracil mechanism

Pyrimidine analog
Inhibits thymidylate synthetase covalently, inhibiting DNA synthesis (S phase)

38

5-Fluorouracil toxicity

Less GI effects than other cancer drugs

39

Cytarabine mechanism

Pyrimidine analog
Converted to cytarabine triphosphate
Inhibits DNA polymerase by competing with deoxycitidine triphosphate
S phase specific

40

Daunorubicin and Doxorubicin mechanism

Intercalate and bind to DNA between base pairs, uncoiling DNA, destroying template (Not CCS)

41

When is the most effect seen with Daunorubicin and Doxorubicin

S phase, but still considered non specific

42

Daunorubicin and Doxorubicin toxicity

Cardiomyopathy (Dilated)
*** Pretty sure this will be a test question.

43

Vinblastine and Vincristine Mechanism

Vinca Alkaloids
Bind to tubulin and disrupt the mitotic spindle apparatus
Prevents segregation of chromosomes in metaphase

44

What phase are Vinca alkaloids specific for?

Mitosis phase (Metaphase)

45

What toxicity is associate with Vincristine and Vinblastine?

Neurological side effects (eg. peripheral neuropathy)
Also general toxicities seen in most cancer drugs

46

Etoposide mechanism

Forms a complex with Topoisomerase II and DNA resulting in DNA breaks and cell death.
Specific for G2 phase

47

What cell cycle phase is Etoposide specific for?

G2

48

Paclitaxel mechanism

Antimicrotubule agent.
Enhances microtubule assembly
Stabilizes microtubules (they can't depolymerize)
Specific for G2 and M phase

49

What cell cycle phase is Paclitaxel specific for?

G2 and M phases

50

Prednisone and Dexamethasone mechanism

Lipid soluble, diffuse into cells, affect transcription of genes in the nucleus.
Suppress mitosis in lymphocytes
G1 phase specific

51

What cell cycle phase are corticosteroids specific for?

G1

52

Tamoxifen mechanism

Non steroidal anti estrogen
Blocks estrogen receptors (nuclear transcription factors) that stimulate growth
G1 phase specific

53

What cell cycle phase is Tamoxifen specific for?

G1

54

Tamoxifen toxicities

Short term: Menopausal symptoms (Hot flashes, headaches, fatigue, etc.)
Long term: visual changes, vaginal bleeding, ocular toxicity, thromboembolism, thrombocytopenia
Most Serious: Can promote tumor growth and increase incidence of endometrial cancer

55

Tamoxifen use

Estrogen receptor positive invasive breast cancer
Often used for breast cancer in men

56

Imantinib mechanism

Inhibits Bcr-Abl tyrosine kinase
Inhibits proliferation and triggers apoptosis in Bcr-Abl-positive leukemia cell lines

57

Imantinib uses (2)

Acute Lymphocytic Leukemia (ALL)
Ph+ (Philadelphia chromosome + 9:22) Chronic Myeloid Leukemia (CML)

58

Trastuzumab mechanism

(Herceptin)
IgG1 monoclonal antibody that binds to the the EGF receptor HER-2
Down regulates the receptor's tyrosine kinase activity which are involved in metastasis
Phase G1 specific

59

Trastuzumab uses

Breast cancers that overexpress EGF2
In combo with paclitaxel is the first line treatment for HER2-overexpressing metastatic breast cancer

60

What is the first line treatment for HER2-overexpressing metastatic breast cancer?

Trastuzumab and Paclitaxel