Anticancer Drugs

Question 1

Alkylating drugs (mitomycin & cisplatin) MOA

Answer 1

carbonium ion –> covalent bonds w/ DNA –>impedes replication

Question 2

Antimetabolites MOA

Answer 2

block or subvert one or more metabolic pathways in DNA synthesis

Question 3

Cytotoxic antibiotics MOA

Answer 3

blocks mammalian cell division

Question 4

Vinca Alkaloids MOA

Answer 4

binds to tubulin –> prevents formation of mitotic spindles–> arrests cell at metaphase

Question 5

Protein kinase inhibitor MOA

Answer 5

blocks tyrosine kinases that tranduce growth signals

Question 6

Methotrexate MOA (2)

Answer 6

inhibits dihydrofolate reduction,

block DTMP & purine synthesis

Question 7

Doxorubicin MOA

Answer 7

blocks topoisomerase II fxn

Question 8

5-fluorouracil MOA

Answer 8

inhibits DTMP synthesis (DNA only)

Question 9

L-asparaginase MOA

Answer 9

catalyses hydrolysis of l-asparagine to l-aspartic acid & ammonia –> deaminates asparagine & inhibits protein synthesis

Question 10

Paclitaxel & Docetaxel (Taxanes) MOA

Answer 10

Stabilizes microtubules in the polymerized state

Question 11

What is commonly seen w/ BM toxicity due to chemotherapuetics?

Answer 11

leukopenia

Question 12

BCG MOA

Answer 12

stimulates immune system to recognize tumor cells

Question 13

What molecule dissociates once Cisplatin enters the cell?

Answer 13

Cl

Question 14

Methotrexate is a _____ ANTagonist.

Answer 14

folate

Question 15

Solubility of methotrexate

Answer 15

low lipid solubility

actively taken up by cells via folate transport system

Question 16

4 reasons for using combos of cancer drugs on a TX schedule (TQ)

Answer 16

1. Incr. cytotoxicity w/o increasing gen. toxicity
2. Decr. resistance to individual agents
3. Permit BM regeneration
4. More effective when given as 1 or 2 LG doses

Question 17

Main problem of alkylating agents

Answer 17

Strong cross-resistance

Question 18

What enzyme activates Cyclophosphamide in the liver? (it’s a pro-drug) (TQ)

Answer 18

CYP450

Question 19

Slowest working alkylating agent? Benefits?

Answer 19

Chlorambucil

lowest toxicity

Question 20

Do NOT use cytotoxic antibiotics w/ what other form of therapy?

Answer 20

radiotherapy (toxicity)

Question 21

Doxorubicin & dactinomycin inhibit DNA synthesis by interferring w/ _____.

Answer 21

Topoisomerase II

Question 22

What type of cells does bleomycin work on?

Answer 22

non-dividing cells

Question 23

Depletion of EXTRAcellular stores of _____ lead to inhibition of protein synthesis.

Answer 23

L-asparaginase

Question 24

L-asparaginase only attacks cells lacking what enzyme?

Answer 24

L-asparagine synthetase

Question 25

List 2 taxanes derived from Taxus spp plants (bark of yew tree).

Answer 25

Paclitaxel | Docetaxel

Question 26

Which drugs should you NEVER give to horses (death!)?

Answer 26

Paclitaxel | Docetaxel

Question 27

List the 3 tyrosine kinase inhibitors

Answer 27

Imatinib Toceranib Mastinib

Question 28

Tyrosine kinase inhibitors block _______.

Answer 28

angiogenesis (slows down tumor growth)

Question 29

Bevacizumab blocks the ______ receptor.

Answer 29

vascular endothelial growth factor receptor

Question 30

Cetuximab blocks the _____ receptor.

Answer 30

epidermal growth factor receptor

Question 31

Trastuzumab blocks the _____ receptor.

Answer 31

human epithelial R2

Question 32

Imatinib blocks the ______ receptor.

Answer 32

platelet derived growth factor receptor

Question 33

List the 3 antibodies that target epidermal growth factor receptors.

Answer 33

Cetuximab Trastuzumab Bevacizumab

Question 34

Which antibody works on ErbB-1 expressing tumors?

Answer 34

Cetuximab

Question 35

Which anitbody works on ErbB-2 expressing tumors?

Answer 35

Trastuzumab

Question 36

Which antibody works on VEGFR in mastocytoma cells?

Answer 36

Bevacizumab

Question 37

Possible problem when using glucocorticoids & chemotherapeutics together.

Answer 37

Mutli-drug resistance | via induction of PgP (permeability glycoprotein)

Question 38

Which 3 drugs have demonstrated resistance due to decreased accumulation of cytotoxic drugs? (TQ)

Answer 38

Doxorubicin Vinblastine Dactinomycin

Question 39

Mode of resistance for methotrexate? (TQ)

Answer 39

Decreased drug uptake by the cell

Question 40

Mode of resistance for 5-fluorouracil? (TQ)

Answer 40

Insufficient activation of the drug

Question 41

Mode of resistance for antimetabolites. (TQ)

Answer 41

Increased utilization of alternative metabolic pathways

Question 42

Mode of resistance for alkylating agents. (TQ)

Answer 42

Rapid repair of drug induced lesions

Question 43

Mode of resistance for Doxorubicin? (TQ)

Answer 43

Altered activity of the drug's target (topoisomerase II)

Question 44

Active metabolite of Cyclophosphamide

Answer 44

Acrolein

Question 45

List 5 nitrogen mustards (alkylating agents).

Answer 45

Cyclophosphamide Melphalan Chlorambucil Ifosfamide

Question 46

Alkyl sulfonate alkylating agent

Answer 46

Busulfan

Question 47

Non-classical alkylating agent

Answer 47

Dacarbazine

Question 48

Nitrosurea alkylating agent

Answer 48

Lomustine

Question 49

List 2 platinum coordination complex alkylating agents

Answer 49

Cisplatin | Carboplatin

Question 50

List 4 cytotoxic antibiotics

Answer 50

Doxorubicin Dactinomycin Bleomycin Mitomycin