Cancer Cytotoxic Agents Pharmacology

Question 1

Antimetabolites exampls

Answer 1

Folic acid analogues
Purine analogs
Pyrimidine analogs

Question 2

Antimetabolites MOA

Answer 2

Act at S phase as structural analogs and antagonists of endogenous biochemiclas that inhibit purine and pyrimidine

Question 3

Methotrexate MOA

Answer 3

Inhibit dihydrofolate reducttion, blocks thymidine & purine synthesis (S-phase)

Question 4

5-fluorouracil MOA

Answer 4

Inhibits thymidylate synthesis (S-phase)

Question 5

Leucovorin Rescue

Answer 5

Used to replenish folate pools in normal cells. The window is tight and must be used within a 48 hour window

Question 6

6MP and 6TG specific MOA

Answer 6

Activation by HGPRT to form triphosphate metabolite. Inhibits biosynthesis of endogenous purines

Question 7

Fludarabine monophosphate (Fludara) MOA

Answer 7

Phosphorylation causes activation and then inhibits DNA polymerase causing DNA chain termination

Question 8

Cladribine (Leustatin) MOA

Answer 8

Phosphorylation causes activation and inhibits DNA synthesis and repair

Question 9

5-fluorouracil MOA

Answer 9

FdUMP is formed from 5-FU. FdUMP inhibits thymidylate synthase activity causing thymine starvation and DNA synthesis

Question 10

Capecitabine (Xeloda) MOA

Answer 10

Prodrug that requires many enzymes to being active form 5FU. Leads to cytotoxicity similar to 5FU

Question 11

TAS-102 (Lonsurf)
Trifluridine and tipiracil
MOA

Answer 11

Trfluridine is inactive parent form. Tipiracil is an enzyme that degrades trifluridine which will then inhibit thymidylate synthase

Question 12

Cytarabine (ara-C) MOA

Answer 12

Ara-C bioactivated to araCMP which inhibits DNA polymerase alpha and beta blocking DNA synthesis and repair.

Question 13

Gemcitabine MOA

Answer 13

Structure and MOA similar to ara-C. (DNA polymerase alpha and beta blocking synthesis and repair)

Question 14

Methotrexate dose limiting toxicities

Answer 14

myelosuppression (immune suppression) and mucositis (oral and intestinal ulcerations)

Question 15

6-MP dose limiting toxicities

Answer 15

myelosuppression, mucositis, GI distress, and hepatotoxicity

Question 16

5-FU dose limiting toxicities

Answer 16

myelosuppression, mucositis, GI distress, hand-foot syndrome, neurotoxicity

Question 17

Antimitotics classes and location of MOA

Answer 17

Taxanes
Vinca alkaloids
Antimicrotubule inhibitors
ALL act at M phase

Question 18

Vinca alkaloids specific MOA

and examples

Answer 18

Bind to tubulin preventing the formation of microtubules by inhibiting tubulin polymerization
-Vincristine (greater neurotoxicity)
-Vinblastine
Vinorelbine

Question 19

Taxanes MOA and examples

Answer 19

Bind to microtubules to promote tubulin polymerization resulting in inhibition of mitosis and cell division.
Paclitaxel
Albumin-bound paclitaxel
Docetaxel
Cabazitaxel

Question 20

Topoisomerase I inhibitors location and examples

Answer 20

S-phase
Irinotecan
Liposome irinotecan

Question 21

Topoisomerase II inhibitors location and examples

Answer 21

G1 - S phase
Etoposide
Teniposide

Question 22

Topoisomerase inhibitors MOA

Answer 22

inhibit topoisomerases leading to inhibition of DNA replication and transcription

Question 23

Antitumor antibiotics: Bleomycin MOA

Answer 23

Acts on G2 phase by binding DNA resulting in formation of free radicals that result in DNA strand breakage and inhibition of DNA synthesis

Question 24

Mitomycin MOA

Answer 24

CCNS antibiotic that requires bio-activation producing an alkylating agent that cross-links DNA

Question 25

Dactinomycin MOA

Answer 25

CCNS antibiotic that intercalates into DNA blocking RNA and protein synthesis

Question 26

Platinum analogs
Alkylating agents
Mitomycin
Temozolomide
MOA

Answer 26

Form abducts with DNA when DNA is made

Question 27

L-asparaginase MOA

Answer 27

Deaminates asparagine and inhibits protein synthesis during RNA messaging

Question 28

Atra
Arsenic trioxide
Histone deacetylase inhibitors
MOA

Answer 28

Induce differentiation