Cancer Chemotherapy Agents

Question 1

Akylating Agents

Answer 1

Non cell cycle specific

Question 2

Where do alkylating agents originate from

Answer 2

sulfur and nitrogen mustard warfare agents

Question 3

Later generation mustard agents

Answer 3

Akylating Agents
Non cell cycle specific

• cyclophosphamide
• ifosfamide generate
• BCNU (carmustine
• CCNU (lomustine)
• thiotepa

Question 4

Cyclophosphamide

Answer 4

Akylating Agents
Non cell cycle specific

• Later generation mustard agent
• generates acrolein, which is toxic to the bladder

Question 5

Ifosfamide

Answer 5

Akylating Agents
Non cell cycle specific

• later generation mustard agents
• generate acrolein, which is toxic to the bladder

Question 6

BCNU

carmustine

Answer 6

Akylating Agents
Non cell cycle specific
Later generation mustard agent

Question 7

CCNU

lomustine

Answer 7

Akylating Agents
Non cell cycle specific
later generation mustard agent

Question 8

All mustard agents

Answer 8

• prodrugs
• – need metabolic activation
• orally active

Question 9

Thiotepa

Answer 9

Akylating Agents
Non cell cycle specific

• lipophilic
• – penetrates well into brain and can kill metastases of non-neuronal neoplasms in the brain

Question 10

Hydrazines

Answer 10

alylating agent (non cell cycle specific)
- prodrugs

Question 11

Procarbazine

Answer 11

hydrazine (alkylating agent, non cell cycle specific)

Question 12

Dacarbazine

Answer 12

hydrazine (alkylating agent, non cell cycle specific)

Question 13

Temozolomide

Answer 13

hydrazine (alkylating agent, non cell cycle specific)

• orally active
• penetrates brain blood barrier
• useful for gliomas

Question 14

Alkylating Agents Mechanism of Action

Answer 14

• non cell cycle specific
• highly reactive
• – alkylate protein, RNA, DNA and cause strand breaks, crosslinks and mismatches, disrupting DNA synthesis/replication

Question 15

Alkylating Agents Adverse Effects

Answer 15

• classical - nausea, allopecia, myelosuppresion/immunosuppression

Question 16

Akylating Agents

Resistance Mechanisms

Answer 16

• increased glutathione conjugation
• increased glutathione synthesis
• increased DNA repair
• decrease cellular update
• increased cellular efflux

Question 17

Antimetabolites

Answer 17

S phase specific

Question 18

Methotrexate

Answer 18

Antifolates

• taken up and polygultamylated
• inhibits dihydrofolate reductase (DHFR) and thymidiylate synthetase (TS)

Question 19

Methotrexate Active In

antifolate

Answer 19

Antimetabolites (s phase specific)

• wide variety of cancers
• – leukemia
• – lymphoma
• – solid tumors

Question 20

Methotrexate Adverse Effects

antifolate

Answer 20

antimetabolites (s phase specific)
- nephrotoxicity

Folate analogue LEUCOVORIN used as a rescue agent

Question 21

Leucovorin

Answer 21

rescue agent for nephrotoxicity seen with methotrexate

Question 22

Methotrexate Resistance

antifolate

Answer 22

antimetabolites (s phase specific)

• cellular transport: less in, more out
• decreased metabolic activiation
• altered enzyme target
• increased salvage of folate

Question 23

Purine/Pyrimidine Analogs

Answer 23

antimetabolites (s phase specific)

• 6-mercaptopurine
• 5-fluorouracil
• cytosine arabinoside

Question 24

6-mercaptopurine

Answer 24

Purine/Pyrimidine Analogs
antimetabolites (s phase specific)
- prodrug
- inhibits purine synthesis
- incorporated into RNA and DNA

Question 25

5-fluorouracil

Answer 25

``` Purine/Pyrimidine Analogs antimetabolites (s phase specific) - prodrug that looks like thymine - inhibits thymidylate synthetase - incorporated into RNA and DNA ```

Question 26

Cytosine Arabinoside

Answer 26

Purine/Pyrimidine Analogs antimetabolites (s phase specific) - inhibits DNA polymerase - incorporated into RNA and DNA

Question 27

Platinum Compounds

Answer 27

Cisplatin and other -platins | non cell cycle specific

Question 28

Platinum Compounds | Action

Answer 28

Cisplatin and other -platins non cell cycle specific - bind DNA and cause DNA double strand breaks - BRCA 1/2 deficient tumors especially sensitive --- acquired resistance due to their reversion

Question 29

Platinum Compounds Adverse Events

Answer 29

``` Cisplatin and other -platins non cell cycle specific - NAUSEA & VOMITING - myelosuppression - renal and ototoxicity ```

Question 30

Poly (ADP-Ribose) Polymerase (PARP) Inhibitors

Answer 30

similar effects on DNA to the platins

Question 31

Anthracyclines

Answer 31

Doxorubicin (adriamycin) | non cell cycle specific

Question 32

Doxorubicin

Answer 32

Adriamycin non cell cycle specific Anthracyclines

Question 33

Cisplatin and other -platins

Answer 33

- non cell cycle specific | - platinum compounds

Question 34

Anthracyclines Action

Answer 34

Doxorubicin (adriamycin) non cell cycle specific - DNA intercalator & topoisomerase inhibitor

Question 35

Anthracyclines Adverse Effects

Answer 35

``` Doxorubicin (adriamycin) non cell cycle specific - nausea & vomiting - vesicant - cardiotoxicity ```

Question 36

Tubulin Disrupting Agents

Answer 36

M phase specific poisons - vinca alkaloids - taxanes: taxol (paclitaxel) and variants

Question 37

Vinca Alkaloids

Answer 37

Tubulin Disrupting Agents (M phase specific poisons) - Inhibit microtubule polymerization causing mitotic arrest

Question 38

Vincristine

Answer 38

Tubulin Disrupting Agents (M phase specific poisons) Vinca Alkaloids - neurotoxic (microtubules are necessary for axonal transport)

Question 39

Vinblastine

Answer 39

Tubulin Disrupting Agents (M phase specific poisons) Vinca Alkaloids - vesicant

Question 40

Taxol (paclitaxel) and variants | Action

Answer 40

Tubulin Disrupting Agents (M phase specific poisons) - promotes tubulin assembly and causes mitotic arrest

Question 41

Taxol (paclitaxel) and variants | Adverse Effects

Answer 41

``` Tubulin Disrupting Agents (M phase specific poisons) - peripheral neuropathy - allergic reaction due to solvent used (cremaphore) - myelosuppresion - allopecia ```

Question 42

Cremaphore

Answer 42

solvent used for Taxols | - can illicit allergic reactions