Cancer Pharm

Question 1

What are the 7 classes of anti-cancer drugs based on their MOI?

Answer 1

1. Alkylating agents
2. Antimetabolites
3. DNA intercalating agents
4. Microtubule inhibitors
5. Topoisomerase inhibitors
6. Hormones and their antagonist
7. Molecularly targeted small molecules (MAbs)

Question 2

What order kinetics does the killing of cancer cells follow?

A given dose of drug kills a constant number or fraction of cells?

Answer 2

This is the Log-Kill hypothesis:
The killing of cancer cells by chemotherapeutic cells follow First order kinetics-a given dose of drug kills a CONSTANT FRACTION of cells, not a constant number

Question 3

What is the method of action of alkylating agents?

Cell cycle specific or non-specific?

Answer 3

Alkylating agents transfer alkyl groups to DNA, many of which are bi-functional and promotes cross-linking of DNA and therefore DNA damage.

Cell cycle non-specific-acts on both proliferating and resting cells

Question 4

Nitrogen mustards belong to which type of anticancer drug?

What are the 3 Nitrogen mustards?

Answer 4

Alkylating agents

1. Cyclophosphamide
2. Ifosfamide
3. Bendamustine

Question 5

What are the 4 classes of alkylating agents?

Answer 5

1. Nitrogen mustards
2. Notrisoureas
3. Triazenes
4. Platinum Analogs

Question 6

Hemorrhagic cystitis is a very specific toxicity due to which chemotherapy drug?

Answer 6

Cyclophosphamide

nitrogen mustard, alkylating agent

Question 7

What 2 drugs belong to the nitrosoureas group of alkylating agents?

Answer 7

1. Carmustine

2. Lomustine

Question 8

What nitrosoureas chemotherapy drug is used primarily to treat brain tumors (glioma, glioblastoma)?

Answer 8

Carmustine-highly lipophilic

May result in CNS toxicity (Dizziness)

Question 9

What nitrogen mustard is used to treat testicular sarcomas?

Answer 9

ifosfamide

Question 10

What are the 2 Triazene drugs from the Alkylating agents?

Answer 10

1. Dacarbazine

2. Temozolomide

Question 11

What are the 3 platinum analogs in the alkylating agents?

Answer 11

All end in platin

1. Cisplatin (the only inorganic one…no carbons)
2. Carboplatin
3. Oxaplatin

Question 12

What is the mechanism of action for platinum analogs?

Answer 12

DNA cross-linking

Cisplatin, carboplatin, oxaplatin

Question 13

What toxicities are associated with platinum analogs of the alkylating agents?

Answer 13

Cisplatin: Nephrotoxicity (kidney damage), ototoxicity (hearing loss),
Oxaoplatin: neurotoxicity (nerve damage)

Question 14

What are the 3 groups of antimetabolites?

What is the method of action?

Are they cell cycle specific or non-specifc?

Answer 14

1. Folate analogs
2. Pyrimidine analogs
3. Purine analogs
   MOA: inhibit enzymes required for nucleotide synthesis, or compete with endogenous nucleotides in DNA/RNA synthesis

Cell cycle specific, since they act specifically in the S phase (DNA Synthesis) of cell cycle

Question 15

What are the 2 folate analogs?

Answer 15

1. Methotrexate

2. Pemetrexed

Question 16

What is the most widely used antimetabolite in cancer chemotherapy? Which group of antimetabolites does it belong to?

Answer 16

Methotrexate, belonging to folate analog group

Question 17

What is the MOA of methotrexate?

Is it cell cycle specific, and if so where in the cell cycle?

Answer 17

Methotrexate, of folate analog group.

MOA: folic acid antagonist that inhibits DHFR, which is required for thymidine and purine biosynthesis

(S-phase)

Question 18

Can methotrexate penetrate the CNS?

Answer 18

No, it is administered intrathecally (into spine) for meningeal leukemia and meningeal metastases

Question 19

Methotrexate salts can crystalize and cause what kind of toxicity?

Answer 19

Renal toxicity

Also can cause hepatotoxicity with long-term use

Question 20

Which Folate analog drug is used to treat osteosarcomas and choriocarcinomas?

Answer 20

Methotrexate (MTX)

Folate analog of antimetabolite group

Question 21

The amplification of DHFR and decreased affinity of DHFR is a resistance mechanism used against which Drug?

Answer 21

Methotrexate

Question 22

What are the 3 pyrimidine analogs that belong to the antimetabolites?

Answer 22

1. 5-fluorouracil
2. Cytarabine
3. Gemcitabine

Question 23

What is the mechanism of 5-flurouracil?

Is 5-fluroruracil cell cycle specifc? If so which phase?

Answer 23

Pro-drug that requires activation within cells (this makes is susceptible to resistance mechanisms)

Inhibits synthesis of DNA via inhibition of Thymidine.

S-phase specific

Question 24

Which drug belonging to the Pyrimidine analog of antimetabolites can cause hand-foot syndrome as a toxicity factor?

Answer 24

5-fluroruracil

Hand-foot syndrome-swelling, redness, sensitivity to the palms and soles

Question 25

How is 5-fluorouracil administered ? Why is it administered this way?

Answer 25

Administered IV due to rapid metabolic degradation in the gut and liver

Question 26

Cytarabine belongs to which class and group of drugs? How does it work?

Answer 26

Pyrimidine analog of the antimetabolites It works by inhibiting DNA polymerase, therefore inhibiting transcription and replication

Question 27

Which drug is the MOST important drug for the tx of AML?

Answer 27

Cytarabine Pyrimidine analog Antimetabolites

Question 28

What 2 drugs belong to the purine analogs group of the antimetabolites?

Answer 28

1. 6-mercaptopurine | 2. Fludarabine

Question 29

What is the mechanism of action for 6-mercaptopurine?

Answer 29

Pro-drug that requires activation within cells (this makes is susceptible to resistance mechanisms) Causes reduction of purine levels resulting in inhibition of DNA and RNA synthesis in tumor cells (inhibiting purines will inhibit DNA synthesis)

Question 30

The resistance mechanism used against this drug involves reduced metabolic conversion of 6-MP to active nucleotide due to decreased expression of HGRPT?

Answer 30

6-Mercaptopurine This also has a drug interaction with allopurinol