Anticancer Drugs 2

Question 1

Mechanism of action of 6 Mercaptopurine

Answer 1

It is an analog of hypoxanthine and guanine
Converted to thio-IMP by HGPRT and thio-IMP inhibits first step of de novo purine ring biosynthesis and blocks formation of AMP and GMP from IMP

Question 2

Function of thio-IMP

Answer 2

• inhibits first step of de novo purine ring biosynthesis

- blocks formation of AMP and GMP from IMP

Question 3

6 mercaptopurine is metabolized to _____________ by __________

Answer 3

Thiouric acid; xanthine oxidase

Question 4

What does administering allopurinol do to the levels of 6 mercaptopurine

Answer 4

↑ so must ↓ the dose of 6 mercaptopurine given

Question 5

Adverse effects of 6 mercaptopurine

Answer 5

Nausea, vomiting, diarrhea, bone marrow suppression, hepatotoxicity

Question 6

6 thioguanine is converted to thioguanine monophosphate (TGMP) which then inhibits _______ and _______

Answer 6

Purine synthesis; phosphorylation of GMP to GDP

Question 7

What is 6 thioguanine used for?

Answer 7

Acute non lymphocytic leukemia

Question 8

What is the effect of allopurinol when given with 6 thioguanine

Answer 8

Allopurinol DOES NOT potential it’s action because very little is metabolized to thiouric acid

Question 9

Mechanism of action of 5- fluorouracil

Answer 9

1. Converted to 5- FdUMP which inhibits thymidilate synthase and so DNA synthesis is inhibited
2. Converted to 5-FUTP and incorporated to RNA interfering with RNA processing and function

Question 10

Name the pyrimidine analogs

Answer 10

5- Fluorouracil
Capecitabine
Cytarabine

Question 11

5-FU is mainly metabolized by ____ and what are some adverse effects in patients with that enzyme deficiency

Answer 11

Dihydropyrimidine dehydrogenase (DPD) 
Myelosuppresion, neurotoxicity and life threatening diarrhea

Question 12

5-FU + leucovorin is used as a chemotherapy for ________

Answer 12

Colorectal cancer

Leucovorin potentiates the activity of 5-FU because it ↑ the levels of N5,N10 methylene THF

Question 13

How does 5-FU inhibit thymidylate synthase?

Answer 13

Forms a ternary complex involving thymidylate synthase, 5 FdUMP and N5,N10 methylene THF

Question 14

Adverse effects of 5-FU

Answer 14

Nausea, voting, alopecia and bone marrow suppression; very toxic to the GI tract so people with a DPD deficiency are at risk for life threatening diarrhea

Can also see hand-foot Syndrome in which there is an erythematous desquamation of the palms and soles

Question 15

What is capecitabine

Answer 15

Orally availabe prodrug of 5-FU and has the same cytotoxic activity as 5-FU

Question 16

Mechanism of action of cytarabine

Answer 16

It is an analog of deoxycytidine and is phopshoryatled into a triphoshate and when it gets incorporated into DNA, it inhibits DNA polymerase

given via IV

Question 17

cytarabine inhibits _______

Answer 17

DNA polymerase

Question 18

Mechanism of action of antitumor antibiotics

Answer 18

Binds to DNA between bases and blocks synthesis of new RNA/DNA and causes DNA strand breakage and interferes with replication

Question 19

Name antitumor antibiotics

Answer 19

Anthracyclines : doxorubicin and daunorubicin

Bleomycin

Question 20

____________ an anthracyline, is one of hte most widely used anti cancer drug

Answer 20

Doxorubicin

Question 21

Anthracyclines inhibit the enzyme __________

Answer 21

Topoisomeriase II (DNA gyrase)

Question 22

Name the 4 mechanisms of anthracyclines

Answer 22

• Inhibition of toposiomersae II
• intercalation in DNA with blcokade of DNA and RNA synthesis and strand breakage
• binding to cell membranes to alter fluidity and ion transport
• generation of free radicals

Question 23

What is the cause of cardiac toxicity when taking anthracyclines and what do you give to reduce the cardiotoxicity

Answer 23

Generation of free radicals; dexrazoxane

Question 24

Bleomycin is cell cycle specific and arrests cells in ___________

Answer 24

G2

Question 25

Mechanism of bleomycin

Answer 25

Has 2 binding sites: one for DNA and another for ferrous iron DNA-bleomycin Fe2+ is oxidized to Fe3+ and the liberated electrons form free radicals which causes strand breaks in DNA

Question 26

Adverse effects of bleomycin

Answer 26

Most important and serious: pulmonary toxicity (pneumonitis, fibrosis) Little myelosuppression

Question 27

____________ is the most widely used alkylating agent

Answer 27

Cycophosphamide

Question 28

Which group of anti cancer drugs are mutagenic and carcinogenic

Answer 28

Alkylating agents

Question 29

List alkylating agents

Answer 29

Nitrogen mustards: melphalan, cyclophosphamide, mechlorethamine Nitrosureas Other Platinum coordination complexes

Question 30

____________ is an unstable alkylating agent that is a powerful vessicant and must be given via _______

Answer 30

Mechlorethamine; IV

Question 31

Cyclophosphamide is a product that is activated by

Answer 31

CYP2B

Question 32

What is the metabolite that is responsible for the hemorrhagic cystitis that can result from using cyclophosphamide

Answer 32

Acrolein

Question 33

Adverse effects of melphalan and what kind of drug is it

Answer 33

Bone marrow suppression; | Alkylating agent

Question 34

What makes nitrosureas unique for certain cancer treatments

Answer 34

Useful in treating brain tumors It is very lipophilic so it can cross the blood brain barrier

Question 35

Adverse effects of busulfan

Answer 35

``` Myelosuppresion (main) Pulmonary fibrosis (also caused by bleomycin) ```

Question 36

Mechanism of dicarbazine

Answer 36

Methylation agent after it is activated in the liver

Question 37

Procarbazine’s adverse effects

Answer 37

Bone marrow depression, weak MAOI which can cause hypertensive reactions if gtibvne sympathomimetic agents or tyramine containing foods, disulfiram like reactions, mutagenic and teratogenic (alkylating agent)

Question 38

Examples of platinum coordination complexes

Answer 38

Cisplatin and carboplatin

Question 39

Mechanism of platinum coordination complexes

Answer 39

Does not alkylate DNA but binds to DNA and inhibits DNA synthesis by forming cross links

Question 40

Adverse effects of cisplatin

Answer 40

Myelosuppresion, ototoxicity, peripheral neuropathy, and nephrotoxicity

Question 41

_________ is given to reduced the renal toxicity associated with cisplatin

Answer 41

Amifostine

Question 42

What is the dose limiting toxicity for carboplatin?

Answer 42

Myelosuppresion

Question 43

What are some additional adverse effects you see in a patient taking I-Phosphamide that you dont see in someone taking cyclophosphamide

Answer 43

- neurotoxicity | - nephrotoxicity

Question 44

describe the effects of 6-MP on someone with Lesch Nyan Syndrome

Answer 44

6 MP would not be as effective and there would be more resistance to it because these patients have low levels of HGPRT

Question 45

6-MP and 6-TG are also metabolized by _______ and patients with a deficiency in this enzyme are at risk for ________

Answer 45

TPMT (thiopurine methyltransferase); myelosuppression