Week 2: anti-fols and other antimetabolites

Question 1

Name the anti-folate

Answer 1

methotrexate

Question 2

Name pyrimidine analogs?

Answer 2

5-fluorouracil, cytarabine, gemcitabine

Question 3

What are the platers of 1-carbon metabolism?

Answer 3

Folic acid, Vitamin B12, SAM

Question 4

What is the mechanism of methotrexate?

Answer 4

blocks dihydrofolate reductase, which impairs DNA synthesis by depleting thymidine

Question 5

What is folate used for?

Answer 5

shuttling one-carbon fragments for multiple uses, including de-novo nucleic acid synthesis

Question 6

What 2 things does Vit B12 do/

Answer 6

isomerize methyl malonate, generate SAM

Question 7

What should folate always be prescribed with?

Answer 7

Vitamin B12

Question 8

What patients should methotrexate never be given to? and why? What’s the treatment for the side effect?

Answer 8

anasarca, ascites, large pleural effusions; will build up in the fluids and leak out over a long period of time causing mucositis and stomatitis; GIVE REDUCED FOLATES (LEUCOVORIN)

Question 9

what is the DLT of methotrexate?

Answer 9

stomatitis

Question 10

Where does most of the efficacy of 5-FU metabolism come from?

Answer 10

DNA dysfunction; binds and prevents thymidylate synthase from carrying out all other functions, creating a dead enzyme

Question 11

What is the most important anti-metabolite drug?

Answer 11

5-FU

Question 12

What cancers if 5-FU used for?

Answer 12

GI cancers, head and neck, breast cancer

Question 13

What are side effects of 5-FU?

Answer 13

Actinic recall, myelosuppressition (bolus), GI toxicity (infusion), hand/foot syndrome

Question 14

What is the antidote to 5-FU overdose?

Answer 14

uridine

Question 15

What are the pyrimidine analogs?

Answer 15

5-FU, gemcitabine, Ara-C, dFdU, Ara-U

Question 16

What chemotherapy drug rarely causes alopecia?

Answer 16

gemcitabine

Question 17

T/F: gemcitabine is strongly schedule-dependent

Answer 17

True; very self-potentiating

Question 18

What is Ara-C used to treat?

Answer 18

AML and salvage therapy for lymphomas

Question 19

What drugs are purine analogs?

Answer 19

6-mercaptopurine, cladaribine, fludarabine, clofarabine

Question 20

What is the only use of 5-mercaptopurine?

Answer 20

childhood leukemia

Question 21

What drug is VERY active against Hairy Cell leukemia?

Answer 21

2-CdA, also may be useful in MS and B-cell malignancies

Question 22

What are the DLTs of 5-FU?

Answer 22

stomatitis, diarrhea, hand/foot syndrome, actinic recall

Question 23

What pyrimadine analogs is strongly synergistic with DNA damaging agents?

Answer 23

Gemcitabine

Question 24

What drug is a “magic bullet” for hairy cell leukemia?

Answer 24

cladribine (2-CdA)

Question 25

T/F: purine analogs are quite immuno-suppressive

Answer 25

True