Intracellular Poisons: Antimetabolites

Question 1

Important anti-fol and anti-metabolites

Answer 1

methotrexate
5-FU
Gemcitabine
Cytarabine

Question 2

Players in 1-C metabolism

Answer 2

folic acid
vitamin B12
SAM

Question 3

Methotrexate blocks ________ which impairs DNA synthesis by depleting Thymidine.

Answer 3

Methotrexate blocks Dihydrofolate Reductase, which impairs DNA synthesis by depleting Thymidine.

Question 4

Folate shuttles one-carbon fragments for multiple uses, including __________

Answer 4

de-novo nucleic acid synthesis: No Folate = no DNA or RNA

Question 5

Vitamin B12, which is not made by mammals, does two important things:

Answer 5

Isomerize methyl malonate, and generate SAM

Question 6

Folate supplementation can mask ____________, correcting the anemia but allowing neuro damage to progress

Answer 6

B12 deficiency

methylmalonate builds up in the brain (and homocysteine)

Question 7

Methotrexate
cured what
used for what
mechanism

Answer 7

solid tumor choriocarcinoma
combination regimens for lymphomas and bladder cancer

blocks DHFR which impairs DNA synthesis by depleting thymidine

Question 8

methotrexate
myelosuppression?
Contraindications?
DLT
Antidote

Answer 8

Can be profoundly myelosuppressive if not cleared normally. Thus, it must not be given to patients with:
anasarca, ascites or large pleural effusions
impaired renal function
Usual DLT is mucositis
Antidote is to give reduced folates in form of leucovorin

Question 9

Methotrexate depletes_________, and can thus prime a cell for other stressors

Answer 9

Thymidine

Question 10

Given at high dose, Methotrexate can

Answer 10

get into CNS and provide important contribution to treatment of aggressive lymphomas and ALL

Question 11

DLT is usually ________

Answer 11

stomatitis

Question 12

DNA synthesis, and the normal convention for representing sequences, is 5’ to 3’

Answer 12

5’ to 3’

Question 13

important pyrimidine analogs

Answer 13

5-FU

ARa-C
Gem (gemcitabine)

Question 14

for 5-FU most of the toxicity comes from what and most efficacy comes from

Answer 14

tox - RNA dysfunction

efficacy - DNA dysfunction

Question 15

FdUMP is a _______

Answer 15

suicide substrate on Thymidylate synthase

Question 16

most important anti-metabolite drug

Answer 16

5-FU

Question 17

5-FU remains an effective

Answer 17

radiosensitizer for many contexts of chemoradiation for locally advanced cancers. It is sunscreen in reverse!

Question 18

5-FU useful in

Answer 18

It remains the backbone for all GI cancers, and is an important drug in Head and Neck and Breast cancer.

Question 19

DLT by bolus route vs infusion

Answer 19

DLT by bolus route is myelosuppression;
DLT by infusion is GI toxicity: stomatitis, diarrhea, odynophagia and hand/foot syndrome

give w/ leucovorin

Question 20

actinic recall a thing for

Answer 20

5-FU

Question 21

antidote for 5-FU

Answer 21

uridine tri-acetate

Question 22

what enzyme de-activates 5-FU

Answer 22

DPD

dihydropyrimidine dehydrogenase

Question 23

Gemcitabine is a ____ drug

Answer 23

pyrimidine analog

Question 24

Gemcitabine
use
strikingly self-potentiating thus
strongly interacts w/ 
can be safely give to 
rarely causes

Answer 24

broad spectrum (hem and solid)
schedule-dependent
DNA-damaging agents, like pt drugs and radiotherapy
renal failure ok 
no alopecia

Question 25

Ara-C is a ______ drgu

Answer 25

pyrimidine analog

Question 26

Ara-C
use
not use
clearance
route

Answer 26

AML, salvage for lymphomas
no use for solid tumors
cleared to Ara-U = inactive
intrathecally

Question 27

important purine analogs

Answer 27

6-mercaptopurine

2-chloro-deoxyadenosine

Question 28

6-MP
immunosuppressive?
use?
administration

Answer 28

remarkably IS
childhood leukemia
long-term okay

Question 29

which one against hairy cell leukemia

Answer 29

2-cdA, cladribine

Question 30

DLTs of 5-FU

Answer 30

stomatitis, diarrhea, hand/foot syndrome and actinic recall

Question 31

most important anti-mitotic drug after cyclophosphamide

Answer 31

5-FU

Question 32

What rivals cisplatin for breadth of spectrum of clinical activity, and is strongly synergistic with DNA damaging agents

Answer 32

Gemcitabine

Question 33

No end in sight for production of drugs in what class

Answer 33

nucleoside analogs

Question 34

The ___________ are quite immuno-suppressive and are used in the clinic for this as much or more as they are for cancer

Answer 34

purine analogs