Antimetabolites

Question 1

What are antimetabolites?

Answer 1

Chemicals that inhibit action of metabolites therefore, INTERFERE WITH NORMAL METABOLISM

Question 2

What phase of the cell cycle do antimetabolites act in

Answer 2

S phase: synthesis and replication of DNA

Question 3

What is the two major mechanisms of antimetabolits

Answer 3

INHIBIT PRODUCTION of dexoyribonucleoside triphosphates (inhibits the replication of the DNA), INCORPORATE INTO THE DNA (cytotoxic effect on the cell)

Question 4

What are the three different types of antimetabolites

Answer 4

Anti-purines, anti-folates, and anti-pyrimidines

Question 5

What pathway for synthesizing DNA/RNA does tumors rely on

Answer 5

De novo pathway

Question 6

What are the purines, pyrimidines

Answer 6

Adenine and guanine/ cytosine, uracil, and thymine

Question 7

What are the two major anti-purines and what do they substitute for

Answer 7

6-mercatopurine (6-MP) –> Adenosine

6-thioguanine (6-TG) –> Guanine

Question 8

What is the breaking point in the De novo purine nucleotide biosythensis

Answer 8

Inosine monophosphate

Question 9

What are the two MOAs of anti-purines

Answer 9

Inhibit nucleotide synthesis at several step of de novo biosynthesis, incorporation into nucleic acids

Question 10

Which antipurine blocks IMP from being converted to AMP

Answer 10

6-MP

Question 11

T/F: When anti-purines are incorportated into DNA the repair pathways have trouble distinguishing them from regular purines but DNA/RNA polymerase never replicate them

Answer 11

True

Question 12

What are the side effects of 6-MP

Answer 12

fatigue, diarrhea, nausea, skin rash, alopecia

Question 13

What are the side effects of 6-TG

Answer 13

leukopenia, neutropenia, thrombocytopenia, anemia, anorexia

Question 14

What are the two groups for anti-pyrimidines

Answer 14

Cytdine analogs and fluropyrimidine analogs

Question 15

What are the cytdine analogs, fluropyrimindine analogs

Answer 15

Cytarabine and gemcitabine/ 5-flurouracil and capecitabine

Question 16

What are the two MOA of 5-flurouracil

Answer 16

Inhibits synthesis of thymidine nucleotide (major), incorporates into RNA and DNA

Question 17

What is the enzyme that interactes with 5-flurouracil not allowing for thymidine synthesis

Answer 17

Thymidylate synthase

Question 18

What is a difference between 5-flurouracil and capectiabine that also connects the two

Answer 18

Capecitabine is a prodrug that to 5-FU by the liver

Question 19

What tumors are most sensitive capecitabine and what cancers are usually treated by capecitabine

Answer 19

Tumors that overexpress thymidine phosphorylase, breast and colon cancers

Question 20

Since 5-FU and capecitabine can be fatal what drugs can be given to reverse action

Answer 20

Uridine triacetate

Question 21

Which drug contains a combination of fluropyrimidine analogs

Answer 21

Trifluridine/Tipiracil (TFT/TPI)

Question 22

What is the MOA of TFT

Answer 22

The triphosphate form of TFT/TPI can be incorporated into DNA inducing DNA fragmentation, inhibits thmidylate synthase reducting the nucleotide pool levels required for DNA replication

Question 23

What is the TPI MOA

Answer 23

Inhibits thymidine phosphorylase, increase bioavailabitly of TFT

Question 24

What is the MOA of cytarabine, what type of cancer does it treat, toxicities

Answer 24

Incorporates into DNA and prevents DNA elongation/ leukemias/ myelosuppression, mucositis, fever, pains

Question 25

What is the Dual MOA of gemcitabine, biggest setback

Answer 25

Inhibition of ribonuclotise reductase (ribonucleotides cannot convert to deoxy-ribonucleotides), Triphosphate form incoporates into DNA/ Half-life of 8 mins

Question 26

Where does folate (vitamin B9) come from

Answer 26

Food (leafy greens)

Question 27

What is the role of folate in thymidine synthesis

Answer 27

Folate aids in the co-factor N5,N10-methylene THF (essential for converting dUMP into dTMP)

Question 28

What is the important co-factor in purine synthesis, how is it acquired

Answer 28

Formyltetrahydrofoloate, folate is converted to tetrahydrofolfate by dihydrofolate reductase (DHFR)

Question 29

What is the MOA of methotrexate

Answer 29

Competitively Inhibits DHFR due to 1000 fold higher affinity (inhibts purine and pyrimidine synthesis)

Question 30

What are the side effects of methotrexate

Answer 30

Memory loss (neurotoxicity), heptaotoxicity, myelosuppresion, GI toxicitites

Question 31

T/F: Methotrexate is NOT safe in pregnancies

Answer 31

True

Question 32

What medication is used as a rescue from methotrexate

Answer 32

Leucovorin (Folinic acid)

Question 33

What category of anti-metabolite is pralatrexate, why is it special, which cancers is it used against

Answer 33

Anti-folate, accumulates preferentially in cancer cells and has high tumor uptake, refractory peripheral T- cell lymphoma

Question 34

What are the the three enzymes that pralatrexate inhibits

Answer 34

DHFR, Thymidylate synthase, GARFT