Antimetabolites- Fitz Flashcards Preview

IHO WEEK 3 > Antimetabolites- Fitz > Flashcards

Flashcards in Antimetabolites- Fitz Deck (17):
1

MOA of 5-Fluorouracil

inhibits thymidylate synthase (enzyme that catalyzes the rate limiting step in DNA syntehsis)

Decreases synthesis of pyrimidines

2

What drug is converted to 5-Fluorouracil SELECTIVELY in cancer cells?

Capecitabine

3

What drug will increase the binding of 5-FU to thymidylate synthase, increasings its half life?

Leucovorin

4

What are the two forms of resistances for 5-FU and Capectiabine?

Changes in target enzymes -- increased expression of TS

Decreased activation of prodrugs -- decreased pyrimidine monophosphate kinase activity

5

How does capecitabine exhibit selective toxicity?

Last step of activation process done by thymidine phosphorylase

which is over expressed in many tumors = SELECTIVE TOXICITY!

6

Which has more selective toxicity, capecitabine or 5-FU?

Capecitabine

7

MOA of 6-Thioguanine and 6-Mercaptopurine

Converted to 6-thioGMP

Poor substrate for PRPP, PNP, HGPRT

Leads to build up of IMP and GMP

Cuases "pseudofeedback inhibtion" of PNP, PRPP glutamyl amidotransferase, and HGPRT

**Interference with DNA and RNA synthesis
**Inhibition of purine nucleotide interconversion
**Decrease intracellular levels of guanine nucleotides

8

What enzyme is needed to activate 6-mercaptopurine and 6-thioguanine?

HGPRT

9

What are the mechanisms of resistance against 6-MP and 6-TG?

Change in target enzyme- decreased ability to inhibit enzyme

Decreased activation by HGPRT

Increased degradation of prodrugs or metabolites

10

Which dosage needs to be adjusted in conjunction with allopurinol? 6-MP or 6-TG?

6-MP!!!

11

What is tumor lysis syndrome?

Cuased by the sudden, rapid death of million of cells. Results from development of electrolyte and metabolic disturbances

Causes life threatening complications = hyperuricemia

Give allopurinol (xanthine oxidase inhibitor)

12

Why do you frequently give allopurinol during chemotherapy of hemtologic cancers?

To prevent hyperuricemia due to tumor cell lysis

Inhibits xanthine oxidase

Prevents nephrotoxicity and acute gout that would otherwise be produces with excessive uric acid

**NOTE: adjust 6-MP dose!!!!!

13

Why do you need to change the dosage of 6-Mercaptopurine when giving allopurinol to prevent hyperuricemia?

6-MP is metabolized by xanthine oxidase

produces excessive 6-MP toxicity!!

Reduce dose by 25-30%

14

MOA Cytarabine

converted to compound that mimics CDP and CTP (pyrimidines)

gets incorporated into DNA, blocks DNA polymerase (synthesis and repair) and ribonucleotide synthase

15

MOA of Gemcitabine

converted to compound that mimics CDP and CTP (pyrimidines)

gets incorporated into DNA, blocks DNA polymerase (synthesis and repair) and ribonucleotide synthase

16

MOA Cladribine

converted to compound that mimics ADP and ATP (purine)

gets incorporated into DNA, blocks DNA polymerase (synthesis and repair) and ribonucleotide synthase

17

MOA of Fludarabine

converted to compound that mimics ADP and ATP (purine)

gets incorporated into DNA, blocks DNA polymerase (synthesis and repair) and ribonucleotide synthase