Antimetabolites

Question 1

Methotrexate MOA

Answer 1

MOA: folic acid antagonist, inhibits dihydrofolate reductase (DHFR), CANT PENETRATE CNS, Cell cycle specific (inhibit s phase)

Question 2

Methotrexate USES

Answer 2

USES: child ALL, choriocarcinoma, Burkitt’s, breast/ovary/head/neck/bladder carcinoma, intrathecal route: meningeal leukemia/mets, high dose: osteosarcoma

Question 3

Methotrexate Toxicity

Answer 3

Toxicity: renal toxicity (crystals in urine), give leucovorin to rescue normal cells

Question 4

Pemetrexed MOA & use

Answer 4

folate analog, inhibits DHFR and thymidylate synthase (TS)

uses: colon cancer, mesothelioma, non-small cell lung cancer, pancreatic cancer

Question 5

5-Fluorouracil MOA

Answer 5

1) pyrimidine analog, prodrug converted to 5-FdUMP and 5-FdUTP
2) 5-FdUMP inhibits thymidylate synthetase = no thymidine made
3) 5-FdUTP incorporated into RNA via RNA pol = intereference with RNA fxn

Question 6

5-Fluorouracil USES

Answer 6

1) Given IV
2) combo therapy: breast, colorectal, gastric, head/neck, ceverical, pancreatic
3) Topical: basal cell carcinoma
4) Capecitabine = oral form, metastatic breast cancer, colorectal cancer

Question 7

5-Fluorouracil Toxicity

Answer 7

Hand and food syndrome = erythema

Cardiac toxicity = acute chest pain

Question 8

Cytarabine MOA

Answer 8

S phase specific, pyrimidine analog

1) cytarabine&raquo_space; araCTP
2) araCTP competitively inhibits DNA polymerase
3) premature DNA chain termination

Question 9

Cytarabine USES

Answer 9

AML, also ALL and blast phase CML

Question 10

Cytarabine Toxicity

Answer 10

severe myelosuppression

GI tract toxicity (ulceration, stomatitis, diarrhea)

Question 11

Gemcitabine MOA

Answer 11

NOT s phase specific, pyrimidine analog
analog of deoxycytidine
1) dFdCDP inhibits ribonucleotide reductase = depletion of deoxyribonucleotide for DNA
2) dFdCTP incorporates into DNA = termination of DNA synthesis

Question 12

Gemcitabine USES

Answer 12

pancreatic carcinoma
Better than cytarabine for solid tumors
non-small cell lung, ovarian, bladder, esophageal, head/neck cancer

Question 13

Gemcitabine Toxicity

Answer 13

Myelosuppression

flu-like symptoms

Question 14

6-Mercaptopurine MOA

Answer 14

1) purine analog, prodrug metabolized by HGPRT into TIMP
2) TIMP inhibits de novo synthesis of purine bases
3) TIMP blocks formation of AMP&XMP from IMP
4) TIMP&raquo_space; Thio-GMP incorporated into DNA/RNA = inhibition of DNA/RNA synthesis

Question 15

6-Mercaptopurine USES

Answer 15

maintain remission for ALL

Question 16

6-MP Toxicity

Answer 16

1) bone marrow suppression
2) hepatotoxicity
3) Allopurinol interaction: allopurinol blocks XO so 6-MP rises to toxic levels since it is normally broken down by XO

Question 17

6-MP Mechanisms of Resistance

Answer 17

1) Decreased expression of HGPRT

2) Decreased drug transport