Pharm Antineoplastic I, Pyrimidine Antimetabolites

Question 1

*5-Flurouracil (5FU) MOA and Antimetabolite and what cell cycle does it work on.

Answer 1

• Pyrimidine antimetabolite
• ACTIVE METABOLITES: FdUMP inhibits thymidylate synthase (inhibits dTMP synthesis)
• FdUTP and FUTP damage DNA and RNA respectfully
• S phase

Question 2

Capecitabine Distinctions and Antimetabolite

Answer 2

• Pyrimidine antimetabolite

- Oral pro-drug of 5FU

Question 3

*5-Flurouracil Therapeutic uses

Answer 3

-TOPICAL-BASAL CELL CARCINOMA

Solid tumors: colorectal and other GI, breast, ovarian carcinomas.

Question 4

*5-Flurouracil Toxicity

Answer 4

• -INVIDUDUALS WITH DPYD MUTATION/DPD DEFICIENCY EXPERIENCE TOXICITY
• NEURO seen first
• GI intolerance, mucosistis, myelosuppression

Question 5

Floxuridine Distinctions and Antimetabolite

Answer 5

• Pyrimidine antimetabolite

- I.V. pro-drug of 5FU activated by and active in liver (metastasis)

Question 6

Gemcitabine Distinctions and Antimetabolite

Answer 6

• Pyrimidine antimetabolite

- Kinases convert gemcitabine to nucleotide anaologs–inhibit DNA synthesis

Question 7

*Cytarabine (Ara C) Distinctions and Antimetabolite

Answer 7

• Pyrimidine antimetabolite

- Kinases convert Ara-C to AraCTP–inhibits DNA synthesis (inhibits DNA POLYMERASE/DNA synthesis)

Question 8

Capecitabine Uses

Answer 8

Colorectal cancer, metastatic breast cancer (resistant to paclitaxel anthracycline)

Question 9

*Floxuridine uses

Answer 9

-LIVER METASTASES

Question 10

*Gemcitabine uses

Answer 10

PANCREATIC CANCER

Question 11

*Cytarabine (Ara C) uses

Answer 11

-ACUTE MYELOGENOUS LEUKEMIA (with 6-thioguanine, daunorubicin)

Question 12

*Capecitabine Dose-Limiting Toxicity

Answer 12

• HAND/ FOOT SYNDROME

- Similar to 5FU

Question 13

Floxuridine Dose-Limiting Toxicity

Answer 13

-Similar to 5FU-sever risk due to intra-arterial administration

Question 14

Gemcitabine Dose-Limiting Toxicity

Answer 14

Myelosuppression-neurtropenia

Question 15

Cytarabine (Ara C) toxicity

Answer 15

Severe myelosuppression-granulocytopenia

Question 16

*Cytarabine (Ara C) Mech of resistance

Answer 16

-Cytidine Deaminase (CDA) inactivates Ara C–liver and spleen have CDA, so in AML it may be hard to treat with Ara C if in liver/spleen