Antimetabolite

Question 1

Antimetabolite MOA and example of drug

Answer 1

The anti-metabolites are drugs that are structurally related to naturally occurring compounds found in the body (amino acids, DNA, RNA).
These agents exert their damage on DNA in one of two mechanisms
- Compete for binding sites on enzymes –AntifolateAgents (Methotrexate)
- Incorporate directly into DNA or RNA –Analogues (Purine and Pyrimidine)

Question 2

MOA for MTX

Answer 2

In normal cells, folic acid is converted to folinic acid by enzymes DHFR.
Folinic acid is required for synthesis of purine nucleotide
MTX binds to DHFR thereby inhibiting conversation of folic acid to folinic acid. As a result, purine synthesis is halted. Without Purine nucleotide, DNA replication / transcription cannot take place and cell dies.

Question 3

IF pt is on MTX we must supply ______

Answer 3

Leucovorin as rescue (folinic acid)

Question 4

Dosage and administration: given over a wide range of doses (Intravenous, Intrathecal or Oral).
- Non-oncology usages are also common, but doses are generally much lower (e.g. for rheumatoid arthritis).

Answer 4

• Dosage and administration: given over a wide range of doses (Intravenous, Intrathecal or Oral).
• Non-oncology usages are also common, but doses are generally much lower (e.g. for rheumatoid arthritis).

Question 5

High dose methotrexate therapy (_______ g/m2) require _________and __________until methotrexate levels are____________uM.

Answer 5

High dose methotrexate therapy (>1 g/m2) require therapeutic drug monitoring and folinic acid rescue until methotrexate levels are less than 0.1uM.

Question 6

MTX toxicity increases in pt with _________

Answer 6

• Methotrexate escapes into third spaces -hence, patients with ascities or pleural effusions are in high risk for methotrexate toxicity (accumulation and slow elimination).

Question 7

MTX toxicities

Answer 7

Dose limiting myelosuppression, nephrotoxicity, mucositis, diarrhea, hepatitis, pulmonary pneumonitis, central nervous system toxicities

Question 8

Avoid administration of drugs that interfere with methotrexate excretion ________________________

Answer 8

• NSAIDs
• Penicillin
• Ascorbic acid (Vitamin C)
• Probenecid, Sulfonamides
• Salicylates
• Omeprazole

and acidic condition (dont drink coke)

Question 9

Pyrimidine analogue and MOA

Answer 9

Cytarabine (ara-c),
Gemcitabine (Gemzar®)
5-Fluorouracil (5-FU),
Capecitabine (Xeloda®)

Pyrimidine analogue, inhibits synthesis of DNA/RNA

Question 10

Cytarabine (ara-c),

Answer 10

Pyrimidine analogue

Question 11

Gemcitabine (Gemzar®)

Answer 11

Pyrimidine analogue

Question 12

5-Fluorouracil (5-FU),

Answer 12

Pyrimidine analogue

Question 13

Capecitabine (Xeloda®)

Answer 13

Pyrimidine analogue

Question 14

5-Fluorouracil toxicities

Answer 14

5-Fluorouracil toxicities

• Dose-limiting leucopenia and thrombocytopenia and anemia (with bolus administration)
• Dose-limiting hand-foot syndrome (Palmar Plantar Erythrodysethesias[PPE]) and diarrhea (with continuousinfusions)
• Skin discoloration and nail changes can occur

** Capecitabine (Xeloda®) is an oral active prodrug of 5-FU; toxicities mimic infusional5-FU

• give lotion to prevent PPE