Antineoplastic: Antimetabolites Flashcards
1
Q
Methotrexate
A
- mechanism: Depletes thymidine due to inhibition of dihydrofolate reductase (DHFR), prevents the conversion of FH2 to FH4
- kinetics: intramuscular, IV, and intrathecal (does not cross BBB)
- clinical: choriocarcinoma, acute leukemias, non-Hodgkin’s and primary central nervous system lymphomas, breast cancer, head and neck cancer, and bladder cancer.
- toxicity/interactions: bone marrow suppression, erythema, rash, urticaria, alopecia
- misc: toxic effect such as BMS can be rescued via administration of LEUCOVORIN (taken in more readily by normal cells compared to tumor cells)
2
Q
5-Fluorouracil
A
- mechanism: Fluorouracil is converted in cells to 5-fluoro-2’-deoxyuridine-5’-monophosphate (5-FdUMP), which inhibits thymidylate synthase
- kinetics: IV, for skin cancer, topically, penetrates CNS
- clinical: breast, colon, rectum, pancreas, or stomach cancer
- toxicity/interactions: nausea, vominiting, bone marrow suppression, severe ulceration of the oral and GI mucosa, anorexia, HAND-FOOT SYNDROME
- misc: extended infusion can lead to hand-foot syndrome, use of allopurinol has been shown to reduce oral toxicity
3
Q
Cytarabine
A
- mechanism: Converted to ara-C which acts as a pyrimidine antagonist and blocks DNA polymerase leading to lack of DNA elongation/repair
- kinetics: IV
- clinical: acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelocytic leukemia
- toxicity/interactions: nausea, vomiting, diarrhea, bone marrow suppression, cerebellar ataxia
4
Q
6-Mercaptopurine
A
- mechanism: Inhibits de novo purine nucleotide synthesis; incorporation of triphosphate into RNA; incorporation of triphosphate into DNA
- kinetics: oral (fasting)
- clinical: AML
- toxicity/interactions: Myelosuppression, immunosuppression, and hepatotoxicity
- misc: drug activated by HGPR transferase (enzyme deficient in Lesch Niehan patients), also must reduce dose if used with allopurinol
5
Q
6-Thioguanine
A
- mechanism: Inhibits de novo purine nucleotide synthesis; incorporation of triphosphate into RNA; incorporation of triphosphate into DNA
- kinetics: oral (fasting)
- clinical: ALL, AML
- toxicity/interactions: Myelosuppression, immunosuppression, and hepatotoxicity
- misc: people with low TPMT activity will accumulate higher concentrations of thioguanine toxic metabolites, results in severe myelosuppression
6
Q
Hydroxyurea
A
- mechanism: inhibition of the enzyme ribonucleotide reductase leads to decreased production of deoxyribonucleotides
- kinetics: oral
- clinical: CML, melanoma
- toxicity/interactions: nausea, vomiting, bone marrow suppression,
