Antimetabolites Flashcards
Name the 3 classes of antimetabolites. Are they cell cycle specific?
Folate-analogs, pyrimidine analogs, purine analogs. CCS (S phase)
Name the 2 folate-analogs
Methotrexate, pemetrexed
Name the 4 pyrimidine-analogs
5-FU (fluorouracil), capecitabine, cytarabine, gemcitabine
Name the purine-analog chemotherapy agent
6-MP (mercaptopurine)
Which of the bases A, T, C, G, and U are purines and which are pyrimidines?
AG - purines, CTU - pyrimidines
What drug counteracts or “rescues” healthy cells from the otherwise lethally toxic effects of methotrexate?
Leucovorin
Name 2 THF-dependent enzymes inhibited by the active/metabolized polyglutamate forms of pemetrexed.
DHFR (dihydrofolate reductase) and TS (thymidylate synthase)
What antimetabolite is the most widely used and can be given orally to treat childhood ALL, choriocarcinoma, and many other cancers?
Methotrexate
A high dose of methotrexate is needed to treat which kind of cancer?
Osteosarcoma
What does it mean to administer methotrexate intrathecally, and for what cancers is this route used?
Inject directly into the CNS/CSF for meningeal leukemia or meningeal metastases
Which antimetabolite is used to treat mesothelioma, as well as non-small cell lung cancer, pancreatic cancer, and colon cancer?
Pemetrexed
5-FU is enzymatically converted into what 2 active forms, and how do these forms interfere with cell processes?
5-FdUMP which competitively inhibits TS (thymidine synthetase), and 5-FdUTP which interferes with RNA function
What is the function of TS (thymidylate synthase)?
Makes dUMP into dTMP
What is the newer form of 5-FU, and how does its administration differ from that of the original form?
Capecitabine; can be given orally whereas 5-FU is only given intravenously
What antimetabolite is used in a wide variety of combination therapies, but comes at the cost of hand-foot syndrome and severe GI toxicity?
5-FU
What cancer is topical 5-FU used to treat?
Basal cell carcinoma
What cancers is capecitabine approved to treat?
Metastatic breast cancer and colorectal cancer
What are the longer names for the antimetabolites 5-dFdU, Ara-C, and dFdC?
5-dFdU is the active form of capecitabine, Ara-C is cytarabine, dFdC is gemcitabine
Describe the 2-step transformation of cytarabine into its active form, and how this form inhibits DNA synthesis
Ara-C –> Ara-CMP –> Ara-CTP, which competes with dCTP to be incorporated into DNA
How does deoxycytidine kinase act on cytarabine and gemcitabine?
adds a phosphate: converts Ara-C to Ara-CMP, and dFdC to dFdCMP
Compare cytarabine and gemcitabine in terms of cell cycle specificity and tumor specificity
Gemcitabine is more effective against solid tumors and is active throughout the cell cycle, while cytarabine is only active during S phase
Cytarabine is the most effective agent for treating what cancer?
AML (and it can also treat ALL and blast phase CML)
Gemcitabine is the first-line treatment for what cancer?
Pancreatic carcinoma
How is 6-MP (mercaptopurine) activated and what is this active form?
6-MP is metabolized by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) into TIMP (6-thioinosinic acid)
