Anti-metabolites
What cancer is pemetrexed used in?
Lung
What cancer is pralatrexate used in?
Lymphoma
T/F: 5-FU can incorporate into both DNA and RNA
True Blocks DNA and protein synthesis
What happens if a normal adult is deficient in folic acid?
Macrocytic anemia Peripheral neuropathy Depression
What are the folic acid analogs (antifolates)
Methotrexate Pemetrexed Pralatrexate (I take folic acid in the PPM)
Purines have ____ rings and pyrimidines have ____ rings
2, 1
How many enzymes alter capecitabine to make 5-FU
3
What are the pyrimidine analogs?
5-FU Capecitabine Cytarabine Gemcitabine
What 2 antimetabolites are available PO?
6-mercaptopurine Hydroxyurea
What are the purine analogs?
6-mercaptopurine Fludarabine Pentostatin Clofarabine Nelarabine
Clofarabine is used in _____ cancer
ALL
What cancers is 6-Mercaptopurine used in?
ALL
What cancer types is Methotrexate used for?
ALL Breast Lymphoma
Nelarabine is used in _____ and _____ cancers
ALL and lymphoma
What cancer types is cytarabine used in?
AML ALL (All my cytosines, all my cytosines *Beyonce voice*)
Fludarabine is used in _____ cancers
AML, CLL, lymphoma
Folic acid is a water-soluble ____ vitamin
B
What cancer types is gemcitabine used in?
Breast and lung
What cancer type is hydroxyurea used in?
CML (also melanoma, ovarian, head/neck)
What is folate's biological function as THF forms
Carry one-carbon groups for methylation reactions in amino acid and nucleotide synthesis
What cancer type is capecitabine used for?
Colorectal (Also breast and pancreatic)
What cancer types is 5-FU used in?
Colorectal Breast
Methotrexate-PGs inhibit what 2 enzymes?
DHFR Thymidylate synthase (More effective in some cancers, but also more toxic)
Which purine inhibitor is adenosine deaminase-resistant?
Fludarabine
Gemcitabine (dFdC)
GEMZAR
The primary effects of purine analogs are
Gradual myelosuppression GI (mucositis) Opportunistic infections Some hepatotoxicity
How do purine analogs work?
Inhibit de novo synthesis of purine nucleotides Inhibit RNA/DNA synthesis
How does pralatrexate work?
Inhibits DHFR Inhibits polyglutamylation by the enzyme folypolyglutamyl synthetase (further depletes dTMP)
How does methotrexate work?
Inhibits DHFR so there is NO THF, No dTMP
How does 5-FU work?
Inhibits thymidylate synthase (no dTMP made)
How does hydroxyurea work?
It inhibits ribonucleotide reductase so there is no biosynthesis of DNA because of lack of deoxynucleotides.
Name the drug that is a reduced folic acid (folinic acid)
Leucovorin
What can you give with 5-FU to enhance it?
Leucovorin (makes the 5-FU stay around longer)
What clinical toxicity can you see with hydroxyurea?
Myelosuppression GI Disturbances Alopecia
What are the primary toxic effects of pyrimidine analogs?
Myelosuppression GI issues (mucositis) Alopecia
Is 5-FU the active form?
No, it is a prodrug that is converted in the body to 5dUMP
What is capecitabine?
Prodrug of 5-FU (prodrug of a prodrug!) INCEPTION drug (dream within a dream)
All antimetabolites are ____ phase specific drugs
S
How does pemetrexed work?
Same as methotrexate-PGs...inhibits DHFR and thymidylate synthase
How does cytarabine work?
Think cytarabine-CYTOSINE competes with dCTP for DNA incorporation and blocks DNA synthesis
What is the other S phase specific inhibitor?
Topoisomerase inhibitors
T/F: Leucovorin is used in combo with other chemotherapy drugs to enhance effectiveness or chemoprotect
True
Is THF essential for DNA synthesis?
YES!
Can leucovorin be used as an antidote to effects of chemo?
Yes
What happens if you are pregnant and deficient in folic acid?
Your baby can have neural tube defects and other issues
Clinical toxicity of methotrexate is reduced by _____, a reduced folate coenzyme
folinic acid
The primary toxic effects of antifolates is on rapidly dividing cells of the bone marrow and GI epithelium. This causes
mucositis myelopsupression thrombocytopenia
Folic acid is the _____ form and folate is the ______ form which both coexist in water
protonated- acid deprotonated- ion
Structurally, folic acid contains a ______ ring, PABA, and glutamic acid groups
pteridine
antimetabolites inhibit DNA ________
synthesis (think S phase- synthesis)