Intracellular Poisons: Antimetabolites Flashcards
Important anti-fol and anti-metabolites
methotrexate
5-FU
Gemcitabine
Cytarabine
Players in 1-C metabolism
folic acid
vitamin B12
SAM
Methotrexate blocks ________ which impairs DNA synthesis by depleting Thymidine.
Methotrexate blocks Dihydrofolate Reductase, which impairs DNA synthesis by depleting Thymidine.
Folate shuttles one-carbon fragments for multiple uses, including __________
de-novo nucleic acid synthesis: No Folate = no DNA or RNA
Vitamin B12, which is not made by mammals, does two important things:
Isomerize methyl malonate, and generate SAM
Folate supplementation can mask ____________, correcting the anemia but allowing neuro damage to progress
B12 deficiency
methylmalonate builds up in the brain (and homocysteine)
Methotrexate
cured what
used for what
mechanism
solid tumor choriocarcinoma
combination regimens for lymphomas and bladder cancer
blocks DHFR which impairs DNA synthesis by depleting thymidine
methotrexate myelosuppression? Contraindications? DLT Antidote
Can be profoundly myelosuppressive if not cleared normally. Thus, it must not be given to patients with:
anasarca, ascites or large pleural effusions
impaired renal function
Usual DLT is mucositis
Antidote is to give reduced folates in form of leucovorin
Methotrexate depletes_________, and can thus prime a cell for other stressors
Thymidine
Given at high dose, Methotrexate can
get into CNS and provide important contribution to treatment of aggressive lymphomas and ALL
DLT is usually ________
stomatitis
DNA synthesis, and the normal convention for representing sequences, is 5’ to 3’
5’ to 3’
important pyrimidine analogs
5-FU
ARa-C
Gem (gemcitabine)
for 5-FU most of the toxicity comes from what and most efficacy comes from
tox - RNA dysfunction
efficacy - DNA dysfunction
FdUMP is a _______
suicide substrate on Thymidylate synthase
most important anti-metabolite drug
5-FU
5-FU remains an effective
radiosensitizer for many contexts of chemoradiation for locally advanced cancers. It is sunscreen in reverse!
5-FU useful in
It remains the backbone for all GI cancers, and is an important drug in Head and Neck and Breast cancer.
DLT by bolus route vs infusion
DLT by bolus route is myelosuppression;
DLT by infusion is GI toxicity: stomatitis, diarrhea, odynophagia and hand/foot syndrome
give w/ leucovorin
actinic recall a thing for
5-FU
antidote for 5-FU
uridine tri-acetate
what enzyme de-activates 5-FU
DPD
dihydropyrimidine dehydrogenase
Gemcitabine is a ____ drug
pyrimidine analog
Gemcitabine use strikingly self-potentiating thus strongly interacts w/ can be safely give to rarely causes
broad spectrum (hem and solid) schedule-dependent DNA-damaging agents, like pt drugs and radiotherapy renal failure ok no alopecia
