Sketchy Pharm: Methotrexate, Leucovorin, 5-Fluorouracil, and Hydroxyurea Flashcards
What are the substrates for thymidine synthetase?
dUMP and tetrahydrofolate
The reaction that produces thymidine (dTMP) changes tetrahydrofolate to _____________.
dihydrofolate; it also removes one methyl group, because thymidine is just uracil with a methyl group
(Think of the guy removing the C-shaped sushi – representing the single carbon – knocking off the two leaves. Tetrahydrofolate is represented by four leaves, because folate = foliage.)
Tetrahydrofolate is regenerated by ___________.
the enzyme dihydrofolate reductase (represented by the sushi masters adding two more leaves and one sushi back to the boat with only two leaves)
What drug is an irreversible inhibitor of dihydrofolate reductase?
Methotrexate (represented by the methotrexate meatstick that has irreversibly interrupted the sushi cycle)
True or false: methotrexate is specific to the S phase.
True. While it will disrupt DNA anytime, it is most deleterious during the S phase.
Other than cancer, in what disorders is methotrexate used?
Psoriasis (represented by the silver-plaque protective gear that the teens who are stealing meatsticks are wearing) Abortions of intra- and extra-uterine pregnancies (uterus backpack) Hydatidiform moles (mole keychain on uterus backpack) Rheumatoid arthritis (bone lantern)
What are the side effects of methotrexate?
Myelosuppression (old man spilling cells from the bone-shaped platter)
Megaloblastic anemia
Pulmonary fibrosis (lung-shaped bonsai)
Hepatotoxicity (liver-shaped stain on chef’s apron)
Alopecia (bald chef)
Mucositis (guy burning his mouth with a meatstick fresh off the hot grill)
There is a drug that can rescue someone from excessive methotrexate use. What is it?
Leucovorin (folinic acid): a folate analog that does not need dihydrofolate reductase
(Think of the LucKy cat: felinic acid.)
How does 5-fluorouracil work?
It forms a complex with thymidylate synthase and tetrahydrofolate and prevents the reaction from completing (just like the FULl patron waving FIVE fingers to stop the other patron from grabbing another C-shaped sushi).
5FU also inhibits DNA synthesis directly.
What are the side effects of 5FU?
GI upset (potent!), myelosuppression, and photosensitivity
(Think of the guy vomiting, having diarrhea, and being PHOTOgraphed in a sensitive state; also, he’s next to the waiter spilling the bone plate.)
True or false: leucovorin can help with the side effects of 5FU.
False. 5FU works by a different mechanism.
What is the mechanism of hydroxyurea?
It inhibits ribonucleotide reductase (which converts UDP to dUDP; all of the deoxyribonucleotides come from dUDP, so DNA synthesis is impaired).
(Think of the mom running to get her kids out of the HYDRO-ROCK zen garden and how she disrupts the U Dining in; Please sign in sign.)
Why does hydroxyurea help with sickle cell anemia?
Because it stimulates the production of fetal hemoglobin, which is normal in those with sickle cell.
