5-fluorouracil Flashcards
What is fluorouracil?
-pyrimidine analogue which is an antineoplastic antimetabolite.
Interferes with DNA synthesis by blockng thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid
What class of compounds does fluorouracil belong to?
antimetabolites
What are other drugs in the same class as fluorouracil?
methotrexate
azacitidine
thioguanine
What is fluorouracil indicated for?
- palliative treatment of malignant tumours esp. breast, colon, rectum
- treatment of gastric, primary hepatic, pancreatic, uterine, ovarian, bladder cancer
What is the role of fluorouracil in breast/porstate cancer therapy?
Use only when other proven measures fail or are impractical
What is the dose of fluorouracil given?
determined using a variety of methods incl. body surface area/bodyweight.
What is the mechanism of action of fluorouracil?
- binding of the deoxyribonucleotide of the drug and the folate cofactor to thymidylate synthase to form covalently bound ternary complex
- results in inhibition of thymidylate formation from uracil.
- inhibits DNA and RNA synthesis and cell death.
What are the relevant PK and PD parameters with fluorouracil?
PD: prevents building blocks of DNA (purine or pyrimidine) from being incorporated into DNA during the S phase of cell cycle which stops the normal development and division.
PK: about 28-100% absorbed and 8-12% bound to proteins
Hepatically metabolised
7-20% of drug excreted unchanged in urine
half life of 10-20minutes
What are the adverse effects with fluorouracil use?
myelosuppression, mucositis, cerebella syndrome
on prolonged infusion, a desquamative hand-foot syndrome may occur
What are the cautions associated with fluorouracil use?
special handling required pregnancy class D
What are the drug interactions with fluorouracil use?
avoid concurrent use with BCG vaccines
toxicity of fluorouracil is increased by metronidazole
