Pyrimidine Analog Antimetabolites Flashcards
List pyrimidine antimetabolites
Fluorouracil (5-FU)
Capecitabine (Xeloda; oral prodrug of 5-FU)
Cytarabine
Gemcitabine
MOA of pyrimidine antimetabolites
Inhibit pyrimidine DNA synthesis during the S PHASE of the cell cycle
Q. what can be given to 5-FU to increase its efficacy
Q. what is the L-isomer called
- Leucovorin
- levoleucovorin
What are the safety concerns for pyrimidine antimetabolites
- Hand-Foot Syndrome (HFS) = Palmar Plantar Erythrodysenthesia
- Diarrhea
- Mucositis
- DPD (dihydropyrimidine dehydrogenase deficiency): Increased risk of SEVERE TOXICITY (myelosuppression, GI toxicity)
- Drug interactions with Warfarin (can significantly increase INR)
safety concerns for cytarabine specifically
- Neurotoxicity
- Cytarabine syndrome occurring hours following administration (fever, weakness, chest pain, bone pain)
Q. prevention strategies for DPD
Q. tx strategies
- pharmacogenomic testing (not routine)
- ANTIDOTE: use URADINE TRIACETATE (Vistogard) within 96 hours for overdose or early onset toxicity
- symptomatic care specific to toxicity
what monitoring parameters should be observed for HFS
painful erythema, skin peeling
monitoring parameters for mucositis
PAINFUL MOUTH ULCERS, difficulty eating/drinking, s/sx of infection (thrush)
what prevention strategies can be implemented for mucositis
- good ORAL HYGIENE (use soft toothbrush)
- hold ice chips in mouth (can cause local vasoconstriction, leading to decreased delivery of mucotoxic agents)
- FREQUENT rinsing with BLAND RINSES (sodium bicarbonate or sodium chloride solns)
Tx for mucositis
- good oral hygiene and frequent rinsing
- symptomatic care (VISCOUS LIDOCAINE 2%, MAGIC MOUTHWASH, systemic analgesics for pain)
- thrush tx (NYSTATIN ORAL SUSPENSION, CLOTRIMAZOLE TROCHES) if indicated
- parenteral nutrition or IV hydration may be needed in some cases
HFS management strategies
- Limit or modify daily activities to reduce pressure to hands and feet
- Avoid heat exposure to hands and feet
- Cold compresses may provide temporary relief
- use EMOLLIENTS (ammonium lactate, urea cream, Aquaphor) to retain moisture in hands and feet
- topical steroids (clobetasol) and pain meds can lessen inflammation and pain
- dose modifications or therapy interruptions may be required for severe cases
prevention strategies for neurotoxicity in cytarabine
dose modifications for select patients (older age, pre-existing renal/hepatic dysfunction)
prevention/ treatment strategies for cytarabine syndrome
systemic steroids
prevention strategies with drug interactions with warfarin
frequent INR monitoring
What antidote is used to treat DPD
URIDINE TRIACETATE (Vistogard)
