Antimetabolites

Question 1

What is the MOA of Fluorouracil “5-FU”

Answer 1

• 5-FU is a prodrug which, upon metabolic activation to 5-fluorodeoxyuridine monophosphate (5F-dUMP), forms a “ternary complex” with thymidylate synthase (TS) and the reduced folate N5,N10-methylenetrahydrafolate
• The irreversible inhibition of TS causes dTMP production to halt, and cells die a “thymineless death” since they lack a critical nucleotide used in the synthesis of DNA

Question 2

Capecitabine (Xeloda)

Answer 2

Oral capecitabine (5-FU prodrug) is absorbed via the intestinal tract, the carbamate is then hydrolyzed in the liver by carboxylesterase to 5’-deoxy-5F-cytidine, then in the liver and tumor tissues by cytidine deaminase to 5’-deoxy-5F-uridine, and finally in the tumor by thymidine phosphorylase to 5-FU

Question 3

Hand foot syndrome

Answer 3

• Early signs: Erythema, numbness, tingling, dysesthesia, or paresthesia on palms/soles
• Later signs: Painful swelling, desquamation, ulceration or blistering
• Resolves rapidly with dose-reduction or discontinuation

Question 4

What are the treatment for hand-foot syndrome?

Answer 4

• Topical emollients and creams
• Immerse hands/feet in cool water
• Avoid extremes of temperature, pressure, and friction on the skin
• Cushion sore with soft pads
• Topical wound care and consultation with a dermatologist for blistering or ulceration

Question 5

Uridine triacetate

Answer 5

Uridine triacetate is a pyrimidine analog indicated for the emergency treatment of patients after a fluorouracil or capecitabine overdose within 96 hours following the end of fluorouracil or capecitabine administration
* If patient vomits within 2 hours of dose, give an extra dose ASAP

Question 6

What are the fluoropyrimidine analogues?

Answer 6

• Fluorouracil
• Capecitabine
• Uridine triacetate (not a metabolite)

Question 7

How do you prevent methotrexate toxicity to normal rapidly dividing tissues?

Answer 7

• Leucovorin rescue 24-36 hrs after admin

Question 8

How to prevent methotrexate-induced acute kidney injury?

Answer 8

• Solubility of methotrexate in aqueous solution is increased 5-8 fold when the pH is raised from 6 (acidic) to >= 7
• Methotrexate is less likely to crystallize at dilute concentrations
• Maintain a dilute urine (give IV fluids +- furosemide, if needed)
• give bicarb

Question 9

Glucarpidase

Answer 9

Carboxypeptidase enzyme that hydrolyzes the terminal glutamate from methotrexate
* Converts methotrexate to inactivate metabolite, DAMPA

Question 10

Which drugs are folate antagonist?

Answer 10

• Methotrexate
• Glucarpidase
• Pemetrexed

Question 11

What are the cytidine analogues?

Answer 11

• Cytarabine
• Gemcitabine
• Azacitabine
• Decitabine
• Decitabine/cedazuridine

Question 12

What are the purine analogs?

Answer 12

• Mercaptopurine
• Fludarabine phosphate