Antimetabolites used in Practice Flashcards
What are the folate antimetabolites
Methotrexate and Pemetrexed
What is the main Purine antimetabolite
6-MP
What are the pyrimidine antimetabolites
5-FU, Capecitabine, Trifluridine/tipiracil, Cytarabine, Gemcitabine
What is the MOA of methotrexate
Inhibits DHFR there for not allowing for purine or pyrimidine synthesis
What are the doses for methotrexate
Low dose (less than 50mg/m2), Intermediate dose (50-500mg/m2), High dose (greater than 500 mg/m2)
T/F: Patients are more likely to receive low dose and mid dose methotrexate to treat cancer
False: Patients will recieve high dose methotrexate IV in order to treat cancer
What should the pH of a patient’s urine be if they are taking methotrexate, why
Basic (alkalinzation), Aides in the elimination of the drug
T/F: Before patients take methotrexate they should be fully hydrated with a high urine output with NO ascites
True
What drug-drug interactions with mexthotrexate compete for excretion
NSAIDS, probenecid, penicllins
What drug-drug interactions delay clearance of methotrexate
PPIs
What drug-drug interactions would display methotrexate from protiens
Salicylates and sulfonamides
When hydrating patients for methotrexate what liquids are given, how much, when
NaCl 0.9% or Dextrose 5%, 100-150 ml/hr, 6-12 hours before methotrexate dose and continued for 24 hours post dose completion
How is the urine alkilized
Add 100-150 mEQ of sodium bicarbonate to each liter of hydration OR sodiumc bicarbonate orally every 6 hours
What is the biggest concern of the kidneys when using methotrexate, how does it occur
Renal Tubular Necrosis, precipitation of methotrexate metabolites in renal tubules
What drug is given as rescue for methotrexate, why is it given, when is it given
Leucovorin (reduced form of folic acid), replenishes supply of folate metabolites in normal cells BUT NOT malignant cells, 24 hours after high dose methotrexate
T/F: The longer the wait for leucovorin distribution after methotrexate the more likely the dose will need to be higher
True
How is leucovorin administered, what toxicities are reducued from giving leucovorin after methotrexate
IV/ Myelosuppresion and mucositis
What are the most prominent adverse effects of methotrexate
Leuopenia, thrombocytopenia, renal tubular necrosis, transaminitis, N/V and mucositis
What is the last resort for a methotrexate overdose, moa
Glucarpidase, bacterial enzyme that hydrolyzes folic acid and antifolates (including leucovorin/must wait 2 hours)
What are the two ways to do intrathecal methotrexate delivery
Lumbar puncture, Ommaya reservoir (MUST BE PRESERVATIVE FREE)
What is the MOA of pemetrexed
Inhibits DHFR, Thymidylate synthetase, and GRAFT
What is the main contraindication of pemetrexed
CrCl less than 45ml/min
How should NSAIDs be used if there is concurrent pemetrexeduse
CrCl between 45 and 79 use with caution, Short Half life NSAIDS should be avoided 2 days before and 2 days after, Long half life NSAIDs should be avoid 5 days before and 2 days after
In order to combat myelosuppression seen in pemetrexed use what precautions should be taken
ANC count greater than 1500 cells prior to cycle initiation, start B12 1000 ,cg IM one week prior to therapy then every 9 weeks, Folic acid every day
What is another large adverse effect of premetrexed that can be combated, how
Rash, dexamethasone 4 mg by mouth twice daily for 3 days starting the day before chemotherapy
What is the dosing for 6-MP
50-75 mg/m2 by mouth daily, give 50 mg tablets and round the weekly dose to the nearest 50 mg (give on an empty stomach)
What are the drug interactions of 6-MP
Azathioprine, tacrolimus, allopurinol, febuxostat, 5- aminosalicylic acid derivatives
When would the dose be adjusted for 6-MP
Renal/Hepatic dysfucntion, meyelosuppresion, TPMT deficiencies
Why is azathioprine a drug-drug interaction with 6-MP, allopurinol and febuxostat
Azathioprine is converted to 6-MP without enzymes, inhibit xanthine oxidase which is an enzyme that metabolizes 6-MP to an inactive metabolite
What is the side effects of bolus administration, continous infusion, managment of continous infusion side effect
Myelosuppresion, mucositis, diarrhea/ Hand foot-syndrome (avoid hot water, moisturize hand and feet, analgesics)
What enzyme metabolizes 5-FU
Dihydropyrimidine dehydrogenase (DPD)
What drug is used with 5-FU to increase cytotoxic activity, why
Leucovorin (prior to bolus), incfreases the binding affinity of 5-FU to thymidylate synthetase
What is the prodrug of 5-FU, dosing, contraindication
Capecitabine, BID for 14 days then every 21 days (1000MG/M2), CrCl less than 30
What are the two biggest side effects of capecitabine
Hand and foot syndrome and diarrhea (loperamide and fluids to reduce)
What are the drug drug interactions of capecitabine
Warfarin (BBW: increases anticoagulation effect), phenytoin: increases 5-FU levels, CYP2C9 substrates
What are the pre-medications for cytarabine
Antiemetics prior to IV or SC, dexamethasone eye drops in both eyes every 6 hours during and for 2-7 days after completion of cytarabine
T/F: Gemciatabine is more toxic over time because it is saturable
True
Which anti-pyrimidine is used in relapsed metastatic colorrectal cancer, side effects, dosing
Trifluridine/Tipiracil/ myelosuppression N/V/D, fatigue and weakness/ Monday through Friday two weeks in a row
