Antimetabolites used in Practice

Question 1

What are the folate antimetabolites

Answer 1

Methotrexate and Pemetrexed

Question 2

What is the main Purine antimetabolite

Answer 2

6-MP

Question 3

What are the pyrimidine antimetabolites

Answer 3

5-FU, Capecitabine, Trifluridine/tipiracil, Cytarabine, Gemcitabine

Question 4

What is the MOA of methotrexate

Answer 4

Inhibits DHFR there for not allowing for purine or pyrimidine synthesis

Question 5

What are the doses for methotrexate

Answer 5

Low dose (less than 50mg/m2), Intermediate dose (50-500mg/m2), High dose (greater than 500 mg/m2)

Question 6

T/F: Patients are more likely to receive low dose and mid dose methotrexate to treat cancer

Answer 6

False: Patients will recieve high dose methotrexate IV in order to treat cancer

Question 7

What should the pH of a patient’s urine be if they are taking methotrexate, why

Answer 7

Basic (alkalinzation), Aides in the elimination of the drug

Question 8

T/F: Before patients take methotrexate they should be fully hydrated with a high urine output with NO ascites

Answer 8

True

Question 9

What drug-drug interactions with mexthotrexate compete for excretion

Answer 9

NSAIDS, probenecid, penicllins

Question 10

What drug-drug interactions delay clearance of methotrexate

Answer 10

PPIs

Question 11

What drug-drug interactions would display methotrexate from protiens

Answer 11

Salicylates and sulfonamides

Question 12

When hydrating patients for methotrexate what liquids are given, how much, when

Answer 12

NaCl 0.9% or Dextrose 5%, 100-150 ml/hr, 6-12 hours before methotrexate dose and continued for 24 hours post dose completion

Question 13

How is the urine alkilized

Answer 13

Add 100-150 mEQ of sodium bicarbonate to each liter of hydration OR sodiumc bicarbonate orally every 6 hours

Question 14

What is the biggest concern of the kidneys when using methotrexate, how does it occur

Answer 14

Renal Tubular Necrosis, precipitation of methotrexate metabolites in renal tubules

Question 15

What drug is given as rescue for methotrexate, why is it given, when is it given

Answer 15

Leucovorin (reduced form of folic acid), replenishes supply of folate metabolites in normal cells BUT NOT malignant cells, 24 hours after high dose methotrexate

Question 16

T/F: The longer the wait for leucovorin distribution after methotrexate the more likely the dose will need to be higher

Answer 16

True

Question 17

How is leucovorin administered, what toxicities are reducued from giving leucovorin after methotrexate

Answer 17

IV/ Myelosuppresion and mucositis

Question 18

What are the most prominent adverse effects of methotrexate

Answer 18

Leuopenia, thrombocytopenia, renal tubular necrosis, transaminitis, N/V and mucositis

Question 19

What is the last resort for a methotrexate overdose, moa

Answer 19

Glucarpidase, bacterial enzyme that hydrolyzes folic acid and antifolates (including leucovorin/must wait 2 hours)

Question 20

What are the two ways to do intrathecal methotrexate delivery

Answer 20

Lumbar puncture, Ommaya reservoir (MUST BE PRESERVATIVE FREE)

Question 21

What is the MOA of pemetrexed

Answer 21

Inhibits DHFR, Thymidylate synthetase, and GRAFT

Question 22

What is the main contraindication of pemetrexed

Answer 22

CrCl less than 45ml/min

Question 23

How should NSAIDs be used if there is concurrent pemetrexeduse

Answer 23

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

Question 24

In order to combat myelosuppression seen in pemetrexed use what precautions should be taken

Answer 24

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

Question 25

What is another large adverse effect of premetrexed that can be combated, how

Answer 25

Rash, dexamethasone 4 mg by mouth twice daily for 3 days starting the day before chemotherapy

Question 26

What is the dosing for 6-MP

Answer 26

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)

Question 27

What are the drug interactions of 6-MP

Answer 27

Azathioprine, tacrolimus, allopurinol, febuxostat, 5- aminosalicylic acid derivatives

Question 28

When would the dose be adjusted for 6-MP

Answer 28

Renal/Hepatic dysfucntion, meyelosuppresion, TPMT deficiencies

Question 29

Why is azathioprine a drug-drug interaction with 6-MP, allopurinol and febuxostat

Answer 29

Azathioprine is converted to 6-MP without enzymes, inhibit xanthine oxidase which is an enzyme that metabolizes 6-MP to an inactive metabolite

Question 30

What is the side effects of bolus administration, continous infusion, managment of continous infusion side effect

Answer 30

Myelosuppresion, mucositis, diarrhea/ Hand foot-syndrome (avoid hot water, moisturize hand and feet, analgesics)

Question 31

What enzyme metabolizes 5-FU

Answer 31

Dihydropyrimidine dehydrogenase (DPD)

Question 32

What drug is used with 5-FU to increase cytotoxic activity, why

Answer 32

Leucovorin (prior to bolus), incfreases the binding affinity of 5-FU to thymidylate synthetase

Question 33

What is the prodrug of 5-FU, dosing, contraindication

Answer 33

Capecitabine, BID for 14 days then every 21 days (1000MG/M2), CrCl less than 30

Question 34

What are the two biggest side effects of capecitabine

Answer 34

Hand and foot syndrome and diarrhea (loperamide and fluids to reduce)

Question 35

What are the drug drug interactions of capecitabine

Answer 35

Warfarin (BBW: increases anticoagulation effect), phenytoin: increases 5-FU levels, CYP2C9 substrates

Question 36

What are the pre-medications for cytarabine

Answer 36

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

Question 37

T/F: Gemciatabine is more toxic over time because it is saturable

Answer 37

True

Question 38

Which anti-pyrimidine is used in relapsed metastatic colorrectal cancer, side effects, dosing

Answer 38

Trifluridine/Tipiracil/ myelosuppression N/V/D, fatigue and weakness/ Monday through Friday two weeks in a row