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Phar 509 > Antimetabolites used in Practice > Flashcards

Antimetabolites used in Practice Flashcards

1
Q

What are the folate antimetabolites

A

Methotrexate and Pemetrexed

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2
Q

What is the main Purine antimetabolite

A

6-MP

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3
Q

What are the pyrimidine antimetabolites

A

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

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4
Q

What is the MOA of methotrexate

A

Inhibits DHFR there for not allowing for purine or pyrimidine synthesis

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5
Q

What are the doses for methotrexate

A

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

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6
Q

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

A

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

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7
Q

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

A

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

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8
Q

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

A

True

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9
Q

What drug-drug interactions with mexthotrexate compete for excretion

A

NSAIDS, probenecid, penicllins

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10
Q

What drug-drug interactions delay clearance of methotrexate

A

PPIs

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11
Q

What drug-drug interactions would display methotrexate from protiens

A

Salicylates and sulfonamides

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12
Q

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

A

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

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13
Q

How is the urine alkilized

A

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

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14
Q

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

A

Renal Tubular Necrosis, precipitation of methotrexate metabolites in renal tubules

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15
Q

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

A

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

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16
Q

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

A

True

17
Q

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

A

IV/ Myelosuppresion and mucositis

18
Q

What are the most prominent adverse effects of methotrexate

A

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

19
Q

What is the last resort for a methotrexate overdose, moa

A

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

20
Q

What are the two ways to do intrathecal methotrexate delivery

A

Lumbar puncture, Ommaya reservoir (MUST BE PRESERVATIVE FREE)

21
Q

What is the MOA of pemetrexed

A

Inhibits DHFR, Thymidylate synthetase, and GRAFT

22
Q

What is the main contraindication of pemetrexed

A

CrCl less than 45ml/min

23
Q

How should NSAIDs be used if there is concurrent pemetrexeduse

A

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

24
Q

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

A

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

25
Q

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

A

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

26
Q

What is the dosing for 6-MP

A

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)

27
Q

What are the drug interactions of 6-MP

A

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

28
Q

When would the dose be adjusted for 6-MP

A

Renal/Hepatic dysfucntion, meyelosuppresion, TPMT deficiencies

29
Q

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

A

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

30
Q

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

A

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

31
Q

What enzyme metabolizes 5-FU

A

Dihydropyrimidine dehydrogenase (DPD)

32
Q

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

A

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

33
Q

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

A

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

34
Q

What are the two biggest side effects of capecitabine

A

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

35
Q

What are the drug drug interactions of capecitabine

A

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

36
Q

What are the pre-medications for cytarabine

A

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

37
Q

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

A

True

38
Q

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

A

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

Phar 509 (22 decks)

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