Chemotherapy IV: Anti-metabolites Flashcards Preview

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Flashcards in Chemotherapy IV: Anti-metabolites Deck (41):
1

Methotrexate MOA

Binds to dihydrofolate reductase decreasing tetrahydrofolate conversion from folic acid, causing cessation of nucleic acid synthesis

Cell cell specific (s phase)

2

How does polyglutamation effect methotrexate?

Slows methotrexate exit from cell

3

What can you administer to rescue the cell from cytotoxicity of methotrexate?

Tetrahydrofolate (leucovorin)
(only if not polyglutamated!)

4

Methotrexate SE

Nausea, vomiting, stomatitis, myelosuppression

5

In which patients should you dose reduce methotrexate?

Renal insufficiency

6

Which drugs can you administer intrathecally?

Methotrexate, cytosine arabinoside (cytarabine)

7

What color is methotrexate?

Yellow

8

Methotrexate indication

Lymphoma, leukemia, brain tumors, breast cancer, rheumatoid arthritis, psoriasis

9

Which drugs can potentiate the toxicity of Methotrexate and why?

ASPIRIN, PENICILLINS, SULFONAMIDES, PROBENECID


Aspirin, sulfonamides, penicillins (protein bound)

Aspirin, penicillins (all excreted in kidney as salt of weak acid- block excretion of MTX)

Probenecid blocks the organic acid transport system, interferes with excretion

10

When is methotrexate contraindicated?

Ascites
Pleural effusions
Renal insufficiency

11

How can you promote the excretion of Methotrexate?

Alkalinize urine (give IV or oral Na bicarbonate) >= 7 before administration

12

Is methotrexate able to penetrate the CNS?

Yes at high doses- can provide protection to CNS against tumor spread

13

How should methotrexate be administered?

-Alkalize urine (>7)
-High dose methotrexate (3-8 g/m2)
-IV/oral Leucovorin rescue (every 6 hours)
-Stop rescue when MTX is

14

Pemetrexed MOA

Inhibition of thmidylate synthase

15

Pemetrexed SE

MYELOSUPPRESSION = d-l
Rash, stomatitis, diarrhea, hand foot syndrome

16

What can you pretreat with to prevent myelosuppression associated with Pemetrexed?

Vitamin B-12
Oral Folic Acid

17

Pemetrexes Indication

Lung cancer
Mesothelioma

18

Cytosine Arabinoside (cytarabine) MOA

Pyrimidine analog
Inhibits DNA polymerase and chain elongation

19

Cytosine Arabinoside (cytarabine) SE

MYELOSUPRESSION
nausea, vomiting, hair loss, stomatitis, hepatic toxicity

20

Cytosine Arabinoside (cytarabine) Indication

Leukemia (AML)

"cancer" meningitis

21

Cytosine Arabinoside (cytarabine) has schedule dependent cytotoxicity, short half-life and is cell cycle specific... how should you administer?

3+ 7 regimen for AML

3 days of IV anthracycline

7 days of continuous cytosine arabinoside

22

What are the SE of high dose cytosine arabinoside?

Myelosuppression, cerebellar toxicity, conjunctivitis

23

What is an absolute indication to stop cytosine arabinoside?

cerebellar toxicity

24

Gemcitabine SE

MYELOSUPPRESSION

25

Gemcitabine Indication

Pancreas cancer
Lung cancer

26

5- Fluorouracil MOA

Pyrimidine antagonist
S phase specific

27

5- Fluorouracil SE

Nausea, vomiting, stomatitis, rash, diarrhea, and myelosuppresion

Hyperpigmentation of palms

Photosensitivity

Coronary artery vasospasm, cerebellar toxicity (rare)

Excess lacrimation, hand-foot syndrome

28

What drug enhances the cytotoxicity of 5-FU?

Leucovorin

5-FDUMP + luecovorin form strong inhibitory complex with thymidylate synthase > thymineless death!

29

What are the differences in effect of leucovorin on Methotrexate vs. 5-FU?

Leucovorin enhances the cytotoxicity of 5-FU and GI toxicity
Diminishes the toxicity/cytotoxicity of methotrexate

30

What mutation can cause a patient to experience severe toxicity when given 5-FU?

Deficient in DPD (dihydropyrimidine dehydrogenase)

Autosomal recessive (3-5%)

31

5-FU indication

breast, head, neck cancers
GASTROINTESTINAL CANCER

Radiation sensitizer (pancreas, rectal cancer)

32

Capecitabine MOA

Prodrug of 5-FU (hydrolyze to active form by thymidine phosphorylase...more of this in tumor cells > normal cells!)

33

Capecitabine Administration

ORAL!

Can replace IV 5-FU

34

Capecitabine Indication

Gastrointestinal tract malignancies

Breast cancer

35

Capecitabine SE

Rash
HAND FOOT SYNDROME
DIARRHEA
stomatitis

36

6-Mercaptopurine MOA

Inhibits enzymes needed for purine nucleotide synthesis'

S-phase specific

37

Which enzyme in the body will metabolize 6-Mercaptopurine to the inactive form?

Xanthine oxidase

(Inhibited by allopurinol)

38

What should you do to the dose of 6-Mercaptopurine when co-administered with allopurinol?

Dose reduce 50-75%

39

6-Mercaptopurine SE

MYELOSUPRESSION= d-l

40

6-Mercaptopurine Indication

Childhood Leukemia

41

6-thioguanine and allopurinol

Can be used at full dose because deamination does not involve xanthine oxidase