Hematology & Oncology: Antimetabolites

Front 1

3 classes of antimetabolite agents?

Back 1

-Folate analogs
-Pyrimidine analogs
-Purine analogs

Front 2

Folice acid analogs?

Back 2

Methotrexate and pemetrexed

Front 3

Pyrimidine analogs?

Back 3

-5-FU
-Capecitabine
-Cytarabine
-Gemcitabine
-Azacytidine
-Decitabine

Front 4

Purine analogs?

Back 4

-6-mercaptopurine
-Fludarabine
-Pentostatin
-Cladribine
-Clofarabine
-Nelarabine

Front 5

What phase of the cell cycle is effected by antimetabolite drugs?

Back 5

All antimetabolites are S-phase specific

Front 6

Purines?

Back 6

Adenine and Guanine

Front 7

Pyrimidines?

Back 7

Thymine and Cytosine

Front 8

Inhibition of thymidine synthesis via thymidylate synthase selectively inhibits __________?

Back 8

DNA synthesis over RNA synthesis

Front 9

Ribonucleotide reductase inhibitor?

Back 9

hydroxyurea

Front 10

Methotrexate competitively and reversibly inhibits __________?

Back 10

dihydrofolate reductase (DHFR)

Front 11

The primary target of methotrexate is?

Back 11

dihydrofolate reductase (DHFR)

Front 12

Methotrexate and Pemetrexed also inhibit purine synthesis through inhibition of?

Back 12

-Thymidylate synthase (TS) -Glycinamide ribonucleotide transferase (GARFT)
-AICAR transformylase

TS, GAR transformylase,
AICAR transformylase, and
DHFR

Front 13

Methotrexate requires IV infusion 30 mg/m2 on days 3 and 10 every 3 weeks, or 120-200 mg/m2 day 8 and 15 every 3-4 weeks, or 400 mg/m2 every 4 weeks for 3 cycles, or 1-1.5 g/m2 every 3 weeks. Which cancers are treated with MTX?

Back 13

acute lymphoblastic leukemia (ALL), lymphoma and breast cancer

Front 14

Toxicities associated with methotrexate include?

Back 14

-myleosupporession
-GI toxicity (stomatitis, diarrhea)
•hepatotoxicity high dose

Front 15

Methotrexate PK considerations?

Back 15

dose reduction for renal impairment

Front 16

Rescue treatment for MTX toxicity?

Back 16

Leucovarin ((folinic acid, N5-formyl FH4), a reduced folate coenzyme.

Front 17

Advantage of pemetrexed over MTX?

Back 17

-more potent inhibitor of TS and GAR transformylase
-better transported into tumor cells due to lipophilicity

Front 18

Pemetrexed is dosed IV 500 mg/m2 on day 1 of each 21-day cycle and is used to treat?

Back 18

Lung cancer

Front 19

Clinical toxicities associated with pemetrexed?

Back 19

Myelosuppression and GI toxicity (stomatitis, diarrhea)

Front 20

MOA of 5-Fluorouracil?

Back 20

• incorporated into both DNA and RNA
• blocks thymidylate synthesis
• S-phase-specific

Front 21

5-Fluorouracil is dosed 300-3,000 mg/m2 IV in a weekly bolus or continuous infusion and is used to treat?

Back 21

Colorectal and breast cancer

Front 22

coadministration of _______ enhances the efficacy of 5-FU?

Back 22

Leucovarin

Front 23

Clinical toxicities associated with 5-FU include?

Back 23

- GI toxicity (stomatitis and diarrhea)
- myelosuppression
(less toxicities with iv infusion than bolus)

Front 24

PK considerations of 5-FU?

Back 24

metabolized in many tissues, particularly the liver, but no dose
reduction for hepatic impairment is required

Front 25

Prodrug of 5-FU?

Back 25

Capecitabine

Front 26

Capecitabine is dosed at 2500 mg/m2 PO twice daily for 2 weeks at 3 week intervals and is used to treat?

Back 26

Colorectal and breast cancer

Front 27

Clinical toxicities associated with Capecitabine?

Back 27

-Myelosuppression
-GI toxicity (N/V)
-Hand/Foot syndrome

Front 28

Cytosine analogs can be identified by?

Back 28

an amine group at position 4 and a keto group at position 2

Front 29

Cytarabine is a cytosine analog that competes with___ for DNA incorporation, thus causing terminal
differentiation of leukemic
cells.

Back 29

Deoxycytidine triphosphate (dCTP)

Front 30

Cytarabine dosing:
100 mg/m2 infusion, every 12 hours for 5-7 days or 100-200 mg/m2 infusion for 5-7 days or _________?

Back 30

DEPOCYT: intrathecal formulation for sustained release in CSF

Front 31

Cytarabine is used to treat?

Back 31

AML, ALL and CML

Front 32

Clinical toxicities associated with Cytarabine?

Back 32

-Myelosuppression
-GI toxicity
-CNS toxicity with high dose or intrathecal deliver

Front 33

Gemcitabine competes with dCTP
for DNA incorporation and is also an
inhibitor of?

Back 33

DNA polymerase

Front 34

Gemcitabine also inhibits?

Back 34

ribonucleotide reductase

Front 35

Gemcitabine is dosed at 1-1.2 g/m2 through weekly infusion for 3 weeks every 4 weeks and is used to treat?

Back 35

breast and lung cancer

Front 36

Clinical toxicities associated with Gemcitabine include?

Back 36

-myelosuppression
-hepatotoxicity
-GI toxicity (N/V)

Front 37

_______inhibits methyltransferase, causing demethylation in DNA?

Back 37

Azacitidine

Front 38

Azacitidine is dosed SC 75 mg/m2/day for 7 days every 4 weeks and is used to treat?

Back 38

acute myelogenous leukemia (AML)

Front 39

Clinical toxicities associated with Azacitidine include?

Back 39

• myelosuppression
• GI toxicity

Front 40

The other antimetabolite that inhibits methyltransferase, causing
demethylation in DNA?

Back 40

Decitabine

Front 41

Decitabine is Azacitidine without _____?

Back 41

1 OH- group

Front 42

Decitabine is dosed 5-15 mg/m2/day IV for 5 days/week for 2 weeks every 6 weeks an is used to treat?

Back 42

acute myelogenous leukemia (AML) and chronic myelogenous (or myeloid) leukemia (CML)

Front 43

MOA of purine analogs?

Back 43

-inhibits de novo synthesis of purine
bases and nucleotides
-triphosphate derivatives are
incorporated into DNA

Front 44

6-Mercaptopurine is dosed IV 50-100 mg/m2 daily with a lower maintenance dose and is used to treat ______?

Back 44

Acute lymphoblastic leukemia (ALL)

Front 45

Clinical toxicities with 6-Mercaptopurine include?

Back 45

Myelosuppression and hyperuricemia

Front 46

Hyperuricemia associated with 6-Mercaptopurine is treated with?

Back 46

Allopurinol, which inhibits
xanthine oxidase to reduce the accumulation of uric
acid and facilitates a dose reduction by 75%

Front 47

6-Mercaptopurine also requires?

Back 47

dose reduction for renal
impairment

Front 48

6-Mercaptopurine is a ___________ analog?

Back 48

adenosine

Front 49

Fludarabine is an adenosine analog that is resistant to_______?

Back 49

adenosine deaminase

Front 50

All purine analogs cause CNS toxicities except?

Back 50

6-Mercaptopurine

Front 51

The purine analog that causes hepatotoxicity?

Back 51

Pentostatin

Front 52

Pentostatin also requires?

Back 52

dose reduction for
renal impairment

Front 53

Purine analog based on guanine?

Back 53

Nelarabine

Front 54

Purine analogs with halogen groups?

Back 54

Cladribine and Clofarabine

Front 55

Antimetabolite that inhibits ribonucleotide reductase?

Back 55

hydroxyurea

Front 56

Hydroxyurea requires?

Back 56

dose reduction for renal impairment

Front 57

Only clinical toxicity associated with hydroxyurea?

Back 57

Myelosuppression