Antimetabolites

Question 1

methotrexate (MTX) general

Answer 1

antimetabolite, folate analog
most widely used
usually given orally

Question 2

MTX MOA

Answer 2

folic acid antagonist; inhibits dihydrofolate reductase (DHFR) blocking thymidine and purine biosynthesis

Question 3

MTX TU

Answer 3

childhood ALL, choriocarcinoma
in combo for Burkitts lymphoma
breast, ovary, head and neck, bladder
intrathecal for meningeal leukemia
high-dose for osteosarcoma

Question 4

MTX Tox

Answer 4

myelosuppression
GI (oral ulceration, stomatitis)
renal tox (can crystallize in urine)
long term use - hepatic fibrosis, cirrhosis

Question 5

MTX resistance

Answer 5

decreased drug uptake, DHFR amplification, decreased affinity of DHFR for MTX

Question 6

pemetrexed general/MOA

Answer 6

antimetabolite, folate analog;

inhibits DHFR, thymidylate synthetase

Question 7

pemetrexed TU

Answer 7

colon, mesothelioma, NSCLC, pancreatic

Question 8

leucovorin

Answer 8

rescue to prevent MTX toxicity; N-5-formyltetrahydrofolate
given several hours after otherwise lethal dose of MTX
hypothesis is tumor cells can’t uptake folinic acid, but normal cells can and therefore bypass the need for DHFR

Question 9

5-fluorouracil (5-FU) general

Answer 9

antimetabolite, pyrimidine analog
prodrug, enzymatically converted to f-FdUMP
must be IV bc of gut toxicity and rapid metabolic degradation

Question 10

5-FU MOA

Answer 10

5-FdUMP inhibits thymidylate synthetase - no thymidine

5-FUTP incorporated into RNA, inhibiting RNA synthesis

Question 11

5-FU TU

Answer 11

in combos for breast, colorectal, gastric, head and neck, cervical, pancreatic
topical for basal cell carcinoma

Question 12

capecitabine

Answer 12

prodrug of 5-FU used in breast and colorectal

Question 13

5-FU Tox

Answer 13

hand-foot syndrome = erythema, sensitivity of palms and soles
cardiac toxicity - acute chest pain
anorexia, nausea, mucosal ulceration, stomatitis, diarrhea, thrombocytopenia, anemia

Question 14

cytarabine (Ara-C) general/MOA

Answer 14

antimetabolite, pyrimidine analog

analog of 2’-deoxycytidine; converted to Ara-CMP and Ara-CTP, which competes with dCTP and inhibits DNA synthesis

Question 15

cytarabine TU

Answer 15

most effective Tx for AML

also used in ALL and blast phase CML

Question 16

cytarabine Tox

Answer 16

severe myelosuppression
GI toxicity (ulceration, stomatitis, diarrhea)

Question 17

gemcitabine general/MOA

Answer 17

antimetabolite, pyrimidine analog
difluoro analog of deoxycycytidine (dFdC)
dFdCDP - inhibits ribonucleotide reductase
dFdCTP - competes with dCTP for DNA synthesis

Question 18

gemcitabine TU

Answer 18

better than Ara-C for solid tumors
first-line Tx in pancreatic cancer
NSCLC, ovarian, bladder, esophageal, head and neck

Question 19

gemcitabine Tox

Answer 19

myeolsuppression, flu-like symptoms

Question 20

6-mercaptopurine (6-MP) general/MOA

Answer 20

antimetabolite, purine analog
prodrug, conversion by HGPRT to ribonucleotide TIMP
inhibits 1st step in de novo synthesis of purine bases
blocks formation of AMP and XMP from IMP
converted to thio-GMP, incorporated into DNA/RNA and inhibits it

Question 21

6-MP TU

Answer 21

primarily to maintain remission in ALL

Question 22

6-MP Tox

Answer 22

bone marrow suppression, hepatotoxicity in long-term use

Question 23

6-MP resistance

Answer 23

decreased HGPRT expression

decreased drug transport

Question 24

6-MP drug interaction

Answer 24

allopurinol inhibits XO, needed to inactivate 6-MP

must decrease dose of 6-MP to avoid accumulation and exacerbation of toxicities