Drug Table - Antimetabolites

Question 1

Antimetabolites in general

Answer 1

Structural analogs of folic acid or of the
purine/pyramidine bases found in DNA; act
in S-phase (cell cycle specific)

Question 2

Antimetabolites list

Answer 2

Methotrexate (Trexall)
Pemetrexed (Alimta)
5-Fluorouracil (5-FU, Carac)
Cytarabine (AraC, Depocyt)
Gemcitabine (dFdC, Gemzar)
6-Mercaptopurine (Purinethol)

Question 3

Methotrexate (Trexall) class

Answer 3

Folate analogs

Question 4

Methotrexate (Trexall) mech

Answer 4

Inhibits dihydrofolate reductase (DHFR),
which converts dietary folate to
tetrahydrofolate (THF) needed for thymidine
and purine synthesis; given orally or
intrathecally

Question 5

Methotrexate (Trexall) Therapeutics

Answer 5

Childhood ALL and choriocarcinoma;
combination therapy for Burkitt's
lymphoma and carcinomas of breast,
ovary, head and neck, and bladder;
administered intrathecally for
meningeal leukemia and meningeal
metastases of tumors (can't cross
BBB); high-dose for osteosarcoma

Question 6

Methotrexate (Trexall) Imp Side effects

Answer 6

Renal toxicity (crystallization in
urine at high doses), hepatotoxicity
(long-term, fibrosis/cirrhosis),
reproductive (defective oogenesis
or spermatogenesis, abortion)

Question 7

Methotrexate (Trexall) Other side effects

Answer 7

Bone marrow
(myelosuppression,
spontaneous hemorrhage); GI
toxicity (oral ulceration,
stomatitis)

Question 8

Methotrexate (Trexall) Misc

Answer 8

Can use leucovorin to prevent toxic
effects of MTX, as healthy cells can
take it up a lot better than tumor cells

Question 9

Pemetrexed (Alimta) class

Answer 9

Folate analogs

Question 10

Pemetrexed (Alimta) Mech

Answer 10

Polyglutamate forms that inhibit THFdependent
enzymes (e.g., DHFR, TS);
metabolized to polyglutamate forms that
inhibit THF-dependent enzymes (e.g.,
DHFR, thymidylate synthase (TS))

Question 11

Pemetrexed (Alimta) Therapeutics

Answer 11

Colon cancer, mesothelioma, non-small

cell lung cancer, pancreatic cancer

Question 12

5-Fluorouracil (5-FU, Carac) class

Answer 12

Pyramidine analogs

Question 13

5-Fluorouracil (5-FU, Carac) Mech

Answer 13

5-FU is converted to active metabolites: 5-
FdUMP inhibits TS; 5-FdUTP incorporates
into RNA & interferes with RNA function;
prodrug [capesitabine] ribosylated and phophosrylated into
5-FdUMP

Question 14

5-Fluorouracil (5-FU, Carac) Therapeutics

Answer 14

Combination therapy for breast,
colorectal, gastric, head and neck,
cervical and pancreatic cancer;
topically for basal cell carcinoma

Question 15

5-Fluorouracil (5-FU, Carac) Imp Side Effects

Answer 15

Hand-foot syndrome (erythema,
sensitivity of palms and soles),
cardiac toxicity (acute chest pains)

Question 16

5-Fluorouracil (5-FU, Carac) Other side effects

Answer 16

Anorexia and nausea; mucosal
ulcerations, stomatitis, diarrhea;
thrombocytopenia and anemia

Question 17

5-Fluorouracil (5-FU, Carac) Misc

Answer 17

Leucovorin can potentiate effects of
5-FU; must be given IV (GI toxicity
and rapid degradation + metabolism
in gut and liver)

Question 18

Cytarabine (AraC, Depocyt) Class

Answer 18

Pyramidine

analogs

Question 19

Cytarabine (AraC, Depocyt) Mech

Answer 19

Ara-C converted by deoxycytidine kinase to
Ara-CMP –> Ara-CTP; terminates DNA
synthesis as Ara-CTP

Question 20

Cytarabine (AraC, Depocyt) Therapeutics

Answer 20

AML (most effective treatment), ALL

and blast phase CML

Question 21

Cytarabine (AraC, Depocyt) Other side effects

Answer 21

Severe myelosuppression
(leucopenia, thrombocytopenia,
anemia), GI tract toxicity
(ulceration, stomatitis, diarrhea)

Question 22

Gemcitabine (dFdC, Gemzar) class

Answer 22

Pyramidine

analogs

Question 23

Gemcitabine (dFdC, Gemzar) Mech

Answer 23

Converted to active metabolites: dFdCDP
inhibits ribonucleotide reductase (lowers
deoxyribonucleotide); dFdCTP incorporates
into DNA, terminating DNA synthesis

Question 24

Gemcitabine (dFdC, Gemzar) Therapeutics

Answer 24

Pancreatic cancer; effective against
non-small cell lung cancer, ovarian,
bladder, esophageal, and head and
neck cancer

Question 25

Gemcitabine (dFdC, Gemzar) Other side effects

Answer 25

Myelosuppression (leucopenia, | thrombocytopenia, anemia), flulike

Question 26

Gemcitabine (dFdC, Gemzar) Misc

Answer 26

More effective against solid tumors | than cytarabine

Question 27

6-Mercaptopurine (Purinethol) Class

Answer 27

Purine analogs | antimetabolites

Question 28

6-Mercaptopurine (Purinethol) Mech

Answer 28

Prodrug metabolized by hypoxanthineguanine phosphoribosyl transferase (HGPRT) to 6-thioinosinic acid (TIMP); TIMP inhibits first step of de novo purine base synthesis and the formation of AMP and xanthinylic acid from inosinic acid, reducing purine levels. As well, TIMP is converted to thio-guanine ribonucleotides, inhibiting DNA and RNA synthesis

Question 29

6-Mercaptopurine (Purinethol) Therapeutics

Answer 29

Maintain remission in acute ALL

Question 30

6-Mercaptopurine (Purinethol) Imp side effects

Answer 30

Hepatotoxicity in prolonged use

Question 31

6-Mercaptopurine (Purinethol) Other side effects

Answer 31

Bone marrow suppression

Question 32

6-Mercaptopurine (Purinethol) Misc

Answer 32

``` Drug interaction with allopurinol (for gout), which inhibits xanthine oxidase; decrease 6-MP dose to avoid drug accumulation and toxicities ```