Drug Table - Antimetabolites Flashcards Preview

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Flashcards in Drug Table - Antimetabolites Deck (32)
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1

Antimetabolites in general

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

2

Antimetabolites list

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

3

Methotrexate (Trexall) class

Folate analogs

4

Methotrexate (Trexall) mech

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

5

Methotrexate (Trexall) Therapeutics

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

6

Methotrexate (Trexall) Imp Side effects

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

7

Methotrexate (Trexall) Other side effects

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

8

Methotrexate (Trexall) Misc

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

9

Pemetrexed (Alimta) class

Folate analogs

10

Pemetrexed (Alimta) Mech

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))

11

Pemetrexed (Alimta) Therapeutics

Colon cancer, mesothelioma, non-small
cell lung cancer, pancreatic cancer

12

5-Fluorouracil (5-FU, Carac) class

Pyramidine analogs

13

5-Fluorouracil (5-FU, Carac) Mech

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

14

5-Fluorouracil (5-FU, Carac) Therapeutics

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

15

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

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

16

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

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

17

5-Fluorouracil (5-FU, Carac) Misc

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

18

Cytarabine (AraC, Depocyt) Class

Pyramidine
analogs

19

Cytarabine (AraC, Depocyt) Mech

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

20

Cytarabine (AraC, Depocyt) Therapeutics

AML (most effective treatment), ALL
and blast phase CML

21

Cytarabine (AraC, Depocyt) Other side effects

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

22

Gemcitabine (dFdC, Gemzar) class

Pyramidine
analogs

23

Gemcitabine (dFdC, Gemzar) Mech

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

24

Gemcitabine (dFdC, Gemzar) Therapeutics

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

25

Gemcitabine (dFdC, Gemzar) Other side effects

Myelosuppression (leucopenia,
thrombocytopenia, anemia), flulike

26

Gemcitabine (dFdC, Gemzar) Misc

More effective against solid tumors
than cytarabine

27

6-Mercaptopurine (Purinethol) Class

Purine analogs
(antimetabolites)

28

6-Mercaptopurine (Purinethol) Mech

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

29

6-Mercaptopurine (Purinethol) Therapeutics

Maintain remission in acute ALL

30

6-Mercaptopurine (Purinethol) Imp side effects

Hepatotoxicity in prolonged use