Antimetabolites

Question 1

Methotrexate (Trexall) mech

Answer 1

Inhibits dihydrofolate reductase (DHFR),which converts dietary folate totetrahydrofolate (THF) needed for thymidineand purine synthesis; given orally or intrathecally

Question 2

Methotrexate (Trexall) Therapeutics

Answer 2

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 3

Methotrexate (Trexall) Imp Side effects

Answer 3

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

Question 4

Methotrexate (Trexall) Other side effects

Answer 4

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

Question 5

Methotrexate (Trexall) Misc

Answer 5

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

Question 6

Pemetrexed (Alimta) Mech

Answer 6

Polyglutamate forms that inhibit THF dependentenzymes (e.g., DHFR, TS);

Question 7

Pemetrexed (Alimta) Therapeutics

Answer 7

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

Question 8

5-Fluorouracil (5-FU, Carac) Mech

Answer 8

5-FU is converted to active metabolites: 5-FdUMP inhibits TS; 5-FdUTP incorporates into RNA & interferes with RNA function;

Question 9

5-Fluorouracil (5-FU, Carac) Therapeutics

Answer 9

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

Question 10

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

Answer 10

Hand-foot syndrome (erythema,sensitivity of palms and soles), cardiac toxicity (acute chest pains). Anorexia and nausea; mucosalulcerations, stomatitis, diarrhea; thrombocytopenia and anemia

Question 11

Cytarabine (AraC, Depocyt) Mech

Answer 11

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

Question 12

Cytarabine (AraC, Depocyt) Therapeutics

Answer 12

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

Question 13

Cytarabine (AraC, Depocyt) Other side effects

Answer 13

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

Question 14

Gemcitabine (dFdC, Gemzar) Mech

Answer 14

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

Question 15

Gemcitabine (dFdC, Gemzar) Therapeutics

Answer 15

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

Question 16

Gemcitabine (dFdC, Gemzar) Other side effects

Answer 16

Myelosuppression (leucopenia,thrombocytopenia, anemia), flulike

Question 17

6-Mercaptopurine (Purinethol) Mech

Answer 17

Prodrug metabolized by 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 18

6-Mercaptopurine (Purinethol) Therapeutics

Answer 18

Maintain remission in acute ALL

Question 19

6-Mercaptopurine (Purinethol) Imp side effects

Answer 19

Hepatotoxicity in prolonged use, Bone marrow suppression

Question 20

6-Mercaptopurine (Purinethol) Misc

Answer 20

Drug interaction with allopurinol (forgout), which inhibits xanthineo xidase; decrease 6-MP dose toavoid drug accumulation andtoxicities