Antimetabolites

Question 1

What are antimetabolies an structural analog of and when do they act upon the cell?

Answer 1

Structural analogs of folic acid or of the purine/pyramidine bases found in DNA–act in S-phase

Question 2

Name the two folate analog antimetabolites…

Answer 2

Methotrexate

Pemetrexed

Question 3

Which folate analog antimetabolite inhibits dihydrofolate reductase–which is needed to convert folate to THF-needed for thymidine and purine synthesis?

Answer 3

Methotrexate

Question 4

What enzyme is inhibited by methotrexate?

Answer 4

Dihydrofolate reductase

Question 5

What does methotrexate ultimately inhibit the synthesis of?

Answer 5

Thymidine and purine

Question 6

Which folate analog is used in the treatment of Childhood ALL and choriocarcinoma?

Answer 6

Methotrexate

Question 7

Methotrexate is used in combination therapies for which cancers?

Answer 7

Burkitt's Lymphoma
Carcinomas of:
-Breast
-ovary
-head and neck
-Bladder

Question 8

Why does methotrexate have to be administered intrathecally for meningeal leukemia and meningeal metastases of tumors?

Answer 8

Unable to cross the BBB

Question 9

What cancer can Methotrexate treat if given in high doses?

Answer 9

Osteosarcoma

Question 10

What substance is formed to inhibit the THF-dependent enzymes when using the folate analog, pemetrexed?

Answer 10

Polyglutamate

Question 11

Which folate analog forms polyglutamate and what is caused by this formation?

Answer 11

Pemetrexed–inhbits the THF dependent enzymes

Question 12

Pemetrexed is used for the treatment of….

Answer 12

Colon cancer
Mesothelioma
Non-small cell lung cancer
pancreatic cancer

Question 13

Name the side effects that can be seen with methotrexate?

Answer 13

Renal toxicity
hepatotoxicity
reproductive
myelosuppression
GI toxicity

Question 14

What can be used to prevent the toxic effects of methotrexate?

Answer 14

Leucovorin–taken up much easier by healthy cells compared to tumor cells

Question 15

Name the 3 pyramidine analog antimetataboties…

Answer 15

5-Fluorouracil
Cytarabine
Gemcitabine

Question 16

Cytarabine is in what drug class?

Answer 16

pyrimidine analog

Question 17

5-Fluorouracil is in what drug class?

Answer 17

pyrimidine analog

Question 18

Gemcitabine is in what drug class?

Answer 18

pyrimidine analog

Question 19

What are the two active metabolites of 5-Fluorouracil used to interrupt DNA synthesis and RNA function, respectfully?

Answer 19

DNA synthesis– FdUMP

RNA function– FdUTP

Question 20

What is the mechanism for action of 5-Fluorouracil?

Answer 20

Creates active metabolites that interrupt DNA synthesis and RNA function

Question 21

Cytarabine is a pyrimidine analog that terminates DNA synthesis, how is this done?

Answer 21

Converted by deoxycutidine kinase to Ara-CTP which terminates DNA synthesis

Question 22

What is the mechanism of action for Gemcitabine? what does it inhibit?

Answer 22

Converted to active metabolites which inhibit ribonucleotide reductase–incorpotates into DNA and terminates synthesis

Question 23

5-Fluorouracil is used in combination therapy for what type of cancers?

Answer 23

Breast
Colorectal
Gastric
Head and neck
Cervical
Pancreatic
Basal cell carcinoma

Question 24

What pyrimidine analog is considered the most effective treatment for AML?

Answer 24

Cytarabine

Question 25

What pyrimidine analog is used for the treatment of AML, ALL and blast phase of CML?

Answer 25

Cytarabine

Question 26

Gemcitabine is used for the treatment of...

Answer 26

``` Pancreatic cancer non-small cell lung cancer ovarian bladder esophageal head and neck cancers ```

Question 27

Hand-foot syndrome and cardiac toxicity are side effects seen with the use of which pyrimidine analog?

Answer 27

5-Fluorouracil

Question 28

What are other symptoms of 5-Fluorouracil?

Answer 28

``` Anorexia Nausea Mucosal ulcerations stomatitis diarrhea thrombocytopenia anemia ```

Question 29

What drug can be given to potentiate the effects caused by the use of 5-Fluoruacil?

Answer 29

Leucovorin

Question 30

What are some side effects of Cytarabine, a pyrimidine analog?

Answer 30

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

Question 31

What are the side effects of Gemcitabine, a pyrimidine analog?

Answer 31

Myelosuppression-- leucopenia, thrombocytopenia, anemia | Flu-like symptoms

Question 32

Which pyrimidine is more effective against solid tumors when compared to Cytarabine, also a pyrimidine analog?

Answer 32

Gemcitabine

Question 33

What is the one purine analog antimetabolite?

Answer 33

6-Mercaptopurine

Question 34

What metabolizes 6-Meracaptopurine to cause it to be in its active form and what is its active form?

Answer 34

Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) Active form---TIMP (6-thioinosinic acid)

Question 35

6-meracaptopurine is converted to TIMP, its active form, by HGPRT. What are the two mechanisms of action of TIMP?

Answer 35

1) inhibits first step of de novo purine base synthesis and the formation of AMP and xanthinylic acid from inosinic acid--reduces purine levels 2) converted to thio-guanine ribonucleotides--inhibits DNA and RNA synthesis

Question 36

What is the primary use of 6-Mercaptopurine?

Answer 36

Maintain remission in acute ALL

Question 37

What are the side effects of 6-Mercaptopurine?

Answer 37

hepatotoxicity in prolonged use | Bone marrow suppression

Question 38

What drug interaction is seen with the use of 6-Mercaptopurine, why?

Answer 38

Allopurinol--inhibits xanthine oxidase