Pharm Antineoplastic II, Purine Antimetabolites

Question 1

*6-Mercaptopurine MOA

Answer 1

• PURINE (thiol) ANLOG
• Inhibits purine ring synthesis and nucleotide interconversion–disrupts DNA and RNA integrity
• ACTIVATED BY HPRT (aka HGPRTase)
• Same as 6-Thio

Question 2

*6-Mercaptopurine Therapeutic uses

Answer 2

-MAINTENANCE OF REMISSION in Acute Lymphocytic Leukemia

Question 3

**6-Mercaptopurine Toxicity

Answer 3

• DOSE ADJUSTMENT WITH ALLOPURINOL or FEBUXOSTAT (XANTHINE OXIDASE INHIBITOR)
• Hepatotoxicity (jaundice)
• Myelosuppression

Question 4

*6-Thioguanine MOA

Answer 4

• Inhibits purine ring biosynthesis and nucleotide interconversion–disrupts DNA and RNA integrity
• Same as 6-Mercaptopurine

Question 5

*6-Thioguanine Therapeutic uses

Answer 5

-Acute NON-lymphocytic leukemia (WITH DAUNORUBICIN and CYTARABINE)

Question 6

6-Thioguanine Toxicity

Answer 6

• Myelosuppression

- Hepatotoxicity with long term use

Question 7

Fludarabine (2-F-araA) MOA (low yield?)

Answer 7

-Tumor cell kinases convert 2-F-araA to nucleotide triphosphates–inserted into DNA, RNA and disrupt DNA and RNA synthesis

Question 8

*Fludarabine (2-F-araA) Theraputic uses

Answer 8

• CHRONIC LYMPHOCYTIC LEUKEMIA

- Hair-cell leukemia, Non-Hodgkin’s lymphoma

Question 9

Fludarabine (2-F-araA) Toxicity (low yield?)

Answer 9

• Myelosuppression

- I.V. only intestinal bacteria generate toxic metabolite–fluorodenine

Question 10

Cladribine (2-Cl-deoxyadenosine) MOA (low yield?)

Answer 10

• Tumor cell kinases convert it to nucleotide analogs
• Inhibit DNA synthesis
• Inhibits ribonucleotide reductase

Question 11

*Cladribine (2-Cl-deoxyadenosine) Therapeutic Uses

Answer 11

• HAIRY CELL LEUKEMIA

- Non-Hodgkin’s lymphoma, CLL

Question 12

Cladribine (2-Cl-deoxyadenosine) Toxicity (low yield?)

Answer 12

• Myelosuppression

- Drug fever

Question 13

*6-Thioguanine overdose associated with what NZ and CAN BE GIVEN WITH ALLOPURINAL

Answer 13

-TPMT (association with 6-MP too)