Anti-Topoisomerase Agents

Question 1

What are topoisomerases?

Answer 1

Bind to DNA, nicks one strand and prevent the free rotation of the helix by remaining bound to each broken strand then it passes the other strand through the break and ligates the cut ends (uncoiling the supercoiled DNA)

Question 2

Topoisomerase I Function

Answer 2

introduces break into one of the two DNA chains to remove supercoil

Question 3

Topoisomerase II Function

Answer 3

introduces breaks in BOTH chains

Question 4

Topoisomerase Agents Cause

Answer 4

Accumulation of DNA cleavable complexes composed of protein-linked DNA strand breaks

Question 5

Epipodophyllotoxins Drugs

Answer 5

Etoposide/VePeside

Teniposide/vumon

Question 6

Epipodophyllotoxins SE

Answer 6

 Neutropenia
 Myelosuppression
 Secondary leukemias

Question 7

Etoposide Use

Answer 7

Lymphomas, lung and testicular cancers

IV/PO

Question 8

Teniposide Use and SE

Answer 8

 Use: pediatric leukemia
 IV only
 Much more potent than etoposide
 SE: Hypersensitivity

Question 9

Camptothecin Drugs

Answer 9

Irinotecan/Topotecam

Topo I Inhibitor

Question 10

Irinotecan (CPT-11) Use and SE

Answer 10

 PRODRUG
 SN-38 is the active drug that inhibits Topo I
 De-toxified to APC and NPC
 SE: Diarrhea

Question 11

Topotecan SE

Answer 11

Most important: diarrhea
• Myelosuppression
• Neutropenia