B36 topoisomerase inhibitors and mitotic spindle inhibitors

Question 1

What are the anthracycline drugs?

Answer 1

‘-rubicins’
rubies on the sunken pirate ship

Doxorubicin - most widely used one. very common cancer drug.

Daunorubicin
Idarubicin
Idarubicin
Epirubicin

Question 2

MoA of the anthracyclines

Answer 2

Multiple mechanisms:

1) Form free radicals, superoxides and hydrogen peroxides, which can directly oxidize phosphodiester bonds, or any other molecules in the cell. Lipid peroxidation.
2) Interchelate in the DNA and form a stable bond with DNA-Topoisomerase 2 complex, after it has cut both DNA strands, preventing annealing.

They are NOT cycle specific, can kill anytime.

Question 3

Main Anthracycline drug, and its indications

Answer 3

Doxorubicin.

Very widely used, for many solid and hematologic tumors.

Question 4

Doxorubicin

Kinetics and SEs

Answer 4

Doxorubicin, and all of the anthracyclines must be given I.V.
They Do NOT penetrate to the CNS or to the testes.

Metabolized by the liver, and excreted mostly in bile must be adjusted if liver is impaired.
Minor excretion in the urine.

SEs:

• Extravasation and necrosis at the injection site.
• Red urinary discoloration (from drug excretion)
• Irreversible Dialative Cardiomyopathy
• Marrow depletion

Question 5

What agent is used to lessen/prevent the worst side effect of Doxorubicin?

Answer 5

Dexrazoxane

Dex Razox Ane

Question 6

Daunorubicin indication

Answer 6

Acute luekemias

Question 7

Mitoxantrone
class and indication

Answer 7

Anthracycline, for prostate cancer.

Question 8

What are the anthracyclines that have the least cardiotoxicity?

Answer 8

Idarubicin and Epirubicin

Liposomal encased doxorubicin also has lowered tox.

Question 9

What drugs inhibit Topo 1

Answer 9

The camptothecins -

Camptothecin
Topotecan
Irinotecan

Question 10

Topo2 inhibitors

Answer 10

Etoposide and Teniposide

Question 11

Etoposide

MoA

Answer 11

Inhibits Topo2, stabilizing double strand break

Cells accumulate in late S, G2 phase

Question 12

Etoposide indications

Answer 12

Lung cancer
Hodgkins and non Hodkins lymphoma
Testicular cancer

Question 13

Topotecan Rx

Answer 13

Ovarian cancer

Small cell lung cancer

Question 14

Irenotecan Rx

Answer 14

Colon cancer

Question 15

Camptothecins
MoA

SEs

Answer 15

Inhibit Topo1
Cells accumulate in S-phase

SEs;
myelosuppression,
diarrhea
severe, late onset diarrhea with irenotecan, 2-10 days after treatment. Can cause severe dehydration or ion loss.

Question 16

What are the mitotic spindle inhibitors

Answer 16

The Vinca alkaloids and the Taxanes

Question 17

What are the vinca alkaloids

and their MoA

Answer 17

Vincristine
Vinblastine
Vinorelbine

bind tubulin and inhibit polymerization

Question 18

The taxanes

and their MoA

Answer 18

Paclitaxel
Docetaxel
Cabazitaxel

Facilitate polymerization, stabilize microtubules, prevent depolymerization

Question 19

Review the sketchy page for the taxanes and vincas

Answer 19

did you do it bitch?