B36 topoisomerase inhibitors and mitotic spindle inhibitors Flashcards Preview

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Flashcards in B36 topoisomerase inhibitors and mitotic spindle inhibitors Deck (19)
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1
Q

What are the anthracycline drugs?

A

‘-rubicins’
rubies on the sunken pirate ship

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

Daunorubicin
Idarubicin
Idarubicin
Epirubicin

2
Q

MoA of the anthracyclines

A

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.

3
Q

Main Anthracycline drug, and its indications

A

Doxorubicin.

Very widely used, for many solid and hematologic tumors.

4
Q

Doxorubicin

Kinetics and SEs

A

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
5
Q

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

A

Dexrazoxane

Dex Razox Ane

6
Q

Daunorubicin indication

A

Acute luekemias

7
Q
Mitoxantrone
class and indication
A

Anthracycline, for prostate cancer.

8
Q

What are the anthracyclines that have the least cardiotoxicity?

A

Idarubicin and Epirubicin

Liposomal encased doxorubicin also has lowered tox.

9
Q

What drugs inhibit Topo 1

A

The camptothecins -

Camptothecin
Topotecan
Irinotecan

10
Q

Topo2 inhibitors

A

Etoposide and Teniposide

11
Q

Etoposide

MoA

A

Inhibits Topo2, stabilizing double strand break

Cells accumulate in late S, G2 phase

12
Q

Etoposide indications

A

Lung cancer
Hodgkins and non Hodkins lymphoma
Testicular cancer

13
Q

Topotecan Rx

A

Ovarian cancer

Small cell lung cancer

14
Q

Irenotecan Rx

A

Colon cancer

15
Q

Camptothecins
MoA

SEs

A

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.

16
Q

What are the mitotic spindle inhibitors

A

The Vinca alkaloids and the Taxanes

17
Q

What are the vinca alkaloids

and their MoA

A

Vincristine
Vinblastine
Vinorelbine

bind tubulin and inhibit polymerization

18
Q

The taxanes

and their MoA

A

Paclitaxel
Docetaxel
Cabazitaxel

Facilitate polymerization, stabilize microtubules, prevent depolymerization

19
Q

Review the sketchy page for the taxanes and vincas

A

did you do it bitch?