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IHO Ben > Week 3: Intracellular poinsions; topoisomerase inhibitors, antimicrotubule agents, proteasome inhibitors > Flashcards

Week 3: Intracellular poinsions; topoisomerase inhibitors, antimicrotubule agents, proteasome inhibitors Flashcards

1
Q

What drug is a Topo-1 inhibitor?

A

Irinotecan

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2
Q

What drugs are Topo-II inhibitors?

A

Doxorubicin, Etoposide

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3
Q

What drug is a taxane (anti-tubule)?

A

Paclitaxel

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4
Q

What is the active metabolite of irinotecan?

A

SN-38

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5
Q

What is the MOA of irinotecan (SN-38)?

A

inhibits re-ligation step of Topo-I activity

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6
Q

What is the DLT of irinotican?

A

diarrhea

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7
Q

What is the toxicity caused by doxorubicin?

A

Cardiac toxicity

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8
Q

How do topo-II inhibitors inhibit the enzyme?

A

intercalation into the DNA

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9
Q

What is the DLT for doxorubicin?

A

stomatitis and myelosuppression, cardiac damage years longer

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10
Q

What are contraindications of doxorubicin?

A

patient isn’t normal to begin with, given in the context of radiation, given with other cardiotoxic drugs

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11
Q

HOw do you mitigate doxorubicin effects?

A

Prolonged infusion schedules, iron chelator

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12
Q

What is DLT of etoposide?

A

myelosuppression

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13
Q

What is etoposide essential in the treatment for?

A

small cell carcinoma of the lung, germ cell tumors

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14
Q

What can be the problem with etoposide use?

A

causes acute leukemia (AML) that is rapidly fatal

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15
Q

What should also be taken when on irinotecan?

A

Loperamide

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16
Q

What are anthracyclines (doxorubicin) the standard therapy for?

A

breast cancer, AML, lymphoma, small cell lung cancer, ovarian cancer and sarcomas

17
Q

What is the MOA of paclitaxel (taxanes)?

A

inhibits tubulin polymerization causing mitotic arrest; binds to inner surface of microtubule where GDP binds the beta-subunit and STABALIZES THE STRUCTURE, preventing depolymerization

18
Q

What is the DLT of paclitaxel (taxane)?

A

neuropathy

19
Q

What are inhibitors of the proteasome?

A

bortezomib, carilzomib, ixazomib

20
Q

What is the MOA of bortezomib?

A

blocks the 26s proteasome proteolytic activity (a threonine protease)

21
Q

What are DLTs of bortezomib?

A

fatigue, neuropathy and myelosuppression

22
Q

What is main DLT of proteasome inhibitors?

A

neuropathy

IHO Ben (27 decks)

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