Week 3: Intracellular poinsions; topoisomerase inhibitors, antimicrotubule agents, proteasome inhibitors Flashcards
What drug is a Topo-1 inhibitor?
Irinotecan
What drugs are Topo-II inhibitors?
Doxorubicin, Etoposide
What drug is a taxane (anti-tubule)?
Paclitaxel
What is the active metabolite of irinotecan?
SN-38
What is the MOA of irinotecan (SN-38)?
inhibits re-ligation step of Topo-I activity
What is the DLT of irinotican?
diarrhea
What is the toxicity caused by doxorubicin?
Cardiac toxicity
How do topo-II inhibitors inhibit the enzyme?
intercalation into the DNA
What is the DLT for doxorubicin?
stomatitis and myelosuppression, cardiac damage years longer
What are contraindications of doxorubicin?
patient isn’t normal to begin with, given in the context of radiation, given with other cardiotoxic drugs
HOw do you mitigate doxorubicin effects?
Prolonged infusion schedules, iron chelator
What is DLT of etoposide?
myelosuppression
What is etoposide essential in the treatment for?
small cell carcinoma of the lung, germ cell tumors
What can be the problem with etoposide use?
causes acute leukemia (AML) that is rapidly fatal
What should also be taken when on irinotecan?
Loperamide
What are anthracyclines (doxorubicin) the standard therapy for?
breast cancer, AML, lymphoma, small cell lung cancer, ovarian cancer and sarcomas
What is the MOA of paclitaxel (taxanes)?
inhibits tubulin polymerization causing mitotic arrest; binds to inner surface of microtubule where GDP binds the beta-subunit and STABALIZES THE STRUCTURE, preventing depolymerization
What is the DLT of paclitaxel (taxane)?
neuropathy
What are inhibitors of the proteasome?
bortezomib, carilzomib, ixazomib
What is the MOA of bortezomib?
blocks the 26s proteasome proteolytic activity (a threonine protease)
What are DLTs of bortezomib?
fatigue, neuropathy and myelosuppression
What is main DLT of proteasome inhibitors?
neuropathy
