B. Cancer Chemotherapy III (Topisomerase inhibitors. inhibitors of mitotic spindle) Flashcards
list the microtubules inhibitors (mitotic spindle inhibitors)
Vincristine
Vinblastine
Docetaxel
Paciltaxel
which phase in the cell cycle do the microtubule inhibitors affect?
M phase (CCS)
what are microtubules inhibitors?
natural products (plant-derived substances), used as anticancer drugs
how do the microtubules inhbitors work?
they interfere with the process of mitotic spindle formation by affecting the equilibrium between the polymerized and depolymerized forms of the microtubules–> resulting in cytotoxicity
what does Vincristine do?
inhibits microtubules polymerization (‘spindle poison’)
what is Vincristine and Vinblastine?
Vinca alkaloids
what is Docetaxel and Paciltaxel?
naturally occurring taxanes
what does Docetaxel do?
inhibits microtubules disassembly into tubulin monomers
indications for Vincristine
acute leukemia
lymphomas
wilm’s tumor
Neuroblastoma
indications for Docetaxel
Breast cancer
ovarian cancer
prostate cancer
lung cancer
side effects of Vincristine
neurotoxicity (peripheral neuropathy)
autonomic dysfunction (paralytic ileus)
alopecia
myelosuppression
side effects of Docetaxel
myelosuppression (severe neutropenia) neurotoxicity hypersensitivity reaction cardiotoxicity onycholysis (dissolving nails) hepatotoxicity
list the topoisomerase inhibitors
Etoposide
Teniposide
Irinotecan
Doxorubicin
what are Etoposide and Teniposide?
semisynthetic derivatives of the plant alkaloid podophyllotoxin
which agents inhibit topoisomerase II?
Etoposide
Teniposide
Doxorubicin
Daunorubicin
which agents inhibit topoisomerase I?
Irinotecan
which topoisomerase inhibitor is a CCNS?
Doxorubicin
Daunorubicin
what is Irinotecan?
- Semisynthetic derivative of a more toxic drug–> camptothecin
- prodrug, activated to the posted metabolite SN-38
what is Doxorubicin?
an antitumor antibiotics
what does doxorubicin cause?
it generates free radicals intercalates DNA (↓ replication)
indications of Etoposide and Teniposide
small cell lung carcinoma
germ cell tumors
etoposide–> Kaposi sarcoma
teniposide–> ALL
side effects of etoposide
nausea, vomiting
myelosuppression
alopecia
Indication of Irinotecan
colon cancer (metastatic disease)
side effects of Irinotecan
myelosuppression (severe neutropenia)
Diarrhea
indications for doxorubicin
hodgkin's lymphoma non-Hodgkin's lymphoma breast cancer ovarian cancer lung cancer (SCLC)
side effects of doxorubicin
nausea, vomiting
myelosuppression
alopecia
cardiotoxicity (ECG abnormalities, arrhythmias, cardiomyopathy, CHF) - most problematic!!
what drug can protect against cardiotoxicity when giving doxorubicin?
Dexrazoxane
an inhibitor of iron-mediated free radical generation
