Antineoplastic Agents II Flashcards
Cyclophosohamide MOA
Uses (2)
Primary toxicity and antidote
Nitrogen mustard alkylating agent
Solid tumors and hematological malignancies
Hemorrhagic cystitis…antidote is mesna
Carmustine (BCNU) MOA
Use
Primary toxicity
Nitrosource alkylating agent
Brain tumors (wafers and stuff)
Myelosuppression
4 adverse effects of alkylating agents
- Mutagenic
- Myelosuppressive
- Leukemia
- Strong vesicant properties
Common resistance mechanisms to alkylating agents
- Inactivation by glutathione
- Reduced uptake
- Accelerated DNA repair
- Increased expression of MGMT (removed alkyl groups from guanine)
MOA of non-classical alkylating agents
Lead to DNA cross-linkages but do NOT have alkyl groups
3 common non-classical alkylating agents (Platinum compounds)
- Cisplatin
- Carboplatin
- Oxaliplatin
Adverse effects of Cisplatin (2)
- Peripheral motor and sensory neuropathy
2. Nephrotoxicity
Primary differences between Cisplatin and Carboplatin (2)?
- Carboplatin causes less nausea, neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin
- Dose-limiting toxicity for carboplastin is myelosuppresion
Vinacristine MOA
Primary toxicity
Inhibits microtubule formation preventing mitotic spindle formation. This causes cell to arrest in mitosis causing cell death
Primary toxicity is neurological
Vinablastine MOA
Primary toxicity
Inhibits microtubule formation preventing mitotic spindle formation. This causes cell to arrest in mitosis causing cell death
Primary toxicity is myelosuppresion
Paclitaxel MOA
Primary toxicity
Kills tumor cells by preventing depolymerization of microtubules thereby arresting cells in mitosis
Primary toxicity is peripheral neuropathy
What drug is commonly given with paclitaxel to reduce myelosuppression?
Filgrastin (G-CSF)
Topoisomerase I inhibitors (2)
Topoisomerase II inhibitor
- Irinotecan and Topotecan
2. Etoposide
Doxorubicine MOAs (2) Primary toxicity and antidote
- Intercalates with DNA and inhibits topoisomerase II thereby causing DNA damage
- Also binds to iron and generates free radicals which cause DNA and protein damage
- Primary toxicity is irreversible cardiomyopathy. Antidote is dexrazoxane
Bleomycin MOA
Primary toxicity
- Small peptide that binds to DNA and causes single and double strand breaks. It causes cells to arrest in G2
- Primary toxicity is irreversible pulmonary toxicity