Cytotoxic drugs Flashcards
What are the general characteristics of cell cycle specific agents?
Tumour specific Duration of exposure more important than dose
What are the different types of cell cycle specific agents?
Antimetabolites - impair nucleotide synthesis/incorporation Mitotic spindle inhibitors
What are some examples of antimetabolites?
Methotrexate - inhibits dihydrofolate reductase 6-mercaptopurine/cytosine arabinoside/fludarabine - incorporated into DNA Hydroxyurea - impaired deoxynucleotide synthesis
What are some examples of mitotic spindle inhibitors?
Plant derivatives; vinca alkaloids (vincristine/vinblastine), taxotere (Taxol)
What are the general characteristics of non-cell cycle specific agents?
Non-tumour specific; damage normal stem cells Cumulative dose more important than duration
What are the different types of non-cell cycle specific agents?
Alkylating agents Platinum derivatives Cytotoxic antibiotics
What are some examples of alkylating agents and how do they work?
Chlorambucil/melphalan Bind covalently to bases of DNA Produces DNA strand breaks (mutation) by free radical production
What are some examples of platinum derivatives?
Cis-platinum/carboplatin
What are some examples of cytotoxic antibiotics and how do they work?
Anthracyclines - daunorubicin/doxorubicin/ idarubicin DNA intercalation Impairs RNA transcription Strand breaks in DNA
What are some of the potential immediate side effects of cytotoxic drugs?
Affects rapidly dividing organs - bone marrow suppression, gut mucosal damage, hair loss
What are some examples of drug specific side effects?
Vinca alkaloids - neuropathy Anthracyclines - cardiotoxicity Cis-platinum - nephrotoxicity
What are some examples of drug specific long term side effects?
Alkylating agents - infertility, secondary malignancy Anthracyclines - cardiomyopathy
Why does chemotherapy sometimes fail?
Slow tumour doubling time Tumour sanctuaries Drug resistance mechanisms e.g. increased DNA repair in cis-platinum resistance
Why is intensifying chemotherapy limited and how can this be overcome?
Limited by myelosuppression Overcome by use of haematopoietic growth factors, combine myelosuppressive with non-myelosuppressive agents and intensify dose of active drugs + stem cell rescue
What are the potential sources of stem cells for transplantation?
Tissue source - blood versus bone marrow Patient source; autologous or allogenic (sibling, unrelated)
