Cytotoxic Therapy Flashcards
What is the essential message behind Loeb’s rules of therapeutics?
don’t make the treatment worse than the disease
What are the general characteristics of cell cycle specific agents?
relatively tumour specific; duration of exposure is more importantn than dose
What are the types of cell cycle specific agents?
antimetabolites; mitotic spindle inhibitors
How do antimetabolites work?
impair nucleotide synhthesis/incorporation
What is the MOA of methotrexate?
inhibits dihydrofolate reductase
How does 6-Mercaptopurine work?
incorporates in DNA
How does hydroxyurea work?
impaired deoxynucleotide synthesis by inhibiting ribonucleotide reductase
What is an example of a mitotic spindle inhibitor?
vinca alkaloids eg vincristine
What are the general characteristics of non-cell cycle agents?
non-tumour specific, damage normal sstem cells; cumulative dose more important than duration
Waht is the MOA of alykylating agents?
bind covalently to bases of DNA which produces DNA strand breaks by free radical production
What are examples of platinum derivatives?
cis-platinum or carboplatin
Give examples of alkylating agents?
chlorambucil and melphalan
Give an example of a cytotoxic antibiotic?
anthracyclines
How do cytotoxic antibodies work?
impair RNA transcription
waht are the immediate general SE of cytotoxic drugs?
bone marrow suppression; gut mucosal damage; alopecia
What is a specific SE of vinca alkaloids?
neuropathy
What is a specific SE of anthracyclines?
cardiomyopathy
what is a specific SE of cis-platinum?
nephrotoxicity
What are the SE of alkylating agents?
infertility; secondary malignancy
How does resistance to cyclophosphamide develop?
altered pro-drug metabolism
How is cis-platinum resistance acheived?
increased DNA repair
How is topoisomerase resistance generated?
altered gene expression
What happens with absent of malfunctioning p53?
loss of control of apoptosis; senescence; cell-cycle regulation and DNA repair
What is the dose-limiting effect of chemotherapy?
myelosuppression
