Cytotoxic drugs* Flashcards
classification of cytotoxic drugs
cell cycle specific
non cell cycle specific
cell cycle specific
tumour specific
duration of exposure is more important than dose
examples of cell cycle specific
antimetabolites - impair nucleotide synthesis/incorporation
mitotic spindle inhibitors
metho - inhibits dihydrofolate reductase
6-mercaptopurine/cytosine arabinoside/fludarabine - incorporated into DNA
hydroxyurea - impaired deoxynucleaotide synthesis [enzyme that it inhibits is reibonucleotide reductase]
mitotic spindle inhibitors
plant derivative:
vinca alkaloids - vincristine/vinblastine
taxotere (taxol)
non cell cycle specific agents
non tumour specific - damage normal stem cells
cumulative dose more important than duration
risk of non cell cycle specific agents
secondary malignancies
examples of non cell cycle specific agents
alkylating agents:
chlorambucil/melphalam
bind to bases of DNA
produces DNA strain breaks by free radical production
platinum derivatives:
cis-platinum/carboplatin
cytotoxic antibiotics: anthracyclines: daunorubicin/doxorubicin /idarubicin DNA intercalation - reversible impairs RNA transcription strands break in DNA due to free radiacals
SE of cytotoxic drugs immediate
affect rapidly dividing organs
bone marrow suppression
gut mucosal damage
hair loss - alopecia
why is chemo given in cycles
to allow recovery of the affected organs
short term/immediate SE
vinca alkaloids
anthacyclines
cis-platinum
neuropathy
cardiotoxicity - dose related
nephrotoxicity
long term side effects
alkylating agens
anthacyclines
infertility
secondary malignancy
cardiomyopathy
combination therapy must be
non cross resistant drug comb
non overlapping toxicity spectra
additive/synergistic mechanisms of actions
why does chemo fail
slow tumour doubling time
tumour sanctuaries - mainly CNS, drug can’t get in
drug resistance
drug resistance mechanisms
decreased drug accumulation MDR-1/PGP
altered drug (pro drug) metabolism : cyclophophamide
increased DNA repair, cis platinum resistance
altered gene expression: reduced topoisomerase II
why are high doses not given if tumour is resistant
limited myelosuppression
but can be overcome:
use haematopoietic growth factors
combine myelosuppressive and non myelosuppressive agents
identify dose of active drugs and stem cell rescue
