chemotherapy Flashcards
what is the mechanism of action for multi-drug resistance?
Multi-drug resistance be attributed to mdr1 gene, p170 protein
o This is a glycoprotein with multiple ATP binding sites and cause drug efflux
what is the curative treatment for testicular cancer?
Bleomycin, etoposide and cisplastin
what is combination therapy? and what are its requirements?
combination therapy aims to decrease the probability of resistant strains arising during treatment. it increases overall toxicity towards the tumour, without increasing overall toxicity. drugs used must be:
- all active against that tumour
- with different mechanism of actions
- with different toxicity profiles
how does L-asparginase work? and what is it used to treat?
it exploits a biochemical difference. it breaks down the non essential amino acid L-asparginine in circulation, starving the cells from it. it is used in childhood lymphocyte leukaemia
what is Imantib meyslate? what is it used for?
it is a selective tyrosine kinase inhibitor, used in the treatment of CBR-ABL positive CML
what is Bortezomib?
this is a proteasome inhibitor used in the treatment of multiple myeloma. it prevents the breakdown of IKb, which inhibits NF-Kb (a potent anti-apototic highly expressed in MM)
how do the plant alkaloids work?
Vincristine
• Inhibit microtubule polymerisation
• This stops spindle formation and inhibits mitosis
Taxanes: paclitaxel and docelatel (taxols)
• They increase microtubule size
• Cell undergoes apoptosis once tubules increase beyond a certain size
how does bleomycin work and what is its mechanism of resistance?
- Binds in DNA major groove
- FeII pocket
- Breaks DNA phosphate backbone: forms hydroxyl and superoxide radicals
- Prevent DNA replication and transcription
- Resistance: increased DNA repair and superoxide repair mechanism
how does dactinomycin work? what is the mechanism for resistance?
- Binds in DNA minor groove
- Interacts with RNA polymerase
- Inhibits protein transcription
how does doxorubicin and actinomycin work?
• Stabilise DNA polyermase, Topoismoerase II and DNA complex – this prevents DNA replication and keeps DNA in open configuration liable to attack
how does cytarabine work?
• Recognised as a nucleoside by deoxycytidine kinase
o Phosphorylated and eventually added to DNA chain via DNA polymerase
o Terminates DNA elongation, because of extra moiety
• Resistance: decreased deoxycytidine kinase and increase in dCTP
how does FCU work?
- Converted by thymidine phosphorylase, the product then complexes with tetrahydrofolate to inhibit thymidylate kinase
- This prevents DNA replication
- Resistance: decreased phosphorylase enzyme or affinity
how does methotrexate work?
- Inhibits dihydrofolate reductase
- Glutamate addition increased in tumour cells
- Inhibits purine synthesis (At two points)
- Resistance: decreased transport, decreased affinity of enzyme or increased enzymatic expression
how do the alklyating agents work?
Alkalyting agents: cross link-DNA
• Depend on the formation of a carbonium ion, a positive rich unstable ion. Preferentially attacks guanine
• Most alkalyting drugs are bifunctional
• Cisplastin: cross links guanine and adenine within the same strand
o This increases the rate of mutation and drives towards cellular death
Nitrosurease:
• Comustine and carmustine
• Those form a carbomylated protein, cytotoxic effect
• Are lipophilic and can cross the BBB
Resistance:
• Decreased permeability
• Increased gluthione
• Increased DNA repair
• Increased Metabolism
what is tumour lysis syndrome?
this is a syndrome of metabolic complications associated with the release of cellular content due to their death
