Classical chemotherapy- part 1- Mech Flashcards
what kind of chemotherapy drugs are there?
- alkylating agents
- antimitotic agents
- topisomerase inhibitors
- antimetabolites
- antitumor antibitotics
what are some types of alkylating agents?
-Nitrogen mustards • Nitrosoureas • Aziridines • Alkyl sulfonates • Monoalkylating agents
where are nitrogens mustards derived from?
sulfur mustards
where does nitrogen mustards crosslink with DNA?
• Predominant crosslink is between the N7 of guanine on two strands
- an interstrand crosslink
what is the effect of nitrogen mustards on DNA?
Stops enzymes such as DNA polymerase being able to separate the
strands and thus stops replication.
what is the mechanism of resistance for nitrogen mustards?
-increase amount of glutathione-S- transferase
what is the toxicity of alkylating agents?
Tend to be non-cell cycle specific but target any proliferating cell
• Nitrogen mustards
• Acute - nausea and vomiting
• Delayed - bone marrow depression
what are DNA platinating agents?
Cisplatin is the most frequently used antitumour drug in the clinic
• Used in the treatment of testicular, ovarian, head and neck, lung and bladder
cancers
• Is essentially curative in testicular cancer
whats the mechanism of action for platinating agents?
The positively charged aquated platinum (II) reacts with biological nucleophiles
• The biological target is again thought to be N7 of G
-
what is the effect of platinating agents on DNA?
These intrastrand crosslinks have been suggested to inhibit DNA polymerase
what is the mechanism of resistance
- Increased repair mechanisms for intrastrand crosslinks
- Increased expressed of thiol containing proteins (glutathione, metallothionein)
- Probably a mixture of these factors
what is the toxicity
Carboplatin is another platinum complex currently used
• Cisplatin:
• Acute - nauseas and vomiting. Anaphylactic reactions
• Delayed - Nephrotoxicity
• Carboplatin
• Acute - moderate nausea and vomiting
• Bone marrow depression
