Alkylating Agents Flashcards
What are the 5 classes of alkylating agents?
- Mustards
- Nitrosoureas
- Triazenes
- Platinum complexes
- Miscellaneous
What is the MOA for the mustards?
Weakens the bond between the base and the sugar in DNA, leading to a loss of the base and consequent disruption in the coding sequence; Don’t target a specific phase of cell cycle
What are the 2 mustards?
Cyclophosphamide and Ifosfamide
Describe the mustards
They are pro-drugs and have the same cytotoxic ingredient Phosphoramide Mustard. Also make bladder toxic metabolite acrolein
What is the bladder adverse event seen with mustards? When is it seen?
Hemorrhagic cystitis is seen in high doses with continuous daily administration (NOT intermittent)
How can acrolein be counteracted?
Adequate hydration with Mesna; Prevents hemorrhagic cystitis but does not treat it. For treatment, use saline solution.
What is Ifosfamide’s side effect?
Unique CNS neurotoxicity caused by the metabolite chloroacetaldehyde; Disturbs mitochondrial respiratory chain
What is the antidote to chloroacetaldehyde?
Methylene blue
Describe the MOA for the Nitrosoureas.
- Liberate isocyanates which interact with lysine residues. Inactivates DNA repair enzymes.
- They are highly lipophilic
What are the Nitrosoureas?
Lomustine, Carmustine and Streptozocin
Describe the toxicity of the triazenes.
Cytotoxicity due to the methylation of DNA at O6 and N7 on guanine by the shared metabolite MTIC
Name the Triazenes.
Dacarbazine(lipophobic) and Temozolamide(lipophilic)
Discuss the MOA of platinum complexes
Causes crosslinks between adjacent guanines and guanine and adenine on the same DNA strand. Inhibits replication and transcription; leads to strand breaks and miscoding
Is the toxicity between platinum complexes the same?
NO
Name the platimum complexes.
Cisplatin, Carboplatin and Oxaliplatin
