Week 2: alkylators Flashcards
Name the 5 alkylators
Cyclophosphamide, bendamustine, temozolomide, cisplatin, carboplatin
Where is DNA usually alkylated?
N7 of guanine leading to breakage of the glycosidic bond
What kind of agents are more effective at creating lesions that are difficult to repair?
Bifunctional agents
Are drugs typically nucleophilic or electrophilic?
electrophilic
Name 2 nitrogen mustards?
cyclophosphamide, bendamustine
Name two platinum compounds
Cisplatin, Carboplatin
What is bendamustine used for? Side effect?
B cell malignancies, can cause prolonged neutropenia
What drug is the most important cytotoxic drug ever discovered?
Cyclophosphamide
What are side effects with cyclophosphamide? How do you treat them?
Acrolein can cause hemorrhages in the stomach and 5q-; treat with MESNa
what is the most prescribed cytotoxic drug?
cyclophosphamide
What is so great about mustard use in a clinical setting?
Broad therapeutic index without obvious “ceiling” makes them useful for high-dose chemotherapy with stem-cell rescue
What is the downside of mustard use?
hemorrhagic cystitis, bladder cancer and myelodysplasia (5q-)
What drug class is cisplatin?
Platinum drug
T/F: cisplatin is myelosuppressive
False, not very myelosuppressive at all
What are the toxicities of cisplatin?
damage to 8th CN and long sensory nerves; kidney damage, nausea and vomiting
What is cisplatin used to treat?
germ cell tumors, bladder, head and neck
What is carboplatin used to treat?
lung, GYN and breast cancers
What is the advantage of carboplatin over cisplatin?
much less neurotoxic, emetogenic and neprotoxic
What is the downside of carboplatin?
myelosuppressive, causing thrombocytopenia
T/F: cisplatin is unmatched in broad-spectrum anti-cancer activity, and unmatched in toxicity as well
True
What is the most important toxicity of platinum drugs?
neuropathy
What platinum has the most favorable therapeutic index?
carboplatin
What is the number one side effect of oxaliplatin?
causes extreme cold intolerance
Where do non-classical alkylators do their thing at?
N7 and O6 of guanine, and A3 on adenine
What is temozolomide useful in treating?
CNS tumors
What should be checked before treatment with temozolomide?
expression of MGMT which will remove methylation
What else can non-classical alkylators be used for?
bone marrow transplant conditioning regimens (very toxic to stem cells)
