Alkylating agents Flashcards
Alkylating agent basic MOA
Alkylate DNA and proteins. Bind Covalently
What DNA base is mostly alkylated
N7 of guanine.
Sometimes O6
What DNA bases are most nucleophilic?
Adenine and Guanine. Because they have the most N’s
What cell-cycle do alkylating agents interfere with?
ALL
They are non-cell cycle specific
Nitrogen Mustards
Cl\/\N/\/Cl
Meclorethamine
Chlorambucil
Cyclophosphamide
Mechlorethamine
highly reactive, low stability once mixed
Causes myelosupr, naus/vom, sterility
Chlorambucil
po. Less reactive because N e- delocalization
AEs: powerful vesicant (blistering), N&V, myelosuppression, infertility/sterility,
Carcinogenesis leading to secondary malignancies, mutagenic, teratogenic. Mucositis
Take on an empty stomach
Cyclophosphamide
needs to be metabolically activated (aldehyde oxidase gives non-toxic inactive metabolites, amino aldehyde is non-enzymatic and gives UROTOXIC toxic metabolites)
Major side effect: sterile necrotizing hemorrahagic so give Mesna cystitisFor: ALL, NHL, and Myeloma
Interactions with 2B6 inhibitors
Sterile necrotizing hemorrhagic cystitis
From cyclophosphamide or ifosfamide.
Drink lots of water. Bladder irrigation. Treat with NAC and Mesna
Mesna
cytoprotective agent. Used before AND after cyclophosphamide. Binds to and detoxifies urotoxic metabolites
Platinum Containing Agents MOA
Binds to DNA and bends it. NH3\Pt/NH3
Platinum Agent names
Cisplatin
Carboplatin
Oxaliplatin
Cisplatin
cis isomers, give IV, causes renal toxicity and neuropathies
Give Amifostine to reduce tox
For NHL and HL
Amifostine
reduce renal toxicity and xerostomia. But need to give anti-emetic because of nausea from this med.
Carboplatin:
causes neuropathy
For NHL and HL
interacts with Mesna and immune suppressants.
