Anti-neoplastic drugs III Flashcards
what are the typical alklylating agents?
divided into 5 classes
- nitrogen mustards - mechlorethamine, cyclophosphamide, ifofamide, chlorambucil
- ethylenimine - thioTEPA
- aklylsulfonates - buslfulfan
- nitrosoureas - carmustine, lomustine
the alkylating agents all have what MOA?
alkylation of DNA at guanine & N5 position
mechlorethamine
- what kind of drug?
- MOA?
- indication?
- AEs?
- typical alkylating agents (nitrogen mustards)
- MOA: DNA alkylation at guanine-N-Y position
- indication: advanced N&NH lymphoma
- AEs
- GI
- mutagenic / carcinogenic
- vesicant extravasation → blisters, necrosis
for which of mechlorethamines AEs can be is there an antidote?
what is the antidote?
why is this important?
- for extravasation (blistering necrosis)
- sodium thiosulate: must be available during mechlorethamine administration
extravasation due to which drugs can be treated with an antidote?
what are the antidotes for each?
- - rubicins (anthracyclines) = dexrazoxane
- mechlorethamine (typical alkylating agent) = thiosulfate
cyclophosphamide
- what kind of drug?
- MOA?
- indication?
- AEs?
- typical alkylating agents (nitrogen mustards)
- MOA: DNA alkylation at guanine-N-Y position
- also, is pro-drug that requires activation by CYP-2D6
- MOA: DNA alkylation at guanine-N-Y position
- AE
- hemorrhagic cystitis
- bone marrow suppression
- alopecia
- nausea/vomiting - highly emetogenic
- future risks of cancer
isofosamide
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agents (nitrogen mustards)
- MOA: DNA alkylation at guanine-N-Y position
- AEs:
- severe hemorrhagic cystitis
- severe neurotoxicity → encephalopathy
what is acrolein?
why is it clinically relevant?
- is a corrosive metabolite made by isophosphamide & cyclophosphamide that leads to → hemorrhagic cystitis
- also alopecia for mechlorethamine
- prior to tx with mechlorethamine & cyclophosphamide, pts must be pre-medicated with MENSA therapy
what is the purpose of MENSA therapy?
- necessary pre-medication for pts about to receive:
- isofosamide
- cyclophosphamide
- for prevention of hemorrhagic cystitis
chlorambucil
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agents (nitrogen mustards)
- MOA: DNA alkylation at guanine-N-Y position
- indication: drug of choice for long-term maintenance therapy (i.e., elderly patients)
- AE: mutagenic / teratogenic
what is a benefit of chlorambucil and why is this important
-
is the least toxic alkylating agent & is myeloid sparing.
- thus, it is the drug of choice for long term maintenance therapy (elderly pts)
thioTEPA
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agents (ethylenimine)
- MOA: DNA alkylation at guanine-N-Y position
- also - is only active at a low pH
- MOA: DNA alkylation at guanine-N-Y position
- indication: ovarian & bladder cancer
- AEs - mild myelosuppression
busulfan
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agents (alkylsulfonates)
- MOA: DNA alkylation at guanine-N-Y position
- indication: transplantation prophylaxis
- AEs:
- 100% myelosuppression
- hyperuricemia
- pulmonary fibrosis
which anti-cancer drugs can cause pulmonary fibrosis?
- bleomycin (non-anthracycline)
- busulfan (typically alkylating agent)
nitrosoureas
- are what kind of drugs?
- includes what drugs?
- are typically alkylating agents
- are: -mustines
- lomustine
- carmustine
nitrosoureas share what indication?
-carmustine, lomustine
are all used for brain tumors
carmustine
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agent (nitrosoureas)
- MOA: DNA alkylation at guanine-N-Y position
- indication: brain tumors - specifically, gliomas: implants w/ carmustine are placed into the brain after tumor removal
- AE: none major
lomustine
- what kind of drug?
- MOA?
- indication?
- AEs?
- a typical alkylating agent (nitrosoureas)
- MOA: DNA alkylation at guanine-N-Y position
- indication: brain tumors - in combination therapy
- AE:
- GI
- myelosuppression
lomustine
- what kind of drug?
- MOA?
- indication?
- AEs?