Bleomycin and Antitumor Antibiotics Flashcards
MOA bleomycin
What kind of damage is produced?
oxidative cleavage of DNA initiated by hydrogen abstraction
Single and double strand DNA breaks
How does bleomycin cause DS breaks
by binding of bleomycin/ferrous iron complex to DNA – > DNA intercalation (ie insertion bt base pairs) and unwinding of DNA helix
May also cause DNA strand breaks via REDUCTION of MOLECULAR OXYGEN to SUPEROXIDE or HYDROXYL RADICALS, catalyzed by the bleo/ferrous iron complex
Is bleo cell cycle specific or not?
Bleomycin works preferentially in the G2 PHASE of cell cycle
Once in the cell, what enzyme metabolizes bleo?
bleomycin HYDROLASE
How is bleo eliminated?
unchanged in urine
What is specific about radiation?
SYNERGISTIC w radiation if used w/in 3 hrs (Before or after)
Bleomycin toxicity (4)
Pulmonary fibrosis (careful if o2 w surgery or prior chest irradiation)
Desquamation (fingers elbows)
Raynaud’s phenomenon
HS reactions
Bleomycin, Dactinomycin, and mitomicin C are a product of what?
Streptomyces
What is mitomycin C used for
Yondelis is used as a radiosensitizer with 5FU for epidermoid anal cancer
What is responsible for dactinomycin resistance?
increased efflux by P170 glycoprotein transporter
What 2 things should one know in regard to toxicity with dactinomycin?
EXTRAVASANT
Radiation sensitization and Recall reaction
Mitomycin C:
A quinone containing compound that requires activation to ______ metabolite by reductive metabolism (more active against what type of cells?)
ALKYLATING metabolite
More active against hypoxic cells than aerobic
Mitomycin C:
What are 3 toxicities to know?
- can cause renal failure through hemolytic-uremic syndrome
- pulmonary fibrosis
- delayed myelosuppression
