Bleomycin and Actinomycin D Flashcards
What’s the MOA of bleomycin?
oxidative cleavage of DNA
How is bleomycin eliminated?
renal
What’s are 2 unique side effects of bleomycin?
pulmonary fibrosis & desquamtion
How myelosuppressive is bleomycin?
it doesn’t really cause any myelosuppression
Which enzyme degrades bleomycin?
bleomycin hydrolase, found in both normal and neoplastic cells
the enzyme is found in relatively low concentration in the lungs and skin –> hence it’s toxicities there
Which DNA repair pathway is critical for bleomycin-induced damage repair?
homologous recombination
need BRCA1 and PARP
What are some mechanisms of bleomycin resistance?
- increased hydrolase expression
- increased double strand DNA repair
- decreased drug accumulation
What would sensitize tumour cells to bleomycin?
- up regulation of glutathione (increases resistance to doxorubicin) but more sensitive to bleomycin
Is bleomycin affected by Pgp?
no
What’s the MOA of actinomycin D?
inhibits DNA polymerase
potent inhibition of transcription –> thus inhibiting RNA and protein synthesis
What are the drug interactions of actinomycin D?
none
Is actinomycin D a vessicant?
yes
Does actinomycin D effect RT?
Yes - it’s a radiation sensitizer and can have recall reactions
How does actinomycin D enter the cell?
passive diffusion
What’s the mechanism of resistance for actinomycin D?
Pgp transport efflux
What’s the DLT of actinomycin D?
myelosuppression and GI toxicity
Is actinomycin D a RT sensitizer?
yes
How is actinomycin D eliminated?
minimal metabolism
20% excreted unchanged in the urine, and 14% in the feces
What’s the dose of actinomycin D?
0.5-0.75mg/m2 every 1-3 weeks
