Term
| What are Topo I inhibitors? |
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Definition
- Topotecan - IV or PO. Spontaneous hydrolysis
- Irinotecan - in polysorbate 80. More potent, severe diarrhea. Metabolized to SN-38, which is less hydrolyzed due to protein binding
**Enterohepatic circulation of irinotecan. SN-38 -- SN-38G in liver, back to SN-38 in intestine |
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Term
| How does Topoisomerase work? |
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Definition
Breaks DNA so it can uncoil, then re-ligates
- Topo-I - single strand breaks
- Topo-II - double strand breaks
- All have flat rings, work in S phase |
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Term
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Definition
A type of Topo II inhibitor, 4 member rings:
- Doxorubicin - IV, vesicant. Liposomal is less toxic
- Daunorubicin - highest chance to turn urine red
- Idarubicin
- Mitoxantrone - less toxic
**All turn urine red, are cardiotoxic, vesicants |
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Term
| What is the major toxicity of anthracyclines? |
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Definition
Cardiotoxicity - oxygen on ring C produces free radicals. H2O2 processed by catalase, which is low in heart tissue. Iron aggravates
**Dexrazoxane is an ion chelator
**Do not use w/ cyclophosphamide, trastuzumab |
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Term
| What are epipodophyllotoxins? |
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Definition
Form ternary complexes w/ topo II and DNA, double strand breaks - S and G2
- Etoposide - uses polysorbate 80. IV |
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