Topoisomerase inhibitors Flashcards
Topoisomerase inhibitors inhibits both ______ and ____.
Topoisomerase I and II
What is the functional difference b/w Topoisomerase I and II?
Topoisomerase I cuts only one strand of DNA. Whereas the Topoisomerase II cuts both.
What is the key MOA of Topoisomerase inhibitors?
Inhibition of Topoisomerase enzymes leads to DNA over-winding triggering cell death cascades.
What are the phases of cell cycle in which Topoisomerase inhibitors are most effective ?
Late S and early G2 phase.
What are the common drugs in Camptothecine class of Topoisomerase inhibitors?
irenotecan and topotecan which are derived from the stumps of Camptotheca tree.
What is the MOA of Camptothecine’s ?
Inhibition of Topoisomerase I leading to cell death.
What is the pharmacology of Irenotecan ?
It is a prodrug and is eliminated through the bile and feces.
In who should the dose of Topotecan be reduced ?
As it is eliminated by the kidenye’s, its dose should be reduced in patients with renal impairment.
What are the indications of Camptotechan’s ?
Irenotecan- Metastatic colon cancer
Topotecan- Advanced ovarian cancer and small cell lung cancer.
What are the common side effects of Camptotecans ?
Myelosuppression and GI problems. In general these drugs have fewer toxicity than most other anti-cancer agents.
What are the medications in the class of podophyllotoxins ?
Etoposide and teniposide they are derived from the roots of podophylum peltatum also known as Madrake root.
What is the MOA of podophyllotoxins ?
They act by inhibiting the enzyme Topoisomerase II leading to DNA breakage. They are mainly renally excreted.
What are the indications for podophyllotoxins?
- Solid tumours such as testicular and SCLC
- Leukaemia and Lymphomas.
What are the main side effects of podophyllotoxins?
GI disturbances, alopecia and Myelosuppression.
