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Oncology II

Specific Cell Cycle Cytotoxic Drugs: Topoisomerase I & II Inhibitors

What is the MOA of topoisomerase I inhibitors? - inhibits the coiling and uncoiling of the dDNA during S-PHASE --> breaks DNA & prevents Regulation
Which PHASE of the cell cycle does the topoisomerase I inhibitors acts? S phase ( remember S #1)
What are some common topoisomerase I inhibitors drugs? - Irinotecan - Topotecan
Which topoisomerase I inhibitors associated with high risk of acute and delayed diarrhea? - Irinotecan 2/2 its acute cholinergic sxs
What is the recommended treatment of irinotecan induced acute diarrhea? Atropin
What is the recommended treatment of irinotecan induced delayed diarrhea? Loperamide
what is the loperamide dose in irinotecan indued delayed diarrhea? and how it's different from normal dosing? up to 24mg/day vs 12mg/day
what are some common irinotecan indued anticholinergic sxs ? - flushing - sweating - abd cramps - diarrhea
What are some of the genetic factors that increases the risk of irinotecan indued delayed diarrhea ? homozygous UGT1A1*28
What are some genetic factor that increases the risk of irinotecan indued neutropenia? homozygous UGT1A1*28
What is the TOP TWO factors ( requirements) prior to initiating topotecan in cancer pt? (BBW) - ANC >1500 cells/mm3 - platelets > 100K cells/mm3
What is the COMMON BBW of USING topoisomerase I and II inhibitors? Myelosuppression ( BBW)
What is the MOA of topoisomerase II inhibitors? inhbitis the coiling and uncoiling of the dDNA during the G2 phase --> breaks DNA and prevents regulation
Which PHASE of the cell cycle dose the topoisomerase II inhibitor acts on? G2 phase ---( isomerase II)
What are the three main formulations of topoisomerase II inhibitors drug? - Etoposide 1- Etoposide IV 2- Etoposide phosphate 3- Etoposide refrigerated capsule
what is unique about etoposide capsule? - needs to be refrigerated - if dose > 200--->divide the dose 2/2 low bioavailability
What is the ratio of conversion between etoposide IV ---> etoposide oral ( Capsule)? - capsule has 50% bioavailability - so the oral dose = 2X IV dose
Which patient population benefit from etoposide phosphate formula and why? - pt with FLUID restriction - conc needed >0.4mg/ml - no need to maintain <0.4mg/ml conc
What are some recommendation if etoposide IV to be used in a patient? - infuse over 30-60 min 2/2 infusion rate related HYPOTENSION
What are some concerns of using etopside IV? Infusion rate related hypotension
What are some consideration while preparing etopside IV? - Conc << 0.4 mg/ml 2/2 poor water soluble - use non PVC IV bag and tuve 2/2 leaching of DEHP
What are the topoisomerase II class side effects? 1- hypersensitivity rxn 2- anaphylaxis 3- 2nd malignancies
what are the topoisomerase I class side effects? - GI: n/v/d/ abd pain - alopecia
Created by: Smoham38



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