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Oncology II
Specific Cell Cycle Cytotoxic Drugs: Topoisomerase I & II Inhibitors
| Term | Definition |
|---|---|
| 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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