MD3: Topoisomerases Flashcards
(28 cards)
Topoisomerase I Inhibitors
MOA
Cell Cycle Specific/Non-Specific?
Drug Class?
- Inhibits topoisomerase from religation of the DNA strands (which is needed for replication), pieces of ssDNA accumulates.
- Cell Cycle Specific (S PHASE)
- Camptothecins
Topoisomerase I inhibitor:
Topotecan
Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?
Hycamtin
- Not Prodrug
- IV/PO
- S/E: Myelosuppression [BBW] *Dose Limited*
- Alopecia, N/V/D, Stomatitis, Hepatotoxicity (inc. LFTs)
——————————————————————————————–
Risk Factors for MYLS: previous XRT or BM suppressive chemo
PO formulation has more DIARRHEA
DO NOT CHEW/CRUSH PO formulation
PROTECT FROM LIGHT (PO/IV)
Topoisomerase I inhibitors
Irinotecan
Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?
Camptosar (CPT-11)
- Prodrug—-Active Drug = SN38
- IV
- S/E: Diarrhea [BBW], Myelosuppression [BBW]
- Alopecia, N/V/, Stomatitis, Hepatoxicity(TBili, Alk Phos)
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Glucoronidated by UGT1A1
Mutation: Homozygous UGT1A1*28 –> inc. Toxicity
Topoisomerase I inhibitor:
Irinotecan liposomal
Onivyde
Topoisomerase II Inhibitors
MOA
Cell Cycle Specific/Non-Specific?
Drug Class?
MOA: Prevent resealing of strand breaks, accumulation of “broken” strands
Effects the
Cell Cycle Specific: G2/S Phase
Drug Classe(s):
Epipodophylltoxins [Pure Topo II]
Anthracyclines [Mixed]
Mitoxanthrone [misc]
Topoisomerase II Inhibitor
Etoposide IV
Etoposide phosphate IV
Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?
(VP-16)
IV: Toposar
IV Phos: Etopophos
- No Prodrugs
- IV
- S/E: Myelosuppression [BBW]
- Alopecia, N/V/D, Mucositis, Hypotension, Hypersensitivity, Anaphylactoid Rxns, Secondary Malignancies
————————————————————— - Max Concentration: 0.4mg/mL or (>0.4 mg/mL if PhosIV)
- USE NON-PVC tubing/bag (b/c Poly 80 cause leaching)
- Use 0.22-micron filter
ETOPOSIDE PHOS IV LESS LIKELY TO CAUSE BELOW RXNS
Hypersensitivity + Anaphylactoid Reactions due to Polysorbate 80, Benzyl Alcohol OR FAST Rate of Infusion
HOTN due to FAST Rate of Infusion- d/c infusion, give IV hydration
- BP: decrease rate of drug (infuse over 30-60 min)
Topoisomerase II inhibitor
Etoposide capsules
Vepesid
- No Prodrug
- PO
- S/E: Myelosuppression [BBW]
- Alopecia, N/V/D, Mucositis, Hypotension, Hypersensitivity, Anaphylactoid Rxns, Secondary Malignancies
- 1:2 IV to PO, round to nearest 50 mg
- MAJOR 3A4 SUBSTRATE
- If Dose > 200ng, give in 2-4 divided doses
- Do not puncture
- REFRIGERATE
- PROTECT FROM LIGHT
Anthracyclines
MOA?
Cell Cycle Specific (Yes/No)
Multiple MOA’s
- Inhibit Topoisomerase II
- Intercalates between base pairs
- Forms oxygen free radicals in liver
Cell Cycle NON-specific
Anthracyclines
Doxorubicin
Adriamycin
Anthracyclines
Doxorubicin HCl Liposomal
Doxil
Anthracyclines:
Daunorubicin
Cerubidine
Anthracyclines
Epirubicin
Ellence
Anthracyclines
Idarubicin
Idamycin
Anthracyclines
Valrubicin
Valstar
Anthracycline
List ALL Toxicities
- CEMS [BBW] = Cardiotoxicity, Extravasation, Myelosuppression, Secondary Malignancies
- Alopecia
- Severe N/V & Mucositis
- Hand-Foot Syndrome (Liposomal Formations)
- Hepatotoxicity (dose adj -> bilirubin)
- Gonadal Suppression & Reproductive Toxicity
- Radiation Recall
Anthracyclines Toxicities:
CARDIOTOXICITY!
Monitoring Parameters?
- Baseline ECHO or MUGA required before, during, and after treatment. Increase frequency if dose >300mg/m2
-
Monitor LVEF
- Cardiac Deterioration indicated if:
- 10% decline below normal
- Absolute LVEF = <45%
- 20% decline @ any level
- Cardiac Deterioration indicated if:
Anthracyclines Toxicities:
CARDIOTOXICITY!
Onset S/Sx:
Immediate?
Chronic?
Late-Onset?
- Immediate: ECG Changes, QT Prolongation, Arrhythmias
- Chronic: Tachycardia, Tachypnea, Exercise intolerance, pulmonary congestion, poor perfusion, CHF (eventually)
- Late-Onset: CHF, ventricular dysfunction, arrhythmias
Anthracyclines Toxicities:
CARDIOTOXICITY!
Risk Factors?
- Age > 65
- Pediatric Population
- Chest wall radiation
- Prior exposure to anthracyclines
- Pre-existing cardiac conditions
Anthracyclines Toxicities:
CARDIOTOXICITY!
Monitoring & Prevention?
Anthracyclines Toxicities:
HEPATOTOXICITY!
Significant Considerations?
- Dose Adjustment is based on Bilirubin Levels
- Avoid Anthracyclines in severe hepatic impairment
Anthracyclines Toxicities:
EXTRAVASATION!
Definition?
Result?
MOA?
- All anthracyclines are VESICANTS
- Therefore –> potential for extravasation
- Definition: Chemotherapy leaks out of vein or central line into the surrounding tissue
- Result: Severe Tissue Damage
- MOA: binds to DNA of healthy tissue, cell death occurs, spreads to healthy cells nearby
Anthracyclines Toxicities:
EXTRAVASATION!
Signs and Symptoms?
- Initial S/Sx = Itching without pain
- Mins - Hrs Later = Burning Sensation
- Next Few Weeks = Erythema + Blistering
- If Significant/Does not subside = Small areas of necrosis, requires surgery
Anthracyclines Toxicities:
EXTRAVASATION!
How to Prevent?
- Give Vesicant drugs BEFORE other cytotoxic agents
- If Multiple Vesicants = give agent with the SMALLEST INFUSION VOLUME FIRST
- Continuous infusions can only be given as a CENTRAL VENOUS LINE
Anthracyclines Toxicities:
EXTRAVASATION!
Patients with Higher Risk?
- Elderly Patients (fragile veins)
- Thrombocytopenic Patients
- Diabetic Patients(w/ PN or lymphedema)
- Prolonged peripheral line infusions
- Previous chemo or radiotherapy
