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PHAR 507: Oncology > MD3: Topoisomerases > Flashcards

MD3: Topoisomerases Flashcards

1
Q

Topoisomerase I Inhibitors

MOA

Cell Cycle Specific/Non-Specific?

Drug Class?

A
  • Inhibits topoisomerase from religation of the DNA strands (which is needed for replication), pieces of ssDNA accumulates.
  • Cell Cycle Specific (S PHASE)
  • Camptothecins
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2
Q

Topoisomerase I inhibitor:

Topotecan

Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?

A

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)
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3
Q

Topoisomerase I inhibitors

Irinotecan

Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?

A

Camptosar (CPT-11)

  • Prodrug—-Active Drug = SN38
  • IV
  • S/E: Diarrhea [BBW], Myelosuppression [BBW]
  • Alopecia, N/V/, Stomatitis, Hepatoxicity(TBili, Alk Phos)
    —————————————————-
    Glucoronidated by UGT1A1
    Mutation: Homozygous UGT1A1*28 –> inc. Toxicity
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4
Q

Topoisomerase I inhibitor:

Irinotecan liposomal

A

Onivyde

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5
Q

Topoisomerase II Inhibitors

MOA

Cell Cycle Specific/Non-Specific?

Drug Class?

A

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]

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6
Q

Topoisomerase II Inhibitor

Etoposide IV
Etoposide phosphate IV

Prodrug? (Yes/No)
Route of Admin:
Side Effects/Toxicities?
——————————————-
Special Considerations?

A

(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)
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7
Q

Topoisomerase II inhibitor

Etoposide capsules

A

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
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8
Q

Anthracyclines

MOA?
Cell Cycle Specific (Yes/No)

A

Multiple MOA’s

  1. Inhibit Topoisomerase II
  2. Intercalates between base pairs
  3. Forms oxygen free radicals in liver

Cell Cycle NON-specific

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9
Q

Anthracyclines

Doxorubicin

A

Adriamycin

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10
Q

Anthracyclines

Doxorubicin HCl Liposomal

A

Doxil

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11
Q

Anthracyclines:

Daunorubicin

A

Cerubidine

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12
Q

Anthracyclines

Epirubicin

A

Ellence

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13
Q

Anthracyclines

Idarubicin

A

Idamycin

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14
Q

Anthracyclines

Valrubicin

A

Valstar

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15
Q

Anthracycline

List ALL Toxicities

A
  • 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
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16
Q

Anthracyclines Toxicities:

CARDIOTOXICITY!
Monitoring Parameters?

A
  • 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
17
Q

Anthracyclines Toxicities:

CARDIOTOXICITY!

Onset S/Sx:

Immediate?
Chronic?
Late-Onset?

A
  • Immediate: ECG Changes, QT Prolongation, Arrhythmias
  • Chronic: Tachycardia, Tachypnea, Exercise intolerance, pulmonary congestion, poor perfusion, CHF (eventually)
  • Late-Onset: CHF, ventricular dysfunction, arrhythmias
18
Q

Anthracyclines Toxicities:

CARDIOTOXICITY!

Risk Factors?

A
  • Age > 65
  • Pediatric Population
  • Chest wall radiation
  • Prior exposure to anthracyclines
  • Pre-existing cardiac conditions
19
Q

Anthracyclines Toxicities:

CARDIOTOXICITY!

Monitoring & Prevention?

A
20
Q

Anthracyclines Toxicities:

HEPATOTOXICITY!
Significant Considerations?

A
  • Dose Adjustment is based on Bilirubin Levels
  • Avoid Anthracyclines in severe hepatic impairment
21
Q

Anthracyclines Toxicities:

EXTRAVASATION!
Definition?
Result?
MOA?

A
  • 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
22
Q

Anthracyclines Toxicities:

EXTRAVASATION!
Signs and Symptoms?

A
  • 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
23
Q

Anthracyclines Toxicities:

EXTRAVASATION!
How to Prevent?

A
  • 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
24
Q

Anthracyclines Toxicities:

EXTRAVASATION!
Patients with Higher Risk?

A
  • Elderly Patients (fragile veins)
  • Thrombocytopenic Patients
  • Diabetic Patients(w/ PN or lymphedema)
  • Prolonged peripheral line infusions
  • Previous chemo or radiotherapy
25
Q

Anthracyclines Toxicities:

EXTRAVASATION!
How to Manage if it Occurs?

A

SLAPP the patient!

Stop infusion & disconnect tubing

Leave the needle/cannula in place

Aspirate any available vesicant (gently) & remove the cannula

Physician notification

Provide antidote/Tx

26
Q

ANTHRACYCLINE EXTRAVASATION!
Treatment Options?

A
  • Apply Cold Compress for 20 mins QID x 1-2 Days
  • Dexrazoxane (Totect) IV infusion QD x 3 days
  • DMSO 50-99% w/v Topical Soln, Apply TWICE the size of the affected area Q8H x 7 Days
  • Elevate the affected limb above the heart and gently apply pressure.
27
Q

Dexrazoxane IV

MOA?
Use?

A

Totect

MOA: iron chelation, decreases free radical damage

Used for: Anthracycline Extravasation

28
Q

DMSO

MOA?
Use?

A

NO Brand Name

MOA: Increases skin permeability

Used for Anthracycline Extravasation

PHAR 507: Oncology (2 decks)

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