08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee Flashcards Preview

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Flashcards in 08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee Deck (32):
1

Which cancer drugs require renal dose adjustments?

MTX. Cisplatin. Carboplatin. Cyclophosphamide. Bleomycin. Etoposide

2

Which cancer drugs require hepatic dose adjustments?

Vinca alkaloids. Taxanes. Anthracyclines. Gemcitabine. Irinotecan. Etoposide (renal as well)

3

What are the common toxicities associated with Enzyme Inhibitors?

Myelosuppression (DLT), N/V (except bleomycin), mucositis, alopecia

4

Which Enzyme Inhibitors have cardiac effects?

Anthracyclines (Daunorubicin. Doxorubin. Idarubicin)

5

Which Enzyme Inhibitors have pulmonary effects?

Bleomycin, Mitomycin

6

Which Enzyme Inhibitors have Vesicant effects (induces blistering)?

Doxorubicin

7

What are the ADRs when Anthracyclines are used for Bladder Instillation?

Irritable bladder symptoms, blood in urine, loss of bladder control, painful urination, strong urge to urinate

8

What are the risk factors for Cardiomyopathy caused by Anthracyclines?

Age > 65 or in pediatrics. Pre-existing cardiac disease. RT to chest wall. Chemotherapy-specific (large bolus dose; cumulative lifetime doses; combination w/ other cardiotoxins)

9

What are the results of Doxorubicin-Associated Cardiomyopathy?

Arrythmias (non-dose-related). Subacute - days to weeks. CHF (Chronic effect) - late onset (months to years after receiving anthracyclines, related to cumulative doses, common/life threatening/irreversible)

10

What dose of Doxorubicin do you NOT want to exceed d/t much higher incidence of CHF?

550mg/m2 total dose

11

What is the MOA of cardiotoxicity caused by Anthracyclines?

Iron-dependent O2 free-radical formation: anthracycline-iron-O2 complex --> initiate lipid peroxidation --> damage mitochondrial DNA, gradual loss of myofibrils and decreased contractility

12

How is max dosing of Doxorubicin like for prevention of cardiomyopathy?

< 500-550 mg/m2 if low risk. < 400-450 mg/m2 if high risk. Slow infusion > 6 hrs or smaller weekly dose. Combination with cardioprotectant (Iron chelator dexrazoxane)

13

What is Dexrazoxane (Zinecard, Totect)?

Iron chelator, blocks generation of Fe-doxorubicin complex

14

What are the uses of Dexrazoxane (Zinecard, Totect)?

1) Metastatic breast cancer, received Doxorubicin > 300mg/m2 and will likely continue. 2) Use with other anthracyclines or at risk for cardiac dysfunction. 3) Extravasation (skin damage) from anthracyclines (use Totect only)

15

How is Dexrazoxane dosed?

Dexrazoxaine:Doxorubicin 10:1, IV over < 15 minutes, within 30 minutes of Doxorubicin

16

Which agents are associated with Pulmonary Toxicity through hypersensitivity reaction?

Sudden onset, not-dose related, eosinophils: Bleomycin

17

Which agents are associated with Pulmonary Toxicity through Direct Injury To Lung (Fibrosis)?

Bleomycin!!! Carmustine, Cyclophosphamide, Busulfan (Busulfan Lung), Chlorambucil

18

What is the MOA of Bleomycin Lung Fibrosis?

Bleomycin --> Breaks in DNA by an oxidative process via free radical formation. Damage to pulmonary endothelial cells and type I pneumocytes --> Inflammatory exudate within alveoli and fibrosis that may permanently impair diffusion and decrease lung volumes

19

What is Bleomycin inactivated by?

Aminohydrolases (which is low in skin and lungs)

20

At what Bleomycin dose is pulmonary toxicity a concern?

Bleomycin cumulative dose > 400 units or > 200 units/m2

21

What is prevention like for pulmonary toxicity caused by Bleomycin?

No O2 treatment if risk of fibrosis ("No O2, Bleo Patient"). Limit cumulative dose

22

What is treatment like for pulmonary toxicity caused by Bleomycin?

None. Often irreversible, progressive. Steroids helpful if hypersensitivity-related

23

What is the primary toxicity related to Taxanes (Paclitaxel, Docetaxel)?

Neutropenia. Neurotoxicity - DLT (similar to platinum-induced)

24

What is hypersensitivity like with Paclitaxel?

~40% of patients. Cause: Cremophor EL vehicle (castor oil)

25

What is used to treat Paclitaxel hypersensitivity?

H1, H2, and corticosteroids (mnemonic "ABCD"): Antiemetic, Benadryl, Cimetidine (any H2 blocker), and Dexamethasone

26

What is a unique toxicity related to Taxotere (Docetaxel)?

Pleural effusion, fluid retention. Pre-medicate: Dexamethasone 8mg PO BID x3 days, starting 1 day prior to treatment

27

What is the BBW for Rituximab?

Infusion-Related Reaction: Hypotension, bronchospasm, MI, arrythmias. Can pre-medicate with Benadryl, Famotidine, Dexamethasone

28

How should Etoposide (TOP II Inhibitor) be administered?

Infuse at least over 60 minutes. RX prep: Concentration-dependent stability

29

What is the dose limiting ADR for Irinotecan (TOP I Inhibitor)?

Diarrhea. Treat early diarrhea w/ anticholinergics (atropine). Late diarrhea w/ Loperamide

30

Which agent can cause extreme Extravasation (skin wasting) and tissue necrosis?

Doxorubicin

31

What is the management of Extravasation with Anthracycline use?

Local antidote: Dexrazoxane (Totect). Cold compresses

32

What is the management of Extravasation with Vinca Alkaloid use?

Hyaluronidase. Warm compresses