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

Thera IX > 08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee > Flashcards

Flashcards in 08b Major Organ Toxicities (Enzyme and Microtubule Inhibitors) Lee Deck (32)
Loading flashcards...
1
Q

Which cancer drugs require renal dose adjustments?

A

MTX. Cisplatin. Carboplatin. Cyclophosphamide. Bleomycin. Etoposide

2
Q

Which cancer drugs require hepatic dose adjustments?

A

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

3
Q

What are the common toxicities associated with Enzyme Inhibitors?

A

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

4
Q

Which Enzyme Inhibitors have cardiac effects?

A

Anthracyclines (Daunorubicin. Doxorubin. Idarubicin)

5
Q

Which Enzyme Inhibitors have pulmonary effects?

A

Bleomycin, Mitomycin

6
Q

Which Enzyme Inhibitors have Vesicant effects (induces blistering)?

A

Doxorubicin

7
Q

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

A

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

8
Q

What are the risk factors for Cardiomyopathy caused by Anthracyclines?

A

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
Q

What are the results of Doxorubicin-Associated Cardiomyopathy?

A

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
Q

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

A

550mg/m2 total dose

11
Q

What is the MOA of cardiotoxicity caused by Anthracyclines?

A

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

12
Q

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

A

< 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
Q

What is Dexrazoxane (Zinecard, Totect)?

A

Iron chelator, blocks generation of Fe-doxorubicin complex

14
Q

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

A

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
Q

How is Dexrazoxane dosed?

A

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

16
Q

Which agents are associated with Pulmonary Toxicity through hypersensitivity reaction?

A

Sudden onset, not-dose related, eosinophils: Bleomycin

17
Q

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

A

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

18
Q

What is the MOA of Bleomycin Lung Fibrosis?

A

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
Q

What is Bleomycin inactivated by?

A

Aminohydrolases (which is low in skin and lungs)

20
Q

At what Bleomycin dose is pulmonary toxicity a concern?

A

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

21
Q

What is prevention like for pulmonary toxicity caused by Bleomycin?

A

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

22
Q

What is treatment like for pulmonary toxicity caused by Bleomycin?

A

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

23
Q

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

A

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

24
Q

What is hypersensitivity like with Paclitaxel?

A

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

25
Q

What is used to treat Paclitaxel hypersensitivity?

A

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

26
Q

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

A

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

27
Q

What is the BBW for Rituximab?

A

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

28
Q

How should Etoposide (TOP II Inhibitor) be administered?

A

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

29
Q

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

A

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

30
Q

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

A

Doxorubicin

31
Q

What is the management of Extravasation with Anthracycline use?

A

Local antidote: Dexrazoxane (Totect). Cold compresses

32
Q

What is the management of Extravasation with Vinca Alkaloid use?

A

Hyaluronidase. Warm compresses