10 Chemotherapy Induced N/V Hsu Flashcards by Chris Clark

What are the Emesis (N/V) risk factors?

Type of chemotherapy and dosage! Previous episodes of N/V! Age < 50 years. Female. History of motion sickness. High anxiety (anticipatory). History of low alcohol consumption (chronic alcoholism = decreased risk of emesis)

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What is Acute Onset Emesis?

Occurs several minutes to hours after chemotherapy. Peaks in 5-6 hours and resolves within 24 hours

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What is Delayed Onset Emesis?

Occurs > 24 hours after chemotherapy. Common drugs: Cisplatin > Carboplatin > “AC” Doxorubicin + Cyclophosphamide

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What is Anticipatory Emesis?

Occurs prior to chemotherapy

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What is Breakthrough Emesis?

Occurs while already on antiemetic therapy. Patients generally given additional medications PRN

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What are the Emesis Neurotransmitters (NT)?

Primary NT pathways (Serotonin, Substance P/NK, Dopamine). Other NT associated with Nausea (Corticosteroids, Cannabinoid, Opiates, Histamine, Acetylcholine)

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What are the 5HT3 Receptor Antagonists used?

Ondansetron (Zofran). Granisetron (Kytril, Sancuso). Dolasteron (Anzemet). Palonosetron (Aloxi)

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Which 5HT3 Receptor Antagonist is used as a patch?

Granisetron (Sancuso)

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Which 5HT3 Receptor Antagonist can only be given IV?

Palonosetron (Aloxi)

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Which 5HT3 Receptor Antagonist has efficacy in delayed N/V?

Palonosetron (Aloxi) d/t its long half-life (~40 hrs)

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What are the general class indications of 5HT3 Receptor Antagonists?

Prevention of chemotherapy, radiation, post-op N/V. Effective as mono and combination therapy. Most commonly used agent for mod-high emetogenic risk

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What are 5HT3 Receptor Antagonists NOT effective for?

Breakthrough emesis

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What are 5HT3 Receptor Antagonists LESS effective for?

Delayed N/V with the exception of Palonosetron (long half-life)

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What are the ADRs associated with 5HT3 Receptor Antagonists?

HA (dose/rate dependent). QT prolongation. Constipation > diarrhea

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What are the corticosteroids used?

Dexamethasone (Decadron) - preferred steroid for N/V

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How is Dexamethasone (Decadron) administered?

PO or IV

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What are the common ADRs associated with Dexamethasone (Decadron)?

GI stomach upset. CNS (insomnia, mood changes). Lab changes (increased glucose and WBC)

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What is the MOA of NKI-Antagonist (Emend)?

Substance P/Neurokinin I (NKI) receptor antagonist - GI and CNS receptor activity. No dopamine or serotonin receptor affinity

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What are the ADRs associated with NKI-Antagonists?

Hiccups! GI. LFT elevation. Emend regimen AE are similar to 5HT3 alone

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What are the DDIs with NKI-Antagonists?

3A4 inhibitor and substrate, 2C9 inducer. Decrease Dexamethasone dose by 50%!!!!

What is the indication for NKI-Antagonists?

Prevention of acute and delayed nausea and vomiting associated with moderate to high emetogenic chemotherapy. IV formulation = 150mg on day 1 ONLY

What is done for high emetogenicity dosing?

NKI-Antagonists to be used in combination with steroids and 5HT3 antagonist as a specific regimen

What are the NKI-Antagonists used?

Aprepitant or Fosaprepitant

What is the MOA of Dopamine Receptor Antagonists?

Antagonize dopamine receptors in the chemo trigger zone of the CNS. Increases GI motility via cholinergic response from peripheral dopamine antagonism. Both help decrease N/V

What are the Dopamine Receptor Antagonists used?

Metoclopramide (Reglan). Prochloperazine (Compazine)

What are the ADRs associated with Dopamine Receptor Antagonists?

CNS - EPS (parkinson's like symptoms). Manage with anticholinergic drugs

What are the Dopamine Receptor Antagonist uses?

May be used as single agents for CINV for LOW emetic regimens (Give one dose 30-60 minutes prior to chemo). Primarily for breakthrough N/V given PRN. Not as effective as serotonin antagonists

Which Dopamine Receptor Antagonist requires renal adjustment?

Metoclopramide (Reglan). Renal Cl < 40 = 50% dose

What are some Adjunctive antiemetic drug therapy agents?

Benzodiazepines (Lorazepam)

What is the MOA of Lorazepam (Ativan)?

Acts on GABA receptors to produce anxiolytic effects

What are the ADRs associated with Lorazepam?

CNS (drowsiness, dizziness, confusion). Respiratory depression (don't use with other CNS depressant agents)

What are the uses of Benzodiazepiens?

First line for anticipatory N/V. Not recommended as single agents for treatment or prevention of N/V

What are the directions for Lorazepam use?

Anticipatory: Start the night before chemotherapy and take a dose the morning of chemotherapy. May also be given PRN Q4-6 hrs (anxiety or nausea)

What is Dronabinol (Marinol)?

Cannabinoid, another antiemetic for mild to moderate CINV refractory or intolerant to other antiemetics

What is Promethazine (Phenergan)?

Another antiemetic used for breakthrough emesis

What is a BBW associated with Promethazine (Phenergan)

Severe tissue injury, DO NOT give SQ

What are the antipsychotic agents that can be used for emesis?

Olanzapine (Zyprexa). Haloperidol (Haldol)

What are some GI agents that can be used for emesis?

H2 blockers, PPIs, H1 blockers (antihistamines; diphenhydramine). NOT for monotherapy. May add as adjunctive therapy, particularly if patient has history of dyspepsia

What are the principles of Antiemesis?

PO and IV formulations have equal efficacy. Generally try PO first if tolerated (or for home use). Choose IV if actively vomiting (breakthrough emesis) or unable to take orals

Which agents have the highest causes of emesis?

CIsplatin. Combo: Cyclophosphamide + Doxorubicin (Anthracycline). Carmustine

Which agents cause minimal emesis?

Targeted agents (monoclonal antibodies). TKIs (orals) - minimal to low emetogenicity

What treatment plan is given to High Risk (>90%)?

Combination therapy required. 5-HT3 Serotonin Receptor Antagonist (any) + Dexamethasone + Emend (PO or IV)

How long is each agent used for?

Aprecitant (Emend) for 3 days (120mg PO, 80mg PO, 80mg PO). Dexamethasone for 4 days (12mg, 8mg, 8mg, 8mg). 5HT3 Antagonist used only on day 1

What is Dexamethasone use like for Moderate Risk?

Steroids past day 1 not required for moderate emetic regimens

What is used for low risk emesis?

Single agent treatment (Dexamethasone, Reglan, Compazine). Add PRN meds as appropriate

What is best for delayed emesis?

Aprepitant (Emend), but not always indicated. Steroids are a good choice but expensive

What is the treatment duration for Delayed Emesis?

3 days for high, 2 days for moderate

What are some key points for breakthrough emesis?

Consider around the clock rather than PRN (prevention > treatment). IV may be better than PO if vomiting. Serotonin antagonists are a poor choice

What are the key points of Anticipatory Emesis?

Benzodiazepines (start the night prior to chemotherapy and can give a dose the morning of chemo). Controlling acute and delayed emesis will decrease risk of future anticipatory emesis