CINV Flashcards by Nicole Gaudreau

Per patient perceptions what is the number one severe side effects of chemo?

Fatigue

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What are the CINV RFs?

Female
age < 50
H/o motion sickness
H/o N/V associated with pregnancy
EtOH consumption (< 10 drinks/week)
H/o CINV
GI radiation
Brain involvement

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What is the definition of nausea?

Awareness of the urge to vomit

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What is the definition retching?

Non-productive attempt to vomit

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What is the definition of vomiting?

Forceful expulsion of GI contents

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What is intractable nausea?

N/V not adequately controlled after multiple antiemetics are used in series and combinations

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What is anticipatory nausea?

N/V occurring as a result of a conditioned response from previous treatment

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What is acute CINV?

0-24 hours after chemotherapy

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What is delayed CINV?

> 24 hours after chemotherapy

Often associated with highly emetogenic chemo agents, esp cisplatin regimens

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What is non-pharm treatment of CINV?

Avoidance of strong odors
Eating small meals more frequently
Psychological relaxation techniques
Acupuncture/acupressure
P6 stimulation (relief band)

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What is the pathophysiology of CINV?

Chemoreceptor trigger zone
Cerebral cortex
Peripheral pathways
Vestibular system

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What is the Chemoreceptor trigger zone?

Exposure to toxins in the blood stream or CSF stimulates the vomiting center

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How is the cerebral cortex involved in CINV?

Gains input from the senses, meningeal inrritation and increased ICP that activate vomiting centers

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How are peripheral pathways involved in CINV?

GI and viscera mechano- and chemoreceptors transmit messages via the vagus and splanchnic serves, sympathetic ganglia and glossopharyngeal nerves

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How is the vestibular system involved in CINV?

N/V triggered by motion

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What is the incidence of CINV for high risk antineoplastic agents?

> 90%

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What is the incidence of CINV for moderate risk antineoplastic agents?

30-90%

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What is the incidence of CINV for low risk antineoplastic agents?

10-30%

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What is the incidence of CINV for minimal risk antineoplastic agents?

< 10%

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What are the two CINV high risk antineoplastic agents he circled?

Anthracycline/cyclophosphamide combination

Cisplatin

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What drugs can be used as antiemetics?

Corticosteroids
Betyrophenones
Serotonin antagonists
Antimuscarinic
NK1 antagonists
Benzo
Phenothiazines &amp; dopamine antagonists
Cannabinoids

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What is the MOA of dexamethasone in CINV?

Overall unknown
Inhibition of PG synthesis
Decreased BBB permeability of chemo agents
Inhibition of cortical input to vomiting center

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What is the place in therapy of dexamethasone in CINV?

Brain tumor or CNS involvement
Malignant bowel obstruction
Chemotherapy incuded N/V

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What are the serotonin antagonists?

Ondansetron
Granisetron
Palonosetron

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What is the MOA of serotonin agonists?

Block serotonin receptors in the GI tract

When are serotonin antagonists effective at preventing acute emesis?

After chemo, radiation and anesthesia

What are AEs of serotonin antagonists?

HA | Constipation

What dose of ondansetron for high emetic risk?

PO: 24 mg IV: 8 mg or 0.15 mg/kg

What is the dose of ondansetron for moderate emetic risk?

PO: 16 mg IV: 8 mg or 0.15 mg/kg

What are the doses of high/ moderate emetic risk granesitron?

PO: 2 mg IV: 1 mg or 0.01 mg/kg SC: 10 mg qweekly

If dosed appropriately, can we consider all serotonin agonists equivalent?

Yes

What is the place in therapy for NK1 receptor antagonists?

For the prevention of acute and delayed N/V following highly emetogenic regimens

What are the DDIs for NK1 receptor antagonists?

Warfarin | Dexmethasone

What are the advantages of NK1 RAs?

Administration as an all-oral regimen Single-dose schedule given on day of chemo Possible dexamethasone sparing regimen

What are the challenges of NK1 RAs?

Pts unable to tolerate PO | Cost, procurement, and reimbursement

What does NEPA contain?

Netupitant/palonosetron

What is netupitant?

Highly selective substance P/NK 1 receptor

What is olanzapine?

5-HT2 and DA antagonist for antiemetic activity

What are the SEs of olanzapine?

Drowsiness Akathisia Pseudoparkinsonism

What are DDIs for olanzapine?

Metoclopramide/kaloperidol | Increased risk of extrapyramidal SE

What are the phenothiazines?

Prochloroperazine Promethazine Thiethylperizine Perphenazine

What is the MOA for phenothiazines?

Block DA receptors in the chemoreceptor trigger zone

What is the place in therapy for phenothiazines?

Opioid induced n/v | Delayed nausea d/t chemotherapy

What are the AEs of phenothiazines?

Sedation EPS Akathesia

How are phenothiazines usually incorporated into antiemetic plans?

PRN

What is a concern with promethazine use?

Extravasation

What are butyrophenones?

Haloperidol | Droperidol

What is the MOA of btyrophenones?

Block DA receptors in chemoreceptor trigger zone

When can butyrophenones be used?

Potential use in breakthrough and/or refractory N/V after trying other agents

What are AEs of butyrophenones?

Sedation Dystonia Akasthesia

What is droperidol's BBW?

QT prolongation

What is the MOA of metoclopramide at low doses?

DA D2 antagonist

What is the MOA of metoclopramide at high dises?

Some 5HT2 antagonism

What is the place in therapy for metoclopramide?

Opioid induced N/V Malignant bowel obstruction Impaired GI motility Refractory CINV

What are the AEs of metoclopramide?

Diarrhea Dystonic reactions Akathesia Sedation

What was an AE of HD metoclopramide?

Tardive dyskinesia

Why are benzos used as antiemetics?

Combined with 5HT3 antagonists and dexamethasone for anxiolytic and amnestic effects Mitigates metoclopramide-induced agitation

What are effective as an adjunctive agent?

Cannabinoids

What two receptors do cannabinoids work on?

CB1 and CB2

What are CB1 receptors located?

Throughout the CNS

Where are CB2 receptors located?

On the brain stem neurons, most concentrated in periphery

How does cannabinoid prevent CINV?

Acting at central CB receptors by preventing proemetic effects of endogenous compounds

What are the AEs of cannabinoids?

Sedation Dizziness Hypotension Dysphoria

What is a 4-drug combination used for high emetogenic risk?

NK1 receptor antagonist 5HT3 receptor antagonist Dexamethasone Olanzapine

When do we use a 3 drug combination?

Carboplatin AUC 4+

What is the 3 drug combination?

NK1 RA 5-HT3 RA Dexamethasone

When do we ues a 2 drug combination?

Moderate-emetic-risk agents, excluding carbo

What is the 2 drug regimen?

5-HT3 receptor antagonist | Dexamethasone

If a pt is low emetogenic risk what do we give?

5-HT3 or dexamethasone

If the patient has not had olanzapine previously and has N/V despite adequate prophylaxis?

Add olanzapine to the regimen

If the patient is having breakthrough nausea/vomiting, what can be added to the standard regimen?

Anti-emetic with alternative mechanism

When is refractory n/v common?

Regimens containing multiple alkylating agents and stem cell transplants

If a patient has intractable n/v, how are the medications dosed?

Scheduled around the clock

What medications are used for intractable n/v?

Mirtazepine Cannabinoids Olanzapine ODTs, IV or rectal formulations may be required

What are the DOCs for opioid induced n/v?

Metoclopramide Prochloroperazine Haloperidol

What is the most common causes of N/V in patients with end-stage cancer?

Constipation

How does constipation cause n/v?

Slowing of intestinal persitalsis Increased ab pressure and distention of bowel Activation of gut neurotransmitters

What cancers are bowel obstruction common in?

Ovarian | Colorectal