Chemotherapy Induced Nausea and Vomiting

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65 Terms

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nausea

imminent need to vomit; associated with gastric stasis

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retching

labored movement of thoracic and abdominal muscles

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vomiting

forceful expulsion of gastric contents through the mouth; caused by GI retroperistalsis

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neurotransmitters involved in vomiting

serotonin, substance P (neurokinin family), dopamine, acetylcholine, histamine, cannabinoid

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pathophysiology of CINV

chemotherapy agents activate NT receptors in GI tract and CTZ which sends afferent impulses to vomiting center in medulla; vomiting center sends efferent impulses to abdominal muscles, salivation center, cranial nerves, and respiratory center resulting in vomiting

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patient specific factors for increased CINV

younger (<50 years), female, prior chemo, little to no prior alcohol use, prone to motion sickness, history of pregnancy related n/v, anxiety, high pretreatment expectation of nausea

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treatment factors for CINV

chemo agent, dose of chemo, schedule and route of administration, concomitant radiation therapy

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acute CINV

occurs within mins to hours (peak in 5-6 hours), resolves within 24 hours

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delayed CINV

occurs after 24 hours

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delayed CINV is common with which treatments

cisplatin, carboplatin, cyclophosphamide, and doxorubicin

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anticipatory vomiting

occurs before receiving next treatment; conditioned response following a negative past experience

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risk factors for anticipatory vomiting

< 50 years old, n/v, sweating, warm feeling with prior chemo cycle, anxiety or depressive disorder, history of motion sickness

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breakthrough CINV

emesis that occurs despite adequate prophylaxis (10-40% of individuals); may require antiemetic rescue

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refractory CINV

emesis that occurs during subsequent cycles to which prophylaxis and/or rescue therapy have failed previously

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goal of CINV therapy is ______________

prevention

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________ day antiemetic therapy for moderately emetogenic regimens

2 day

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_________ day antiemetic therapy for highly emetogenic regimens

3 day

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antiemetic regimen should be based on...

chemotherapy agent with highest emetic potential

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emetogenicity

likelihood of a chemotherapy agent to cause vomiting

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emetogenicity is based on...

percent of patients who had emesis WITHOUT appropriate prophylaxis

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high emetic risk chemotherapy agents

AC combination (doxorubicin/epirubicin plus cyclophosphamide), carboplatin with AUC > 4, cisplatin, cyclophosphamide > 1500 mg/m2

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moderate emetic risk chemotherapy agents

cyclophosphamide < 1500 mg/m2, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, melphalan, oxaliplatin, temozolomide

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low emetic risk chemotherapy agents

brentuximab vedotin, docetaxel, etoposide, 5-FU, floxuridine, gemcitabine, paclitaxel

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___________ chemotherapy group shows low emetic risk

taxanes

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minimal emetic risk in general

MAb and vincas

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minimal emetic risk chemotherapy agents

bevacizumab, rituximab, vinblastine, vincristine, vincristine liposomal, vinorelbine

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non-pharmacologic strategies to reduce risk of emesis

used in addition to pharmacological strategies, avoidance or moderation of dietary intake of trigger foods, eating smaller, more frequent meals

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emetic trigger foods

fatty or spicy foods, avoid favorite foods if experiencing n/v (food aversion), eating room temp foods

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take anti emetics _____________ before meals

30 mins if needed

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antiemetic classes

serotonin antagonist, corticosteroids, NK-1 antagonists, phenothiazines, benzodiazepines, cannabinoids, atypical antipsychotics, other agents like haloperidol, metoclopramide, scopolamine

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5-HT3 antagonists MOA

blocks serotonin peripherally on afferent vagal nerves in GI tract and centrally in CTZ

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side effects of 5-HT3 antagonists

constipation (can induce n/v), headache, fatigue

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risk of dose dependent ________________ in 5-HT3 antagonists

QT prolongation

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max IV zofran dose

16 mg (single dose)

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most effective for acute n/v

5-HT3 antagonists (exception of palonosetron)

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5-HT3 antagonists used for both acute and delayed CINV

palonosetron

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zofran dose adjustment in patients with...

severe hepatic impairment

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corticosteroid side effects

insomnia, GI symptoms, increased appetite, agitation

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most effective for acute and delayed CINV

corticosteroids

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what to watch out for when using corticosteroids as an anti emetic regimen

an additional corticosteroid should NOT be added for emesis if it is already part of the chemo regimen

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NK-1 receptor antagonist pharmacology

inhibits binding of substance P to NK-1 receptor

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adverse events of NK-1 receptor antagonist

fatigue, headache, injection site reactions, hiccups

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NK-1 receptor antagonists interact with _______________ substrates and inhibitors and ____________ inducers

CYP3A4 substrates and inhibitor and CYP2C9 inducer

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fosaprepitant is dosed on day ___________ only

1

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NK-1 receptor antagonist specific drug interactions

DEXAMETHASONE, ethinyl estradiol, warfarin, cyclophosphamide, ifosfamide, docetaxel, vinorelbine

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phenothiazines pharmacology

dopamine blockade in CTZ; antimuscarinic effects may also enhance antiemetic activity

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phenothiazines ADE

constipation, orthostatic hypotension, xerostomia, urinary retention, dizziness, sedation, extrapyramidal effects including tardive dyskinesia

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IV administration of ______________ may cause severe extravasation

phenothiazines

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most effective for breakthrough n/v

phenothiazines

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benzodiazepines antiemetic pharmacology

may decrease input to vomiting center; has sedative and anxiolytic effects through GABA activation

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benzodiazepine side effects

dizziness, sedation, memory impairment; effects enhanced in elderly

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most common benzodiazepine for CINV

lorazepam

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used for anticipatory or breakthrough CINV

benzodiazepines

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cannabinoid antiemetic pharmacology

may inhibit endorphins in emetic center; may also be due to effects on cannabinoid receptors (CB1) in CNS

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cannabinoid ADE

euphoria, somnolence, xerostomia, increased appetite

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only used for breakthrough and refractory CINV

cannabinoids

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olanzapine antiemetic pharmacology

thiobenzodiazepine atypical antipsychotic; dopaminergic, serotonergic, histaminergic, and muscarinic effects

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olanzapine ADE

sedation, dizziness, headache, xerostomia, constipation; use with caution in elderly

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olanzapine is effective for _______________ CINV

delayed and breakthrough

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olanzapine vs. aprepitant

olanzapine is associated with higher rate of nausea control during delayed period

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typically reserved for refractory n/v or in palliative care setting

haloperidol

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metoclopramide black box warning

tardive dyskinesia

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prokinetic agent

metoclopramide

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use metoclopramide in caution in...

elderly patients and patients with renal impairment

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use scopolamine patches in caution in...

elderly, patients with BPH, narrow angle glaucoma, or asthma