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nausea
imminent need to vomit; associated with gastric stasis
retching
labored movement of thoracic and abdominal muscles
vomiting
forceful expulsion of gastric contents through the mouth; caused by GI retroperistalsis
neurotransmitters involved in vomiting
serotonin, substance P (neurokinin family), dopamine, acetylcholine, histamine, cannabinoid
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
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
treatment factors for CINV
chemo agent, dose of chemo, schedule and route of administration, concomitant radiation therapy
acute CINV
occurs within mins to hours (peak in 5-6 hours), resolves within 24 hours
delayed CINV
occurs after 24 hours
delayed CINV is common with which treatments
cisplatin, carboplatin, cyclophosphamide, and doxorubicin
anticipatory vomiting
occurs before receiving next treatment; conditioned response following a negative past experience
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
breakthrough CINV
emesis that occurs despite adequate prophylaxis (10-40% of individuals); may require antiemetic rescue
refractory CINV
emesis that occurs during subsequent cycles to which prophylaxis and/or rescue therapy have failed previously
goal of CINV therapy is ______________
prevention
________ day antiemetic therapy for moderately emetogenic regimens
2 day
_________ day antiemetic therapy for highly emetogenic regimens
3 day
antiemetic regimen should be based on...
chemotherapy agent with highest emetic potential
emetogenicity
likelihood of a chemotherapy agent to cause vomiting
emetogenicity is based on...
percent of patients who had emesis WITHOUT appropriate prophylaxis
high emetic risk chemotherapy agents
AC combination (doxorubicin/epirubicin plus cyclophosphamide), carboplatin with AUC > 4, cisplatin, cyclophosphamide > 1500 mg/m2
moderate emetic risk chemotherapy agents
cyclophosphamide < 1500 mg/m2, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, melphalan, oxaliplatin, temozolomide
low emetic risk chemotherapy agents
brentuximab vedotin, docetaxel, etoposide, 5-FU, floxuridine, gemcitabine, paclitaxel
___________ chemotherapy group shows low emetic risk
taxanes
minimal emetic risk in general
MAb and vincas
minimal emetic risk chemotherapy agents
bevacizumab, rituximab, vinblastine, vincristine, vincristine liposomal, vinorelbine
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
emetic trigger foods
fatty or spicy foods, avoid favorite foods if experiencing n/v (food aversion), eating room temp foods
take anti emetics _____________ before meals
30 mins if needed
antiemetic classes
serotonin antagonist, corticosteroids, NK-1 antagonists, phenothiazines, benzodiazepines, cannabinoids, atypical antipsychotics, other agents like haloperidol, metoclopramide, scopolamine
5-HT3 antagonists MOA
blocks serotonin peripherally on afferent vagal nerves in GI tract and centrally in CTZ
side effects of 5-HT3 antagonists
constipation (can induce n/v), headache, fatigue
risk of dose dependent ________________ in 5-HT3 antagonists
QT prolongation
max IV zofran dose
16 mg (single dose)
most effective for acute n/v
5-HT3 antagonists (exception of palonosetron)
5-HT3 antagonists used for both acute and delayed CINV
palonosetron
zofran dose adjustment in patients with...
severe hepatic impairment
corticosteroid side effects
insomnia, GI symptoms, increased appetite, agitation
most effective for acute and delayed CINV
corticosteroids
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
NK-1 receptor antagonist pharmacology
inhibits binding of substance P to NK-1 receptor
adverse events of NK-1 receptor antagonist
fatigue, headache, injection site reactions, hiccups
NK-1 receptor antagonists interact with _______________ substrates and inhibitors and ____________ inducers
CYP3A4 substrates and inhibitor and CYP2C9 inducer
fosaprepitant is dosed on day ___________ only
1
NK-1 receptor antagonist specific drug interactions
DEXAMETHASONE, ethinyl estradiol, warfarin, cyclophosphamide, ifosfamide, docetaxel, vinorelbine
phenothiazines pharmacology
dopamine blockade in CTZ; antimuscarinic effects may also enhance antiemetic activity
phenothiazines ADE
constipation, orthostatic hypotension, xerostomia, urinary retention, dizziness, sedation, extrapyramidal effects including tardive dyskinesia
IV administration of ______________ may cause severe extravasation
phenothiazines
most effective for breakthrough n/v
phenothiazines
benzodiazepines antiemetic pharmacology
may decrease input to vomiting center; has sedative and anxiolytic effects through GABA activation
benzodiazepine side effects
dizziness, sedation, memory impairment; effects enhanced in elderly
most common benzodiazepine for CINV
lorazepam
used for anticipatory or breakthrough CINV
benzodiazepines
cannabinoid antiemetic pharmacology
may inhibit endorphins in emetic center; may also be due to effects on cannabinoid receptors (CB1) in CNS
cannabinoid ADE
euphoria, somnolence, xerostomia, increased appetite
only used for breakthrough and refractory CINV
cannabinoids
olanzapine antiemetic pharmacology
thiobenzodiazepine atypical antipsychotic; dopaminergic, serotonergic, histaminergic, and muscarinic effects
olanzapine ADE
sedation, dizziness, headache, xerostomia, constipation; use with caution in elderly
olanzapine is effective for _______________ CINV
delayed and breakthrough
olanzapine vs. aprepitant
olanzapine is associated with higher rate of nausea control during delayed period
typically reserved for refractory n/v or in palliative care setting
haloperidol
metoclopramide black box warning
tardive dyskinesia
prokinetic agent
metoclopramide
use metoclopramide in caution in...
elderly patients and patients with renal impairment
use scopolamine patches in caution in...
elderly, patients with BPH, narrow angle glaucoma, or asthma