Chemo Induced Nausea/Vomiting Flashcards
Acute Chemo-induced Nausea and Vomiting (CINV)
CINV occurring in the first 24h after starting chemo
Delayed CINV
CINV occurring from 24h - several (2-5) days after chemo
Breakthrough CINV
CINV occurring despite appropriate preventative treatment
Anticipatory CINV
CINV occurring before a treatment as a conditioned response to the occurrence of CINV in previous cycle
Refractory CINV
CINV recurring in subsequent cycles of therapy, excluding anticipatory CINV
CINV occurs due to communication between which 3 main neurotransmitters/receptors in the CNS and GI tract
5-HT3
Substance P and NK-1 receptor
Dopamine
CINV Peripheral pathway
5-HT3 moderated
originates in GI tract
Mostly associated with acute emesis
CINV Central pathway
NK-1 receptor mediated
occurs mostly in the brain
mostly associated with delayed CINV
Lifestyle modifications to manage CINV
small frequent meals
eating meals at room temp
CINV risk factors
Age < 50 yrs
female
emetic potential of chemo
little or no previous alcohol use
Hx of CINV or prone to motion sickness
Emesis during pregnancy
Prevention for high risk IV cancer regimens
Option 1 (preferred)
- day 1: Olanzapine, Dexamethasone, NK1-RA, 5-HT3RA
- day 2-4: Olanzapine, Dexamethasone
Option 2
- day 1: Olanzapine, Dexamethasone, Palonosetron
- days 2-4: Olanzapine
Option 3:
- day 1: Dexamethasone, NK1 RA, 5-HT3 RA
- days 2-4: Dexamethasone
Should aprepitant IV ever be given on days 2-3?
NO
Should aprepitant PO ever be given on days 2-3?
only if aprepitant was given day 1
Prevention for moderate risk IV cancer regimens
Option 1:
- day 1: Dexamethasone, 5-HT3 RA
- day 2-3: Dexamethasone OR 5-HT3 RA
Option 2:
- day 1: Olanzapine, Dexamethasone, Palonosetron
- day 2-3: Olanzapine
Option 3:
- day 1: NK1 RA, dexamethasone, 5-HT3 RA
- day 2-3: Aprepitant +/- Dexamethasone
Agents for low emetic risk IV cancer regimens
one of the following:
- Dexamethasone
- Metoclopramide
- Prochlorperazine
- 5-HT3 RA
CINV prevention for minimal emetic risk IV cancer agents
no prophylaxis recommended
CINV prevention for high -moderate risk PO anticancer regimens
5-HT3 RA
CINV prevention for low-minimal risk PO anticancer regimens
PRN recommended
Breakthrough CINV treatment
- Add one agent from a different drug class to the current regimen
- Consider regular admin rather than PRN
- Consider antacid therapy if pt has dyspepsia
Agents:
- olanzapine
- lorazepam (good for anx related sx)
- dronabinol
- 5HT3 RA (not palonosetron: long t1/2)
- prochlorperazine
- dexamethasone
- metoclopramide
- scopolamine
Anticipatory emesis treatment
Avoid strong smells
Lorazepam
Acupuncture
Behavioral therapy
Dexamethasone
MOA: unknown
ADE:
- insomnia (admin in AM)
- dyspepsia (take with food / add H2RA or PPI)
- hyperglycemia
- HTN
5-HT3 RA
MOA: blocks serotonin both peripherally (GI) and centrally (medulla)
ADE:
- HA
- Constipation
QTc prolongation
1st gen: Ondansetron, Granisetron
- good for acute CINV
- short acting
2nd gen: Palonosetron
- good for acute and delayed CINV
- long acting
- never use for breakthrough CINV
NK1-RA
MOA: inhibits substance P/NK1
- augments 5HT3 RA and dexamethasone antiemetic activity
Only used for preventing CINV, not treatment
Agents:
- aprepitant
- fosapretant
- rolapitant (long t1/2, should not be administered < 2 week intervals)
- fosnetupitant
- netupitant
DDI:
- inhibit CYP3A4 and CYP2C9 (decrease dexamethasone dose to 8mg on days 2-4)
ADE:
- fatigue
- GI upset
- HA
- hiccups
Olanzapine
MOA: blocks dopamine, serotonin, muscarinic and histamine receptors
used for prevention and breakthrough
ADE:
- Sedation!!! (admin at bedtime, lower doses in elderly)
- hyperglycemia
- fatigue
- QTc prolongation
Dopamine antagonists
MOA: antagonize dopamine in chemoreceptor trigger zone
- useful for breakthrough CINV
Agents:
- prochlorperazine
- metoclopramide
- promethazine
ADE:
- prochlorperazine, promethazine: drowsiness, constipation
- metoclopramide: drowsiness, diarrhea, QTc prolongation, tardive dyskinesia (avoid > 12 weeks use)
prochlorperazine has the lowest QTc risk
Benzodiazepines
MOA: anxiolytic
- useful for anticipatory CINV or breakthrough CINV with an anxiety component
Agents:
- lorazepam
- alprazolam
admin the night or morning before therapy (or both)
ADE:
- sedation
- dizziness
Cannabinoids
MOA: CB1 antagonism suppresses vomiting + indirect activation of 5HT1a in raphe nucleus
Rarely used; only indicated for refractory disease
Agents:
- dronabinol
ADE:
- sedation
- euphoria, hallucinations
- palpitations
- flushing
- cough
Scopolamine
MOA: anticholinergic
only for breakthrough disease
ADE:
- dry mouth
- somnolence
- blurred vision
