Nausea and Vomiting
James Hallenbeck, MD
Director, Palliative Care Services,
Palo Alto VAHCS, Stanford University
Objectives
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Understand the pathophysiology of nausea and
vomiting
Utilize the “VOMIT” acronym in identifying
causes of nausea
Select antiemetic therapy, based underlying
physiology
Pearl for the Day…
But ferrets do!
So WHY do we have
this disgusting problem?
Consider our Hungry Ancestors…
What protects this guy from
eating something poisonous?
Progressive Failsafe Measures
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Memory
Appearances
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Smell
Taste
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What looks gross, is probably gross
Bitter – bad
Sweet –good
GI Track – mechano and chemoreceptors
CNS
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Chemoreceptor Trigger Zone (CTZ)
Vestibular Apparatus
A Central Final Pathway for
Nausea
(Dopamine, Serotonin)
???
CTZ
CNS
VOMIT
(Acetylcholine,Histamine)
CENTER
VestibularApparatus
(Acetylcholine, Histamine)
GI Tract
(Acetylcholine,Histamine, Serotonin
+ mechanoreceptors)
Receptor Affinity Common
Antiemetics
Drug
Dopamine 2 Musc. Chol. Histamine
Potency: K1 (nanomolar)
Scopolamine
>10,000
.08
>10,000
Promethazine
240
21
2.9
Prochlorperazine 15
2100
100
Chlorpromazine
25
130
28
Metoclopramide
270
>10,000
1,000
Haloperidol
4.2
>10,000
1,600
The lower the number, the stronger this
agent is
Adapted from Perourka, Snyder
at blocking this receptor
Causes of Nausea and Vomiting
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Vestibular
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Obstruction (Opioids)
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Mind (Dysmotility)
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Infection (Irritation)
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Toxins (Taste and other senses)
V
Vestibular Apparatus
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Complaint of nausea with head movement
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Mediated by acetylcholine and histamine receptors
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Doc(s):
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Promethazine (supp)
Scopolamine (patch, injection)
Cyclizine (oral, injection)
Most anticholinergic,
antihistiminic drugs will help!
O
Obstruction
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Most common cause: constipation
May be caused by external or internal obstruction
 In advanced malignant bowel obstruction external
compression most common
May be mediated through both mechano- and
chemoreceptors
DOC(s)
 True bowel obstruction
 Controversy as to best drugs
 Constipation: anti-constipation meds
M
Mind
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Mediates emotional, cognitive aspects of nausea
-- anxiety, memory, meaning
Can be very powerful
Manipulating taste and other senses often
helpful
DOC(s):
Lorazapam (poor solo agent)
 Appetite stimulants
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Megestrol, steroids, Cannibinoids
M
DysMotility
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Multiple causes
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Opioids
Anticholinergic drugs
Stomach/bowel compression, infiltration
Upper intestinal dysmotility-very common, under
appreciated
Doc(s): Prokinetics:
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Metoclopramide (upper only)
Motilin agonists (erythromycin)
Senna (lower only)
I
Infection/Irritation
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Mediated through chemoreceptors :
acetylcholine, histamine, serotonin
Gut and adjacent organ inflammation can
trigger
DOC(s): Anticholinergic/antihistaminic agents,
such as promethazine
T
Toxins
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Most important: drugs we give
Various mechanisms of inducing nausea
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Local irritant
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Changing blood levels (via CTZ)
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opioids, ? SSRIs
Toxic blood levels
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NSAIDs
digoxin
DOC(s): depends on mechanism of action
Opioid Related Nausea
Two mechanisms

Gut effect: Dysmotility of lower and upper
gut
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DOC(s): prokinetics
Effect on CTZ
Mediated through D2 receptor
 Related to changing blood levels
 Improves with steady state blood level
 DOC(s): Haloperidol (po, inj.), Prochlorperizine
(supp, po)
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No good evidence, rationale for using promethazine
5HT3
Antagonists
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Useful for certain forms of chemotherapy
related nausea
May have other special uses:
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In CTZ related nausea, where dopamine blockade
contraindicated
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(Parkinson’s Disease)
? Other refractory CTZ related causes
 ? In certain GI cases
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? Bowel Obstruction
 ? Radiation Enteritis
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Currently very expensive
Newer Agents
Neurokinin 1 Antagonists