Nausea and Vomiting

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Nausea and Vomiting

• James Hallenbeck, MD
• Director, Palliative Care Services,
• Palo Alto VAHCS, Stanford University

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Objectives

• Understand the pathophysiology of nausea and
  vomiting
• Utilize the VOMIT acronym in identifying causes
  of nausea
• Select antiemetic therapy, based underlying
  physiology

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Pearl for the Day
Rodents do not vomit!
But ferrets do!
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So WHY do we have this disgusting problem?
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Consider our Hungry Ancestors
What protects this guy from eating something
poisonous?
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Progressive Failsafe Measures

• Memory
• Appearances
• What looks gross, is probably gross
• Smell
• Taste
• Bitter bad
• Sweet good
• GI Track mechano and chemoreceptors
• CNS
• Chemoreceptor Trigger Zone (CTZ)
• Vestibular Apparatus

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A Central Final Pathway for Nausea
???
(Dopamine, Serotonin)
CTZ
CNS
(Acetylcholine,Histamine)
VOMIT CENTER
GI Tract
VestibularApparatus
(Acetylcholine,Histamine, Serotonin
mechanoreceptors)
(Acetylcholine, Histamine)
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Receptor Affinity Common Antiemetics
Drug Dopamine 2 Musc. Chol.
Histamine Scopolamine gt10,000 .08
gt10,000 Promethazine 240
21 2.9 Prochlorperazine 15
2100 100 Chlorpromazine 25
130 28 Metoclopramide
270 gt10,000 1,000
Haloperidol 4.2 gt10,000
1,600
Potency K1 (nanomolar)
The lower the number, the stronger this agent is
at blocking this receptor
Adapted from Perourka, Snyder
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Causes of Nausea and Vomiting

• Vestibular
• Obstruction (Opioids)
• Mind (Dysmotility)
• Infection (Irritation)
• Toxins (Taste and other senses)

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VVestibular Apparatus

• Complaint of nausea with head movement
• Mediated by acetylcholine and histamine receptors
• Doc(s)
• Promethazine (supp)
• Scopolamine (patch, injection)
• Cyclizine (oral, injection)

Most anticholinergic, antihistiminic drugs will
help!
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OObstruction

• 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

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MMind

• 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
• Megestrol, steroids, Cannibinoids

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MDysMotility

• Multiple causes
• Opioids
• Anticholinergic drugs
• Stomach/bowel compression, infiltration
• Upper intestinal dysmotility-very common, under
  appreciated
• Doc(s) Prokinetics
• Metoclopramide (upper only)
• Motilin agonists (erythromycin)
• Senna (lower only)

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IInfection/Irritation

• Mediated through chemoreceptors acetylcholine,
  histamine, serotonin
• Gut and adjacent organ inflammation can trigger
• DOC(s) Anticholinergic/antihistaminic agents,
  such as promethazine

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TToxins

• Most important drugs we give
• Various mechanisms of inducing nausea
• Local irritant
• NSAIDs
• Changing blood levels (via CTZ)
• opioids, ? SSRIs
• Toxic blood levels
• digoxin
• DOC(s) depends on mechanism of action

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Opioid Related NauseaTwo mechanisms

• Gut effect Dysmotility of lower and upper gut
• 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)

No good evidence, rationale for using promethazine
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5HT3 Antagonists

• Useful for certain forms of chemotherapy related
  nausea
• May have other special uses
• In CTZ related nausea, where dopamine blockade
  contraindicated
• (Parkinsons Disease)
• ? Other refractory CTZ related causes
• ? In certain GI cases
• ? Bowel Obstruction
• ? Radiation Enteritis
• Currently very expensive

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Newer AgentsNeurokinin 1 Antagonists