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Nausea and Vomiting. James Hallenbeck, MD Director, Palliative Care Services, Palo Alto VAHCS, Stanford University. 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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nausea and vomiting

Nausea and Vomiting

James Hallenbeck, MD

Director, Palliative Care Services,

Palo Alto VAHCS, Stanford University

objectives
Understand the pathophysiology of nausea and vomiting

Utilize the “VOMIT” acronym in identifying causes of nausea

Select antiemetic therapy, based underlying physiology

Objectives
pearl for the day
Pearl for the Day…

Rodents do not vomit!

But ferrets do!

consider our hungry ancestors
Consider our Hungry Ancestors…

What protects this guy from eating something poisonous?

progressive failsafe measures
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
a central final pathway for nausea
A Central Final Pathway for Nausea

???

(Dopamine, Serotonin)

CTZ

CNS

(Acetylcholine,Histamine)

VOMIT

CENTER

GI Tract

VestibularApparatus

(Acetylcholine,Histamine, Serotonin

+ mechanoreceptors)

(Acetylcholine, Histamine)

receptor affinity common antiemetics
Receptor Affinity Common Antiemetics

Drug Dopamine 2 Musc. Chol. Histamine

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

Potency: K1 (nanomolar)

The lower the number, the stronger this agent is

at blocking this receptor

Adapted from Perourka, Snyder

causes of nausea and vomiting
Causes of Nausea and Vomiting
  • Vestibular
  • Obstruction (Opioids)
  • Mind (Dysmotility)
  • Infection (Irritation)
  • Toxins (Taste and other senses)
v vestibular apparatus
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!

o obstruction
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
m mind
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
m dysmotility
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)
i infection irritation
IInfection/Irritation
  • Mediated through chemoreceptors : acetylcholine, histamine, serotonin
  • Gut and adjacent organ inflammation can trigger
  • DOC(s): Anticholinergic/antihistaminic agents, such as promethazine
t toxins
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
opioid related nausea two mechanisms
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

5ht3 antagonists
5HT3 Antagonists
  • Useful for certain forms of chemotherapy related nausea
  • May have other special uses:
    • In CTZ related nausea, where dopamine blockade contraindicated
      • (Parkinson’s Disease)
    • ? Other refractory CTZ related causes
    • ? In certain GI cases
      • ? Bowel Obstruction
      • ? Radiation Enteritis
  • Currently very expensive