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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 l.jpg

Nausea and Vomiting

James Hallenbeck, MD

Director, Palliative Care Services,

Palo Alto VAHCS, Stanford University


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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

Objectives


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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 >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


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    Causes of Nausea and Vomiting

    • Vestibular

    • Obstruction (Opioids)

    • Mind (Dysmotility)

    • Infection (Irritation)

    • Toxins (Taste and other senses)


    V vestibular apparatus l.jpg
    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 l.jpg
    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 l.jpg
    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 l.jpg
    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 l.jpg
    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 l.jpg
    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 l.jpg
    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

        • (Parkinson’s 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


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