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Nausea and Vomiting

Nausea and Vomiting

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Nausea and Vomiting

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

  2. Understand the pathophysiology of nausea and vomiting Utilize the “VOMIT” acronym in identifying causes of nausea Select antiemetic therapy, based underlying physiology Objectives

  3. Pearl for the Day… Rodents do not vomit! But ferrets do!

  4. So WHY do we have this disgusting problem?

  5. Consider our Hungry Ancestors… What protects this guy from eating something poisonous?

  6. 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

  7. A Central Final Pathway for Nausea ??? (Dopamine, Serotonin) CTZ CNS (Acetylcholine,Histamine) VOMIT CENTER GI Tract VestibularApparatus (Acetylcholine,Histamine, Serotonin + mechanoreceptors) (Acetylcholine, Histamine)

  8. 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

  9. Causes of Nausea and Vomiting • Vestibular • Obstruction (Opioids) • Mind (Dysmotility) • Infection (Irritation) • Toxins (Taste and other senses)

  10. 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!

  11. 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

  12. 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

  13. 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)

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

  15. 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

  16. 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

  17. 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

  18. Newer AgentsNeurokinin 1 Antagonists