Pathophysiology and Management of Nausea and Vomiting

Mechanisms of Nausea and Vomiting

There is a differential diagnosis to nausea which can be used to choose the most effective initial management.
Nausea and vomiting involves the stimulation of the VC in the medulla by one or more of the following pathways and is
mediated by varying neurotransmitters:
 Peripheral Pathways
o Nausea triggered by mechanoreceptors and chemoreceptors in the GI tract, serosa, and viscera;
transmitted via the vagus and splanchnic nerves, sympathetic ganglia, and glossopharyngeal nerves to
the Chemoreceptor Trigger Zone (CTZ) and VC.
 Vestibular System
o Nausea triggered by motion; transmitted via the vestibulocochlear nerve to the VC.
 Chemoreceptor Trigger Zone (CTZ)
o Nausea triggered by toxins in both the blood stream and CSF.
 Cortex
o Nausea triggered by sensory input, anxiety, meningeal irritation, and increased intracranial pressure.
The Vomiting Center (VC) is the final common pathway for vomiting. This center initiates coordinated responses from the
parasympathetic system and motor efferents to produce vomiting.

Benzodiazepines
Anticholinergics, Antihistamines

Corticosteroids

Phenothiazines, Butyrophenones, 5HT3

antagonists

Corticosteroids, Prokinetics Pharmacologic

intervention

PPIs, Phenothiazines

The Rational Approach to Nausea and Vomiting:

1. Identify all of the potential underlying causes/triggers
2. If possible, eliminate causes/triggers (medications, constipation, etc)
3. Identify the pathway and associated neurotransmitters (see Table 1 and Figure 1)
4. Choose the medications that best target the neurotransmitters involved (See Table 1 and Table 2)
5. Schedule medication ATC and titrate to effect
6. If symptoms are refractory despite adequate dosing, combine several therapies to block multiple pathways.
 Table 1: Differential Diagnosis of Nausea and Vomiting
Differential Examples of Most Common Neural Pathway Receptors
Notable History/ Physical Exam Targeted Pharmacotherapy
Diagnosis Clinical Scenarios Involved to Block
Central Nervous System Origin
Motion sickness; Acoustic neuroma;
Vestibular Nausea worse with movement, Dizziness Vestibular Nucleus AChM, H1 Anticholinergics, antihistamines
Nystagmus; Vertigo
Toxins
 Stimulation of CTZ (via 5HT3 &
NK1) See Chemo Guideline (hyperlink
5HT3, NK-
Chemotherapy Recent emetogenic chemotherapy  Serotonin released in gut, this)
1, D2
stimulating peripheral pathways
 Anxiety
Recent medication changes (additions or If possible, stop offending
Medications (antibiotics, opioids, digoxin, Direct effect on the CTZ via D2
deletions) D2 medication;Prokinetics;
SSRIs, TCAs) (central)
Butyrophenones; Phenothiazines
Metabolic abnormalities (uremia, liver
Treat underlying abnormalities;
failure, infection, ketoacidosis, electrolyte Direct effect on the CTZ via D2
Altered mental status D2 Butyrophenones; Phenothiazines;
abnormalities [hyper/hypocalcemia, (central)
Prokinetics
hyper/hyponatremia, hypokalemia])
Brainstem or cerebellar lesions;
a.m. symptoms, headache, neck stiffness, H1 and Corticosteroids; Antihistamines;
Intracranial Increased intracranial pressure via Cortex
papilledema, neurologic signs AChM Butyrophenones; Phenothiazines
inflammation/edema
Treat underlying anxiety
Nausea without vomiting or weight loss;
(benzodiazepines prn); Consider
Anticipatory nausea and vomiting; History of severe nausea post
Anxiety Cortex SSRIs for patients with chronic
Nausea as a manifestation of anxiety chemotherapy, mood/anxiety disorder,
anxiety (may contribute to
significant history of nausea in youth.
medication induced nausea)
Gastrointestinal Origin
Mechanical Stretch
Large/infrequent vomitus that relieves
nausea; Treat underlying constipation;
Constipation, Malignant Bowel
Crampy abdominal pain; Corticosteroids (for obstruction
Obstruction, Peritoneal carcinomatosis, Peripheral pathways: stimulation of D2,
Decreased frequency of BMs, abdominal and hepatic capsular distension);
Biliary obstruction, Hepatic capsular mechanoreceptors AchM/H1
fullness and distension, hard stools, Butyrophenones; Phenothiazines;
distension
straining with defecation, abnormal BS, Anticholinergics (for cramping)
fecal impaction.
Small-volume emesis, early satiety,
bloating, nausea with movement; h/o Peripheral pathways:
Gastroparesis D2 Prokinetics
neuropathy, hypothyroidism, or diabetes Mechanoreceptors
mellitus; peritoneal carcinomatosis
H2 blockers or PPI (GERD/ PUD)
Induced by GERD, PUD, Radiation, Esophageal burning, sour taste in mouth, Peripheral Pathways: 5HT3 antagonists (Chemo)
GI Mucosal AChM, H1,
Infection, Inflammation, Chemotherapy, worse when supine; epigastric pain Chemoreceptors via Serotonin Corticosteroids (Inflammation)
Irritation D2, 5HT3
Medications radiating to back, fever, diarrhea released in gut Anticholinergics (for cramping)
Treat underlying infection
Oropharyngeal cancer, Thick adherent Peripheral pathways via
Thrush, herpetic lesions; mucositis, Mouthcare (chlorhexidine
Glossopharyngeal mucus, Inflammation (gingivitis, dental stimulation of mechano and
gingivitis; h/o radiation; dysphagia, mouthwash),
Irritation caries), Infection (oropharyngeal chemoreceptors of the
odynophagia Treat the underlying infection
candidiasis, HSV), Radiation glossopharyngeal nerve
 Table 2: Antiemetics
Receptor Affinities
Antiemetic Trade Name Neural Pathway Targeted Dosage Major Adverse Effects
D2 H1 AchM 5HT3
Prokinetics
Peripheral (Decreased Akathisia, EPS, colic in GI obstruction (Risk of
++ + (at high 5-20 mg PO/SC/IV before
Metoclopramide Reglan mechanoreceptor stimulation) ++ perforation in patients with complete GI
(agonist) doses) meals and at bedtime
CTZ obstruction)
Butyrophenones
0.5-2 mg PO/SC/IV/PR
Haloperidol Haldol CTZ +++ Akathisia, EPS, QT prolongation with high doses
q8h and q4h prn
Phenothiazines
CTZ 5-10 mg PO/IV q6h or 25
Prochlorperazine Compazine ++ + Akathisia, EPS, sedation (less than promethazine)
Vestibular mg PR q6h
CTZ 12.5-25 mg PO/IV q6h or Akathisia, EPS (less than haloperidol and
Promethazine Phenergan + + ++
Vestibular 25 mg PR q6h prochlorperazine), sedation
Anticholinergics
1.5 mg transdermal patch Sedation, dry mouth, urinary retention,
Scopolamine Transderm Scop Vestibular ++
every 3 days constipation, delirium
0.125 – 0.25 mg SL/PO Sedation, dry mouth, urinary retention,
Hyoscyamine Levsin Vestibular ++
q4h constipation, delirium
IV/SC: 0.1-0.2 mg q6h Sedation, dry mouth, urinary retention,
Glycopyrrolate Robinul Vestibular ++
PO: 1-2 mg q6h constipation
Antihistamines
25-100 mg/day in divided
Meclizine Antivert Vestibular ++ Sedation, dry mouth, urinary retention
doses TID
Diphenhydramine Benadryl Vestibular ++ + 25-50 mg PO/IV/SC q6h Sedation, dry mouth, urinary retention, delirium
5HT3 antagonists
1 CTZ
Ondansetron Zofran ++ 4-8 mg PO/IV q4-8h Headache, constipation
Peripheral pathways
2
Others
CTZ
Sedation, orthostatic hypotension, weight gain,
Olanzapine Zyprexa Peripheral Pathways ++ ++ ++ + 2.5-10 mg PO daily
hyperglycemia
Vestibular
Cortex Agitation, nausea, hyperglycemia,
Dexamethasone 2-32 mg PO/IV per day in
Corticosteroids Peripheral Pathways immunosuppression; Long term side effects with
(Decadron®) divided doses
(Inflammation) chronic use.
0.25-1 mg PO/SC/IV/PR
Lorazepam (Ativan®)
q4h prn anxiety
Benzodiazepines Cortex Sedation, delirium, agitation
2-10 mg PO/SC/IV/PR q4h
Diazepam (Valium®)
prn anxiety
Histamine2 Famotidine
Peripheral pathways +/0 20 mg PO/IV daily to BID Delirium (adjust dose for renal dysfunction)
Antagonists (Pepcid®)
Proton Pump Esomeprazole 20-40 mg PO/IV daily to
Peripheral pathways
Inhibitors (Nexium®) BID
1
Ondansetron is given as an example of a 5HT3 antagonist. 5HT3 antagonists are most effective for chemotherapy-induced nausea and vomiting. Other agents are available. See the Guidelines
for the Management of Chemotherapy induced Nausea and Vomiting for more specific information. (hyperlink this)
2
Select OSUMC formulary agents are included as examples. Other agents exist in each class of medications.
References:
1) Wood G. Management of intractable nausea and vomiting in patients at the end of life. JAMA 2007;298:1196-1207.
2) Weissman, D. Fast Fact and Concepts #05: Treatment of Nausea and Vomiting. June, 2000. End-of-Life Physician Education Resource Center www.eperc.mcw.edu
3) Jackson WC, Tavernier L. Olanzapine for intractable nausea in palliative care patients. J Pall Med 2003;6:251-5.
Author(s): Hartman, Gustin; Department: Pharmacy, Internal Medicine; Date Originated: May 2009; Committee(s) Approved:

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