N/V
Background (Epidemiology/Etiology)
Nausea is the inclination to vomit or a feeling to alert the person that vomiting is imminent.
Vomiting is the forceful ejection of gastric contents through the mouth
Protective reflexes to help expel potentially toxic substances from the stomach and prevent further ingestion
Pathophysiology
EMESIS
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Nausea
Retching
o Movement of the abdominal and thoracic muscles before vomiting
Vomiting
o Projectile vomiting
 Spontaneous vomiting
 Not preceded by nausea or retching
 Caused by direct stimulation of the Vomiting Center through increased intracranial pressure, tumors, brainstem
aneurysm
VOMITING is triggered by impulses to the Vomiting Center (VTC)
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Sensory centers – Chemoreceptor Triger Zone (CTZ), vestibular system, visceral afferents, and cerebral cortex send impulses to
the VTC
CTZ
o Located outside of the BBB and accessible to emetogenic molecules in the blood or CSF
o Contains Dopamine (D2), Opioid, Serotonin (5-HT3), and Neurokinin (NK1) receptors
o When triggered, it stimulates muscarinic receptors in the VTC, triggering the vomiting reflex
Vestibular System
o Important for balance in space
o Connects to the vestibular nuclei in the brainstem via the vestibulocochlear nerve
o Contains Histamine 1 (H1) receptors and Muscarinic (M1) receptors
o Motion/Morning sickness triggers signals to the CTZ, which sends signals to the VTC etc...
GI
o Stomach is lined by enterochromaffin cells which releases serotonin when exposed to cytotoxic agents
o Activates vagal afferents leading to the CTZ or the VTC
Cereral Cortex
o Exposure to psychiatric disorders, emotions, severe pain, stress, noxious odors stimulates the VTC through M1 receptors
o Anticipatory vomiting prior to chemotherapy also originates from here
Impulses are integrated by the VTC and sent to the salivation center, repiratory, pharyngeal, GI, and abdominal muscles causing
vomiting
VOMITING REFLEX
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Causes the lower esophageal sphincter to relax
Contracts diaphragm and abdominal muscles
o Increases intraabdominal pressure
Autonomic Changes
o Tachycardia
o Salivation
o Peristalsis
Epiglottis closes to protect lungs
Stomach contents gets expelled
Causes/Risk Factors
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Distention of the duodenum or upper small intestinal tract
GI
o Mechanical obstruction
o Gastroparesis
o Non-ulcer dyspepsia
o Irritable bowel syndrome
o Peptic Ulcer Disease
o Peritonitis
o Cholecystitis
o Hepatitis
o Acute gastroenteritis (infection)
CV disease
o Acute Myocardial Infarction
o Congestive Heart Failure
Neuro
o Increased intracranial pressure
o Migraines
o Vetibular disorders
o Hemorrhage
o Epilepsy
o Fainting
Metabolic Disorders
o DKA/Hypoglycemia
o Adrenal insufficiency
o Uremia
Psychiatric
o Psychogenic vomiting
o Anorexia
o Bulimia
o Anxiety
Therapy
o Cytotoxic chemotherapy
o Radiation therapy
o Theophylline
o Anticonvulsants
o Opiates
 Along with withdrawal
o Benzodiazepines
 Withdrawal
o Antibiotics
o Anesthetics
Misc
o Pregnancy
o Noxious smell or sight
o Post operation
Signs/Symptoms
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Pallor, Sweating, Tachycardia
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Simple
o
Queasiness or discomfort
o
Self-limiting, resolves itself, can be managed with symptomatic therapy
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Severe cases
o
Weight loss, fever, abdominal pain
o
Not relieved by antiemetics
o
Patient’s condition worsens due to fluid-electrolyte imbalances
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Usually seen with noxious agents or psychogenic events
Complications
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Fluid Disturbances
o Dehydration (oliguria, weight loss, confusion, reduced skin turgor)
Electrolyte Disturbances
o Hyponatremia
 Thirst, Hypotension
o Hypokalemia
 Muscle weakness, arrhythmia
o Hypochloremia
 Dehydration, weakness
Acid-base disturbances
o Metabolic alkalosis due to loss of H+ in vomit
Diagnosis
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Complex
o Serum electrolyte concentrations
o Upper/lower GI evaluation
I/Os
Medication history
History of behavioral/visual changes, headache, pain, stress
Family history of psychogenic vomiting
Goals of Therapy
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Prevent further vomiting
Minimize nausea
Treatment
Drug Table
Drug
Dose
Side Effects & Monitoring
Precautions & Contraindications
5HT 3 Receptor Antagonists: blocks serotonin receptors on sensory vagal fibers in the gut wall and CTZ
Ondansetron
(Zofran)
Starting dose:
4 mg single dose
Oral, IV
Granisetron
(Kytril)
Dose range:
0.35 to 3 mg PONV
Oral, IV, SubQ,
Transdermal
Dolasetron
(Anzemet)
Starting dose:
100 mg 1 hour
SE:
Indications:
• Post-operative N/V
Headache, weakness,
constipation, dizziness
• CINV
QTc Prolongation
Serotonin Syndrome
•Radiation-induced (RINV)
•Gastroenteritis
•Migraines
Oral
Palonosetron
(Aloxil)
2nd gen
Oral, IV
before chemo
Starting dose:
0.075 mg PONV
0.25 mg CINV
Max dose:
0.5 mg CINV
Phenothiazine : blocks dopamine receptors in the brain/CTZ, inhibits peripheral transmission to VTC
Promethazine
Dose Range:
SEs:
(Phenergan)
12-25 mg q4-6h PO
Sedation, lethargy, skin
sensitization, hypotension,
EPS
25-50 mg q4-6h
IV/IM
Prochlorperazine
Indications:
• PONV, Severe N/V
Dose Range:
5-10 mg q6-8h PO,
IM, IV, PR
Chlorpromazine
Dose Range:
10-25mg q4-6h PO
25-50mg q4-6h
IM/IV
Metoclopramide
Dose Range:
SEs:
(Reglan)
10 mg q4-6h
PO, IV, IM, SubQ,
Nasal
sedation, depression,
hyperprolactemia,
hypertension, diarrhea,
QTc prolongation, EPS
Olanzapine
Dose Range:
SEs:
(Zyprexa)
5-10 mg QD
CNS, CV, Metabolic SEs
REMS
Indications:
• PONV, CINV
Contraindications:
• Parkinson disease (EPS)
DDIs:
•MAOI, TCA, phenothiazines
Indications:
• CINV
PO
Neurokinin 1 receptor antagonists: inhibits NK1 and substance P, augments antiemetic properties of 5HT3 antagonists
Aprepitant
PONV Dose:
SEs:
Indications:
40 mg
Fatigue, hiccups
PONV, CINV
Fosaprepitant
CINV:
IV prodrug
150 mg pm day 1
only
Muscarinic receptor antagonists: block acetylcholine action in the vestibular nuclei
Scopolamine
(Hyoscine)
1 patch: 1 mg for 3
days
SEs:
Indications:
Drowsiness, dry mouth,
blurry vision
Motion sickness, PONV
Histamine receptor antagonist: blocks the CTZ, decreases vestibular stimulation, decreases central anticholinergic act
Dimenhydrinate
Dose Range:
SEs:
Indications:
50-100 mg q4-6h
Sedation, dry mouth
Motion sickness, vertigo, PONV, N/V d/t pregnancy
PO, IM, IV, PR
Diphenhydramine
Dose Range:
25-50 mg
PO, IV, IM
Hydroxyzine
PO, IM
Meclizine
Dose Range:
12.5-25 mg q68/12h PO
Cannabinoids: inhibits VTC by stimulating CB1 receptors in CTZ and VTC
Dronabinol
Dose Range:
SEs:
Indications:
2.5-5 mg capsules
Sedation, tachycardia,
hypotension, euphoria ,
dizziness, anxiety
CINV, anorexia
2
5mg/m CINV
capsules
Oral solution
Nabilone
Dose Range:
1-2 mg BID
Max dose:
6 mg/day in 3 doses
PO
Benzos: increase inhibitory GABA effects, antiemetic d/t sedation, decreased anxiety, maybe VTC depression
Alprazolam
Lorazepam
Dose Range:
SEs:
Indication:
0.5 mg q8h for 24-48
hours PO
Sedation, amnesia,
dependence, withdrawal,
weight gain
CINV, vertigo
Dose Range:
0.5-1 mg q6h prn
Max: 2 mg
PO, IV, SubL
Other agents
Dexamethasone, Histamine antagonists (Cimetidine, Famotidine), Trimethobenzamide
Non-Pharmacologic Treatment
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Remove offending agent
Diet
o Avoid irritating foods
o Spicy, fried
o Eat smaller meals with bland taste
o BRAT diet
o Hydrate
Physical
o Focus on a point in the distance if motion sickness occurs
Psychological
o Relax, hypnosis, distraction
o Yoga
o Desensitization
o Acupuncture?
References
1. DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach. New York, NY: McGraw-Hill; 2019.
Kale-Pradhan P, Nausea and Vomiting. In: PharmacotherapyFirst: A Multimedia Learning Resource. 2019
2. Nausea and Vomiting. In: Wells BG, DiPiro JT, Schwinghammer TL, DiPiro CV. eds. Pharmacotherapy Quick Guide.
McGraw Hill; 2017. Accessed September 14, 2022. https://accesspharmacy-mhmedicalcom.ferris.idm.oclc.org/content.aspx?bookid=2177&sectionid=165472455