Nausea, Vomiting, and Motion Sickness

• Sarah Larose, BScPharm, Instructor at Dalhousie College of Pharmacy, presents study notes on Nausea, Vomiting, and Motion Sickness.

Disclaimer for Lecture

• This lecture was prepared for PHAR 1052 in the academic year 2024-25, developed based on current literature and recommendations, though accuracy isn't guaranteed.
• Alone, these slides are an incomplete picture of the presenter's message; not to be copied or reproduced without permission.
• This lecture supplements learning from PBL cases and expects reviews of anatomy and physiology.

Learning Objectives

• Describe the pathophysiology and etiology of nausea and/or vomiting.
• List known causes and suggest management strategies for clinically significant cases of nausea and/or vomiting.
• Recognize red flags and know when to refer patients with nausea and/or vomiting.
• List goals of therapy for nausea and/or vomiting.
• List complications and understand the mechanisms of nausea and/or vomiting.
• Describe the pharmacologic class, mechanism of action, and most common and serious adverse effects of antiemetic agents.
• Recommend pharmacologic and nonpharmacologic alternatives for managing nausea and/or vomiting based on patient specific factors.

Role of Pharmacists

• Pharmacists can prescribe for nausea and vomiting in BC, SK, ON, QC, NB, NS, PEI, NL, YT, and NWT but not in AB, MB, or NU.

Terminology Review

• Nausea is the unpleasant sensation of imminent vomiting and is a symptom, not a diagnosis.
• Vomiting is the forceful expulsion of gastric contents.
• Retching is the action of the stomach and esophagus trying to vomit (retro-peristalsis).

Pathophysiology of Vomiting

• Four pathways lead to nausea and vomiting and multiple pathways may be involved.
• Each pathway provides input to the vomiting center in the brainstem.
• Nausea and Vomiting occur when minimum threshold are reached.

Drug Induced Nausea and Vomiting

• Cannabis Hyperemesis Syndrome:
• Accounts for up to 6% of patients reporting to ED for recurrent NV.
• It is associated with regular / long-term use, but the exact mechanism is unclear.
• Presents with severe cyclic nausea/vomiting and abdominal pain.
• Resolves with hot showers or baths and cessation of cannabis use.
• Opioid-Induced Nausea/Vomiting:
• Up to 40% of patients started on opioids experience nausea.
• Usually common in first few days of treatment, with tolerance developing rapidly.
• Increased doses can increase to the risk of nausea and vomiting
• Caused by stimulating afferent input into the vomiting centre via the vestibular apparatus, the cerebral cortex or the chemoreceptor trigger zone

Pregnancy Induced Nausea and Vomiting

• Morning Sickness (anytime, not just in the morning) occurs in 50–80% of pregnancies, usually beginning by week 6 and subsiding by week 16.
• Hyperemesis Gravidarum is characterized by intractable vomiting but is less common (≤2%).
• Complications can threaten the survival of the fetus and mother.
• The pathophysiology of nausea and vomiting during early pregnancy is unknown, but metabolic, endocrine, gastrointestinal, and psychologic factors probably play a role.
• Estrogen may contribute since estrogen levels are elevated in patients with hyperemesis gravidarum; prenatal vitamins may also play a role.

Motion Sickness

• The normal physiologic response to unusual perception of motion may be referred to as Carsickness, Airsickness, or Seasickness.
• Symptoms appear to be caused by mismatch between the expected motion and the actual motion sensed by the vestibular apparatus in the ear and is influenced by stimulus and individual susceptibilities.
• Clinical Presentation begins with a feeling of “stomach awareness”, and then leads to nausea, increasing malaise, pallor and sweating
• The movement must be repetitive, relatively slow and prolonged.
• The vertical component is most important in causing motion sickness; ex. Speedboat vs. Ferry

Patient Assessment for Nausea

• History:
• Frequency and Severity: include the timing in relation to meals, time of day, emotion or stress
• Is vomiting involved?: If yes, determine the amount and nature of the vomitus
• Explore possible underlying causes: If diarrhea involved (suggestive of gastroenteritis) or Inquire about last menstrual period to rule out pregnancy.
• Review diet history, including any potential food allergies or intolerances
• Establish any exposure to, or other symptoms of, infection such as gastroenteritis or exposure to others who are ill.
• Obtain a thorough medication history, including use of prescription, nonprescription, herbal or recreational drugs (including cannabis) as well as alcohol, nutritional supplements and vitamins
• Physical exam:
• Determine severity and consequences of symptoms and assess hydration including skin and mucous membranes
• Involves inspection ± palpation

Alarm Features

• Conditions when to consider underlying gastrointestinal, neurological or other systemic disease.
• Individuals with alarm features require additional investigations. RED FLAGS/ALARM FEATURES
• Signs of Dehydration
• Persistent Vomiting (>3 days)
• Abdominal pain
• Drug-induced (included alcohol)
• Induced by stress or psychiatric illness
• Blood in vomit (red or coffee grounds)
• Blood in stool (red or black/tarry)
• Difficulty swallowing
• Anticipatory nausea or post-chemo
• Unintended weight loss
• Altered mental status
• Age >55 y
• Symptoms of stroke, severe headache, dizziness or pressure
• Recent head trauma
• Should have a caveat that the patient is > 55 AND experiencing either CHRONIC nausea and vomiting or In combination with other symptoms consistent with dyspepsia/GERD.

Reversible Causes of Nausea and Vomiting

• Several diseases and conditions can cause/worsen nausea, and optimize management of these diseases to resolve nausea.
• balance the risk of nausea/vomiting vs. the benefit of the medication(s), if possible decrease the dose, discontinue the medication, or switch to another agent with a lower incidence of nausea/vomiting
• Neurologic: migraine, pain, injury/concussion, stroke, increased intracranial pressure.
• Vestibular: Ménière disease, labyrinthitis, motion sickness.
• Gastrointestinal: viral gastroenteritis, constipation, liver diseases, pancreatitis, cholecystitis, gastroparesis, IBS, dyspepsia, GERD.
• Psychiatric conditions: anxiety, depression, fear, grief, eating disorders, functional nausea, anticipatory nausea.
• Other Medical conditions: Hormonal effects of pregnancy, hypothyroidism, malignancy, acute infections.
• Toxins: alcohol, bacterial food poisoning, noxious odours.
• Medications: antibiotics, SSRIs, NSAIDs, chemotherapy, antidiabetics, hormones, opioids, anesthesia, cannabis.

Goals of Therapy

• The goals are to eliminate nausea and vomiting, reduce its severity, prevent complications and recurrence, and minimize impact on quality of life.

Complications of Vomiting

• Esophageal rupture
• Mallory-Weiss tears
• Dehydration
• Electrolyte disturbances (↓ K+, ↓ Mg+,↑↓ Na+)
• Metabolic alkalosis
• Malnutrition & weight loss
• Dental caries
• Aspiration Pneumonia

Complications Explained

• Mallory-Weiss tears are tears of the lower esophagus, and may be caused by violent coughing or vomiting, and diagnosed and treated during an endoscopic procedure
• Complications can lead to Anemia, fatigue, shortness of breath, and even shock
• Vomiting leads to increased contact time between stomach contents (acid) and teeth which leads to erosion of the tooth enamel, causing changes in color and texture and holes.
• Dehydration water then shifts from intracellular & interstitial space into the intravascular space to maintain vascular volume which presents visible signs

Treatment Options

• The focus of treatment is Motion Sickness.

Nonpharmacologic Treatment

• Consider the cause (disease/condition; pain; medication; motion; smell; food).
• Ensure adequate hydration through PO or IV.
• Recommend frequent small meals and snacks.
• Behavioral treatment (desensitization, anxiolytic exercises, and cognitive behavioral therapy) is useful for nausea associated with irritable bowel syndrome, anticipatory nausea and motion sickness.
• Engage the patient in the decisions, if watchful waiting is an alternative: treatment is not always necessary/desired reassure patient when underlying cause is self-limited

Motion Sickness - Dos and Don'ts

• What to Do:
• Increase ventilation and exposure to cool fresh air.
• Focus on a stable external object or the horizon during travel.
• Use controlled breathing and try to stay in a central location while on a boat.
• Sit in the front seat of a vehicle with a clear forward view and drive, if possible.
• What Not to Do:
• Avoid eating a large meal within 3 hours of travel.
• Avoid alcohol, smoking and disagreeable odours during travel.
• Avoid visual stimuli that commonly precipitate motion sickness, such as reading or watching videos during travel

Natural Health Products for Nausea and Vomiting

• Not much evidence for NHPs and alternatives.
• Eating or drinking apricot juice, carrot juice, unroasted pumpkin or squash seeds, parsley, and peppermint tea.
• Ginger root: candied ginger, powder, capsules/tablets and tea

Alternatives

• Sea Bands:
• Knitted elasticated wrist band operating by applying pressure on an acupressure point on each wrist by means of a plastic stud, but have no evidence of effectiveness.
• Can be used by adults and children.

Oral Rehydration Therapy

• ORT were developed in 1969 by UNICEF & WHO for the treatment of clinical dehydration and are available in liquid, powder, dissolving tablets & freezies.
• Avariety of flavors exist (unflavored, orange, grape, lemonade, cherry)

Pharmacologic Treatment

• Start with the most likely etiology, then prescribe an antagonist to the implicated receptors.

Receptor Antagonists

• First line choice depends on the most likely etiology choose an antagonist that targets Serotonin, Dopamine, Muscarinic (Acetylcholine) and Histamine

H1 Antagonist: Antihistamines

• Antiemetic MOA: Block H1 receptors in the vomiting center and muscarinic-cholinergic (Ach) receptors in the vestibular system.
• Drugs include: Diphenhydramine, Dimenhydrinate, Hydroxyzine, and Promethazine.

Meclizine

• What about… Meclizine (US Brand name Bonamine)?
• Very popular – but not available in Canada and is available in Canada.
• It has a longer duration of action and less drowsiness
• It is also less effective but has better marketing

M1 Antagonist: Scopolamine

• Belladonna alkaloid with anticholinergic properties competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist.
• It primarily reduces GI peristalsis and exocrine secretions and is Sedative additive with alcohol or other sedating medications.

Anticholinergic/Antimuscarinic ADR

• Blind as a bat: mydriasis
• Mad as a hatter: delirium
• Heart runs alone: tachycardia
• Hot as a hare: increased temperature
• Dry as a bone: dry mouth, dry eyes, decreased sweating
• Red as a beet: flushed face
• Bladder and bowel lose their tone: constipation & urinary retention

Dopamine Antagonists

• Haloperidol
• First generation antipsychotic with high affinity for D2 receptors and acts as a dopamine antagonist in the CTZ.
• Prochlorperazine
• Also antipsychotic and acts as a nonspecific dopamine receptor antagonist in the CTZ as well as 5-HT2a, alpha-1, histaminic H1, and muscarinic M1.
• Domperidone10mg TID prn (max. 30mg/day) (PO) Does NOT cross BBB = no CNS ADRs
• Metoclopramide
• Antiemetic Activity to Related is to dopamine rececptor antagoism at the chemoreceptor trigger zone by antagonising D2 in the gut

Adverse Drug Reactions for Dopamine Antagonists

• Extrapyramidal effects (especially in elderly patients and young children) including dystonia, dyskinesia, akathisia, opisthotonos.
• Sedation
• Dizziness/orthostatic hypotension
• QTc prolongation** (sudden cardiac death?)

Serotonin (5HT3) Antagonists

• Ondansetron, Palonosetron, Granisetron
• MOA: inhibit serotonin at 5-HT3 receptors in small bowel, vagus nerve, and chemoreceptor trigger zone (CTZ).
• For prevention of nausea and vomiting.
• Dosing: 16-24 mg/day divided Q6-8H (oral tablet or orally disintegrating tablet)
• Minor ADR (uncommon): headache, diarrhea, and fatigue

Summary of Action of other drugs

• Action is classified by indication - Serotonin blocking, Anti-histamines and dopamine antagonists

Practice Pearls

• When should a medication be re-dosed if vomited?
• General rule of thumb is: IF you can see an undissolved tablet in the vomitus THEN REDOSE, If consumed within the last 15 to 30 minutes REDOSE.
• For liquids, oral dissolve tablets or films REDOSE 10-15 minutes AND don't REDOSE - If dose "Stayed down" for at least 30-60 minutes
• Those with frequent vomiting may benefit from quick dissolve or liquid forms for maximal absorption.
• Oral options may not be appropriate - consider suppositories
• Use caution combining agents, because Anticholinergics can reduce the effectiveness of prokinetic agents