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Definition of Nausea & Vomiting
Pharmacological Approach
Etiology/Pathophysiology of Nausea & Vomiting
OBJECTIVES
Treatment in Special Populations (children, pregnancy)
Physiologic Basis of Nausea & Vomiting
Non-pharmacological Approach
Goals of Therapy
Management of Nausea & Vomiting
Nausea is commonly defined as a desire to vomit or a sensation in the throat or epigastric region warning of impending vomiting.
Vomiting is described as the ejection or expulsion of gastric contents through the mouth, which is frequently accompanied by a violent event.
General
Depending on severity of symptoms, patients may present in mild to severe distress
Symptoms
Simple: Self-limiting, resolves spontaneously, and requires only symptomatic therapy
Complex: Not relieved after administration of antiemetics; progressive deterioration of patient secondary to fluid-electrolyte imbalances; usually associated with noxious agents or psychogenic events
Signs
- Simple: Patient complaint of queasiness or discomfort
- Complex: Weight loss; fever; abdominal pain
Laboratory tests
- Simple: None
- Complex: Serum electrolyte concentrations; upper/lower GI evaluation
Other information
Fluid input and output, Medication history, Recent history of behavioral or visual changes, headache, pain, or stress, Family history positive for psychogenic vomiting
Emesis occurs in three stages: nausea, retching and vomiting. Gastric stasis is linked to nausea, the impending want to vomit. The retching is vomiting preceded by a labored contraction of the thoracic and abdominal muscles. Vomiting which occurs as a result of GI retroperistalsis, is the last stage of emesis.
Afferent impulses to the vomiting center, a cluster of cells in the medulla cause vomiting to occur. The chemoreceptor trigger zone (CTZ), the cerebral cortex and visceral afferents from the throat and GI tract are among the sensory sited from which impulses are received. Vomiting occurs when the vomiting center integrates afferent impulses into efferent impulses that are sent to the respiratory center, salivation center, pharyngeal, gastrointestinal (GI) and abdominal muscle.
The overall goal of antiemetic therapy is to prevent or eliminate nausea and vomiting.
This should be accomplished without adverse effects or with clinically acceptable adverse effects.
The choice of antiemetic agent should be based on the emetogenic potential. For example chemotherapeutic treatment.
According to Huebert et al (2018), the general management of nausea and vomiting involves thorough assessment (physical, symptoms), grading scale for the severity of nausea and vomiting, patient education, dietary management and non-pharmacological and pharmacological management.
Physical assessment refers to assessing vital signs, weight, hydration status, abdominal sounds and pain, emesis exam (color, quantity, consistency, odor, blood).
Symptom assessment includes questioning: When did the nausea and vomiting start (before or after medication)? What provokes it? Describe the emesis. What are the symptoms you are experiencing ? How bothered are you by the symptoms, on a scale of 1-10? What medications have you tried? … etc.
Dietary Management advises tea/smoothie with ginger, lemon zest, mint tea, and ginger ale for nausea. Meanwhile, bland foods, clear liquids, dry starchy foods, dairy foods and protein rich foods for vomiting. Sitting upright after eating and avoiding alcohol and tobacco are also advised.
Non-Pharmacological Management refers to modifying the environment ( fresh air, distraction strategies such as music, relaxation, and acupressure bracelets).
Pharmacological Management involves an intervention of medication whether Over-The-Counter or prescription. Antiemetic agents include: antihistamine-anticholinergics, antacids, histamine 2 receptor antagonists, corticosteroids, metoclopramide, cannabinoids, neurokinin 1 receptor antagonists, and 5 hydroxytryptamine-3 receptor antagonists (Pharmacotherapy 10th Edition).
Patient Education involves teaching patients to take note of onset, frequency of occurrence, and seeking immediate medical attention when temperature > 38 degrees, symptoms such as severe abdominal pain or cramps, dizziness & confusion, weakness, projectile vomiting, excessive thirst and nausea & vomiting that does not improve.
Aponvie (apreptitant) is a new drug which was approved by the FDA for the prevention of postoperative nausea and vomiting in adult patients.
This is an intravenous (IV) injectable emulsion formulation designed to directly introduce substance P/ neurokinin-1(NK1) receptor antagonist.
Apovnie single 30-second IV injection allows drug to associate with 97% of receptors in the brain within 5 minutes and maintains therapeutic plasma concentration for up to 48 hours after administration.
The goal of antiemetic therapy is to prevent vomiting and minimise nausea as frequent vomiting can lead to dehydration. Incorporating the adjuvant role of non-pharmacological interventions is an important consideration of antiemetic therapy. Non-pharmacological measures should be implemented in conjunction with pharmacological regimes to allow for the effective management of nausea and vomiting. In severe cases in which hospitalization is needed, enteral nutrition (i.e. Nasogastric/PEG feeds) will have to be considered (Barrow & Di Gregorio, 2019)
Nausea Tips:
> If only occurs between meals then patients should be encouraged to keep something in their stomachs by eating frequently throughout the day. Small snacks may include: smoothies, trail mix, fruits or fruit salads. Meals should not be skipped as nausea may worsen.
> Sipping on cold and clear liquids (can see through it) throughout the day may be easier and more tolerable such as ginger ale, apple juice, tea, broth. As well as eating food at room temperature may decrease its smell and taste.
> Also popsicles or gelatin may be good to help get rid of bad tastes, such as sucking on hard candies with pleasant smells like lemon drops or mints.
> Eating bland foods, such as dry toast and crackers and avoiding fatty, fried, spicy, or very sweet foods. Small amounts of foods high in calories which are easy to eat, example pudding, ice cream, yogurt, and milkshake throughout the day. Tart or sour foods may also be easier to keep down.
> Resting quietly while sitting upright for at least an hour after each meal and distracting oneself with soft music, a favourite TV program, or the company of others.
Source: American Cancer Society (2022). Managing Nausea and Vomiting at Home.
Vomiting Tips:
Along with the aforementioned tips, the following techniques can also be used::
Consuming liquids in the form of ice chips or frozen juice chips as these would slowly dissolve in your mouth.
Biofeedback which uses monitoring devices to aid individuals have conscious control over their physical processes which are usually controlled mechanically. Biofeedback is more beneficial when used in tandem with progressive muscle relaxation.
Non-drug treatments may be used alone for mild nausea, and are often helpful for anticipatory nausea and vomiting, which is a learned or conditioned response wherein the brain associates the treatment such as the sights, sounds, and smells of the treatment area with vomiting (American Cancer Society, 2022).
Using acupuncture, a traditional Chinese technique in which very thin needles are placed into the skin or acupressure, wherein pressure is applied in lieu of needles.
Complementary or alternative (non-drug) treatments for nausea and vomiting
Even though antiemetics and anti-nausea are mainstay treatments, non- drug treatments which involves harnessing one's mind and body with the help of a qualified therapist or even hypnotherapy can also be utilized.
> Antacids
> Antihistaminic-Anticholinergic Agents
> Benzodiazepines
> Butyrophenones
> Cannabinoids
> Corticosteroids
> Histamine (H2) Antagonists
> Neurokinin 1 (NK1) receptor antagonists
> Phenothiazines
> 5-Hydroxytryptamine-3 receptor antagonists
> Miscellaneous Agents
Goal of treatment: Achieve symptomatic control through the administration of agents with different pharmacological mechanisms of action.
Simple Nausea and Vomiting: Treatment involves utilizing non-prescription and/or single prescription drugs in small infrequently administered doses.
Complex Nausea and Vomiting: Treatment involves using multiple agents with different MOAs to control symptoms.
Chemotherapy-induced Nausea and Vomiting (CINV)
Radiation-induced Nausea and Vomiting
Postoperative Nausea and Vomiting (PONV)
Depending on the type of nausea and vomiting that a person experiences, there are different drugs that can be used to treat such type.
These are medicines that counteract (neutralise) the acid in your stomach to relieve indigestion and heartburn
Normally utilized by patients who experience simple, acute nausea and vomiting.
Active ingredient(s): Magnesium hydroxide/aluminium hydroxide
Examples: Federgel, Dica, Maalox
MOA: known to inhibit acetylcholine, depressing the CNS and reduce inner ear stimulation
Adverse drug reaction: Drowsiness, confusion, blurred vision, dry mouth, urinary retention
Examples: Dimenhydrinate (Gravol), Diphenhydramine (Benadryl)
Used in ANV but is contraindicated with olanzapine
MOA: CNS depression
Adverse drug reactions: Dizziness, sedation, appetite changes, memory impairment
Examples: Alprazolam (Xanax), Lorazepam (Ativan)
Used for breakthrough CINV
MOA: Inhibits dopamine receptors
Adverse drug reactions:
Haloperidol: sedation, constipation, hypotension
Droperidol: QTc prolongation
Examples: Haldol (Haloperidol), Droperidol (Inapsine)
Used for breakthrough CINV
MOA: Interactions with the vomiting center leading to suppression
Adverse drug reactions: Euphoria, somnolence, xerostomia
Examples:
Dronabinol (Marinol), Nabilone (Cesamet)
Useful as single agent or combination therapy for prophylaxis of CINV or PONV
MOA: Not quite understood in the management of NV
Adverse Drug reactions: Insomnia, GI symptoms, agitation, appetite stimulation, hypertension, and hyperglycemia
Example: Dexamethasone (Decadron)
Useful for nausea that is secondary to GERD or heartburn
MOA: Blocks H2 receptors of gastric parietal cells, leading to blockage of gastric secretions which calms nausea and vomiting
Adverse drug reactions: Headache, constipation or diarrhea.
Examples: Cimetidine (Tagamet HB), Famotidine (Pepcid AC), Ranitidine (Zantac)
Useful in combination therapy for prophylaxis of CINV and PONV
MOA: act centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy.
Adverse drug reaction: Constipation, diarrhea, headache, hiccups, dyspepsia, and fatigue
Examples: Fosaprepitant, Aprepitant, Rolapitant
Useful in simple nausea and vomiting or breakthrough CINV
MOA: Antagonizes dopamine receptors and may depress vomiting center activity
Adverse Drug Reactions: Prolonged QTc interval, constipation, dizziness, tachycardia, drowsiness, tardive dyskinesia
Examples:
Chlorpromazine (Thorazine), Prochlorperazine (Compazine), Promethazine (Phenergan)
Useful as a single agent or combination therapy for prophylaxis of CINV or PONV
MOA: binds to serotonin receptors in the periphery and CNS and acts mainly on the GI tract
Adverse Drug Reactions: Constipation Asthenia, headache
Examples: Granisetron (Kytril), Ondansetron (Zofran)
Metoclopramide: Prokinetic activity useful in diabetic gastroparesis
Adverse drug reactions: headache, somnolence, Asthenia
Olanzapine: To be used with caution in elderly patients, contraindicated with benzodiazepines
Adverse drug reactions: sedation, prolonged QTc intervals, EPS
Pyridoxine: Used in NVP, may be used alone or with doxylamine 12.5mg
Adverse drug reactions: drowsiness, headache
Vomiting can cause children to lose a lot of fluids and minerals. Therefore it is important to ensure that these substances are replaced to avoid worsening and/or life threatening events.
For babies: about 1 tablespoon (tbsp.) of oral electrolyte solution (ORS) every 15–20 minutes; shorter but more frequent breastfeeding
For kids: 1–2 tbsp. every 15 minutes of ORS, ice chips, flat ginger ale or lemon-lime soda, clear broth, ice pops (pedialyte), or diluted juice
Ondansetron: 0.15 mg/kg (maximum 8 mg) IV every 8 hours or, if the oral form is used, for children 2 to 4 years, 2 mg every 8 hours; for those 4 to 11 years, 4 mg every 8 hours; for those ≥ 12 years, 8 mg every 8 hours
Severe Nausea and Vomiting
Promethazine: For children > 2 years, 0.25 to 1 mg/kg (maximum 25 mg) orally, IM, IV, or rectally every 4 to 6 hours
Prochlorperazine: For children > 2 years and weighing 9 to 13 kg, 2.5 mg orally every 12 to 24 hours; for those 13 to 18 kg, 2.5 mg orally every 8 to 12 hours; for those 18 to 39 kg, 2.5 mg orally every 8 hours; for those > 39 kg, 5 to 10 mg orally every 6 to 8 hours
Metoclopramide: 0.1 mg/kg orally or IV every 6 hours (maximum 10 mg/dose)
During pregnancy, nausea and vomiting are usually mild and self-limiting. It usually starts within the first trimester of the pregnancy. Initial care is conservative and involves dietary adjustments, counselling, and vitamin B6 supplementation. The goal of treatment should be to lessen symptoms with the fewest risks possible to the mother and fetus.
> Vitamin B6 ( Pyridoxine) 10 to 25 mg 1-4 times daily is the first line treatment. It is more
effective in improving symptoms of nausea, although the reduction in vomiting is less clear.
> Doxylamine (12.5–20 mg one to four times daily)- may use lower does in the morning and midday, and larger dose at nights.
> Combination therapy with vitamin B6 and doxylamine is highly recommended a it as a very
effective in the treatment of nausea and vomiting and safe to use in the first trimester.
American Cancer Society. (September 10, 2020). Treatment & Survivorship: Managing nausea and vomiting at home. Retrieved November 17, 2022 from https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/eating-problems/nausea-and-vomiting/managing.html#:~:text=Eat%20bland%20foods%2C%20such%20as,milkshakes)%20several%20times%20a%20day
Barrow, L & Di Gregorio C. (February, 2019). Chemotherapy induced nausea and vomiting.The Royal Children's Hospital Melbourne. Retrieved November 18, 2022 from https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/Chemotherapy_induced_nausea_and_vomiting/#Non-pharmacological
DiPiro J.T., & Talbert R.L., & Yee G.C., & Matzke G.R., & Wells B.G., & Posey L (Eds.), (2017). Pharmacotherapy: A Pathophysiologic Approach, 10e. McGraw Hill. Retrieved November 10, 2022 from https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861§ionid=146028752
Whittlesea C. & Hodson K. (2019). Clinical pharmacy and therapeutics (Sixth). Elsevier. Retrieved November 10, 2022 from https://elsevierelibrary.co.uk/product/clinical-pharmacy-therapeutics-ebook.
Herrell, H.E. (2014) Nausea and vomiting of pregnancy, American Family Physician. Available at: https://www.aafp.org/pubs/afp/issues/2014/0615/p965.html (Accessed: November 18, 2022).
Huebert, K., Bellerive, J., & Van der Meer, L. (2018). Symptom management guidelines: Nausea and vomiting - BC cancer. Symptom Management Guidelines: Nausea & Vomiting. Retrieved November 16, 2022, from http://www.bccancer.bc.ca/nursing-site/documents/11.%20nausea%20and%20vomiting.pdf
Whittlesea C. & Hodson K. (2019). Clinical pharmacy and therapeutics (Sixth). Elsevier. Retrieved November 10, 2022 from https://elsevierelibrary.co.uk/product/clinical-pharmacy-therapeutics-ebook.
Schwinghammer, T.L, DiPiro, J.T, Ellingord, V.L, DiPiro, C.V. (2021) Pharmacotherapy Handbook. (11th Edition). McGrawHill Education.