Antiemetics

Last updated: September 28, 2023

Summary

Antiemetics are a heterogeneous group of drugs used to treat various causes of nausea and vomiting. Different antiemetics act on different receptors, and they may have a peripheral effect, a central effect, or both. Whereas serotonin antagonists, for example, bind 5-HT₃ receptors and effectively combat cytotoxic drug nausea, certain anticholinergic drugs target M₁receptors and specifically treat motion sickness (kinetosis). Hospitals and clinics commonly use the dopamine D₂antagonist metoclopramide. However, because of its strong central effect and possible extrapyramidal side effects, metoclopramide must be used with caution.

Overview

Overview of antiemetics
Antiemetic class	Drug	Mechanism of action	Clinical use	Side effects
Dopamine receptor antagonists	Prochlorperazine ^[1]	D₂antagonist Central antiemetic effect at the area postrema	Antipsychotic agent Hyperemesis gravidarum	Gastrointestinal Diarrhea Pain Hyperprolactinema Neurological Depression, anxiety Fatigue Drowsiness Restlessness Lowering of seizure threshold Overdose leads to reversible extrapyramidal syndrome (e.g., dystonia, parkinsonism, tardive dyskinesia, and akathisia) and neuroleptic malignant syndrome Do not combine metoclopramide with antipsychotics because this increases the risk of dyskinesia! Antidote: benztropine, biperiden (anticholinergic agents) Avoid combination with digoxin and antidiabetic drugs. Contraindicated in patients with suspected small bowel obstruction
	Metoclopramide ^[2]	D₂antagonist, serotonin receptor antagonist Central antiemetic effect at the area postrema Peripheral antiemetic effect in the gastrointestinal tract (prokinetic effect); causes increase in : Gastric contractions Duodenal and jejunal motility Resting tone of the lower esophageal sphincter Together with decreased pylorus sphincter activity allows food to pass more quickly through the stomach and the small intestine No influence on colon motility	Prokinetic effect used to treat diabetic and postsurgery gastroparesis (delayed gastric emptying) Hyperemesis gravidarum Persistent GERD
	Domperidone	D₂antagonist Central antiemetic effect at the area postrema Prokinetic effect (due to blockage of peripheral dopamine receptors)	Nausea and vomiting Gastrointestinal motility disorders	Gastrointestinal Diarrhea Pain Hyperprolactinema Domperidone, in contrast to metoclopramide and prochlorperazine, crosses the blood-brain-barrier only minimally, hence neurological side effects are limited May cause cardiac arrhythmias
Serotonin receptor antagonists (5-HT₃ antagonists)	Ondansetron ^[3] Granisetron Dolasetron Palonosetron	5-HT₃ antagonist Strong central antiemetic effect at the area postrema Peripheral antiemetic effect via inhibition of the vagus nerve	Ondansetron is commonly used for generalized nausea. Chemotherapy-induced vomiting, radiation-induced vomiting, and postoperative nausea and vomiting (PONV)	Headaches Constipation or diarrhea QT interval prolongation (torsades de pointes) Increase in liver enzymes Serotonin syndrome
Anticholinergic agents ^[4]	Scopolamine	Nonspecific muscarinic antagonist Central antiemetic effect at the area postrema and on the vestibular system Peripheral antiemetic effect via inhibition of the vagus nerve	Motion sickness, vestibular-induced nausea, and vomiting	Anticholinergic side effects: dry mouth, mydriasis, tachycardia, urinary retention Antidote: physostigmine (cholinesterase inhibitor)
Antihistamines	Meclizine Dimenhydrinate Diphenhydramine Doxylamine Promethazine	H₁antagonist Central antiemetic effect at the area postrema and vestibular system	Strong sedative Nausea and vomiting due to vestibular causes ^[5] Hyperemesis gravidarum (also see antiemetics during pregnancy)	Antihistamine effects: drowsiness and confusion Anticholinergic side effects: dry mouth, dilated pupils, blurred vision, reduced bowel sounds, and urinary retention (antidote: physostigmine)
Neurokinin receptor antagonists	Aprepitant Fosaprepitant	NK₁ antagonist Inhibition of NK₁receptors in the solitary nucleus and area postrema → central antiemetic effect ^[6] Additional inhibition of substance P-induced vomiting due to antagonism	CINV prophylaxis	Gastrointestinal: diarrhea Fatigue Hypersensitivity reactions Infusion site reactions Increased levels of other drugs due to weak CYP3A4 enzyme inhibition
Glucocorticoids	Dexamethasone Methylprednisolone	Exact mechanism unknown Central antiemetic effect possibly mediated by interaction with glucocorticoid receptors in the solitary nucleus. ^[7]	Dexamethasone CINV prophylaxis PONV prophylaxis PONV treatment Methylprednisolone: hyperemesis gravidarum	Cushing syndrome Hyperglycemia
Benzodiazepines ^[8]^[9]	Lorazepam	GABA agonist Central antiemetic effect likely due to depression of the chemotrigger zone ^[9]	CINV prophylaxis CINV treatment	Sedation Drowsiness, confusion Ataxia Dizziness Anterograde amnesia Can raise IOP and trigger angle-closure glaucoma. Respiratory depression
Atypical antipsychotics ^[8]^[9]^[10]^[11]	Olanzapine	Central antiemetic effect via inhibition of multiple neurotransmitters (e.g., dopamine, serotonin, histamine)	CINV prophylaxis CINV treatment	Sedation Weight gain Diabetes mellitus (prolonged use) . Hypertriglyceridemia, hypercholesterolemia Extrapyramidal adverse effects QT interval prolongation
Cannabinoids ^[8]^[12]^[13]	Dronabinol solution Dronabinol capsules Nabilone	Cannabinoid (CB1 and CB2) agonists Central antiemetic effect: CB1 agonism in the brain stem suppresses the emetic reflex. Peripheral antiemetic effect: CB2 agonism in the gastrointestinal tract inhibits gastrointestinal motility.	CINV treatment Anorexia causing weight loss in patients with advanced HIV	Ataxia, dizziness, dry mouth Euphoria, dysphoria Paranoia, hallucinations Abdominal pain Paradoxical worsening of nausea and vomiting (cannabinoid hyperemesis syndrome).

Mechanism of Action: Antiemetic drugs

Indications

Nonspecific nausea and vomiting
Chemotherapy-induced nausea and vomiting
Vertigo (e.g., vestibular neuritis, Ménière's disease)
Motion sickness
Gastrointestinal motility disorder (e.g., due to diabetic gastroparesis)
Postoperative nausea and vomiting

References:^[14]

Contraindications

Dopamine receptor antagonists
- Intestinal obstruction (ileus)
- Prolactin-dependent tumors
- Parkinson disease: unlike domperidone, metoclopramide can cross the blood-brain barrier and exacerbate the pre-existing dopamine deficiency that causes parkinsonism.
Serotonin receptor antagonists: : severe liver disease, prolonged QT interval
Anticholinergic agents and antihistamines

References:^[14]

We list the most important contraindications. The selection is not exhaustive.

References

Prochlorperazine. https://www.drugbank.ca/drugs/DB00433. Updated: December 8, 2016. Accessed: February 21, 2017.
FDA Requires Boxed Warning and Risk Mitigation Strategy for Metoclopramide-Containing Drugs Agency warns against chronic use of these products to treat gastrointestinal disorders. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm149533.htm. Updated: April 18, 2013. Accessed: February 21, 2017.
Ondansetron. https://www.drugs.com/pro/ondansetron.html. Updated: February 21, 2017. Accessed: February 21, 2017.
Pedigo NW Jr, Brizzee KR. Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis.. Brain Res Bull. 1985; 14 (2): p.169-77.
Flake Z, Linn B, Hornecker J. Practical Selection of Antiemetics in the Ambulatory Setting. Am Fam Physician. 2015.
Garcia-Recio S, Gascón P. Biological and Pharmacological Aspects of the NK1-Receptor. BioMed Research International. 2015; 2015: p.1-14.doi: 10.1155/2015/495704 . | Open in Read by QxMD
James E. Tisdale. Drug-induced Diseases: Prevention, Detection, and Management. American society of health-system phramacists : p. 834
NCCN clinical Practice Guidelines in Oncology: Antiemesis, Version 1.2019. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Updated: February 28, 2019. Accessed: September 16, 2019.
Perwitasari DA, Gelderblom H, Atthobari J, et al. Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics. International Journal of Clinical Pharmacy. 2011; 33 (1): p.33-43.doi: 10.1007/s11096-010-9454-1 . | Open in Read by QxMD
Tan L, Liu J, Liu X, et al. Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting. Journal of Experimental & Clinical Cancer Research. 2009; 28 (1): p.131.doi: 10.1186/1756-9966-28-131 . | Open in Read by QxMD
Brafford MV, Glode A. Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting.. Journal of the advanced practitioner in oncology. 2014; 5 (1): p.24-9.
Sharkey KA, Wiley JW. The Role of the Endocannabinoid System in the Brain–Gut Axis. Gastroenterology. 2016; 151 (2): p.252-266.doi: 10.1053/j.gastro.2016.04.015 . | Open in Read by QxMD
Darmani NA. Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting. Pharmaceuticals. 2010; 3 (9): p.2930-2955.doi: 10.3390/ph3092930 . | Open in Read by QxMD
Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014

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