Anti-nauseant and anti-emetic medications

By Marcello Cherchi, MD PhD

For patients

If a person feels disequilibrium (dizziness) and it is very severe, then they sometimes also feel uncomfortable in their stomach (nausea) and may throw up (vomit). If the disequilibrium can be treated, then usually the nausea and vomiting will go away. But in some cases, it may be necessary to treat the nausea/vomiting itself. Several medications can be used to help with nausea/vomiting.

For clinicians

Practical summary

In some disorders of equilibrium, if the symptom of disequilibrium is sufficiently strong, then a patient may also experience nausea and/or vomiting. Ideally, if the underlying cause of disequilibrium can be diagnosed and treated, then the nausea/vomiting may improve and not require treatment. But if the underlying cause of disequilibrium has not yet been ascertained, or if treatment of that underlying disorder has been insufficient, then it is medically reasonable to use a “symptomatic management” strategy for the nausea/vomiting. Most of these medications were originally designed for nausea/vomiting occurring in other contexts (e.g., to treat the adverse effects of chemotherapy). The anti-nauseant/anti-emetic drugs used in otoneurology generally work through antagonism of central serotonin or dopamine receptors, with adverse effects as expected for such mechanisms. Ondansetron is commonly used in otoneurology because of several desirable features, including that it is well-tolerated, it has few drug-drug interactions, it is generally not sedating, and it does not influence ocular motor function.

Introduction

Some commentators sensibly suggest that the pharmacologic treatment of disequilibrium and its sequelae (such as nausea and vomiting) should depend on the underlying diagnosis (Lin and Aligene 2013), and we agree with this position. For many disorders of equilibrium, if the symptom of disequilibrium itself can be controlled adequately, then the other “downstream” symptoms (nausea, vomiting) may be absent or minimized, and therefore not require separate treatment.

In some circumstances — such as when the underlying cause of disequilibrium is unknown, or reasonable attempts at treating the known diagnosis prove inadequate — it may be necessary to use a strategy aimed at that downstream symptom.

No anti-nauseants or anti-emetics were designed specifically for vertiginous disorders; many of these drugs were initially designed for other purposes, such as nausea/vomiting due to post-surgical gastrointestinal paresis, or nausea/vomiting secondary to chemotherapy. Hence, the use of these drugs in otoneurology is an extrapolation (albeit a reasonable one) based on literature pertaining to other diseases.

Several of these drugs are used in otoneurology. The Table below summarizes some of the salient features of each drug.

Medication	Pharmacologic mechanism of action	Main adverse effects	Half-life	Notes	Pregnancy	Lactation
Granisetron (Kytril®, Sustol®, Sancuso®)	Serotonin (5HT3) antagonist	Sedation	6 hours	Available in transdermal formulation (Sancuso®)	Possible teratogenicity	No human data available to assess risk
Ondansetron (Zofran®, Zuplenz®)	Serotonin (5HT3) antagonist	May require dose adjustment in patients with hepatic failure	4.6 – 5.7 hours (in hepatic failure, up to 20 hours)	Available in orally disintegrating tablet formulation (Zofran® ODT)	Possible teratogenicity	No evidence of harm in limited human data
Metoclopramide (Reglan®, Metozolv®, Gimoti®)	Dopamine antagonist	Sedation, extrapyramidal symptoms	5 – 6 hours	Available in nasal formulation (Gimoti®)	No risk of harm based on human data	No risk of harm based on human data
Perphenazine (Trilafon®)	Phenothiazine, with dopamine (D2 receptor) antagonism	Sedation, extrapyramidal symptoms	9 – 12 hours		Some evidence of teratogenicity in animal data	No human data available
Prochlorperazine (Compazine®)	Phenothiazine, with dopamine (D2 receptor) antagonism	Sedation, extrapyramidal symptoms	3 – 5 hours (oral)	Available in suppository formulation	Risk of neonatal extrapyramidal effects	No human data available
Promethazine (Phenergan®)	Phenothiazine, with dopamine antagonism	Sedation, extrapyramidal symptoms	7 – 14 hours	Available in suppository formulation	Risk of neonatal platelet aggregation	No human data available
Trimethobenzamide (Tigan®)	Dopamine antagonist	Sedation, extrapyramidal symptoms	7 – 9 hours		No risk of harm based on human data	No human data available

Table: Properties of some anti-nauseant and anti-emetic drugs used in otoneurology.

Pharmacology

Broadly, anti-nauseant/anti-emetic medications antagonize central serotonin receptors or central dopamine receptors.

Adverse effects

The adverse effects of these anti-nauseant/anti-emetic medications are to be expected based on their pharmacologic mechanism of action. Drugs with serotonin antagonist activity may cause sedation (although ondansetron is an exception in this regard). Those with dopamine antagonist activity can cause sedation and extrapyramidal effects. Many of these drugs have the potential for interactions with other medications (although ondansetron is quite favorable in this regard).

Cautions and contraindications

Drugs with dopamine antagonist activity should be used with caution in patients already diagnosed with extrapyramidal disease related to dopamine insufficiency (such as parkinsonism).

Relevance in otoneurology

As mentioned earlier, anti-nauseant/anti-emetic drugs can be deployed for symptomatic management when the underlying cause of a patient’s disequilibrium has not been determined, or when treatment of the underlying cause has proven inadequate. Patients should be instructed that anti-nauseant/anti-emetic medications generally do not bring about any significant improvement in the disorder of equilibrium.

Other notes

In our practice we favor ondansetron largely because it is well-tolerated, it has few drug-drug interactions, it is generally not sedating, and it does not influence ocular motor function.

References

Lin E, Aligene K (2013) Pharmacology of balance and dizziness. NeuroRehabilitation 32: 529-42. doi: 10.3233/NRE-130875