Fast Fact and Concept #25: Opioids and Nausea

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Title: Fast Fact and Concept #25: Opioids and Nausea

Author(s): Weissman, David E.

Fast Facts, a project of the National Residency End-of-Life Curriculum Project, funded by the Robert Wood Johnson Foundation, are available for downloading at www.eperc.mcw.edu.

Why do patients get nauseated and vomit after receiving an opioid? Commonly ascribed by patients as an "allergy", opioid-induced nausea/vomiting is not an allergic reaction. In fact, rather than indicating a pathologic reaction, nausea indicates normal functioning of the brain! Opioid-induced nausea occurs through two mechanisms:
- At the base of the 4th ventricle lies the chemoreceptor trigger zone (CTZ), a "sampling port", to detect substances that don't belong in the blood. Adjacent to the CTZ lies the medullary vomiting center (VC), which controls the complex muscular sequence of vomiting. When the CTZ detects a noxious chemical in the blood, a signal is sent to the VC and voila! vomiting ensues. Of note, this is the same reason why patients vomit after receiving chemotherapy. Although this mechanism works well for orally ingested chemicals, it was evolutionarily never designed for intravenous morphine!
- A second cause of opioid nausea/vomiting is due to stimulation of the vestibular apparatus-patients note a spinning sensation with their nausea.

Do all opioids produce the same degree of nausea? The standard teaching is that at equianalgesic doses, all mu agonists will produce an equivalent degree of nausea (1). However, in clinical practice, morphine and codeine are often mentioned as the worst offenders; perhaps because they are the most commonly prescribed.

Why are some patients more sensitive to the emetic effects of opioids than others? Unknown.

What is the natural history of opioid-induced nausea? Most patients develop rapid tolerance to the emetic effects, so that within 3-7 days, at a constant opioid dose, the emetic effect will abate.

What are management approaches?
- Anti-emetics-start with low-cost dopamine antagonists (e.g. prochlorperazine) or anti-cholinergics (e.g. scopolamine); use 5HT3 antagonists for more refractory cases. Anti-histamines may be helpful for patients who note a spinning sensation.
- Dose adjustment-if good pain relief is achieved but associated with nausea, it may be possible to lower the dose, still retain good analgesia but eliminate the nausea.
- Switching opioid---since all mu agonist opioids cause nausea, there is little rationale for changing drugs; however, patients may be more sensitive to one opioid compared to another, thus a change is warranted when the above options are not effective. Note: since tolerance to nausea develops rapidly, one never knows if a reduction in nausea is from the change of drug or tolerance.

1. Goodman and Gillman's The Pharmacological Basis of Therapeutics. 9th Ed. Hardman JG and Limbird LE, eds. 1996.

Fast Facts and Concepts was originally developed as an end-of-life teaching tool by Eric Warm, MD, U. Cincinnati, Department of Medicine. See: Warm, E. Improving EOL care--internal medicine curriculum project. J Pall Med 1999; 2: 339-340.

Copyright Notice: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Weissman DE. Fast Fact and Concepts #25: Opioids and Nausea. October, 2000. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 10/2000

Format: Handouts

Purpose: Instructional Aid, Self-Study Guide

Training: Fellows, 1st/2nd Year Medical Students, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice
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Keyword(s): Gastrointestinal, Pain treatment

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