What are the causes of nausea?

From the Guidelines

For the treatment of nausea, ondansetron (Zofran) 4-8mg orally every 8 hours is often the first-line treatment due to its efficacy and minimal side effects. This recommendation is based on the most recent and highest quality study available, which prioritizes the treatment of nausea and vomiting in various contexts, including chemotherapy-induced nausea and vomiting 1.

Causes of Nausea and Vomiting

The causes of nausea and vomiting can be diverse, including:

• Chemotherapy-induced nausea and vomiting, which can be acute, delayed, anticipatory, breakthrough, or refractory 1
• Other causes such as radiotherapy, infection, metabolic disorders, electrolyte disturbances, constipation, gastrointestinal obstruction, cachexia syndrome, metastases, paraneoplasia, and other emetogenic medications 1

Treatment Approaches

Treatment approaches for nausea and vomiting depend on the cause and may include:

• Ondansetron with dexamethasone 4-20mg and possibly aprepitant (Emend) 125mg on day 1, followed by 80mg on days 2-3 for chemotherapy-induced nausea 1
• Vitamin B6 (10-25mg) combined with doxylamine (10mg) for pregnancy-related nausea, with metoclopramide or ondansetron as second-line options
• Scopolamine patches (1.5mg applied behind the ear 4 hours before travel) or dimenhydrinate (Dramamine) 50-100mg every 4-6 hours for motion sickness

Mechanisms of Action

These medications work through different mechanisms, including:

• Ondansetron blocking serotonin receptors
• Promethazine blocking histamine receptors
• Metoclopramide enhancing gastric emptying
• Scopolamine blocking acetylcholine, allowing for targeted treatment based on the cause of nausea 1

From the FDA Drug Label

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like l‑dopa or apomorphine which are known to increase dopamine levels or to possess dopamine-like effects.

Metoclopramide is used as a nausea agent due to its ability to block dopamine receptors in the central and peripheral nervous system, specifically in the chemoreceptor trigger zone (CTZ) 2.

• It works by antagonizing dopamine receptors, which are involved in producing nausea and vomiting.
• The antiemetic properties of metoclopramide make it effective in preventing nausea and vomiting.

From the Research

Nausea Agents

• Nausea agents, such as ondansetron and aprepitant, are used to prevent and treat nausea and vomiting caused by chemotherapy, radiation, and surgery 3, 4, 5, 6, 7.
• Ondansetron is a selective 5-HT3 receptor antagonist that has been shown to be effective in preventing nausea and vomiting caused by chemotherapy and radiation 3, 6.
• Aprepitant is a neurokinin-1 (NK(1)) receptor antagonist that has been shown to be effective in preventing nausea and vomiting caused by chemotherapy and surgery 4, 7.
• Combination therapy with ondansetron and dexamethasone has been shown to be significantly more effective than ondansetron monotherapy in preventing acute high-dose cisplatin-induced emesis 3.
• Aprepitant has been shown to be effective in preventing postoperative nausea and vomiting when administered as a single oral dose prior to surgery 4.
• The most common adverse events associated with ondansetron therapy are headache and constipation, while aprepitant is generally well tolerated 3, 4.

Mechanism of Action

• Ondansetron works by selectively inhibiting the 5-HT3 receptor, which is involved in the transmission of nausea and vomiting signals 3, 6.
• Aprepitant works by antagonizing the effects of Substance P, a neurotransmitter that is involved in the transmission of nausea and vomiting signals 4, 7.
• The 5-HT3 receptor antagonists, such as ondansetron, have been shown to be effective in ameliorating nausea and vomiting in a number of circumstances, including chemotherapy-induced nausea and vomiting, radiation-induced emesis, and postoperative nausea and vomiting 5.