30.1 Antiemetics

Antiemetic Drugs

Nausea and vomiting are controlled by a complex network of receptors and pathways, including the chemoreceptor trigger zone (CTZ), the vomiting center in the medulla, the vestibular system, and the GI tract itself. Antiemetic drugs work by blocking specific receptors along these pathways. Choosing the right antiemetic depends on the cause of the nausea, because different causes activate different receptors.

Main Types and Mechanisms of Action

Each class of antiemetic targets a different receptor type. Knowing which receptor a drug blocks tells you both when to use it and what side effects to expect.

• Serotonin (5-HT3) receptor antagonists block serotonin receptors in the gut and the CTZ, reducing signals to the vomiting center. These are the go-to drugs for chemotherapy-induced nausea. Examples: ondansetron, granisetron, dolasetron, palonosetron.
• Dopamine receptor antagonists block dopamine receptors in the CTZ. They're used for gastroparesis, postoperative nausea, and migraine-associated nausea. Examples: metoclopramide, prochlorperazine, promethazine, droperidol. Metoclopramide also has a prokinetic effect, meaning it speeds gastric emptying.
• Antihistamines (H1 receptor antagonists) block histamine receptors in the vestibular system and vomiting center. This makes them particularly effective for motion sickness and vertigo-related nausea. Examples: dimenhydrinate, meclizine, diphenhydramine.
• Anticholinergics block muscarinic acetylcholine receptors in the vestibular system. Scopolamine is the primary drug in this class and is commonly delivered as a transdermal patch behind the ear for motion sickness or PONV.
• Neurokinin-1 (NK1) receptor antagonists block substance P at NK1 receptors in the gut and brain. Aprepitant is rarely used alone; it's typically part of a three-drug regimen with a 5-HT3 antagonist and a corticosteroid (dexamethasone) for highly emetogenic chemotherapy.
• Cannabinoids activate cannabinoid receptors in the brain, suppressing the vomiting center. Dronabinol and nabilone are reserved for CINV that hasn't responded to other antiemetics, and for appetite stimulation in AIDS and cancer patients.

Indications, Side Effects, and Drug Interactions

Serotonin (5-HT3) Receptor Antagonists

• Indications: chemotherapy-induced nausea and vomiting (CINV), postoperative nausea and vomiting (PONV), radiation-induced nausea and vomiting (RINV)
• Side effects: headache, constipation, dizziness, fatigue, QT prolongation (monitor ECG in at-risk patients)
• Drug interactions: increased risk of serotonin syndrome when combined with other serotonergic drugs (SSRIs, SNRIs, tramadol). Avoid concurrent use with apomorphine due to risk of severe hypotension.

Dopamine Receptor Antagonists

• Indications: gastroparesis, PONV, migraine-associated nausea
• Side effects: extrapyramidal symptoms (EPS) such as dystonia, akathisia, and tardive dyskinesia with prolonged use; hyperprolactinemia; sedation; QT prolongation
• Drug interactions: dopaminergic drugs (e.g., levodopa) decrease their effectiveness. Anticholinergic drugs can increase side effects. The FDA has a black box warning on metoclopramide for tardive dyskinesia with long-term use.

Antihistamines (H1 Receptor Antagonists)

• Indications: motion sickness, vertigo, morning sickness (diphenhydramine and doxylamine are considered safer options in pregnancy)
• Side effects: sedation, dry mouth, blurred vision, urinary retention
• Drug interactions: increased sedation with CNS depressants (alcohol, benzodiazepines, opioids); additive anticholinergic effects with other anticholinergic drugs

Anticholinergics

• Indications: motion sickness, vertigo, PONV
• Side effects: dry mouth, blurred vision, urinary retention, tachycardia, confusion (especially in older adults)
• Drug interactions: additive effects with other anticholinergic drugs. Use caution in patients with glaucoma, BPH, or bowel obstruction.

Neurokinin-1 (NK1) Receptor Antagonists

• Indications: CINV (used in combination therapy, not as monotherapy)
• Side effects: fatigue, diarrhea, hiccups, constipation
• Drug interactions: aprepitant is a moderate CYP3A4 inhibitor and can increase levels of drugs metabolized by this enzyme (e.g., dexamethasone doses are reduced when given with aprepitant). CYP3A4 inducers (e.g., rifampin) decrease aprepitant levels. Aprepitant can also reduce the effectiveness of hormonal contraceptives.

Cannabinoids

• Indications: refractory CINV, appetite stimulation in AIDS and cancer patients
• Side effects: dizziness, euphoria, dysphoria, sedation, dry mouth, tachycardia, potential for abuse
• Drug interactions: increased sedation with CNS depressants; altered metabolism of CYP2C9 and CYP3A4 substrates

Nursing Considerations

1. Assess the cause first. The underlying reason for nausea and vomiting guides drug selection. Chemotherapy-related nausea calls for a 5-HT3 antagonist, while motion sickness responds better to antihistamines or scopolamine.

2. Monitor vital signs closely, especially heart rate and blood pressure. Pay particular attention to patients with cardiovascular disease, electrolyte imbalances, or those on drugs that prolong the QT interval.

3. Watch for dehydration. Persistent vomiting leads to fluid and electrolyte losses quickly. Monitor I&O, assess mucous membranes and skin turgor, and replace fluids as ordered.

4. Monitor for class-specific adverse effects:

   • EPS with dopamine antagonists (watch for involuntary movements, muscle rigidity, restlessness)
   • Excessive sedation with antihistamines, anticholinergics, and cannabinoids
   • Anticholinergic effects in older adults (confusion, falls risk, urinary retention)
   • QT prolongation with ondansetron and dopamine antagonists (check baseline and follow-up ECGs as indicated)

5. Administer medications correctly. Some antiemetics work best when given before the emetogenic stimulus. For example, ondansetron for CINV is typically given 30 minutes before chemotherapy. Scopolamine patches should be applied at least 4 hours before travel.

6. Use non-pharmacological interventions alongside medications: acupressure at the P6 (Nei-Guan) point on the wrist, relaxation techniques, dietary modifications (clear liquids, bland foods), and minimizing strong odors.

7. Reassess and communicate. If the current regimen isn't working or is causing significant side effects, collaborate with the prescriber to adjust the dose or switch to an alternative agent.

Patient Education

• Explain the purpose of the prescribed antiemetic and what side effects to watch for. Patients on ondansetron should know about constipation; patients on scopolamine should expect dry mouth and blurred vision.
• Teach correct administration. For scopolamine patches: apply to clean, dry, hairless skin behind the ear, wash hands after handling, and replace every 72 hours. For oral antiemetics: take as directed, and some may be taken with or without food.
• Advise patients to stay hydrated even when appetite is low. Small, frequent sips of clear fluids are easier to tolerate than large volumes at once.
• Recommend non-drug strategies: eat small, frequent meals; avoid greasy or strong-smelling foods; sit upright after eating; try ginger or peppermint if tolerated.
• Warn patients taking sedating antiemetics (antihistamines, cannabinoids, promethazine) to avoid driving or operating heavy machinery until they know how the drug affects them. Alcohol will increase sedation.
• Instruct patients to tell their provider about all other medications, supplements, and herbal products they're taking to avoid interactions.
• Teach patients to seek immediate medical attention for signs of severe dehydration (little or no urine output, extreme thirst, dizziness on standing), uncontrolled vomiting, or signs of an allergic reaction (rash, swelling, difficulty breathing).