NCLEX Review Guide: Antiemetics

Classification and Mechanism of Action

• Antiemetics are medications specifically designed to prevent or relieve nausea and vomiting by targeting various receptors in the chemoreceptor trigger zone (CTZ), vestibular system, and gastrointestinal tract. These medications work by blocking neurotransmitters involved in stimulating the vomiting center in the medulla oblongata, including dopamine, serotonin, histamine, and acetylcholine.
• The efficacy of antiemetics depends on the cause of nausea and vomiting, which may include motion sickness, pregnancy, chemotherapy, post-operative recovery, or gastrointestinal disorders.

Major Classes of Antiemetics

• Dopamine Antagonists: Medications like prochlorperazine (Compazine), promethazine (Phenergan), and metoclopramide (Reglan) block dopamine receptors in the CTZ. These are effective for general nausea, vertigo, and can enhance gastric emptying.
• Serotonin (5-HT3) Antagonists: Ondansetron (Zofran), granisetron (Kytril), and palonosetron (Aloxi) block serotonin receptors and are particularly effective for chemotherapy-induced and post-operative nausea and vomiting (PONV).
• Antihistamines: Dimenhydrinate (Dramamine) and meclizine (Antivert) work by blocking histamine H1 receptors and are most effective for motion sickness and vertigo-related nausea.
• Anticholinergics: Scopolamine (Transderm Scōp) blocks muscarinic acetylcholine receptors and is primarily used for motion sickness, typically administered as a transdermal patch.
• NK1 Receptor Antagonists: Aprepitant (Emend) blocks substance P receptors and is used for prevention of chemotherapy-induced nausea and vomiting, often in combination with other antiemetics.
• Cannabinoids: Dronabinol (Marinol) and nabilone (Cesamet) activate cannabinoid receptors and are used for chemotherapy-induced nausea resistant to other treatments.
• Corticosteroids: Dexamethasone is often used as an adjunct antiemetic, particularly with chemotherapy regimens, though its exact mechanism as an antiemetic is not fully understood.

Ondansetron (Zofran)

• Mechanism: Selectively blocks serotonin 5-HT3 receptors in the CTZ and GI tract, preventing stimulation of the vomiting center.
• Indications: First-line treatment for chemotherapy-induced nausea and vomiting (CINV), radiation therapy-induced nausea, and postoperative nausea and vomiting (PONV). Also used off-label for hyperemesis gravidarum and gastroenteritis.
• Administration: Available in oral (tablets, orally disintegrating tablets, oral solution) and IV formulations. For PONV, typically administered IV 30 minutes before end of anesthesia or postoperatively.
• Side Effects: Headache, constipation, dizziness, and rare but serious QT interval prolongation (requires ECG monitoring in high-risk patients).
• Nursing Considerations: Monitor for signs of serotonin syndrome when administered with other serotonergic medications. Orally disintegrating tablets should be placed on tongue, not swallowed whole or chewed.

Metoclopramide (Reglan)

• Mechanism: Acts as both a dopamine antagonist and a prokinetic agent that enhances upper GI motility by increasing lower esophageal sphincter tone and accelerating gastric emptying.
• Indications: Diabetic gastroparesis, gastroesophageal reflux, and as an antiemetic for chemotherapy-induced nausea (lower emetogenic potential regimens).
• Administration: Available in oral, IM, and IV formulations. For gastroparesis, typically administered 30 minutes before meals and at bedtime.
• Side Effects: Extrapyramidal symptoms (EPS), tardive dyskinesia (with long-term use), restlessness, drowsiness, and fatigue.
• Important Alert: Metoclopramide carries a black box warning for tardive dyskinesia, which can be irreversible. Limit treatment duration (usually not exceeding 12 weeks) and use lowest effective dose.

Promethazine (Phenergan)

• Mechanism: Acts as both an antihistamine (H1 receptor antagonist) and a dopamine antagonist, affecting the CTZ and vestibular pathways.
• Indications: Motion sickness, vertigo, post-operative nausea, and as an adjunct for anesthesia or analgesia.
• Administration: Available in oral tablets, suppositories, and injectable forms. When given IV, must be administered slowly and in a diluted form through a large vein.
• Side Effects: Significant sedation, anticholinergic effects (dry mouth, urinary retention, blurred vision), and extrapyramidal symptoms.
• Important Alert: IV administration carries risk of severe tissue damage and necrosis if extravasation occurs. Never administer intra-arterially or via IV push; always dilute and administer slowly.

Scopolamine (Transderm Scōp)

• Mechanism: Anticholinergic agent that blocks muscarinic receptors in the vestibular apparatus and vomiting center.
• Indications: Primarily used for prevention of motion sickness and post-operative nausea and vomiting.
• Administration: Most commonly used as a transdermal patch applied behind the ear at least 4 hours before anticipated need. Each patch is effective for up to 72 hours.
• Side Effects: Dry mouth, drowsiness, blurred vision, pupillary dilation, and urinary retention. Can cause confusion and hallucinations, especially in elderly patients.

Differentiating 5-HT3 Antagonists

• While ondansetron (Zofran) and granisetron (Kytril) belong to the same class and have similar efficacy, they differ in pharmacokinetics and dosing schedules. Ondansetron requires more frequent dosing (every 8 hours) compared to granisetron (every 24 hours).
• Palonosetron (Aloxi) is a newer 5-HT3 antagonist with a significantly longer half-life (40 hours vs. 4-9 hours for ondansetron), making it effective for up to 5 days with a single dose and more effective for delayed chemotherapy-induced nausea and vomiting.

Phenothiazines vs. Metoclopramide

• Both phenothiazines (prochlorperazine, promethazine) and metoclopramide are dopamine antagonists that can cause extrapyramidal symptoms, but they have different primary uses. Phenothiazines are used primarily as antiemetics and sometimes antipsychotics, while metoclopramide has the added benefit of increasing GI motility.
• Metoclopramide carries a higher risk of tardive dyskinesia with prolonged use, while phenothiazines tend to cause more sedation and anticholinergic effects.

IV Administration Precautions

• Several antiemetics require specific administration techniques to prevent complications. Ondansetron should be administered over at least 30 seconds (preferably 2-5 minutes) to prevent transient sensation of warmth or flushing.
• Promethazine administration requires extreme caution due to risk of severe tissue damage and arterial spasm. It must never be given via IV push or intra-arterially. When given IV, it should be diluted to a concentration of 25mg/mL or less and administered at a maximum rate of 25mg/minute through a large vein, preferably using a running IV line.

Procedure: Safe IV Promethazine Administration

1. Verify physician order for dose, route, and rate of administration.
2. Assess patency of IV line and ensure it's placed in a large vein.
3. Dilute promethazine to a concentration not exceeding 25mg/mL with normal saline.
4. Administer through a running IV line or inject into the tubing port furthest from the patient's vein.
5. Administer at a rate not exceeding 25mg/minute.
6. Continuously assess the IV site during administration for signs of irritation or extravasation.
7. If extravasation occurs, stop administration immediately, disconnect IV, attempt to aspirate residual drug, and notify physician.
8. Apply cold compresses to the affected area and document the incident.

Patient Education

• Instruct patients taking ondansetron orally disintegrating tablets to allow the tablet to dissolve on the tongue rather than chewing or swallowing it whole. These tablets dissolve quickly and do not require water.
• For patients using scopolamine patches, provide instructions to wash hands thoroughly after application and to avoid touching eyes after handling the patch due to risk of pupillary dilation. The patch should be applied to the hairless area behind the ear and replaced every 72 hours if continued prevention is needed.
• Advise patients about potential sedation with antihistamines and phenothiazines, cautioning against driving or operating machinery until response to the medication is known.

Special Populations Considerations

• Pregnancy: Ondansetron is commonly used for hyperemesis gravidarum, though it's officially Category B. Vitamin B6 and doxylamine combination (Diclegis) is FDA-approved for pregnancy-related nausea. Metoclopramide is considered relatively safe during pregnancy (Category B).
• Pediatric Patients: Dosing is weight-based. Ondansetron is commonly used in pediatrics. Promethazine is contraindicated in children under 2 years due to risk of respiratory depression and should be used cautiously in older children.
• Elderly Patients: More susceptible to anticholinergic effects of scopolamine and phenothiazines, which can cause confusion, urinary retention, and falls. Metoclopramide poses increased risk of extrapyramidal symptoms and tardive dyskinesia in elderly patients.
• Renal/Hepatic Impairment: Dose adjustments may be necessary for patients with severe hepatic impairment, particularly for ondansetron (maximum 8mg/day). Most antiemetics undergo hepatic metabolism.

Antiemetic Selection Based on Cause

• Chemotherapy-Induced Nausea and Vomiting (CINV): The emetogenic potential of the chemotherapy regimen determines antiemetic selection. Highly emetogenic regimens (e.g., cisplatin) require combination therapy with a 5-HT3 antagonist, NK1 receptor antagonist, and dexamethasone. Low emetogenic regimens may be managed with a single agent.
• Post-Operative Nausea and Vomiting (PONV): Risk factors include female gender, non-smoking status, history of PONV or motion sickness, and use of volatile anesthetics or opioids. 5-HT3 antagonists are first-line, often combined with dexamethasone. Scopolamine patches may be applied preoperatively.
• Pregnancy-Related Nausea: First-line treatment includes vitamin B6 (pyridoxine) alone or combined with doxylamine. Metoclopramide or ondansetron may be used for refractory cases.
• Vestibular Disorders: Antihistamines like meclizine or dimenhydrinate are most effective for vertigo-related nausea.

Common Pitfalls in Antiemetic Therapy

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