What are the three least anticholinergic antiemetics?

Least Anticholinergic Antiemetics

The three least anticholinergic antiemetics are 5-HT3 receptor antagonists (particularly palonosetron), NK1 receptor antagonists (such as aprepitant), and dexamethasone. These medications provide effective antiemetic control with minimal anticholinergic burden compared to other antiemetic classes.

5-HT3 Receptor Antagonists

• Palonosetron is the preferred 5-HT3 antagonist due to its superior efficacy in preventing both acute and delayed nausea and vomiting with minimal anticholinergic effects 1
• Other 5-HT3 antagonists including ondansetron, granisetron, and dolasetron also have minimal anticholinergic properties 2
• 5-HT3 antagonists work by selectively blocking serotonin receptors in the chemoreceptor trigger zone and gastrointestinal tract, rather than blocking muscarinic receptors 2
• These agents are particularly effective for chemotherapy-induced and postoperative nausea and vomiting 2, 3
• Common side effects include headache and constipation rather than typical anticholinergic effects like dry mouth, urinary retention, and confusion 3

NK1 Receptor Antagonists

• Aprepitant and fosaprepitant selectively block substance P at NK1 receptors in the central nervous system, providing a mechanism of action distinct from anticholinergic pathways 2
• These agents have shown significant efficacy in controlling both acute and delayed emesis, particularly when combined with 5-HT3 antagonists and dexamethasone 2
• NK1 receptor antagonists were found to be the most effective antiemetic drug class in a comprehensive network meta-analysis, with efficacy comparable to most drug combinations 3
• They have minimal anticholinergic properties, with their primary side effects being fatigue rather than anticholinergic symptoms 2

Corticosteroids (Dexamethasone)

• Dexamethasone is highly effective as an antiemetic with minimal anticholinergic properties 1
• It can be used as a single agent for low emetogenic risk situations or combined with other antiemetics for enhanced efficacy 1
• The recommended dose is 8 mg oral or IV for antiemetic purposes 1
• Dexamethasone works through anti-inflammatory mechanisms rather than anticholinergic pathways 2
• It has been shown to improve the efficacy of antiemetic regimens containing 5-HT3 antagonists without adding anticholinergic burden 2

Antiemetics with Higher Anticholinergic Burden (to avoid when concerned about anticholinergic effects)

• Antihistamines (such as diphenhydramine, dimenhydrinate) have significant anticholinergic properties 4
• Phenothiazines (such as prochlorperazine) have moderate to high anticholinergic effects 5, 4
• Anticholinergic agents like scopolamine should be avoided when anticholinergic burden is a concern 4
• These agents can cause typical anticholinergic side effects including dry mouth, blurred vision, urinary retention, constipation, and confusion 4

Clinical Application

• For patients at risk of anticholinergic side effects (elderly, those with glaucoma, prostatic hypertrophy, or cognitive impairment), prioritize palonosetron, aprepitant, or dexamethasone 5
• When combining antiemetics, use agents from different classes with minimal anticholinergic properties to maximize efficacy while minimizing anticholinergic burden 2, 1
• For chemotherapy-induced nausea and vomiting, a combination of palonosetron, dexamethasone, and aprepitant provides excellent control with minimal anticholinergic effects 2
• For postoperative nausea and vomiting, 5-HT3 antagonists (particularly palonosetron) and dexamethasone are preferred options 3

Dosing Considerations

• Palonosetron: 0.25 mg IV or 0.5 mg oral 1
• Aprepitant: 125 mg oral on day 1, followed by 80 mg on days 2-3; or fosaprepitant 150 mg IV on day 1 only 1
• Dexamethasone: 8 mg oral or IV 1
• Dose adjustments may be necessary in patients with hepatic or renal impairment 5