From the Guidelines
5-HT receptor antagonists are a class of medications that block the action of serotonin at specific receptor sites, primarily targeting 5-HT3 receptors, and are used to prevent and treat nausea and vomiting, particularly in chemotherapy, radiation therapy, and post-operative settings. The most clinically important 5-HT antagonists include ondansetron, granisetron, palonosetron, and dolasetron, which have been shown to be effective in controlling acute chemotherapy-induced nausea and/or vomiting 1. These medications work by blocking serotonin receptors in the chemoreceptor trigger zone and gastrointestinal tract, preventing the stimulation that leads to the vomiting reflex.
Key Characteristics of 5-HT Receptor Antagonists
- Ondansetron is typically given at 8-16 mg IV or orally before treatment, while granisetron is dosed at 1-2 mg orally or 0.01 mg/kg IV 1
- Palonosetron has a higher binding affinity for the 5-HT3 receptor and a longer half-life compared to other serotonin antagonists, making it effective for preventing both delayed and acute emesis 1
- Dolasetron is effective in preventing acute emesis, but seems to be less effective in preventing delayed emesis 1
Side Effects and Quality of Life
- Side effects of 5-HT receptor antagonists are generally mild and may include headache, constipation, and occasionally QT interval prolongation on ECG 1
- These medications have revolutionized the management of nausea and vomiting, significantly improving quality of life for patients undergoing treatments that would otherwise cause severe gastrointestinal distress 1
Clinical Guidelines and Recommendations
- The American Society of Clinical Oncology recommends the use of 5-HT3 receptor antagonists, such as ondansetron, granisetron, and palonosetron, for the prevention of chemotherapy-induced nausea and vomiting 1
- The choice of 5-HT receptor antagonist and dosing regimen should be based on the individual patient's needs and the specific chemotherapy regimen being used 1
From the FDA Drug Label
Granisetron is a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist with little or no affinity for other serotonin receptors, including 5-HT1; 5-HT1A; 5-HT1B/C; 5-HT2; for alpha1-, alpha2- or beta-adrenoreceptors; for dopamine-D2; or for histamine-H1; benzodiazepine; picrotoxin or opioid receptors Ondansetron Injection is a 5-HT3 receptor antagonist
5-Hydroxytryptamine (5-HT) receptor antagonists are drugs that block the action of serotonin at specific receptors.
- Examples of 5-HT3 receptor antagonists include:
- Ondansetron
- Granisetron
- These drugs are used to prevent nausea and vomiting associated with chemotherapy, radiation therapy, and surgery. 2 3 3
From the Research
Definition and Function of 5-Hydroxytryptamine (5-HT) Receptor Antagonists
- 5-HT receptor antagonists are a class of drugs that block the action of serotonin (5-HT) at its receptors, specifically the 5-HT3 receptor subtype 4, 5, 6, 7, 8.
- These drugs are primarily used to prevent and treat nausea and vomiting caused by chemotherapy, radiotherapy, and surgery 4, 5, 6, 7, 8.
Types of 5-HT3 Receptor Antagonists
- Several 5-HT3 receptor antagonists are available, including ondansetron, granisetron, dolasetron, tropisetron, and palonosetron 5, 6, 7, 8.
- These agents have similar efficacy and safety profiles, but may differ in their pharmacokinetic properties and potential side effects 5, 6, 7.
Mechanism of Action and Efficacy
- 5-HT3 receptor antagonists work by blocking the action of serotonin at the 5-HT3 receptor, which is involved in the vomiting reflex 4, 5, 6, 7, 8.
- These agents are effective in preventing acute chemotherapy-induced nausea and vomiting, with response rates ranging from 60-70% 8.
- The efficacy of 5-HT3 receptor antagonists may be enhanced by concomitant administration of dexamethasone 8.
Safety and Tolerability
- 5-HT3 receptor antagonists are generally well-tolerated, with common side effects including headache, gastrointestinal effects, lightheadedness, and sedation 5, 7, 8.
- Some agents, such as dolasetron, may be associated with cardiovascular effects, including QTc prolongation 7.
- The safety and efficacy of 5-HT3 receptor antagonists in pediatric patients and those with comorbid conditions, such as cardiovascular disease and renal or hepatic impairment, should be carefully evaluated 4, 7.