Serotonin-Receptor Antagonists in Pediatrics
Key Points
- Primary role in preventing and treating chemotherapy-induced nausea and vomiting (CINV)
- Effective for postoperative nausea and vomiting (PONV)
- Selective antagonism at 5-HT3 receptors
- High safety profile in pediatric populations
Common Agents
- First Generation
- Ondansetron (Zofran®)
- Granisetron (Kytril®)
- Dolasetron (Anzemet®)
- Second Generation
Pharmacological Properties
Mechanism of Action
- Primary Mechanisms
- Competitive antagonism at 5-HT3 receptors
- Blocks serotonin binding in CTZ (chemoreceptor trigger zone)
- Reduces afferent vagal stimulation
- Inhibits serotonin release in small intestine
- Receptor Distribution
- Central: Area postrema, nucleus tractus solitarius
- Peripheral: GI tract nerve endings
- Vagal afferent neurons
Pharmacokinetics
- Absorption
- Ondansetron: 56-71% bioavailability
- Granisetron: 60% bioavailability
- Palonosetron: 97% bioavailability
- Distribution
- High volume of distribution
- Moderate protein binding
- Good CNS penetration
- Metabolism
- Primarily hepatic via CYP450
- Main enzymes: CYP3A4, CYP2D6
- Active and inactive metabolites
Clinical Applications
Primary Indications
- Chemotherapy-Induced Nausea/Vomiting
- Highly emetogenic chemotherapy
- Moderately emetogenic chemotherapy
- Prevention and treatment
- Postoperative Nausea/Vomiting
- Prophylaxis in high-risk procedures
- Treatment of established PONV
- Other Applications
- Radiation therapy-induced nausea
- Severe gastroenteritis
- Cyclic vomiting syndrome
Clinical Efficacy
- CINV Prevention
- 80-90% efficacy for acute phase
- 60-70% efficacy for delayed phase
- Enhanced efficacy with combination therapy
- PONV Management
- 70-80% prevention rate
- Effective rescue treatment
- Reduced need for rescue antiemetics
Administration & Dosing
Ondansetron Dosing
- CINV Prevention
- Age ≥ 6 months: 0.15 mg/kg/dose IV
- Maximum single dose: 8 mg
- Frequency: Every 8-12 hours
- PONV Prevention
- 0.1 mg/kg IV single dose
- Maximum: 4 mg
- Timing: End of surgery
Granisetron Dosing
- CINV Prevention
- 10-40 mcg/kg/dose IV
- Maximum: 3 mg/day
- Single daily dosing
Palonosetron Dosing
- CINV Prevention
- Age ≥ 1 month: 20 mcg/kg IV
- Maximum: 1.5 mg/dose
- Single dose administration
Monitoring & Safety
Adverse Effects
- Common Effects
- Headache (15-25%)
- Constipation (5-10%)
- Fatigue (5-10%)
- Dizziness (5%)
- Cardiovascular Effects
- QT interval prolongation
- Transient ECG changes
- Usually clinically insignificant
Monitoring Parameters
- Baseline Assessment
- ECG in high-risk patients
- Electrolyte status
- Liver function
- Ongoing Monitoring
- Clinical response
- Hydration status
- Electrolyte balance
Drug Interactions
- Major Interactions
- QT-prolonging medications
- CYP3A4 inducers/inhibitors
- Serotonergic agents
- Precautions
- Congenital long QT syndrome
- Electrolyte abnormalities
- Hepatic impairment
Further Reading
