Serotonin Agonists in Pediatrics

Serotonin Agonists in Pediatrics

Key Points

Primary use in treating migraines and headache disorders
Selective action on specific serotonin receptor subtypes
Important role in pediatric pain management
Requires careful consideration of age-specific factors

Major Classes

Triptans
- Sumatriptan
- Rizatriptan
- Zolmitriptan
- Almotriptan
Other Serotonergic Agents
- Ergotamine derivatives
- 5-HT1 receptor agonists

Pharmacological Properties

Mechanism of Action

Primary Actions
- Selective 5-HT1B/1D receptor agonism
- Cranial vessel vasoconstriction
- Inhibition of neurogenic inflammation
- Modulation of pain pathways
Secondary Effects
- Reduced CGRP release
- Decreased substance P release
- Inhibition of trigeminal nerve activation

Pharmacokinetics

Absorption
- Variable bioavailability by route
  - Oral: 14-17% (sumatriptan)
  - Nasal: 17-30%
  - Subcutaneous: >95%
Distribution
- Rapid distribution phase
- Variable protein binding
- Limited CNS penetration
Metabolism
- Primarily hepatic via MAO-A
- Some CYP450 involvement
- Active/inactive metabolites vary by agent

Clinical Applications

Primary Indications

Acute Migraine Treatment
- Moderate to severe episodes
- With or without aura
- Status migrainosus
Cluster Headaches
- Acute attack treatment
- Prevention in selected cases
Other Headache Disorders
- Chronic daily headache
- Post-traumatic headache

Patient Selection

Age Considerations
- FDA approved ages vary by agent
- Most studied in adolescents
- Limited data in young children
Clinical Factors
- Headache severity
- Previous treatment response
- Comorbid conditions

Administration & Dosing

Dosing Guidelines by Agent

Sumatriptan
- Oral: 25-100 mg/dose
- Nasal: 5-20 mg/dose
- Subcutaneous: 0.06 mg/kg (max 6 mg)
- Maximum daily doses vary by route
Rizatriptan
- Age 6-17 years:
  - < 40 kg: 5 mg/dose
  - ≥ 40 kg: 10 mg/dose
- Maximum: 30 mg/24 hours
Zolmitriptan
- Age ≥ 12 years: 2.5-5 mg/dose
- Maximum: 10 mg/24 hours

Administration Strategies

Timing Considerations
- Early in migraine attack
- With or without food
- Spacing between doses
Route Selection
- Based on symptom severity
- Patient preference
- Previous response

Monitoring & Safety

Adverse Effects

Common Effects
- Paresthesias (10-20%)
- Dizziness (5-15%)
- Fatigue (5-10%)
- Chest tightness (rare)
Route-Specific Effects
- Injection site reactions
- Nasal irritation
- Taste disturbance

Safety Monitoring

Pre-treatment Assessment
- Cardiovascular risk factors
- Baseline blood pressure
- Contraindications screening
Ongoing Monitoring
- Treatment response
- Medication overuse
- Adverse effects

Contraindications

Absolute
- Basilar migraine
- Hemiplegic migraine
- Cardiovascular disease
- Uncontrolled hypertension
Relative
- Cardiovascular risk factors
- Raynaud's phenomenon
- Pregnancy/lactation

Drug Interactions

Major Interactions
- MAO inhibitors
- SSRIs/SNRIs
- Ergotamine derivatives
Monitoring Needs
- Serotonin syndrome risk
- Combined vasoconstrictor effects
- Drug-specific interactions

Further Reading