Leukotriene Receptor Antagonists (LTRAs)
Key Points
- Primary agents: Montelukast, Zafirlukast, Pranlukast
- Target inflammatory mediators in asthma and allergic disorders
- Oral medications with once or twice daily dosing
- Important role in pediatric asthma management
- Effective in exercise-induced bronchospasm
Classification
- Selective competitive antagonists of CysLT1 receptors
- Part of controller medications in asthma
- Alternative to inhaled corticosteroids in mild asthma
- Add-on therapy in moderate-severe asthma
Clinical Pharmacology
Mechanism of Action
- Block binding of cysteinyl leukotrienes to CysLT1 receptors
- Reduce airway inflammation
- Decrease mucus secretion
- Inhibit eosinophil trafficking
- Reduce airway smooth muscle constriction
Pharmacokinetics
- Montelukast:
- Bioavailability: 64-73%
- Peak plasma levels: 2-4 hours
- Half-life: 2.7-5.5 hours
- 99% protein bound
- Zafirlukast:
- Bioavailability: 40%
- Peak plasma levels: 3 hours
- Half-life: 10 hours
- 99% protein bound
Clinical Applications
Primary Indications
- Persistent Asthma:
- Monotherapy in mild persistent asthma
- Add-on therapy to inhaled corticosteroids
- Step-down therapy from higher dose ICS
- Exercise-Induced Bronchospasm:
- Preventive therapy
- Alternative to pre-exercise β2-agonists
- Allergic Rhinitis:
- Seasonal allergic symptoms
- Perennial allergic rhinitis
Special Clinical Scenarios
- Viral-induced wheezing in preschoolers
- Aspirin-sensitive asthma
- Nocturnal asthma symptoms
- Prevention of bronchiolitis obliterans
Specific Agents and Dosing
Montelukast (Singulair®)
- Age-Based Dosing:
- 6-23 months: 4mg oral granules once daily
- 2-5 years: 4mg chewable tablet once daily
- 6-14 years: 5mg chewable tablet once daily
- ≥15 years: 10mg tablet once daily
- Available Forms:
- Oral granules
- Chewable tablets
- Regular tablets
Zafirlukast (Accolate®)
- Age-Based Dosing:
- 5-11 years: 10mg twice daily
- ≥12 years: 20mg twice daily
- Administration: Take on empty stomach
Management Considerations
Adverse Effects
- Common:
- Headache
- Gastrointestinal upset
- Upper respiratory infection
- Serious:
- Neuropsychiatric events
- Churg-Strauss syndrome (rare)
- Hepatotoxicity (rare)
Monitoring Requirements
- Baseline liver function tests (Zafirlukast)
- Mental health monitoring
- Clinical response assessment at 2-4 weeks
- Periodic reevaluation of need
Drug Interactions
- Zafirlukast:
- Warfarin (↑ INR)
- Theophylline
- Erythromycin
- Montelukast: Minimal interactions
Black Box Warning
- Serious neuropsychiatric events:
- Agitation
- Depression
- Suicidal thoughts
- Sleep disturbances
Further Reading
