Leukotriene modifiers target the leukotriene arm of the arachidonic acid inflammatory pathway.

They are primarily used in:

• Asthma
• Allergic Rhinitis
• Aspirin-exacerbated respiratory disease (AERD)

They reduce bronchoconstriction, mucus production, and airway inflammation.

Cell membrane phospholipids

↓ (Phospholipase A2)

Arachidonic acid

Two major pathways:

1) COX pathway → Prostaglandins
2) 5-Lipoxygenase pathway → Leukotrienes

Leukotrienes (LTC4, LTD4, LTE4):

• Potent bronchoconstrictors
• Increase vascular permeability
• Increase mucus secretion
• Promote eosinophilic inflammation

• Montelukast
• Zafirlukast

Mechanism:

Block CysLT1 receptor → prevent leukotriene-mediated bronchoconstriction.

Clinical effects:

• ↓ Bronchospasm
• ↓ Mucus
• ↓ Airway inflammation

• Zileuton

Mechanism:

Inhibits 5-lipoxygenase enzyme → ↓ leukotriene synthesis.

Effect:

Blocks production of all leukotrienes.

Used as:

• Add-on therapy
• Alternative for mild persistent asthma
• Useful in aspirin-sensitive asthma

Not first-line monotherapy in moderate to severe asthma.

See:

• Asthma Management

Less effective than intranasal corticosteroids.

Consider when:

• Asthma + rhinitis coexist
• Patient cannot tolerate antihistamines
• AERD suspected

See:

• Allergic Rhinitis

Montelukast:

• Neuropsychiatric warning (boxed warning)
• Mood changes
• Sleep disturbances

Zafirlukast:

• Hepatotoxicity (rare)

Zileuton:

• Hepatotoxicity (monitor LFTs)

• Leukotrienes are stronger bronchoconstrictors than histamine.
• Montelukast is useful in aspirin-exacerbated respiratory disease.
• Not as effective as inhaled corticosteroids for asthma control.
• Neuropsychiatric effects must be discussed with patients.
• Zileuton blocks synthesis; montelukast blocks receptor.

• Corticosteroids
• Histamine & Antihistamines
• Asthma