====== Leukotriene Modifiers ======

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

They are primarily used in:

  * [[respiratory:clinical:asthma|Asthma]]
  * [[allergy:clinical:allergic_rhinitis|Allergic Rhinitis]]
  * Aspirin-exacerbated respiratory disease (AERD)

They reduce bronchoconstriction, mucus production, and airway inflammation.

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===== Arachidonic Acid Pathway Context =====

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

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===== Drug Classes =====

==== Leukotriene Receptor Antagonists (CysLT1 Blockers) ====

  * [[respiratory:drugs:montelukast|Montelukast]]
  * [[respiratory:drugs:zafirlukast|Zafirlukast]]

Mechanism:
  Block CysLT1 receptor → prevent leukotriene-mediated bronchoconstriction.

Clinical effects:
  * ↓ Bronchospasm
  * ↓ Mucus
  * ↓ Airway inflammation

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==== 5-Lipoxygenase Inhibitor ====

  * [[respiratory:drugs:zileuton|Zileuton]]

Mechanism:
  Inhibits 5-lipoxygenase enzyme → ↓ leukotriene synthesis.

Effect:
  Blocks production of all leukotrienes.

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===== Clinical Role in Asthma =====

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:
  * [[respiratory:clinical:asthma|Asthma Management]]

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===== Clinical Role in Allergic Rhinitis =====

Less effective than intranasal corticosteroids.

Consider when:
  * Asthma + rhinitis coexist
  * Patient cannot tolerate antihistamines
  * AERD suspected

See:
  * [[allergy:clinical:allergic_rhinitis|Allergic Rhinitis]]

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===== Adverse Effects =====

Montelukast:
  * Neuropsychiatric warning (boxed warning)
  * Mood changes
  * Sleep disturbances

Zafirlukast:
  * Hepatotoxicity (rare)

Zileuton:
  * Hepatotoxicity (monitor LFTs)

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===== Comparison =====

^ Drug ^ Mechanism ^ Major Risk ^
| [[respiratory:drugs:montelukast|Montelukast]] | CysLT1 receptor blocker | Neuropsychiatric effects |
| [[respiratory:drugs:zafirlukast|Zafirlukast]] | CysLT1 receptor blocker | Rare hepatotoxicity |
| [[respiratory:drugs:zileuton|Zileuton]] | 5-LO inhibitor | Hepatotoxicity |

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===== Clinical Pearls =====

  * 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.

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===== Related Pages =====

  * [[endocrine:drug_classes:corticosteroids|Corticosteroids]]
  * [[allergy:histamine|Histamine & Antihistamines]]
  * [[respiratory:clinical:asthma|Asthma]]