Leukotrienes: Function and Activity

Leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in many allergic disorders. 
Cysteinyl leukotrienes (CysLT C4,D4,E4) are released from mast cells along with histamine in response to acute inflammatory mediators.  Eosinophils are major producers of cysteinyl leukotrienes in allergy – Mast cells are fixed cells, located in the skin1, nose, eyes, airway, and gut. Eosinophils are attracted into tissues affected by allergic inflammation associated with edema, vasodilation, pain/itching, heat, and evolution of disease chronicity/severity.  Unlike histamines, CysLT levels are elevated acutely (initial phase) and remain elevated for several hours following an allergen challenge (late phase reaction). Elevated urinary CysLT levels are measurable in asthma, rhinitis, and atopic dermatitis. Elevated CysLT levels are measurable in tears (allergic conjunctivitis) and nasal secretions (rhinitis).  

Why Block the Action of Leukotrienes?

Leukotrienes are:
• Potent mediators of acute inflammation
• Released by mast cells along with histamine, and later by eosinophils
• Acted longer than histamine on both an acute and late-phase allergic reactions 
• A bridge to chronic inflammation
• Not blocked by corticosteroids

Leukotriene Receptor Antagonists (LTRAs)

LTRAs are medications which function as a leukotriene related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor antagonist (cysteinyl leukotriene receptors) and consequently oppose the function of inflammatory mediators produced by the immune system that promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in many allergic conditions. 

Advantages vs. Standard-of-Care?

  • A safe non-steroidal treatment option 
  • Work days faster than corticosteroids
  • Can be used for prevention prior to exposure
  • Appropriate for treatment after exposure
  • Well-suited for use with children

Why Topical Zafirlucast?

• Zafirlucast is a potent FDA approved anti-leukotriene
• Drug product is only available as a oral tablet 
• It is particularly suitable for targeted topical development and use for allergic conditions

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