LEUKOTRIENE ANTAGONIST

• Two main approaches to block leukotrienes actions:
• Inhibition of 5-lipoxygenase pathway
• Drugs inhibiting 5-lipoxygenase enzyme will inhibit synthetic pathway of leukotriene metabolism
• MK-886 – Blocks 5-lipoxygenase activating protein (FLAP), inhibiting 5-lipoxygenase enzyme functioning & helps in treating atherosclerosis.
• Antagonism of cysteinyl-leukotriene type 1 receptors
• Eg: Montelukast & Zafirlukast.
• Blocks cysteinyl leukotriene actions at CysLT1 receptor on bronchial smooth muscle via receptor antagonism.
• Helps improve asthma symptoms, reduce asthma exacerbation, limit inflammation markers such as eosinophil counts in peripheral blood & bronchoalveolar lavage fluid. 
• Hence, are anti-inflammatory.

MONTELUKAST:

• A LTRA (Leukotriene receptor antagonist).
• Usually administered orally.
• More acceptable in children.
• Mechanism of action: 

CysLT1 antagonist: 

• Blocks leukotriene D4 action on cysteinyl leukotriene receptor CysLT1 in lungs & bronchial tubes by binding to it. 
• Hence, reduces bronchoconstriction & results in less inflammation.

Indications:

• Indicated for prophylactic therapy of mild to moderate asthma.
• As an alternative to inhaled glucocorticoids.
• Used in maintenance therapy of asthma & relief of seasonal allergies.

Contraindications:

• Not used in terminating asthma episodes.
• Not useful in treating acute asthma attacks. 
• Due to its very specific action, it does not interact with other allergy medications like theophylline.

SIDE EFFECTS:

• Gastrointestinal disturbances
• Hypersensitivity reactions
• Sleep disorders 
• Increased bleeding tendency
• Higher incidence of Churg-Strauss syndrome