Leukotriene Receptor Antagonists

CLASS

• Leukotriene Receptor Antagonists
• example is Montelukast

MECHANISM OF ACTION

• Leukotrienes are central to the pathophysiology of acute asthma
• Leukotrienes are synthesized from arachiodonic acid and released from membrane phospholipids when inflammatory cells are activated
• Ltb4, LtD4, LtC4 and LE4 bind receptor (CysLT) on mast cells, eosinophils and alveolar macrophages produce the features of asthma
• Smooth muscle contraction and bronchoconstriction
• chemotaxis and activation: leukocyte infiltration and stimulation of production of pro-inflammatory cytokines 
• Capillary leak and airway oedema 
• Proliferation of smooth muscle cells and fibroblasts

• LRA -> inhibitors of the leukotriene pathway
• Leukotriene inhibitors are specific for the airway receptors and may block this reaction

ROUTE

• taken PO once or twice daily

USE

• have been shown to have steroid sparing effects
• preventative role in community
• particularly useful in NSAID and aspirin induced asthma
• limited role in ICU
• If a patient is in the recovery phase of an asthma attack and there is a history of frequent attacks then its addition to other preventer medications would be appropriate
• Indicated in management of asthma when inhaled glucocorticoids not tolerated or for patients who have not responded to inhaled glucocorticoids

BENEFICIAL EFFECTS

• shown to reduce the severity of initial response to allergen induced asthma
• attenuates the late and delayed response
•  decreases prolonged airway hyperresponsiveness
•  improves lung function
• decreases need for beta adrenergic agonists
• fewer symptoms of asthma
• decrease exacerbations

ADVERSE EFFECTS

• side effects – increases LFTs
• interactions – wafarin -> increase INR