Leukotriene receptor antagonists

Key examples

• Montelukast

 

Common indications

1.  Adults: leukotriene receptor antagonists may be considered as an add-on therapy for asthma, where symptoms are not adequately controlled by inhaled corticosteroids and long acting β₂ agonists (LABAs).
2. Children aged 5–12 years: as an alternative to LABAs as an add-on therapy where inhaled corticosteroids are insufficient to control asthma symptoms.  
3. Children aged under 5 years: as a first-line preventative therapy in young children with asthma who are unable to take an inhaled corticosteroid.

 

Mechanisms of action

• In asthma, leukotrienes produced by mast cells and eosinophils (amongst other sources) activate the G protein-coupled leukotriene receptor CysLT1. 
• This activates a cascade of pathways that result in the inflammation and bronchoconstriction that contribute to the pathophysiology of asthma. 
• Leukotriene receptor agonists reduce inflammation and bronchoconstriction in asthma by blocking the CysLT1 receptor and damping down the inflammatory cascade.

 

Important adverse effects

• Leukotriene receptor antagonists are generally well tolerated. 
• Headache and abdominal pain are the most common adverse effects; they are usually mild. 
• There is also an increased rate of upper respiratory tract infections in patients taking the drug. 
• Uncommonly, hyperactivity and a reduced ability to concentrate may occur.  
• Churg–Strauss syndrome, an eosinophilic autoimmune disorder, has been seen in association with leukotriene receptor antagonists; however, there is no conclusive evidence that it is an adverse effect of the drug.

 

Warnings

• In general, leukotriene receptor antagonists should not be prescribed for asthma unless asthma is incompletely controlled with inhaled corticosteroids and long-acting β₂-agonists, except in the specific cases listed above. 
• The safety of these drugs in pregnancy is uncertain because of a lack of evidence, although no harmful effects have been demonstrated. It is felt reasonable to continue treatment in pregnancy where leukotriene receptor antagonists are felt to have led to an improvement in asthma symptoms not achieved with other therapies.

 

Important interactions

• There are no important drug interactions between leukotriene receptor antagonists (i.e. montelukast) and other commonly used drugs.