Leukotriene Receptor Antagonists
Examples
- Montelukast
- Zafirlukast
Indications
Prophylaxis of non acute asthma, they are of particular benefit in patients with exercise induced asthma, aspirin induced asthma and in patients with concomitant rhinitis
They are effective if used alone or they can be used in combination with corticosteroids where the two drugs appear to have an additive effect.
Symptomatic relief of hayfever in asthmatic patients.
They are effective if used alone or they can be used in combination with corticosteroids where the two drugs appear to have an additive effect.
Symptomatic relief of hayfever in asthmatic patients.
Contraindications
Contraindication
- In patients with hepatic impairment.
- In pregnancy and breastfeeding.
- In elderly
Mechanism
The leukotriene receptor antagonists block the effects of leukotrienes at the LTC4, LTD4 and LTE4 receptors in the airways, decreasing both the early and late responses to inhaled allergens.
In asthma the underlying pathological process is thickening of the airway wall by cellular infiltration and inflammation (often in response to allergens). The inflammatory process involves the release of metabolites of arachidonic acid , including leukotrienes. The degree to which leukotrienes contribute to the inflammation is asthma varies between individuals. It appears that in exercise induced asthma and aspirin induced asthma, leukotrienes play an important role in the pathogenesis. They are therefore a good therapeutic target.
It is not clear whether leukotriene receptor antagonists modify the underlying inflammatory response in asthma. They are not proven to be steroid sparing.
In asthma the underlying pathological process is thickening of the airway wall by cellular infiltration and inflammation (often in response to allergens). The inflammatory process involves the release of metabolites of arachidonic acid , including leukotrienes. The degree to which leukotrienes contribute to the inflammation is asthma varies between individuals. It appears that in exercise induced asthma and aspirin induced asthma, leukotrienes play an important role in the pathogenesis. They are therefore a good therapeutic target.
It is not clear whether leukotriene receptor antagonists modify the underlying inflammatory response in asthma. They are not proven to be steroid sparing.
Administration
Orally
Adverse Reactions
Common
- Headache
- Gastrointestinal disturbances
- Respiratory infections
- Churg-Strauss syndrome: asthma, eosinophilia, and a systemic vasculitis. It is not clear whether leukotriene receptor antagonists are the cause of this syndrome or whether they unmask an existing disease. Measure FBC, inflammatory markers and liver function tests if Churg-Strauss syndrome is suspected.
- Agranulocytosis
Interactions
Leukotriene receptor antagonists may inhibit P450 enzymes and Zafirlukast should be used with caution in combination with warfarin. Leukotriene receptor antagonists may be affected by enzyme inducers and inhibitors.
See Drug Interactions, Dr Mclay, Principles of disease.
See Drug Interactions, Dr Mclay, Principles of disease.
Education
- Patients should be advised that leukotriene receptor antagonists are for prophylactic treatment and should not be used for acute relief of symptoms
- Give patients advice on the symptoms of Churg- Strauss syndrome
- A vascultitic rash
- Worsening of asthma symptoms
- Ensure the patient has a 'rescue plan' in case their symptoms worsen or they become unwell
- All patents with asthma require regular review, with either a doctor or asthma nurse specialist
Pharmacokinetics
Leukotriene receptor antagonists are hepatically metabolised and plasma levels can be affected by enzyme inducers / inhibitors.
