What do antileukotriene drugs do? A guide to their mechanism and uses in allergies and asthma

October 8, 2025 •

4 min read

Studies have shown that leukotriene modifiers can reduce the risk of asthma exacerbations, particularly in children. This class of medication targets inflammatory substances in the body to manage and prevent symptoms related to asthma, allergic rhinitis, and other respiratory conditions. So, what do antileukotriene drugs do, and how do they work?

Quick Summary

These medications counteract the effects of inflammatory leukotrienes, reducing airway constriction, mucus production, and swelling associated with asthma and allergic rhinitis.

Key Points

Inhibition of Inflammation: Antileukotriene drugs block the effects of inflammatory chemicals called leukotrienes, which are released during allergic reactions and asthma.
Two Primary Mechanisms: These medications either block leukotriene receptors (e.g., montelukast, zafirlukast) or inhibit the production of leukotrienes entirely (e.g., zileuton).
Treatment of Asthma and Allergies: They are used for the long-term management of asthma and allergic rhinitis, but are not for immediate relief of an asthma attack.
Role in Specific Conditions: Antileukotrienes are particularly effective for exercise-induced bronchoconstriction and aspirin-exacerbated respiratory disease.
Potential for Side Effects: Montelukast carries an FDA black box warning for serious neuropsychiatric side effects, while other antileukotrienes like zileuton and zafirlukast require monitoring for potential liver toxicity.
Comparison to Corticosteroids: As monotherapy for asthma, they are generally less effective than inhaled corticosteroids but can serve as useful add-on therapy.
Not a Rescue Medication: It is crucial to remember that antileukotriene drugs are for daily preventative use and cannot stop an acute asthma attack.

Leukotrienes are a group of naturally occurring inflammatory chemicals released by the body in response to an allergic trigger or irritation. In conditions like asthma, these substances cause the airways to tighten, increase mucus production, and promote swelling, leading to symptoms like wheezing, coughing, and shortness of breath. Antileukotriene drugs work to block the production or action of these powerful inflammatory mediators.

The Mechanism of Antileukotriene Drugs

Antileukotriene drugs fall into two main categories, each with a distinct mechanism for inhibiting the leukotriene pathway. By interrupting this process, they prevent or reverse the inflammatory effects of leukotrienes, providing symptomatic relief for patients.

Leukotriene Receptor Antagonists (LTRAs)

This class of antileukotrienes works by blocking the specific receptors where leukotrienes (specifically cysteinyl leukotrienes C4, D4, and E4) normally bind. By competitively binding to the CysLT1 receptor, LTRAs prevent leukotrienes from activating the inflammatory cascade. This mechanism leads to several beneficial outcomes, including:

Reduction in bronchoconstriction: The relaxation of airway smooth muscle helps open up the breathing passages.
Decreased mucus secretion: Less mucus is produced, reducing congestion and airway blockage.
Inhibition of inflammatory cell recruitment: The attraction and activation of immune cells like eosinophils are reduced, lowering overall airway inflammation.

Leukotriene Synthesis Inhibitors (LSTIs)

Unlike LTRAs, leukotriene synthesis inhibitors stop the production of leukotrienes at an earlier stage. The primary example in this class, zileuton, blocks the enzyme 5-lipoxygenase, which is necessary for the formation of leukotrienes from arachidonic acid. This prevents the synthesis of all major leukotrienes, including LTB4 and the cysteinyl leukotrienes.

Clinical Applications and Benefits

Antileukotriene drugs are important maintenance medications used to prevent and manage chronic respiratory conditions. They are not intended for the treatment of acute asthma attacks but are effective for long-term control.

Managing Chronic Asthma

For patients with mild to moderate asthma, antileukotrienes are an effective option, sometimes used as an alternative for those who cannot or will not use inhaled corticosteroids (ICS). They are also a valuable add-on therapy for patients with persistent asthma whose symptoms are not adequately controlled by ICS alone. Benefits include:

Reduced asthma symptoms and exacerbations.
Improved lung function.
Decreased need for rescue inhalers.

Allergic Rhinitis Treatment

Montelukast is approved for managing allergic rhinitis, providing relief from symptoms like sneezing, itchy nose, and nasal congestion. While often less effective than intranasal corticosteroids, it can be a useful alternative or an additional therapy, especially for patients with both asthma and allergies.

Exercise-Induced Bronchoconstriction (EIB)

Antileukotrienes can be particularly effective for preventing EIB, with a single dose protecting against exercise-induced bronchospasm for an extended period. This provides a useful alternative for those who need to manage their symptoms before physical activity.

Aspirin-Exacerbated Respiratory Disease (AERD)

For patients with aspirin-sensitive asthma, antileukotrienes have proven to be especially beneficial. By blocking the leukotriene pathway that is overactive in these individuals, they can provide significant symptom relief and improve overall asthma control.

Comparison of Common Antileukotriene Drugs

The primary antileukotriene drugs available differ in their mechanism of action, approved indications, and potential side effects. The following table provides a comparison of the most common options.


Feature	Montelukast (Singulair)	Zafirlukast (Accolate)	Zileuton (Zyflo)
Mechanism	Leukotriene Receptor Antagonist	Leukotriene Receptor Antagonist	Leukotriene Synthesis Inhibitor
Indications	Asthma, Allergic Rhinitis, EIB	Asthma	Asthma
Formulation	Oral tablet, chewable, granules	Oral tablet	Oral tablet
Dosage	Once daily	Twice daily	Four times daily
Key Side Effects	Neuropsychiatric events (black box warning), headache, GI issues	Liver toxicity (monitor liver enzymes), pharyngitis	Liver toxicity (monitor liver enzymes), dyspepsia
Drug Interactions	Minimal, less affected by food	Decreased bioavailability with food; interacts with warfarin	Interacts with warfarin, theophylline, propranolol

Potential Risks and Considerations

While generally well-tolerated, antileukotriene drugs carry potential risks that patients and prescribers should be aware of.

Neuropsychiatric Events

In 2020, the U.S. Food and Drug Administration (FDA) issued a black box warning for montelukast due to reports of serious neuropsychiatric side effects. These can include agitation, aggression, vivid dreams, hallucinations, depression, insomnia, and suicidal thoughts. A careful risk-benefit analysis is required, especially when considering its use for allergic rhinitis.

Liver Toxicity

Zileuton and, to a lesser extent, zafirlukast have been associated with potential liver enzyme elevations. Regular monitoring of liver function tests is recommended for patients taking these medications. Patients should be advised to contact their doctor immediately if they experience symptoms of liver injury, such as persistent nausea, fatigue, or yellowing of the skin or eyes.

Churg-Strauss Syndrome

In rare cases, systemic vasculitis with eosinophilia (Churg-Strauss Syndrome) has been reported in asthma patients taking antileukotrienes, especially after withdrawing or reducing oral corticosteroid therapy. This condition involves inflammation of blood vessels and may require urgent medical attention.

Conclusion

Antileukotriene drugs are an important class of medications that target the inflammatory leukotriene pathway to provide symptomatic relief for chronic asthma and allergies. They serve as valuable alternatives or add-on therapies, particularly for specific populations like children, those with exercise-induced asthma, or aspirin sensitivity. However, their use requires careful consideration of potential side effects, including the serious neuropsychiatric risks associated with montelukast. As with any medication, a thorough discussion with a healthcare provider is essential to determine if an antileukotriene is the right choice for an individual patient. For further information, consult resources like the National Institutes of Health.

A Final Word

Always follow your doctor's instructions and never stop or change your medication regimen without their approval. Antileukotrienes are preventative medications and should not be used as a rescue medication during an acute asthma attack.

Frequently Asked Questions

Antileukotriene drugs are primarily used to treat chronic asthma, allergic rhinitis (allergies), exercise-induced bronchoconstriction, and aspirin-exacerbated respiratory disease.

No. While both treat inflammation, they work differently. Antileukotrienes block a specific inflammatory pathway, while inhaled corticosteroids are broader anti-inflammatory agents and are generally considered more potent for controlling asthma inflammation.

No, antileukotriene drugs are not for treating an acute asthma attack. They are preventative medications used for long-term symptom control. A rescue inhaler (like a short-acting beta-agonist) should be used for immediate relief during an attack.

Montelukast has a black box warning from the FDA concerning serious neuropsychiatric events, including suicidal thoughts and actions, agitation, depression, and other mental health-related issues.

The risk varies. Zafirlukast and zileuton both carry a risk of liver toxicity, and liver enzyme monitoring is recommended. While rare, serious liver injury has been reported with zafirlukast. The risk appears lower for montelukast.

A leukotriene receptor antagonist (e.g., montelukast) blocks leukotrienes from binding to their receptors. A leukotriene synthesis inhibitor (e.g., zileuton) prevents the body from producing leukotrienes in the first place.

For full therapeutic benefit in managing allergies and asthma, it can take anywhere from a few days to two weeks for antileukotriene inhibitors to show their full effect.

Yes, some antileukotriene drugs, such as montelukast, are approved for use in children. They can be a useful option, especially for children who have difficulty with inhaled medications.