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Leukotriene-receptor antagonists and related compounds

Antileukotrienes constitute an important novel therapy for asthma. Current data indicate that inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneously occurring asthma. There does not appear to be any indication for the use of antileukotrienes in patients with very mild, intermittent asthma, in whom infrequent use of inhaled β2-agonists is adequate to control symptoms. However, for some patients with moderate and severe persistent asthma, it is clear that antileukotrienes will have a place in asthma consensus guidelines.

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 Leukotrienes: Function & Associated Diseases

Leukotrienes are compounds made from arachidonic acid which activate the immune and inflammatory responses. They are required for healthy immune reactions to pathogenic microbes, and they attract and activate white blood cells to prevent and resolve disease. Excess leukotrienes may promote an unhealthy inflammatory reaction. People with asthma, allergies, heart disease, metabolic disorders, and other inflammatory conditions tend to have higher levels of leukotrienes than healthy individuals. Leukotrienes may also increase sensitivity to pain and promote bone loss.

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Singulair, now a generic, is still used by millions of people in the United States even after thousands of patients and dozens of studies have described harm.

Articles of Interest

An update on the role of leukotrienes in asthma

Leukotriene modifiers are an important component of long-term preventative therapy for persistent asthma, either alone in mild persistent asthma as an alternative to an ICS, or in combination with other therapies for asthma of greater severity.

Anti-leukotriene agents compared to inhaled corticosteroids for people with asthma

As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.

Efficacy of leukotriene receptor antagonists and synthesis inhibitors in asthma

These drugs are a viable alternative to low-dose inhaled corticosteroid (ICS) treatment but should be reserved for patients who cannot or will not use ICSs, often because of concerns about potential side effects of ICS treatment, which limits their use, particularly in children. Leukotriene receptor antagonists are also alternatives to long-acting inhaled beta(2)-agonists as add-on therapy to ICSs, but their efficacy together with ICSs is less than that of ICS/long-acting inhaled beta(2)-agonist combinations. Leukotriene receptor antagonists have an excellent safety profile.

Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy

Although our findings suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a LABA as an add-on to an inhaled glucocorticoid, caution is needed in interpreting the results of these pragmatic trials.

Leukotriene Receptor Antagonists (LTRA)

Leukotriene antagonists are considered ‘add on’ therapies to inhaled asthma medication. If symptoms are still troublesome despite patients being on medium dose inhaler steroids and a long acting bronchodilator (LAMA). They may be especially beneficial for night time symptoms, if there are nasal symptoms (rhinitis) or hay fever. They can be helpful in exercise induced asthma.

Leukotrienes: Inhibitors & Natural Ways to Block Them

The most widely used leukotriene receptor blockers are those preventing cysteinyl leukotrienes from binding to their receptor CysLT1. The main commercial drugs in this category are montelukast, zafirlukast, and pranlukast.

Montelukast use over the past 20 years: monitoring of its effects and safety issues

The efficacy of montelukast for pediatric asthma is inferior to that of ICSs. Nonetheless, montelukast has several advantages. First, patients using ICS must use the correct inhalation technique, whereas no special skills are required to administer montelukast. Second, both patients and prescribing physicians prefer to use a drug that is administered only once a day. Third, there is no impact on growth, unlike the use of ICSs, which can potentially impair a child’s growth. Montelukast maintenance therapy is primarily recommended for asthmatic children who experience symptoms more than once a month but less than once a week and is recommended as an alternative method for children with step 2 asthma.

The Leukotriene Receptor Antagonist Montelukast as a Potential COVID-19 Therapeutic

Montelukast was developed as a highly selective CysLTR1 antagonist, which is currently used and approved for the treatment of asthma, allergic rhinitis, exercise-induced bronchoconstriction, and acetylsalicylic acid-sensitive asthmatic patients. Its primary mode of action is via prevented signaling of LTs by blockage of CysLTR1.

Resources

Montelukast

If your asthma symptoms are not well controlled with a preventer inhaler, your GP may prescribe montelukast as an ‘add-on’ treatment.

StatPearls

Montelukast and zafirlukast are cysteinyl leukotriene receptor antagonists indicated to prevent and treat chronic asthma. Leukotrienes are eicosanoid inflammatory mediators derived from arachidonic acid. Neither montelukast nor zafirlukast has a role as rescue medication during an acute asthmatic attack. Montelukast administration is via the oral route, without regard to food or meals. It should be taken a single dose in the evening in patients with asthma and both asthma and allergic rhinitis. For the treatment of allergic rhinitis, administration can be either morning or evening. It should be taken at least two hours before exercise to prevent exercise-induced asthma. Patients should not take another dose within 24 hours.