6️⃣ Leukotriene Modifiers

What is the prototype leukotriene modifier?

Montelukast (Singulair)

What is the therapeutic class of montelukast?

Anti-inflammatory agent

What is the pharmacologic class of montelukast?

Leukotriene receptor antagonist

What are leukotrienes?

Proinflammatory mediators → cause bronchoconstriction, ↑ mucus, airway edema

Where are leukotrienes produced?

Via lipoxygenase pathway of arachidonic acid metabolism

What does montelukast block?

Cysteinyl leukotriene1 receptor

What is the main action of montelukast?

Prevents leukotriene-induced bronchoconstriction & inflammation

How does montelukast affect asthma symptoms?

↓ symptoms, ↓ night symptoms, ↓ beta2 agonist use

Is montelukast effective for acute asthma attacks?

NO — maintenance/prophylaxis only

What is montelukast’s route of administration?

Oral

When is montelukast usually taken?

In the evening or at bedtime

Why give montelukast at night?

Asthma often worsens at night

How fast is montelukast absorbed?

Rapid GI absorption

How is montelukast metabolized?

Liver — CYP3A4, CYP2C8, CYP2C9

How is montelukast excreted?

Mainly feces

What are the main indications for montelukast?

Long-term asthma treatment, exercise-induced asthma, allergic rhinitis

What is the only leukotriene modifier approved for allergic rhinitis?

Montelukast

What type of asthma can montelukast treat?

Mild to moderate persistent asthma

Is montelukast approved for children?

Yes, ≥ 12 months old

What is the adult dose of montelukast?

10 mg PO once daily

What is the dose for 6–14 years?

5 mg chewable tablet once daily

What is the dose for 1–5 years?

4 mg once daily

What is the BLACK BOX WARNING for montelukast?

Neuropsychiatric events: suicidal ideation, depression, aggression

What CNS effects must be monitored?

Agitation, depression, hallucinations, suicidal thoughts

What other adverse effects may occur?

Headache, nausea, diarrhea, hyperkinesia, infection

Is montelukast safe in pregnancy?

No known teratogenic effects; may be used if needed

Is montelukast safe in breastfeeding?

Use with caution; weigh benefits & risks

How does hepatic impairment affect montelukast?

↑ Blood levels, slower elimination, but no dose adjustment for mild/moderate

What are contraindications for montelukast?

Hypersensitivity to drug

What drugs ↑ montelukast levels?

Aspirin → ↑ bleeding risk

What drugs ↓ montelukast levels?

Carbamazepine, erythromycin, phenobarbital, phenytoin, rifampin, theophylline

What herb decreases montelukast effect?

St. John’s Wort

Can montelukast be used with corticosteroids?

Yes — often used in combo

What must patients understand about montelukast use?

Not for acute symptoms; continue during exacerbations

What signs should patients report?

Mood changes, suicidal thoughts

Should montelukast be stopped abruptly?

No — consult provider

How does montelukast compare to ICS?

Less effective than low-dose ICS

What are the other leukotriene modifiers?

Zafirlukast, zileuton

What is zafirlukast’s mechanism?

CysLT1 receptor antagonist

How is zafirlukast given?

Oral, 1 hr before or 2 hrs after meal

Why separate zafirlukast from food?

Food ↓ bioavailability by ~40%

Is zafirlukast safe in pregnancy?

Avoid in lactation (enters breast milk)

What is zileuton’s mechanism?

Inhibits 5-lipoxygenase → blocks leukotriene synthesis

How is zileuton given?

Oral, immediate or extended-release

What is a major side effect of zileuton?

Hepatotoxicity → monitor ALT

What should be monitored with zileuton?

Liver enzymes (ALT)

Are leukotriene modifiers effective in all patients?

Effective in some, but not all

How do leukotriene modifiers fit in asthma step therapy?

Add-on to ICS if needed

How long does it take to see benefits?

May take several days to weeks

Key teaching for montelukast?

Take every night, report mood changes, not a rescue med