Leukotriene Receptor Antagonists Wk 8

Leukotriene Receptor Antagonists

  • Definition: A class of medications that suppress the effects of leukotrienes, which are compounds contributing to asthma via:

    • Smooth muscle constriction

    • Increased blood vessel permeability

    • Triggering inflammatory responses

  • Mechanism of Action:

    • Inhibit bronchoconstriction and inflammation (e.g., airway edema, mucus secretion).

  • Administration: Orally, serving as an alternative to inhaled therapies.

  • Indications: Considered second-line options, used when inhaled glucocorticoids are unsuitable or as add-on therapy when glucocorticoids alone are insufficient.

  • Adverse Effects:

    • Potential neuropsychiatric effects (e.g., depression, suicidal thoughts).

Zilutin

  • Classification: Leukotriene synthesis inhibitor.

  • Indications: Approved for asthma prophylaxis and maintenance therapy in individuals aged 12 and older.

  • Symptom Improvement: Generally observed within 1-2 hours post-dosing; not for aborting ongoing asthma attacks.

  • Effectiveness: Less effective than inhaled glucocorticoids; inferior to long-acting beta-2 agonists (LABAs).

  • Mechanism of Action: Inhibits enzyme 5-lipoxygenase, preventing the conversion of arachidonic acid into leukotrienes.

  • Pharmacokinetics:

    • Rapidly absorbed orally.

    • Plasma levels peak in 2-3 hours post-dosing.

    • Undergoes rapid liver metabolism with metabolites excreted in urine.

    • Short plasma half-life of 2.5 hours necessitating regular dosing.

  • Liver Monitoring:

    • Regular monitoring of ALT levels at least once a month for the first three months, and then every 2-3 months for the first year.

  • Adverse Effects:

    • Hepatotoxicity (increased ALT levels, possible symptomatic hepatitis).

    • Reversible upon discontinuation of drug.

    • Neuropsychiatric effects: anxiety, agitation, hallucinations.

  • Drug Interactions:

    • Metabolized by CYP450; acts as a CYP1A2 inhibitor, affecting the metabolism of drugs like theophylline.

Ceferlucast

  • Classification: First leukotriene receptor antagonist on the market.

  • Indications: Approved for maintenance therapy of chronic asthma in adults and children 5 years and older.

  • Mechanism of Action: Reduces infiltration of inflammatory cells into airways, decreasing bronchoconstriction and improving asthma control.

  • Pharmacokinetics:

    • Rapid oral absorption; food reduces absorption by about 40%.

    • Recommended to take 1 hour before or 2 hours after meals.

    • Hepatic metabolism; excreted in feces.

    • Average half-life of 10 hours; up to 20 hours in older adults.

  • Adverse Effects:

    • Most common: headache, GI upset.

    • Rare: arthralgia, myalgia.

    • Serious: Churg-Strauss syndrome, liver injury (abdominal pain, jaundice, fatigue).

  • Monitoring:

    • Liver function tests for potential hepatotoxicity, more common in females.

    • Monitoring alkaline phosphatase levels during therapy.

Montelukast

  • Classification: Widely used leukotriene receptor blocker.

  • Indications:

    • Prophylaxis and maintenance of asthma in patients aged 1 year and older.

    • Prevention of exercise-induced bronchospasm in patients aged 15 and older.

    • Relief of allergic rhinitis.

  • Effectiveness: Highly effective for maintenance therapy but slow acting (does not abort asthma attacks).

  • Mechanism of Action: Blocks leukotriene receptors, preventing their activation by leukotrienes, reducing inflammation and bronchoconstriction.

  • Pharmacokinetics:

    • Rapid absorption, approximately 64% bioavailability.

    • Peak blood levels in 3-4 hours.

    • Extensive metabolism by CYP450 enzymes; excreted in bile.

    • Half-life of 2.7 to 5.5 hours allows for once-daily dosing.

  • Adverse Effects:

    • Generally well tolerated; adverse effects comparable to placebo.

    • Not associated with liver injury.

    • Possible triggers for Churg-Strauss syndrome, mood changes, suicidality.

  • Drug Interactions:

    • Favorable profile; does not raise alkaline or warfarin levels.

    • Phenytoin may reduce montelukast levels, risking reduced effectiveness.

Cromolyn

  • Classification: Inhalational agent for asthma prophylaxis.

  • Mechanism of Action: Suppresses inflammation, stabilizes mast cell membranes to prevent histamine release, inhibits other inflammatory cells.

  • Administration: Delivered via nebulizer; minimal systemic absorption leads to very few side effects.

  • Effectiveness:

    • Reduces frequency/severity of asthma attacks when used consistently.

    • Particularly effective for seasonal allergic asthma and exercise-induced bronchospasm if used shortly before exertion.

    • Also used for allergic rhinitis.

  • Adverse Effects: Very rare severe side effects; occasional minor issues like cough or bronchospasm after inhalation.