Nonsteroidal Antiasthma Agents

Indications for Nonsteroidal Antiasthma Agents

• Prophylactic management of mild persistent asthma.
• Alternatives to ICS in step 2 care.
• Useful in combination with ICS to reduce steroid dose.

Subgroups of Agents

• Cromolyn-like drugs (mast cell stabilizers).
• Antileukotrienes.
• Monoclonal antibodies.

Identification of Agents

• Cromolyn-Like Agents:
  • Cromolyn (generic only)
• Antileukotrienes:
  • Zafirlukast (Accolate)
  • Montelukast (Singulair)
  • Zileuton (Zyflo, Zyflo CR)
• Monoclonal Antibodies:
  • Omalizumab (Xolair)
  • Benralizumab (Faserna)
  • Mepolizumab (Nucala)
  • Reslizumab (Cinqair)

Mechanisms of Inflammation in Asthma

• Asthma: inflammatory disorder of airways.
• Extrinsic asthma: depends on allergy, atopy.
• Intrinsic asthma: no evidence of sensitization.

Clinical Results of Asthma

• Chronic airway inflammation with acute episodes.
  • Bronchoconstriction.
  • Mucosal swelling.
  • Mucus secretion.
• Primarily an allergic response.

Immunologic Response

• Involves mast cells and IgE.
• Allergy is a mistaken immune response.

Mast Cell Release

• Leukotrienes, prostaglandins, proteases, histamines, PAF, cytokines.

Cell-Mediated Immune Mechanism

• T lymphocytes mediate immune response:
  • Helper/T4 (CD4+) cells (Th1 and Th2 cells).
  • Suppressor/T8 (CD8+) cells.
  • Cytotoxic T cells.
  • Natural killer cells.

Antibody-Mediated Immune Mechanism

• B lymphocytes.
• Classes of antibody: IgE, IgG, IgA, IgM, IgD.

Immune Response Generation

• T lymphocytes interact with antigen.
• IgE binds to mast cells.
• Mast cells release mediators of inflammation.

Cascade of Mediators

• Inflammatory response:
  • Vascular leakage, bronchoconstriction, mucus secretion, mucosal swelling.
• Eosinophil activation leads to airway damage.

Cromolyn (Mast Cell Stabilizer)

• Prophylactic agent.
• Dosage: SVN 20 mg/ampule or 20mg/2mL (1%).
• Mechanism: Prevents mast cell degranulation.
• Side effects: Cough, nasal congestion, wheezing.

Leukotrienes and Inflammation

• Potent bronchoconstrictors causing:
  • Airway edema.
  • Mucus secretion.
  • Ciliary beat inhibition.
  • Inflammatory cell recruitment.

Antileukotriene Agents

• 5-LO inhibitor: Zileuton.
• Leukotriene receptor antagonists: Zafirlukast, Montelukast.
• Monoclonal antibodies: Omalizumab, Benralizumab, Mepolizumab, Reslizumab.

Zileuton

• Dosage: Oral, 600 mg tablets qid.
• Mechanism: Inhibits 5-LO enzyme.
• Side effects: Headache, abdominal pain; monitor liver function; interacts with theophylline and warfarin.

Zafirlukast

• Dosage: Oral, 10 mg bid (5-11 years), 20 mg bid (12+ years).
• Mechanism: Leukotriene receptor antagonist.
• Side effects: Headache, infection, nausea.

Montelukast

• Dosage: Oral, 4 mg, 5 mg (chewable), 10 mg.
• Mechanism: Binds to CysLT1 receptor.
• Side effects: Diarrhea, laryngitis, pharyngitis, nausea.

Role of Antileukotrienes in Asthma Management

• Protection against asthma triggers.
• Chronic persistent asthma.
• Use in relation to corticosteroids.
• Churg-Strauss syndrome.

Clinical Use Summary of Antileukotrienes

• Prophylactic controller drugs.
• Alternative to inhaled corticosteroids or cromolyn.
• Not optimal as monotherapy.
• May reduce ICS dose.
• Safe and effective for wide range of asthma severity.

Advantages of Antileukotrienes

• Oral administration, possible once-daily dosing.
• Safe, few side effects.
• Effective in aspirin sensitivity and exercise-induced asthma.
• Systemic distribution.
• Additive effect with inhaled steroids.
• Pediatric formulation (montelukast).

Disadvantages of Antileukotrienes

• Limited anti-inflammatory action.
• Unknown long-term toxicity.
• Variable response (50-70%).
• No response predictor.
• Systemic drug exposure.
• Not useful as monotherapy.

Monoclonal Antibodies

• Treat severe asthma, require injection/infusion.
• Omalizumab: Blocks IgE attachment to mast cells.
• Benralizumab, mepolizumab, reslizumab: Block IL-5 in eosinophilic asthma.

Monoclonal Antibodies

• Dosage: Parenteral administration.
• Mechanism:
  • Omalizumab: Binds to IgE.
  • Benralizumab, mepolizumab, reslizumab: Blocks IL-5.
• Side effects: Anaphylaxis, injection site reactions, fever, headache.

Clinical Use Summary of Monoclonal Antibodies

• Prophylactic for severe persistent asthma.
• Not for acute relief.
• Not a replacement for ICS.
• Not optimal as monotherapy.
• May reduce ICS dose.
• May reduce rescue agents.

Respiratory Care Assessment

• Evaluate delivery formulation.
• Appropriate device use.
• Controller, not rescue.
• Use peak flow meter.
• Long term:
  • Severity of symptoms, exacerbations, ER visits, PFT.
  • Assess for side effects.