Albuterol (β2-Agonists)

  • Relaxes bronchial smooth muscles (short acting)
  • Used in acute exacerbation

Salmeterol, formoterol (β2-Agonists)

  • Long-acting agents for prophylaxis
  • Adverse effects are tremors and arrhythmia

Inhaled Corticosteroids (fluticasone, budesonide)

  • Inhibits synthesis of all cytokines
  • Inactivates NF-κB (transcription factor that induces production of TNF-α and other inflammatory agents)
  • 1st line therapy for chronic asthma

Muscarinic Antagonists (Tiotropium, Ipratropium)

  • Competitively block muscarinic receptors, preventing bronchoconstriction

Muscarinic Agonist (Methacholine)

  • Nonselective muscarinic receptor agonist.
  • Used in bronchial challenge test to help diagnose asthma.

Antileukotrienes

  • Montelukast, zafirlukast
    • Blocks leukotriene receptors
    • Good for aspirin induced and exercise-induces asthma
  • Zileuton
    • 5-lipoxygenase pathway inhibitor
    • Block conversion of arachidonic acid to leukotrienes

Anti-IgE Monoclonal Therapy (Omalizumab)

  • Binds unbound serum IgE
  • Used in allergic asthma with ↑ IgE resistant to inhaled steroids and long-acting β2-Agonists

Methylxanthines (Theophylline)

  • Bronchodilation by inhibiting phosphodiesterase à ↑ cAMP
  • Narrow therapeutic index
  • Metabolized by cytochrome P-450

Antileukotrienes

 

  • Leukotrienes are potent biochemical mediators that are released from mast cells, eosinophils, and basophils. Leukotrienes work to contract airway smooth muscle, increase vascular permeability and mucus secretions, and attract and activate inflammatory cells in the airways of patients with asthma. They are produced by the oxidation of arachidonic acid through the enzyme lipoxygenase. The action of leukotrienes can be blocked through either of two specific mechanisms: 1) inhibition of leukotriene production and, 2) antagonism of leukotriene binding to cellular receptors. The FDA has approved three products thus far. Zafirlukast and montelukast are both selective and competitive leukotriene receptor antagonists of leukotriene D and E. These are components of slow-reacting substance of anaphylaxis. Zileuton, a specific inhibitor of 5-lipooxygenase, inhibits leukotriene formation, especially LTB1, LTC1, LTD1, LTE1. As a leukotriene antagonist, SingulairR (montelukast) has no effect on lipoxygenase or arachidonic acid function. Arachidonic acid is produced by membrane phospholipids through the enzyme phospholipase A2 which is blocked by corticosteroids. Cyclooxygenase inhibitors (i.e. NSAIDs, COX inhibitors) block the production of prostaglandins. Beta-2 stimulation results in bronchodilation and is the main mechanism of medications such as albuterol and not the leukotriene inhibitors.