Pcol - RsTrc Disorder

• Asthma


  Characterized by airway inflammation and hyperresponsiveness to stimuli that produce bronchoconstriction
• Asthma triggers


  • Allergens (pollen, animal dander, dust, mold, etc.)
  • Air pollution, cigarettes smoking, other noxious chemicals
  • Upper Respiratory Tract Infections
  • Drugs (NSAIDs, Beta-blockers)
  • Cold Air
  • Exercise
• Asthma Pathogenesis

  
  

  What are the Two Factors?

  1. Genetic Factors - Gene Mutations
  2. Environmental Factors - Excessive hygiene, antibiotics etc.
• Asthma

  Trigger Factor -> Airway Inflammation -> a.) Hypersecretion of Mucus, b.) Airway muscle contractions,

  c.) Swelling of Bronchial Membranes -> Narrow Breathing Passages
• Asthma drug treatments


  • Bronchodilators
  • Anti-inflammatory drugs
• Bronchodilators


  Drugs that counteract acute asthmatic attacks by relaxing bronchial smooth muscles
• Bronchodilator drugs


  • Beta-2 adrenoceptor agonists
  • Muscarinic receptor antagonists
  • Theophylline
• Short-acting beta-2 agonists (SABA)


  • Salbutamol
  • Terbutaline
  • Levalbuterol
  • Fenoterol
  • Pirbuterol
• Long-acting beta-2 agonists (LABA)


  • Salmeterol
  • Formoterol
  • Indacaterol
• Muscarinic receptor antagonists


  Produce bronchodilating effects by blocking the bronchoconstricting effect of vagus (parasympathetic) nerve stimulation
• Muscarinic receptor antagonist drugs


  • Ipratropium
  • Tiotropium
• Theophylline


  • Therapeutic range is 5 to 15 mg/mL
  • Indicated for COPD and asthma whose symptoms are not controlled with beta-2 agonists and muscarinic antagonists
  • Adverse effects include gastrointestinal distress, CNS stimulation, and cardiac stimulation
• Anti-inflammatory drugs for asthma

  • Corticosteroids
  • Leukotriene receptor antagonists
  • 5-lipoxygenase inhibitor
  • Mast cell stabilizers
  • Phosphodiesterase 4 inhibitor
  • IgE antagonist
• Corticosteroids


  Most efficacious anti-inflammatory drug for asthma, administered via inhalation to minimize adverse effects
• Corticosteroid drugs


  • Beclomethasone
  • Budesonide
  • Fluticasone
  • Triamcinolone
• Leukotriene receptor antagonists


  Competitive antagonists of cysteinyl leukotrienes receptors.
• Leukotriene receptor antagonist drugs

  • Montelukast
  • Zafirlukast
• 5-Lipoxygenase inhibitor


  Enzyme inhibitor that blocks the formation of leukotrienes (LTs)
• 5-Lipoxygenase inhibitor drug

  • Zileuton
• Mast cell stabilizers


  Non-toxic, non-steroidal compounds that stabilize the plasma membranes of mast cells and eosinophils, preventing the release of inflammatory mediators
• Mast cell stabilizer drugs

  • Cromolyn sodium
  • Nedocromil
  • Lodoxamide
• Phosphodiesterase 4 inhibitor

  Increases cAMP levels & it's anti-inflammatory mechanism not well established
• Phosphodiesterase 4 inhibitor drug

  • Roflumilast
• Immunoglobulin E (IgE) antagonist

  Sensitizes mast cells to block allergens from binding.
• IgE antagonist drug

  • Omalizumab
• Antitussives


  • Dextromethorphan
  • Noscapine
  • Propoxyphene
  • Codeine
  • Butamirate citrate
  • Levodroproprizine
• Antitussives


  Inhibit the cough center in the brain, elevating cough threshold
• Expectorants


  • Guaifenesin
  • Sodium citrate
  • Potassium citrate
  • Ammonium chloride
• Expectorants


  Facilitate the coughing up of mucus and other materials from the lungs, reduce the adhesiveness and surface tension of respiratory tract secretions
• Mucolytics


  Break down the bonds holding together mucus, making it less sticky and thick
• Second Exposure to triggers - Two types

  1. Early Response (0-2 hrs)
  2. Delayed Response (4 - 12 hrs)
• Delayed Response ( 4- 12hrs) Lane

  1. Activated mast cells and helper T cells to release cytokines.
  2. Induce maturation of granular WBC like eosinophils.

  Eosinophils migrates to:

  • Airways -> Bronchiole constriction
  • Eyes -> Conjunctivitis
  • Nose -> Rhinitis
• Early Response ( 0-2 hrs ) Lane

  1. Allergens cross-link lgEs on mast cells.
  2. Mast cells release histamines, leukotrienes, and other inflammatory mediators.

  Results to Airway Obstruction:

  • Vasodilation that turns to edema
  • Goblet cell hyperplasia -> increased mucus secretion
  • Bronchial smooth muscle contraction
• Qa: Asthma pathogenesis

  
  

  Atopy - predisposition to allergic hyper-sensitivity in airways.
• Qa: Asthma Pathogenesis

  
  

  First exposure to triggers - Sensitizes helper T cells
• Qa: Asthma Drug treatment

  
  

  1.) Bronchodilators

  • B2 adrenoceptor agonists
  • Muscarinic receptor antagonist
• Qa: Asthma Drug treatment

  
  

  2.) Anti-inflammatory Drugs

  • Corticosteriods
  • Leukotriene receptor Antagonist
  • lgE Antagonist
  • Lipoxygenase Inhibitor
  • Phosphodiesterase Inhibitor
  • Mast Cell Stabilizers
• Asthma - Narrow Breathing Passages

  Common Signs and Symptoms

  • Shortness of breath
  • Chest tightness
  • Wheezing (When Exhaling)
  • Coughing (esp. at night)
• SABA oral formulations have slower onset of action and have high potential for systemic adverse effect.
• Ipratropium

  Isopropyl derivative of Atropine