9. Drugs for Respiratory disorders

• Short term relief for asthma is achieved with?

  bronchodilators
• Bronchodilators works by increasing airway by relaxing airway smooth muscles
• What is the most widely used bronchodilators?

  B2 agonist
• B2 agonist MOA

  • direct airway smooth muscle relaxation - dilation
  • inhibit release of broncho-constricting mediator from mast cells
  • prevent microvascular leakage
  • prevent development of bronchial mucosal edema
  • increase mucociliary transport by increase ciliary activity
• B2 agonist

  1. activates B2 receptor
  2. activates adenylyl cyclase (AC) via Gs
  3. increase in cAMP
  4. activate PKA
  5. decrease MLCK
  6. decrease Ca2+

  • Leads to smooth muscle relaxation and bronchodilation
• B2 agonist is choice for mild intermittent asthma because it's short acting
• VLABA - once daily B2 agonist

  • ends in terol
• Once daily B2 agonist - VLABA

  • used as monotherapy for treatment of COPD
  • can be combined with ICS - synergistic action
• B2 agonist - Adverse effect

  • Chronic use can lead to
  • skeletal muscle tremors
  • tachycardia - increase peripheral vasodilation
  • ** hypokalemia
  • high dose leads to cardiac arrhythmias
  • hyperglycemia
• High risk of myocardial infarction when use B2 agonist
• Continuous treatment with B2 agonist will?

  down regulate B2 receptor
• B2 agonist tolerance to

  tremors and cardiovascular effect
• What can prevent development of tolerance to B2 agonist in airway smooth muscle?

  corticosteroid
• Antimuscarinic agents MOA

  • inhibit effect of ACh at M3 receptor
• Antimuscarinic agents uses

  • COPD
  • bronchial asthma
• Short term use - antimuscarinic agent?

  Ipratro (ipratropium)
• Antimuscarinic agent enhance bronchodilation with B2 agonist

  • use for acute severe asthma - status asthmaticus
• Antimuscarinic agent are more effective in COPD

  • reverse vagally mediated bronchoconstriction
• Methylxanthines (theophylline)

  • elimination kinetics change from first order to zero order
  • narrow therapeutic index
• Methylxanthines (Theophylline)

  • monitor blood level upon initiation of therapy
• Methylxanthines (Theophylline) Adverse effect

  • >20 mg/L
  • anorexia
  • headaches
  • >40 mg/L
  • seizures
  • cardiac arrythmias
• Theophylline Adverse effects

  • CNS
  • seizure - children are more prone
  • CVS - arrhythmias
• Theophylline - drug interaction

  • increased clearance
  • enzyme induction (CYP1A2)
  • smoking
  • decrease clearance
  • CYP inhibition - cipro (ciprofloxacin)
• Overdose of theophylline - treatment

  • B-blocker such as metoprolol to reduce cAMP levels
  • theo increase cAMP levels
• Inhalational corticosteroid (ICS) DOC in preventing asthma exacerbation in pts with persisting asthma

  • to avoid side effect - inhalation route preferred
• Inhalational corticosteroids (ICS) - better in long term control of asthma
• Corticosteroid reduce airway inflammation

  • do not directly relax airway smooth muscle - little effect on acute bronchoconstriction
• ICS has no effect on early response to allergen

  • inhibit late response - take several weeks to months to achieve maximal effects on airway
• glucocorticoid - adverse drug reaction

  • ** oral thrush - inhaled steroid
  • can be prevented by using valved holder chamber or a spacer
• inhaled steroid can cause oral thrush

  • treated with clotri (clotrimazole) or nystatin
  • mouth rinsing
• Cicle (ciclesonide) - a prodrug activated by bronchial esterase

  • corticosteroid associated with less frequency candidiasis
• Cicle (ciclesonide) - activated by bronchial esterase so it works better toward the base of the lung
• -lukast

  • antagonist of leukotriene receptor LT1
  • block action of leukotrienes
• -lukast

  • reduce bronchoconstriction
  • reduce inflammatory cell infiltration
  • effective to control early and late phase of bronchial asthma
• -lukast adverse effect

  • elevation of liver enzyme
  • churg-strass syndrome
• zile (zileuton) MOA - inhibit 5-lipoxygenase
• zile (zileuton) - Adverse effect

  • hepatotoxicity
  • monitor liver function
• omali (omalizumab) - anti monoclonal antibody

  • block binding of IgE antibody
  • reduce
  • early phase degranulation
  • late phase mediator - reduce airway inflammation
• omali (omalizumab) - prevent release of proinflammatory substances
• NSAID - like aspirin can trigger asthma symptoms