topic 16: antiinflmmatory agents used in bronchial asthma. Antitussive agents and expectorants

Question 1

effects nad mechanisms of corticosteroids.

Answer 1

Effects:

• Inflammation reduced
• Hyperactivity of airways reduced
• Expression of b₂ receptors ­INCREASED
• Onset of effect needs hours (intracellular nuclear receptors)

Mechanism of action:

• Phospholipase A₂ inhibition -> inhibition of the release of arachidonic acid-> anti-inflammatory properties in the airways
• Targets underlying airway inflammation by decreasing the inflammatory cascade (eosinophils, macrophages and T lymphocytes) , reversing mucosal edema, decreasing the permeability of capillaries and inhibiting the release of leukotrienes (rather than affecting the airway smooth muscle).
  
  • After a couple months of use, decrease hyper-responsiveness of the airway smooth muscle to different bronchoconstriction stimuli (allergens, irritants, cold air, exercise).

Question 2

Clinical use of corticosteroids

Answer 2

Clinical use:

• Long-term control of persistent asthma

Question 3

routes of administration

Answer 3

Routes of administration:

• Inhalation:
  
  • Proper inhalation techniques are required for the success of the therapy
• Oral/systemic:
  
  • Used in patients with severe exacerbation of asthma
    
    • Methylprednisolone or oral prednisone
• IV (severe cases):
  
  • Methylprednisolone
  • Dexamethasone

Question 4

adverse effects of corticosteroids:

Answer 4

Adverse effects:

• Infections: oropharyngeal candidiasis
• Hyperglycemia, diabetes
• Peptic ulcer
• Cushing syndrome
• Osteoporosis, avascular necrosis of femoral head
• reduced growth
• Muscle weakness, decrease muscle mass
• CNS:
  
  • Seizures
  • Depression
  • ­ intracranial pressure
• GH, LH, TSH secretion decreased
• Glaucoma, hypokalemia, delayed wound healing, thinning of skin
• Acute adrenal insufficiency (if chronic treatment tis stopped suddenly)

Question 5

contraindications for antiinflammatory

Answer 5

Contraindications:

• Cardiovascular diseases
• Peptic ulcer
• Glaucoma
• Diabetes
• Osteoporosis
• Psychosis
• Infections (HSV, TBC)

Question 6

Inhaled corticosteroid drugs:
which drugs do you know?
theraputic effects

Answer 6

Inhaled corticosteroids:

Drugs:

• Beclemothasone, dipropionate (prodrug)
• Budesonie
• Fluticasone
• Ciclesonide (prodrug)

Therapeutic effects:

• Anti-inflammatory/immunosuppressive effect:
  
  • Vasodilation decreased, extravasion and edema decreased
  • Neutrophil migration decreased, activity of leukocytes and macrophages decreased
  • Annexin-1 ­ decreased COX-2 expression ¯, PLA_2decreased
  • Pro-inflammatory cytokines decreased (IL-1, IL-6, IL-8, TNF-a, GM-CSF)
  • iNOS expression decreased
  • Histamine release decreased
  • IgG production decreased
  • Complement cascade decreased
• Bronchial hyperactivity decreased
• b₂-adrenoceptor expression­ increased

Problems:

• ø bronchodilation, slow onset (> 4h) ® used only to prevent asthmatic attacks
• Relatively flat dose-response curve
• “Non-responder” patients (steroid resistance)

Question 7

what are the problems with inhaled corticosterods?

Answer 7

Problems:

• no bronchodilation, slow onset (> 4h) ® used only to prevent asthmatic attacks
• Relatively flat dose-response curve
• “Non-responder” patients (steroid resistance)