Drugs Used in Asthma

1. Drugs Used in Asthma Dr. Sasan Zaeri (PharmD, PhD) Department of Pharmacology

2. Asthma A chronic inflammatory disorder of bronchial airways that result in bronchospasm in response to external stimuli (pollen, cold air, tobacco smoke etc.)

3. Symptoms of asthma • Asthma produces recurrent episodic attack of • Acute bronchoconstriction • Shortness of breath • Chest tightness • Wheezing • Rapid respiration • Cough

4. Pathophysiology of Immunologic Asthma

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7. Aims of Anti-asthmatic Drugs • To relieve acute episodic attacks of asthma (bronchodilators, quick relief medications) • To reduce the frequency of attacks, and • nocturnal awakenings (anti-inflammatory drugs, prophylactic or control therapy )

8. Bronchodilators (Quick relief medications) treat acute episodic attack of asthma • 2-agonists • Antimuscarinics • Methylxanthines Anti-inflammatory Agents (control medications or prophylactic therapy) • reduce the frequency of attacks • Corticosteroids • Mast cell stabilizers • Leukotrienes antagonists • Anti-IgE monoclonal antibody Anti-asthmatic Drugs

9. - adrenoceptor agonists • Mechanism of Action • Direct 2stimulation  stimulate adenyl cyclase  Increase cAMP  bronchodilation

10. Classification of  agonists • Non selective  agonists • epinephrine - isoproterenol • Selective 2 – agonists (Preferable) • Salbutamol (Albuterol) • Terbutaline • Salmeterol • Formeterol

11. Nebulizer Inhaler

12. Selective 2 –agonists • Short acting ß2 agonists (salbutamol, terbutaline) • Drugs of choice for acute attack of asthma • Long acting ß2 agonists (salmeterol, formoterol) • Used for nocturnal asthma (long acting relievers) • Combined with inhaled corticosteroids to control asthma (decreases the number and severity of asthma attacks)

13. Adverse effects of selective 2 –agonists • Skeletal muscle tremor • Tachycardia and arrhythmia • Tolerance and tachyphylaxis

14. Muscarinic antagonists Ipratropium • Act by blocking muscarinic receptors • Given by aerosol inhalation • Quaternary derivatives of atropine • Do not enter CNS • Does not diffuse into the blood • Minimal systemic side effects

15. Effects • Inhibit bronchoconstriction and mucus secretion • Less effective than β2-agonists Uses • Main choice in chronic obstructive pulmonary diseases (COPD) • In acute severe asthma combined with β2-agonists & steroids

16. Methylxanthines Theophylline - Aminophylline • Mechanism of Action • Phosphodiestrase (PDE) inhibition cAMP bronchodilation • Adenosine receptor antagonists

18. Uses • Second line drug in asthma (theophylline in nocturnal asthma) • For status asthmatics (aminophylline is given asslow infusion)

19. Side Effects • CVS:arrhythmia • GI:nausea & vomiting,↑ gastric acid secretion • CNS:tremors, nervousness, insomnia, convulsion • Kidney: ↑renal blood flow, weak diuretic action

20. Drug interactions • Metabolized by Cyp P450 enzymes in liver • Enzyme inducers e.g. phenobarbital, rifampin, tobaco smoke → ↑metabolism of theophylline • Enzyme inhibitors e.g. erythromycin→ ↓ metabolism of theophylline

21. Anti - inflammatory Agents (control medications / prophylactic therapy) By reducing inflammation, they reduce bronchial hyper-reactivity and bronchospasm

22. Anti-inflammatory Agents • Glucocorticoids • Leukotrienes antagonists • Mast cell stabilizers • Anti-IgE monoclonal antibody (Omalizumab)

23. Glucocorticoids • Mechanism of action • Inhibition of phospholipase A2 → ↓ prostaglandin and leukotrienes • Mast cell stabilization →↓ histamine release • Upregulation of β2 receptors

25. Routes of administration • Inhalation • Budesonide, Fluticasone, Beclomethasone • Less side effects • Oral • Prednisolone • Parenteral • Hydrocortisone, Methylprednisolone • Status asthmaticus (IV infusion)

26. Glucocorticoids • Are not bronchodilators • Given as prophylactic medications, used alone or combined with beta-agonists

27. Side effects of systemic corticosteroids • Adrenal suppression • Growth retardation in children • Osteoporosis • Fluid retention, weight gain, hypertension • Hyperglycemia • Susceptibility to infections • Glaucoma • Cataract • Fat distribution, wasting of the muscles • Psychosis

28. Inhalation therapy has less side effects • Oropharyngeal candidiasis (thrush) • Dysphonia (voice hoarseness) Withdrawal • Abrupt stop of corticosteroids should be avoided and dose should be tapered (adrenal insufficiency syndrome)

29. Mast cell stabilizers Cromolyn - Nedocromil • Act by stabilization of mast cell membrane • Have poor oral absorption • Given by inhalation

30. Mast cell stabilizers • Notbronchodilators • Not effective in acute attack of asthma • Prophylactic anti-inflammatory drugs • Children respond better than adults

31. Uses • Prophylactic therapy in asthma especially in children • Allergic rhinitis • Conjunctivitis Side effects • Bitter taste • minor upper respiratory tract irritation (burning sensation)

32. Leukotrienes antagonists • Leukotriene B4 • chemotaxis of neutrophils • Leukotrienes C4 and D4 • bronchoconstriction

33. Leukotriene receptor antagonists Zafirlukast, Montelukast • Taken orally • Are bronchodilators • Are NOT effective to relieve acute attack of asthma • Have anti-inflammatory action

34. Uses • Prophylaxis of • Mild to moderate asthma • Aspirin-induced asthma • Antigen and exercise-induced asthma • Can be combined with glucocorticoids (low dose of glucocorticoids can be used)

35. Anti-IgE monoclonal antibody Omalizumab • A monoclonal antibody directed against human IgE • It binds to the IgE on sensitized mast cells and prevents activation by asthma triggers and subsequent release of inflammatory mediators • Expensive-not first line therapy

36. Summary