1. Department of Pharmacology
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

6. http://link. brightcove. com/services/player/bcpid236059233

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. Anti-inflammatory Agents (control medications or prophylactic therapy)
Anti-asthmatic Drugs
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

9. - adrenoceptor agonists
Mechanism of Action
Direct 2 stimulation  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 Uses 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. Theophylline - Aminophylline
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 as slow 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. ↓ metabolism of theophylline
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 Act by stabilization of mast cell membrane
Cromolyn - Nedocromil
Act by stabilization of mast cell membrane
Have poor oral absorption
Given by inhalation

30. Mast cell stabilizers Not bronchodilators
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