Drugs Used in Asthma Dr Sasan Zaeri Pharm

Drugs Used in Asthma Dr. Sasan Zaeri (Pharm. D, Ph. D) Department of Pharmacology 1

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

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

Pathophysiology of Immunologic Asthma 4

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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 ) 7

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

- adrenoceptor agonists • Mechanism of Action Ø Direct 2 stimulation stimulate adenyl cyclase Increase c. AMP bronchodilation 9

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

Nebulizer Inhaler 11

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

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

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

Effects Ø Inhibit bronchoconstriction and mucus secretion Ø Less effective than β 2 -agonists Uses Ø Ø Main choice in chronic obstructive pulmonary diseases (COPD) In acute severe asthma combined with β 2 agonists & steroids 15

Methylxanthines Theophylline - Aminophylline • Mechanism of Action Ø Phosphodiestrase (PDE) inhibition c. AMP bronchodilation Ø Adenosine receptor antagonists 16

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• Uses Ø Second line drug in asthma (theophylline in nocturnal asthma) Ø For status asthmatics (aminophylline is given as slow infusion) 18

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

• Drug interactions Ø Metabolized by Cyp P 450 enzymes in liver Ø Enzyme inducers e. g. phenobarbital, rifampin, tobaco smoke → ↑metabolism of theophylline Ø Enzyme inhibitors e. g. erythromycin→ ↓ metabolism of theophylline 20

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

Anti-inflammatory Agents Ø Glucocorticoids Ø Leukotrienes antagonists Ø Mast cell stabilizers Ø Anti-Ig. E monoclonal antibody (Omalizumab) 22

Glucocorticoids • Mechanism of action – Inhibition of phospholipase A 2 → ↓ prostaglandin and leukotrienes – Mast cell stabilization →↓ histamine release – Upregulation of β 2 receptors 23

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

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

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 27

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) 28

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

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

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

Leukotrienes antagonists Ø Leukotriene B 4 Ø chemotaxis of neutrophils Ø Leukotrienes C 4 and D 4 Ø bronchoconstriction 32

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

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

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

Summary 36