UNIT 8: DRUGS USED IN THE TREATMENT OF RESPIRATORY DISORDERS

1. UNIT 8: DRUGS USED IN THE TREATMENT OF RESPIRATORY DISORDERS UNIT INSTRUCTIONAL OUTCOMES: At the end of this unit, the student should be able to, • List drugs used in the treatment of respiratory disorders • Recall vital information about the drugs used in respiratory disorders • Apply pharmacological knowledge gained in the clinical scenario.

2. DRUGS AFFECTING THE RESPIRATORY SYSTEM Dr A. Shyam Sundar, Associate Professor in Pharmacology, University of Nizwa, Sultanate of Oman

3. OVERVIEW Asthma is a reversible obstructive disease of the lower airway. With asthma, there is increasing airway obstruction caused by bronchoconstriction, inflammation and edema of the lining of the bronchioles, and the production of thick mucus that can plug the airway.

4. DRUGS USED IN RESPIRATORY DISORDERS Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

5. There are three types of Asthma 1. Extrinsic Asthma (also referred to as allergic asthma and caused in response to an allergen such as pollen, dust, and animal dander). 2. Intrinsic asthma (also called non-allergic asthma and caused by chronic or recurrent respiratory infections, emotional upset, and exercise). 3. Mixed asthma (caused by both intrinsic and extrinsic factors). In asthma,there will be Contraction of bronchial smooth muscle, Inflammation of the bronchial wall, Increased mucous secretion. ASTHMA Lippincott's Illustrated Reviews: Pharmacology, 4th Edition.

6. Drugs addressing bronchoconstriction and inflammatory issues Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

7. Sympathomimetic Agents • They work by increasing cAMP which results in bronchodialation. • Pirbuterol, Terbutaline, Albuterol and Salmeterol* are four commonly used drugs in this class. • Most of these drugs are inhaled, which minimize their systemic side effects. • Because of their rapid onset, they are used in acute attacks. • Tremor and Tachycardia are the most common side effects. *Salmeterol is long acting and hence cannot be used in acute attacks

8. CORTICOSTEROIDS • Act by reducing inflammation(reverse mucosal edema, decrease permeability of capillaries, inhibit the release of cytokines and leukotrienes) • Acute exacerbations: Systemic steroids are used. IV or PO based on the severity. • Maintenance therapy: Inhaled corticosteroids are used. • Beclonethasone, Flunisolide, Triamcinolone, Fluticasone are common drugs in this class.

9. CORTICOSTEROIDS • Cough, Oral thrush and Dysphonia are common side effects of inhaled corticosteroids. • Abnormal glucose metabolism, increased weight gain, hypertension, adrenal suppression are the common side effects of systemic corticosteroids such as prednisone.

10. ANTICHOLINERGICS • Parasympathetic stimulation causes bronchoconstriction and mucus secretion. Anticholinergics block these effects and maintain bronchodialation of the airway. • Ipratropium is an example for inhaled anticholinergics. • Used in the treatment of asthma and COPD • Dry mouth and sedation are the most common side effects. Poor systemic absorption and hence minimal side effects.

11. LEUKOTRIENE INHIBITORS Examples: Zileuton and Zafirlukast Oral Route Clinical Role: They prevent bronchoconstrictiction and airway inflammation. Used in chronic maintenance therapy of asthma. Not used in acute bronchospasm. Mechanism of Action: Zileuton inhibits 5-lipoxygenase. Zafirlukast acts as LTD4 receptor antagonist Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

12. Methylxanthines- Theophylline • Theophylline is a methylxanthine derivative. • Acts by increasing the levels of cAMP by inhibiting phosphodiesterase enzyme which results in bronchodialation. It has mild anti-inflammatory action as well. • Cimetidine and Erythromycin both increase plasma levels of theophylline. • Phenytoin and Quinolones decrease plasma levels of Theophylline. • Mild overdose results in tremor, insomnia, gastrointestinal distress and nausea. Moderate to severe overdose will result in seizures and arrhythmias.

13. Cromolyn Sodium and Nedocromil • Effective prophylactic agents. • Acts by stabilizing mast cells and prevent the mediator release, probably by blocking calcium gates. • Cannot be used in acute bronchospasm. • Used in the prophylaxis of allergen- induced asthma and exercise induced bronchoconstriction. • Cromolyn Sodium causes infrequent laryngeal edema, cough and wheezing. • Nedocromil causes unpleasant taste.

14. Acute and Long-term management of asthma • Status asthmaticus is a life threatening attack of asthma. • IV Corticosteroids and bronchodilators are first-line therapy followed by Theophylline administration. Long-term management of Asthma in the outpatient setting: Mild, persistent symptoms are managed with inhaled steroids such as Fluticasone propionate. Acute attacks are treated with Beta2 adrenergic agonists. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

15. Summary- Anti-Asthmatic Drugs

16. Antitussives,Mucolytics and Expectorants An antitussive is a drug used to relieve coughing. A mucolytic is a drug that loosens respiratory secretions. An expectorant is a drug that aids in raising thick, tenacious mucus from the respiratory passages. The mucolytic acetylcysteine may be used as part of the treatment of bronchopulmonary diseases such as emphysema,as adjunctive therapy in chronic bronchopulmonary diseases, such as chronic emphysema, emphysema with bronchitis, chronic asthma, tuberculosis, and bronchiectasis, pneumonia and tracheobronchitis,cysticfibrosis,in acetaminophen overdosage. Expectorants are used to help raise respiratory secretions. An expectorant may also be included along with one or more additional drugs, such as an antihistamine, decongestant, or antitussive, in some prescription and nonprescription cough medicines.

17. Rhinitis Agents • Rhinitis is the inflammation of the mucous membranes of the nose. • Mostly caused by viruses or by hypersensitivity responses to airborne allergens. • Avoidance therapy should be tried first for allergic rhinitis. • Medical Options include • Nasal Corticosteroids • Cromolyn sodium • Antihistamines • Alpha adrenergic agonists Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

18. Rhinitis Agents • Beclomethasone and Flunisolide are the commonly used Corticosteroids in the management of chronic rhinitis. • Diphenhydramine, Chlorpheniramine, Cyproheptadine, Diphenhydramine and Promethazine are the antihistamines used in the treatment of rhinitis. • Antihistamines act by blocking Histamine-1 receptors. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

19. Rhinitis Agents • Ephedrine and Pseudoephedrine are the alpha adrenergic agonists used in the treatment of rhinitis. • They constrict dialatedarteriolesin the nasal mucosa and reduce airway resistance. They are given as an aerosol. • Prolonged useof nasal decongestants will result in rebound nasal congestion

20. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer

21. Anand, M.D. Ramachandran, Pharmacology Recall, Second Edition, Wolters Kluwer