1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 76 Drugs for Asthma

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Asthma  Chronic inflammatory disorder of the airway  Characteristic signs and symptoms  Sense of breathlessness  Tightening of the chest  Wheezing  Dyspnea  Cough  Cause: immune-mediated airway inflammation

3. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Pathophysiology  Symptoms of asthma result from a combination of inflammation and bronchoconstriction, so treatment must address both components

4. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 Overview of Drugs for Asthma  Two main pharmacologic classes  Anti-inflammatory agents Glucocorticoids (prednisone) Glucocorticoids (prednisone)  Bronchodilators Beta 2 agonists (albuterol) Beta 2 agonists (albuterol)

5. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Inhalation Drug Therapy  Three obvious advantages  Therapeutic effects are enhanced  Systemic effects are minimized  Relief of acute attacks is rapid  Three types  Metered-dose inhalers (MDIs)  Dry-powder inhalers (DPIs)  Nebulizers

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.6 Anti-Inflammatory Drugs  Foundation of asthma therapy  Taken daily for long-term control  Principal anti-inflammatory drugs are the glucocorticoids

7. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Anti-Inflammatory Drugs: Glucocorticoids  Include budesonide and fluticasone  Considered the most effective anti-asthma drugs available  Reduce bronchial hyperreactivity  Also decrease airway mucus production and increase the number of bronchial beta 2 receptors as well as their responsiveness to beta 2 agonists.  Usually administered by inhalation, but IV and oral are also options

8. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Anti-Inflammatory Drugs: Glucocorticoids  Mechanism of action = Suppress inflammation  Decreased synthesis and release of inflammatory mediators  Decreased infiltration and activity of inflammatory cells  Decreased edema of the airway mucosa

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 Anti-Inflammatory Drugs: Glucocorticoids  Adverse effects  Minor when taken acutely  Can be severe when used long-term (adrenal suppression, osteoporosis, hyperglycemia, and others)

10. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Anti-Inflammatory Drugs: Leukotriene Modifiers  Suppress effects of leukotrienes  Less effective than inhaled glucocorticoids  Available agents  Zileuton (Zyflo)  Zafirlukast (Accolate)  Montelukast (Singulair)

11. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 Anti-Inflammatory Drugs: Cromolyn  Used for prophylaxis, not for quick relief  Suppresses inflammation; not a bronchodilator  Route—inhalation  Nebulizer  MDI  Adverse effects  Safest of all antiasthma medications  Cough  Bronchospasm

12. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Bronchodilators  Provide symptomatic relief but do not alter the underlying disease process (inflammation)  In almost all cases, patient taking a bronchodilator should also be taking a glucocorticoid for long-term suppression of inflammation  Principal bronchodilators are the beta 2 - adrenergic agonists

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Bronchodilators: Beta 2 -Adrenergic Agonists  Include albuterol, salmeterol, terbutaline  Most effective drugs for relief of acute bronchospasm and prevention of exercise- induced bronchospasm  Use in asthma: both quick relief and long- term control

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.14 Bronchodilators: Beta 2 -Adrenergic Agonists  Adverse effects  Inhaled preparations Systemic effects: tachycardia, angina, and tremor Systemic effects: tachycardia, angina, and tremor  Oral preparations Excessive dosage: angina pectoris, tachydysrhythmias Excessive dosage: angina pectoris, tachydysrhythmias Tremor Tremor

15. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.15 Bronchodilators: Beta 2 -Adrenergic Agonists  Mechanism of action  Activate beta 2 receptors in smooth muscle of lung, promoting bronchodilation and thereby relieving bronchospasm  Also suppress histamine release in lung and increase ciliary motility

16. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 Bronchodilators: Methylxanthines  Theophylline  Benefits derive primarily from bronchodilation  Narrow therapeutic index  Plasma level 10 to 20 mcg/mL  Toxicity is related to theophylline levels  Other methylxanthines include aminophylline and dyphylline

17. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.17 Glucocorticoid/LABA Combinations  Available combinations  Fluticasone/salmeterol (Advair)  Budesonide/formoterol (Symbicort)  Indicated for long-term maintenance in adults and children  Not recommended for initial therapy LABA = long-acting beta 2 agonist.

18. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.18 Management of Chronic Asthma  Tests of lung function  Forced expiratory volume in 1 second (FEV 1 )  Forced vital capacity (FVC)  Peak expiratory flow (PEF)

19. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.19 Management of Chronic Asthma  Four classes of chronic asthma  Intermittent  Mild persistent  Moderate persistent  Severe persistent

20. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.20 Management of Chronic Asthma  Treatment goals  Reducing impairment  Reducing risk

21. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.21 Management of Chronic Asthma  Long-term drug therapy  Agents for long-term control (eg, inhaled glucocorticoids)  Agents for quick relief of ongoing attack (eg, inhaled SABAs)

22. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.22 Management of Chronic Asthma  Stepwise therapy  Step chosen for initial therapy is based on pretreatment classification of asthma severity  Moving up or down a step is based on ongoing assessment of asthma control

23. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.23 Management of Chronic Asthma  Important to reduce exposure to allergens and triggers  Sources of allergens: house dust mites, pets, cockroaches, mold  Factors that can exacerbate asthma: tobacco smoke, wood smoke, household sprays

24. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.24 Drugs for Acute Severe Exacerbations  Requires immediate attention  Goal is to relieve airway obstruction and hypoxemia, and normalize lung function as quickly as possible.  Initial therapy consists of Giving oxygen to relieve hypoxemia Giving oxygen to relieve hypoxemia Giving a systemic glucocorticoid to reduce airway inflammation Giving a systemic glucocorticoid to reduce airway inflammation Giving a nebulized high-dose SABA to relieve airflow obstruction Giving a nebulized high-dose SABA to relieve airflow obstruction Giving nebulized ipratropium to further reduce airflow obstruction. Giving nebulized ipratropium to further reduce airflow obstruction.

25. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.25 Reducing Exposure to Allergens and Triggers  Measures to control or avoid dust mites and their feces include  Encasing the patient’s pillow, mattress, and box spring with covers that are impermeable to allergens  Washing all bedding and stuffed animals weekly in a hot-water wash cycle (130 °F)  Removing carpeting or rugs from the bedroom  Avoiding sleeping or lying on upholstered furniture  Keeping indoor humidity below 50%