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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 76 Drugs for Asthma
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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
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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
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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)
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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
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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
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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
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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
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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)
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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)
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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
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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
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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
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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
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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
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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
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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.
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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)
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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
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.20 Management of Chronic Asthma Treatment goals Reducing impairment Reducing risk
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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)
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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
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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
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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.
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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%
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