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Chapter 76

Chapter 76. Drugs for Asthma. 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. Pathophysiology.

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Chapter 76

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  1. Chapter 76 Drugs for Asthma

  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. Pathophysiology • Symptoms of asthma result from a combination of inflammation and bronchoconstriction, so treatment must address both components

  4. Overview of Drugs for Asthma • Two main pharmacologic classes • Anti-inflammatory agents • Glucocorticoids (prednisone) • Bronchodilators • Beta2 agonists (albuterol)

  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. Anti-Inflammatory Drugs • Foundation of asthma therapy • Taken daily for long-term control • Principal anti-inflammatory drugs are the glucocorticoids

  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 beta2 receptors as well as their responsiveness to beta2 agonists. • Usually administered by inhalation, but IV and oral are also options

  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. Anti-Inflammatory Drugs:Glucocorticoids • Adverse effects • Minor when taken acutely • Can be severe when used long-term (adrenal suppression, osteoporosis, hyperglycemia, and others)

  10. Anti-Inflammatory Drugs:Leukotriene Modifiers • Suppress effects of leukotrienes • Less effective than inhaled glucocorticoids • Available agents • Zileuton (Zyflo) • Zafirlukast (Accolate) • Montelukast (Singulair)

  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. 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 beta2-adrenergic agonists

  13. Bronchodilators: Beta2-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. Bronchodilators: Beta2-Adrenergic Agonists • Adverse effects • Inhaled preparations • Systemic effects: tachycardia, angina, and tremor • Oral preparations • Excessive dosage: angina pectoris, tachydysrhythmias • Tremor

  15. Bronchodilators: Beta2-Adrenergic Agonists • Mechanism of action • Activate beta2 receptors in smooth muscle of lung, promoting bronchodilation and thereby relieving bronchospasm • Also suppress histamine release in lung and increase ciliary motility

  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. 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 beta2agonist.

  18. Management of Chronic Asthma • Tests of lung function • Forced expiratory volume in 1 second (FEV1) • Forced vital capacity (FVC) • Peak expiratory flow (PEF)

  19. Management of Chronic Asthma • Four classes of chronic asthma • Intermittent • Mild persistent • Moderate persistent • Severe persistent

  20. Management of Chronic Asthma • Treatment goals • Reducing impairment • Reducing risk

  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. 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. 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. 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 a systemic glucocorticoid to reduce airway inflammation • Giving a nebulized high-dose SABA to relieve airflow obstruction • Giving nebulizedipratropium to further reduce airflow obstruction.

  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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