Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 CHAPTER 32 Bronchodilator Drugs and the Treatment of Asthma

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2 Common Diseases Affecting the Respiratory Tract Chronic bronchitis – condition caused by chronic respiratory irritation, inflammation, and characterized by increased secretions and infection (COPD) smoking Emphysema – disease characterized by destruction of alveoli, labored respiratory gas exchange, and shortness of breath (↓exhale) Asthma – inflammatory disease of the respiratory passageways characterized by bronchoconstriction and shortness of breath

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 3 Emphysema Destruction of alveolar walls – dose dependently related to smoking Limits exercise tolerance – requires supplemental O 2

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 4 Asthma 5% of US population – 5000 deaths / y Bronchoconstriction – reversible smooth muscle contraction – controlled by –Contraction - parasympathetic – AC –Dilation – sym – β 2 adrenergic receptor Inflammation of bronchiolar mucosa Shortness of breath, cough, wheezing, smothering feeling,  mucous secretion

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5 COPD Affects 20% of Us pop. Secondary to smoking “mucous escalator” Combination of chronic bronchitis and emphysema irreversible, progressive does respond to treatment

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6

7 Inflammatory Mediators of the Respiratory Tract Histamine Eosinophilic chemotactic factor of anaphylaxis (ECF-A) Prostaglandins and leukotrienes Slow-reacting substance of anaphylaxis (SRS-A)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8 Autonomic Control of the Respiratory Tract Bronchiolar smooth muscle is relaxed by beta-2 adrenergic receptor stimulation Bronchiolar smooth muscle is contracted by cholinergic receptor stimulation Respiratory secretions are increased by cholinergic stimulation Drugs that increase intracellular levels of cyclic AMP produce bronchodilation

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 9 Bronchodilator Drugs Sympathomimetics – drugs that stimulate beta-2 adrenergic receptors Xanthine derivatives – theophylline Parasympatholytics – drugs that block cholinergic receptors (anticholinergic drugs)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 10 Bronchodilators Short acting – “rescue inhalers” 4-6 hr –Terbutaline (Brethine) –Albuterol (Proventil) Long acting – 12 hr –Salmeterol (Severent) Drugs of choice for mild asthma

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 11 Beta Adrenergic Drugs Epinephrine and isoproterenol are nonselective beta-1 and beta-2 agonists Albuterol, terbutaline, and salmeterol are selective beta-2 agonists that do not cause excessive cardiac stimulation Selective beta-2 drugs are preferred for the control of asthma Epinephrine SC is the drug of choice to treat an acute attack of asthma

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 12 Theophylline Increases cyclic AMP levels to cause bronchodilation and inhibition of chemical mediator release from mast cells Theophylline is usually administered orally In COPD theophylline decreases secretions and stimulates respiration Overdosage produces cardiac and CNS stimulation, and may cause seizures

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 13 Corticosteroids Drugs of choice for moderate – severe asthma Anti-inflammatory – decrease airway lymphocytes & eosinophills - no effect on muscle spasm –Mucosal edema –Leukotriene secretion –Mucous secretion

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 14 Corticosteroids Given by aerosol BID-QID Must use a “spacer” – prevents thrush Beclomethasone (Vanceril) Budesonide (Pulmocourt)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 15 Corticosteroids Adrenal gland hormone derivatives used in inflammatory and allergic conditions Administered orally or parenterally in acute asthmatic and inflammatory diseases Administered by oral inhalation for the chronic control of asthma and related inflammatory conditions Inhalation limits systemic toxicity

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 16 Anticholinergic Drugs Ipratropium bromide (Atrovent) is the only drug currently available By blocking cholinergic receptors ipratropium produces bronchodilation and decreased respiratory secretions The drug is administered by oral inhalation

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17 Leukotrienes Inhibitors Anti-inflammatory drugs that interfere with the inflammatory actions of the leukotrienes Zafirlukast (Accolate) and montelukast (Singulair) block leukotriene receptors Zileuton (Zyflo) blocks the enzyme required for the formation of leukotrienes Drugs are indicated for the chronic treatment and control of asthma

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 18 Ant allergic Drugs Cromolyn and nedocromil (Tilade) inhibit the antigen-antibody reaction on mast cells that triggers allergic reactions Administration is by oral inhalation Drugs are used on a daily basis and are intended to prevent or decrease allergic reactions Several weeks are usually required for the full therapeutic effect

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 19 Mucolytics Mucolytics are intended to break apart and liquefy thick respiratory secretions to facilitate easier removal Acetylcysteine (Mucomist) is the most widely used mucolytic and is inhaled by nebulization Administration is usually followed by postural drainage and tracheal suction