Drugs for Asthma and Chronic Obstructive Pulmonary Disease Chapter 76 Drugs for Asthma and Chronic Obstructive Pulmonary Disease

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

Chronic Obstructive Pulmonary Disease (COPD) Chronic, progressive, largely irreversible disorder characterized by airflow restrictions and inflammation Characteristic signs and symptoms Chronic cough Excessive sputum production Wheezing Dyspnea Poor exercise tolerance Cause: Smoking cigarettes

Pathophysiology Symptoms of COPD result largely from two pathologic processes: Chronic bronchitis and emphysema Both processes are caused by an exaggerated inflammatory reaction to cigarette smoke Chronic bronchitis, which is defined by a chronic cough and excessive sputum production, results from hypertrophy of mucus-secreting glands in the epithelium of the larger airways

Pathophysiology Emphysema is enlargement of the air space within the bronchioles and alveoli, brought on by deterioration of the walls of these air spaces Among individuals with COPD, the relative contribution of these two processes can vary

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

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) Respimats Dry-powder inhalers (DPIs) Nebulizers

Anti-Inflammatory Drugs Foundation of asthma therapy Taken daily for long-term control Principal anti-inflammatory drugs are the glucocorticoids (for example, budesonide, fluticasone)

Anti-Inflammatory Drugs: Glucocorticoids Mechanism of action Considered the most effective antiasthma drugs available Decrease synthesis and release of inflammatory mediators Reduce infiltration and activity of inflammatory cells Decrease edema of the airway mucosa caused by beta2 agonists Usually administered by inhalation, but IV and oral routes are also options

Anti-Inflammatory Drugs: Glucocorticoids Mechanism of action = suppress inflammation Reduce bronchial hyperreactivity and decrease airway mucus production May increase the number of bronchial beta2 receptors and their responsiveness to beta2 agonists

Anti-Inflammatory Drugs: Glucocorticoids Use Prophylaxis of chronic asthma Dosing must be on a fixed schedule, not as needed (PRN) Not used to abort an ongoing attack because beneficial effects develop slowly

Anti-Inflammatory Drugs: Glucocorticoids Inhaled use First-line therapy for management of inflammatory component of asthma Most patients with persistent asthma should use these drugs daily Inhaled glucocorticoids are very effective and much safer than systemic glucocorticoids

Anti-Inflammatory Drugs: Glucocorticoids Oral use For patients with moderate to severe persistent asthma or for management of acute exacerbations of asthma or COPD Potential for toxicity; should be used only when symptoms cannot be controlled with safer medications (inhaled glucocorticoids, inhaled beta2 agonists) Treatment should be as brief as possible

Anti-Inflammatory Drugs: Glucocorticoids Adverse effects of inhaled forms Adrenal suppression Oropharyngeal candidiasis Dysphonia

Anti-Inflammatory Drugs: Glucocorticoids Adverse effects of inhaled forms (Cont.) Glucocorticoids can slow growth in children and adolescents; however, these drugs do not decrease adult height Promotion of bone loss Increased risk of cataracts Increased risk of glaucoma

Anti-Inflammatory Drugs: Glucocorticoids Adverse effects of oral forms Short-term therapy Long-term therapy Adrenal suppression Osteoporosis Hyperglycemia Peptic ulcer disease In young patients: Growth suppression

Anti-Inflammatory Drugs: Glucocorticoids Adrenal suppression Prolonged glucocorticoid use can decrease the ability of the adrenal cortex to produce glucocorticoids of its own Life-threatening at times of severe physiologic stress (for example, surgery, trauma, or systemic infection) High levels of glucocorticoids are required to survive severe stress Adrenal suppression prevents production of endogenous glucocorticoids Patients must be given increased doses of oral or IV glucocorticoids at times of stress Failure to do so can prove fatal

Anti-Inflammatory Drugs: Glucocorticoids Adrenal suppression Discontinuing treatment Must be done slowly Recovery of adrenocortical function takes several months Dosage of exogenous sources must be reduced gradually During this time, patients ‒ including those switched to inhaled glucocorticoids ‒ must be given supplemental oral or IV glucocorticoids at times of severe stress

Anti-Inflammatory Drugs: Leukotriene Modifiers Suppress effects of leukotrienes Leukotrienes: Promote smooth muscle constriction, blood vessel permeability, and inflammatory responses through direct action and recruitment of eosinophils and other inflammatory cells In patients with asthma, leukotriene modifiers can reduce bronchoconstriction and inflammatory responses such as edema and mucus secretion

Anti-Inflammatory Drugs: Leukotriene Modifiers Second-line agents Generally well tolerated but can cause adverse neuropsychiatric effects, including depression, suicidal thinking, and suicidal behavior Available agents Zileuton [Zyflo] Zafirlukast [Accolate] Montelukast [Singulair]

Anti-Inflammatory Drugs: Leukotriene Modifiers Zileuton [Zyflo] Mechanism of action Adverse effects

Anti-Inflammatory Drugs: Leukotriene Modifiers Zafirlukast [Accolate] Mechanism of action Adverse effects

Anti-Inflammatory Drugs: Leukotriene Modifiers Montelukast [Singulair] Mechanism of action Adverse effects

Anti-Inflammatory Drugs: Cromolyn Used for prophylaxis, not for quick relief Suppresses inflammation; not a bronchodilator

Anti-Inflammatory Drugs: Cromolyn Mechanism of action: Stabilizes cytoplasmic membrane of mast cells, thereby preventing release of histamine and other mediators; in addition, inhibits eosinophils, macrophages, and other inflammatory cells

Anti-Inflammatory Drugs: Cromolyn Route: Inhalation Nebulizer Therapeutic use Chronic asthma Exercise-induced bronchospasm (EIB) Allergic rhinitis

Anti-Inflammatory Drugs: Cromolyn Adverse effects Safest of all antiasthma medications Cough Bronchospasm

Monoclonal Antibody: Omalizumab [Xolair] Mechanism of action Antagonism of immunoglobulin E (IgE), a type of antibody Therapeutic use Patients age 12 years or older with moderate to severe asthma that (1) is allergy related and (2) cannot be controlled with an inhaled glucocorticoid

Monoclonal Antibody: Omalizumab [Xolair] Adverse effects Injection-site reactions Viral infection Upper respiratory infection Sinusitis Headache Pharyngitis Cardiovascular events Malignancy Life-threatening anaphylaxis

Bronchodilators Provide symptomatic relief but do not alter the underlying disease process (inflammation) In almost all cases, patients taking a bronchodilator should also be taking a glucocorticoid for long-term suppression of inflammation Principal bronchodilators are the beta2-adrenergic agonists

Bronchodilators: Beta2-Adrenergic Agonists Mechanism of action Through activation of beta2 receptors in the smooth muscle of the lung, these drugs promote bronchodilation, relieving bronchospasm Beta2 agonists have a limited role in suppressing histamine release in the lung and increasing ciliary motility

Bronchodilators: Beta2-Adrenergic Agonists Use in asthma and COPD Inhaled short-acting beta2 agonists (SABAs) Taken PRN to abort an ongoing attack EIB: Taken before exercise to prevent an attack Hospitalized patients undergoing a severe acute attack: Nebulized SABA is the traditional treatment of choice Delivery with an MDI in the outpatient setting may be equally effective

Bronchodilators: Beta2-Adrenergic Agonists Use in asthma and COPD Inhaled long-acting beta2 agonists (LABAs) Long-term control in patients who experience frequent attacks Dosing is on a fixed schedule, not PRN Effective in treating stable COPD When used to treat asthma, must always be combined with a glucocorticoid Use alone in asthma is contraindicated

Bronchodilators: Beta2-Adrenergic Agonists Adverse effects Inhaled preparations Systemic effects: Tachycardia, angina, tremor Oral preparations Excessive dosage: Angina pectoris, tachydysrhythmias Tremor

Bronchodilators: Methylxanthines Theophylline Other methylxanthines include aminophylline and dyphylline

Bronchodilators: Methylxanthines Theophylline Produces bronchodilation by relaxing smooth muscle of the bronchi Narrow therapeutic index Plasma level 10 to 20 mcg/mL Toxicity is related to theophylline levels The drug is usually administered by mouth but may also be administered intravenously

Bronchodilators: Methylxanthines Use in asthma and COPD Oral theophylline is used for maintenance therapy of chronic stable asthma Theophylline is no longer recommended for treatment of COPD Toxicity Plasma levels below 20 mcg/mL: Adverse effects uncommon Plasma levels of 20-25 mcg/mL: Nausea, vomiting, diarrhea, insomnia, restlessness Plasma levels above 30 mcg/mL: Severe dysrhythmias (for example, ventricular fibrillation) and convulsions Death may result from cardiorespiratory collapse

Bronchodilators: Methylxanthines Toxicity treatment Stop theophylline Activated charcoal together with a cathartic Dysrhythmias respond to lidocaine Intravenous diazepam may help control seizures Interactions Caffeine Tobacco and marijuana Cimetidine Fluoroquinolone antibiotics

Anticholinergic Drugs: Ipratropium Improves lung function by blocking muscarinic receptors in the bronchi, thereby reducing bronchoconstriction Action and use Administered by inhalation to relieve bronchospasm Therapeutic effects begin within 30 seconds, reach 50% of maximum in 3 minutes, and persist about 6 hours Adverse effects Dry mouth and irritation of the pharynx Glaucoma Cardiovascular events

Anticholinergic Drugs: Tiotropium Long-acting, inhaled anticholinergic agent approved for maintenance therapy of bronchospasm associated with COPD Not approved for asthma Relieves bronchospasm by blocking muscarinic receptors in the lung Therapeutic effects begin about 30 minutes after inhalation, peak in 3 hours, and persist about 24 hours With subsequent doses: Bronchodilation continues to improve, reaching a plateau after eight consecutive doses (8 days)

Anticholinergic Drugs: Tiotropium Adverse effect: Dry mouth Minimal anticholinergic effects

Anticholinergic Drugs: Aclidinium Newest long-acting anticholinergic for management of bronchospasm associated with COPD Relieves bronchospasm by blocking muscarinic receptors in the lung Peak levels have occurred within 10 minutes of drug delivery Intended only for maintenance therapy Not for acute symptom relief

Anticholinergic Drugs: Aclidinium Adverse effects Headache Nasopharyngitis Cough

Glucocorticoid/LABA Combinations Available combinations Fluticasone/salmeterol [Advair] Budesonide/formoterol [Symbicort] Mometasone/formoterol [Dulera] Indicated for long-term maintenance in adults and children Not recommended for initial therapy

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

Management of Asthma Four classes of asthma severity Intermittent Mild persistent Moderate persistent Severe persistent

Management of Chronic Asthma Treatment goals Reducing impairment Reducing risk

Management of Chronic Asthma Long-term drug therapy Agents for long-term control (for example, inhaled glucocorticoids) Agents for quick relief of ongoing attack (for example, inhaled SABAs)

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

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

Drugs for Acute Severe Exacerbation This condition requires immediate attention Goals: Relieve airway obstruction and hypoxemia, and normalize lung function as quickly as possible Initial therapy consists of administering: Oxygen ‒ To relieve hypoxemia A systemic glucocorticoid ‒ To reduce airway inflammation A nebulized, high-dose SABA ‒ To relieve airflow obstruction Nebulized ipratropium ‒ To further reduce airflow obstruction

Drugs for Exercise-Induced Asthma Cause: Bronchospasm secondary to loss of heat and/or water from the lung Starts either during or immediately after exercise, peaks in 5 to 10 minutes, and resolves 20 to 30 minutes later SABA or cromolyn administered prophylactically Inhaled SABAs generally preferred over cromolyn Beta2 agonists should be inhaled immediately before exercise Cromolyn should be inhaled 15 minutes before exercise

Reducing Exposure to Allergens and Triggers Measures to control or avoid dust mites and their feces Encase the patient’s pillow, mattress, and box spring in covers impermeable to allergens Wash all bedding and stuffed animals weekly in a hot-water wash cycle (130º F) Remove carpeting or rugs from bedroom Avoid sleeping or lying on upholstered furniture Keep indoor humidity below 50%

Management of COPD Measurement of lung function Classification of COPD severity Mild Moderate Severe Very severe

Management of COPD Treatment goals Reduce symptoms, thereby improving the patient’s health status and exercise tolerance Reduce risks and mortality by preventing progression of COPD and by preventing and managing exacerbations

Management of COPD Patient classification Group A: Few symptoms; low risk Group B: Increased symptoms; low risk Group C: Few symptoms; high risk Group D: Increased symptoms; high risk

Management of Stable COPD Pharmacologic management Bronchodilators Glucocorticoids Phosphodiesterase-4 inhibitors

Management of COPD Exacerbations Pharmacologic management SABAs (specifically inhaled, either alone or in combination with inhaled anticholinergics) are preferred for bronchodilation during COPD exacerbations Systemic glucocorticoids Antibiotics Supplemental oxygen to maintain an oxygen saturation of 88% to 92%

Question 1 A patient with asthma is prescribed albuterol [Proventil], two puffs 3 times per day. The nurse should teach the patient to do what? A. Rinse the mouth after taking the prescribed dose. B. Take an extra dose if breathing is compromised. C. Wait 1 minute between puffs from the inhaler. D. Take adequate amounts of calcium and vitamin D. Answer: C Rationale: Patients should be taught to wait at least 1 minute between puffs. Extra doses should not be taken unless prescribed by the health care provider. Glucocorticoid inhalation requires oral rinses to prevent the development of dysphonia and oropharyngeal candidiasis. Patients should take adequate amounts of calcium and vitamin D with glucocorticoid therapy.

Question 2 A patient with asthma is prescribed triamcinolone acetonide [Azmacort]. What should the nurse do? A. Take the patient’s pulse before administering the medication. B. Teach the patient to use a spacer to prevent a fungal infection. C. Instruct the patient to use this drug to treat an acute attack. D. Encourage the patient to avoid weight-bearing activity. Answer: B Rationale: Acetonide is an inhaled glucocorticoid. Spacers disperse the medication into the lungs, leaving less in the oropharyngeal mucosa; this reduces the incidence of fungal infection. Beta2-adrenergic agonists may cause tachycardia and are used to abort acute asthma attacks. Patients taking glucocorticoids should engage in weight-bearing activities to prevent osteoporosis. This drug should not be used to treat an acute attack.

Question 3 Which information should the nurse include when teaching a patient about inhaled glucocorticoids? A. Inhaled glucocorticoids have many significant adverse effects. B. The principal side effects of inhaled glucocorticoids include hypertension and weight gain. C. Use of a spacer can minimize side effects. D. Patients should rinse the mouth and gargle before administering inhaled glucocorticoids. Answer: C Rationale: Inhaled glucocorticoids are generally very safe. Their principal side effects are oropharyngeal candidiasis and dysphonia, which can be minimized by using a spacer device during administration and by rinsing the mouth and gargling after use.

Question 4 Which of the following is NOT a serious adverse effect of long-term oral glucocorticoid therapy? A. Adrenal suppression B. Osteoporosis C. Hypoglycemia D. Peptic ulcer disease Answer: C Rationale: Serious adverse effects include adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer disease, and growth suppression.