Chapter 40: Drugs for Asthma and other Pulmonary Disorders

Autonomic Control of Airways: Sympathetic branch

-Activates beta 2 adrenergic receptors and causes bronchiolar smooth muscle to relax -The airway diameter increases (bronchodilation

Autonomic Control of Airways: Parasympathetic branch

-Causes bronchiolar smooth muscle to contract -The airway diameter is narrowed ▪Bronchoconstriction occurs ▪Results in less airflow

Disadvantages of aerosol therapy

-Difficult to measure precise dose -Usually, only 10 to 50% of drug is placed -Instruction may be complicated for some patients -Side effects occur if patient swallows drug or does not rinse mouth after inhalation

Autonomic Control of Airway: Brochioles

-Lined with smooth muscle that controls amount of air entering lungs -Diameter of airways controlled by autonomic nervous system

Oral therapy

-Longer duration of action -Frequent side effects -Tolerance may develop

Bronchioles

-Muscular, elastic structures -Diameter (lumen) varies with contraction or relaxation of smooth muscle

Devices used for Aerosol Therapy: Dry powder inhaler (DPI)

-Patient inhales powdered drug -Device activated by inhalation

Devices used for Aerosol Therapy: Metered-dose Inhaler (MDI)

-Propellant delivers measured dose of drug -Patient times inhalation to puffs of drug

Role of the Nurse: Corticosteroid Therapy for Asthma- Steroid Inhalers

-Use cautiously with hypertension, G I disease, congestive heart failure, thromboembolic disease

Devices used for Aerosol Therapy: Nebulizer

-Vaporizes liquid drug into fine mist -Uses small machine and face mask

Prototype Drug: Ipratropium (Atrovent)

Actions and Uses Ipratropium is an anticholinergic drug that is delivered by the inhalation and intranasal routes. The inhalation form is approved to relieve and prevent the bronchospasm that is characteristic of asthma and C O P D. When combined with albuterol (Combivent Respimat), it is a first-line drug for treating bronchospasms due to C O P D, including bronchitis and emphysema. Although it has not received U.S Food and Drug Administration (F D A) approval for the treatment of asthma, it is prescribed off-label for the disorder. The primary role of ipratropium is as an alternative to S A B A s and for patients experiencing severe asthma exacerbations. It is sometimes combined with beta agonists or corticosteroids to provide additive bronchodilation. The nasal spray formulation of ipratropium is approved for the symptomatic relief of runny nose associated with the common cold and allergic rhinitis. The drug inhibits nasal secretions but does not have decongestant action. Treatment is limited to 3 weeks.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Actions and Uses Albuterol is a S A B A that is used to relieve the bronchospasm of asthma. Its rapid onset and excellent safety profile have made inhaled albuterol a preferred drug for the termination of acute bronchospasm. In addition to relieving bronchospasm, the drug facilitates mucus drainage and can inhibit the release of inflammatory chemicals from mast cells. When inhaled 15 to 30 minutes prior to physical activity, it can prevent exercise-induced bronchospasm. Short-acting beta 2 agonists such as albuterol are not recommended for asthma prophylaxis. Oral forms of albuterol include immediate-release and extended-release tablets (VoSpire) and an oral solution. The oral forms have a longer onset of action and are not suitable for terminating acute asthma attacks.

Prototype Drug: Beclomethasone (Q V A R)

Actions and Uses Beclomethasone is a corticosteroid available through aerosol inhalation for asthma (Qvar) or as a nasal spray (Beconase A Q, Qnasl) for allergic rhinitis. Beclomethasone and other drugs in this class are preferred drugs for the long-term management of persistent asthma in both children and adults. Three or four weeks of therapy may be necessary before optimal benefits are obtained. Beclomethasone acts by reducing inflammation, thus decreasing the frequency of asthma attacks. It is not a bronchodilator and should not be used to terminate asthma attacks in progress. Intranasal beclomethasone is effective at reducing the symptoms of allergic rhinitis. Beconase A Q is also approved to prevent recurrence of nasal polyps following surgical removal.

Montelukast (Singulair)

Actions and Uses Montelukast is used for the prophylaxis of persistent, chronic asthma, exercise-induced bronchospasm, and allergic rhinitis. It prevents airway edema and inflammation by blocking leukotriene receptors in the airways. The drug is given P O and acts rapidly, although it is not recommended for termination of acute bronchospasm. It is the only agent in this class that is approved for pediatric use. To aid in administration, montelukast is available in chewable tablets and as granules that are recommended by the manufacturer to be mixed with applesauce, mashed carrots, or ice cream.

Prototype Drug: Beclomethasone (Q V A R)

Administration Alerts • Do not use if the patient is experiencing an acute asthma attack. • Oral inhalation products and nasal spray products are not to be used interchangeably. • Pregnancy category C.

Montelukast (Singulair)

Administration Alerts • Do not use to terminate acute asthma attacks. • If preventing exercise-induced bronchospasm, take drug at least 2 hours before the activity. • Pregnancy category B.

Prototype Drug: Ipratropium (Atrovent)

Administration Alerts • The proper use of the M D I is important to the effective delivery of drug. Observe and instruct the patient in proper use. • Wait 2-3 minutes between dosages. • Avoid contact with eyes; otherwise, blurred vision may occur. • Pregnancy category B.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Administration Alerts • The proper use of the inhaler is important to the effective delivery of the drug; use only the actuator that comes with the canister. Observe and instruct the patient in proper use . • Pregnancy category C.

Prototype Drug: Beclomethasone (Q V A R)

Adverse Effects Inhaled beclomethasone produces few systemic adverse effects. Because small amounts may be swallowed with each dose, the patient should be observed for signs of corticosteroid toxicity. Local effects may include hoarseness, dry mouth, and changes in taste. Inhaled corticosteroid use has been associated with the development of cataracts in adults. Long-term intranasal or inhaled corticosteroids may cause growth inhibition in children. As with all corticosteroids, the anti-inflammatory properties of beclomethasone can mask signs of infections, and the drug is contraindicated if an active infection is present. A significant percentage of patients who take beclomethasone on a long-term basis will develop oropharyngeal candidiasis, a fungal infection in the throat, due to the constant deposits of drug in the oral cavity.

Montelukast (Singulair)

Adverse Effects Singulair produces few serious adverse effects. Headache is the most common complaint, and nausea and diarrhea are reported by some patients. Although rare, some patients have experienced serious neuropsychiatric events, including suicidal ideation, hallucinations, aggressiveness, or depression.

Prototype Drug: Ipratropium (Atrovent)

Adverse Effects Because very little is absorbed by the lungs, ipratropium produces few systemic adverse effects. Irritation of the upper respiratory tract may result in cough, drying of the nasal mucosa, or hoarseness. It produces a bitter taste, which may be relieved by rinsing the mouth after use. Intranasal administration may cause epistaxis and excessive drying of the nasal mucosa.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Adverse Effects Serious adverse effects from inhaled albuterol are uncommon. Some patients experience palpitations, headaches, throat irritation, tremor, nervousness, restlessness, and tachycardia. Less common adverse reactions include insomnia and dry mouth. Uncommon adverse effects include chest pain, paradoxical bronchospasm, and allergic reactions.

Montelukast (Singulair)

Contraindications: The only contraindication is hypersensitivity to the drug. Because a few rare cases of hepatic failure have been reported in patients who are taking montelukast, those with pre-existing hepatic impairment should be treated with caution.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Contraindications: Use is contraindicated in patients with hypersensitivity to the drug. Because albuterol may exhibit cardiovascular effects in some patients, caution is required when administering these drugs to persons with a history of cardiac disease or hypertension (H T N)

Prototype Drug: Beclomethasone (Q V A R)

Contraindications: Beclomethasone is contraindicated in those with hypersensitivity to the drug. The growth of pediatric patients should be monitored carefully, because inhaled corticosteroids may reduce growth velocity in some children.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Drug-Drug: Concurrent use with beta blockers will inhibit the bronchodilation effect of albuterol. Patients should also avoid monoamine oxidase inhibitors (M A O I s) within 14 days of beginning therapy.

Prototype Drug: Ipratropium (Atrovent)

Drug-Drug: Use with other drugs in this class such as atropine may lead to additive anticholinergic side effects. Ipratropium should not be used concurrently with the antidiabetic drug pramlintide because both slow peristalsis and can cause serious or life-threatening G I symptoms.

Montelukast (Singulair)

Drug-Drug: Singulair exhibits fewer drug-drug interactions than other medications in this class.

Prototype Drug: Beclomethasone (Q V A R)

Drug-Drug: Unknown.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Lab Tests: May cause hypokalemia at high doses. Herbal/Food: Products containing caffeine may cause nervousness, tremor, or palpitations.

Montelukast (Singulair)

Lab Tests: Montelukast may increase serum alanine aminotransferase (A L T) values. Herbal/Food: None known

Prototype Drug: Ipratropium (Atrovent)

Lab Tests: Unknown. Herbal/Food: Unknown

Prototype Drug: Beclomethasone (Q V A R)

Lab Tests: Unknown. Herbal/Food: Unknown.

Montelukast (Singulair)

Therapeutic Class: Anti-Inflammatory Drug for Asthma Prophylaxis Pharmacologic Class: Leukotriene Modifier

Prototype Drug: Beclomethasone (Q V A R)

Therapeutic Class: Anti-Inflammatory Drug for Asthma and Allergic Rhinitis Pharmacologic Class: Inhaled corticosteroid

Prototype Drug: Ipratropium (Atrovent)

Therapeutic Class: Bronchodilator Pharmacologic Class: Anticholinergic

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Therapeutic Class: Bronchodilator Pharmacologic Class: beta 2-adrenergic agonist

Prototype Drug: Beclomethasone (Q V A R)

Treatment of Overdose: Overdose does not occur when the drug is given by the inhalation route.

Albuterol (ProAir H F A, Proventil, H F A, Ventolin H F A, VoSpire E R)

Treatment of Overdose: Overdose results in an exaggerated sympathetic activation, causing dysrhythmias, hypokalemia, and hyperglycemia. In severe cases, administration of a cardioselective beta-adrenergic antagonist may be necessary.

Prototype Drug: Ipratropium (Atrovent)

Treatment of Overdose: Overdose with ipratropium does not occur because very little of the drug is absorbed when given by aerosol.

Montelukast (Singulair)

Treatment of Overdose: There is no specific treatment for overdose.

Asthma

• A chronic disease • Has both inflammatory and bronchospasm components • Symptoms occur -From exposure to triggers -Upon exertion (exercise-induced) • Status asthmaticus—prolonged attack • Drugs used to -Prevent asthmatic attacks -Terminate attack in progress

Role of the Nurse: Corticosteroid Therapy for Asthma- Assess

• Assess patient for presence/history of conditions -Asthma, allergic rhinitis, hypertension, heart disease -Blood clots, Cushingsyndrome -Fungal infections, diabetes mellitus • Assess for signs and symptoms of infection

Role of the Nurse: Anticholinergic Therapy for Asthma

• Assess respiratory rate before and after first dose of M D I • Monitor vital signs -Respiratory rate and pulse, respiratory effort -Skin color, oxygen saturation level, lung sounds • Assess for history of narrow-angle glaucoma, benign prostatic hyperplasia, renal disorders, urinary bladder neck obstruction -Contraindicated in patients with history of these and in elderly

Role of the Nurse: Methylxanthine Therapy for Asthma

• Assess vital signs -Respiratory and pulse rate, cardiac rhythm, lung sounds -Respiratory effort, skin color, oxygen saturation level • Contraindicated with certain conditions -Coronary artery disease, angina pectoris -Severe renal or liver disorders, peptic ulcer -Benign prostatic hyperplasia, diabetes mellitus • Used with caution in elderly patients and children • Not recommended in women who are breastfeeding

Role of the Nurse: Beta-Adrenergic Agonist Therapy for Asthma

• Assess vital signs prior to administration -Respiratory and pulse rate, lung sounds -Respiratory effort, skin color, oxygen saturation level • Do not administer if patient has history of dysrhythmia or M I • Use limited in children younger than 6 years • Not recommended for women who are breastfeeding

Goals of Therapy: Asthma

• Asthma has both bronchoconstriction component and inflammation component • Goals of drug therapy are twofold -To terminate acute bronchospasms in progress (quick-relief medications) -To reduce the frequencyof asthma attacks (long-acting medications) • Quick-relief medications: beta2 -adrenergic agonists, anticholinergics, systemic corticosteroids • Long-acting medications: inhaled corticosteroids, mast cell stabilizers, leukotriene modifiers, long-acting beta2 -adrenergic agonists, methylxanthines, and immunomodulators

Anticholinergics

• Block parasympathetic nervous system with bronchodilator effect • Occasionally used as alternative to beta-agonists in asthma therapy • Used in inhaled form

Administration by Inhalation

• Common route of administration for pulmonary drugs • Rapid and efficient • Rich blood supply allows for quick absorption and onset of action • Delivers drugs directly to sites of action

Monoclonal Antibodies for Asthma Prophylaxis

• Designed to attach to specific receptor on a target cell or molecule • Omalizumab (Xolair) -First biologic therapy approved to treat asthma -Attached to receptor on immunoglobulin E (I g E)

Methylxanthines

• Group of bronchodilators related to caffeine • Once mainstay of chronic asthma pharmacotherapy -Example: theophylline • Narrow margin of safety • Interact with numerous drugs Side effects common -Nausea, vomiting,C N S stimulation • Administered by intravenous or oral routes • Primarily used for long-term prophylaxis of asthma that is unresponsive to beta agonists or corticosteroids

Mast Cell Stabilizers

• Inhibit mast cells from releasing histamine and other chemical mediators • Are safe for prophylaxis of asthma • Less effective than inhaled corticosteroids • Ineffective at relieving acute bronchospasm

Leukotriene Modifiers

• Leukotrienes are mediators of immune response -Involved in allergic and asthmatic reactions • Leukotriene modifiers primarily used for asthma prophylaxis -Reduce inflammatory component of asthma • Oral medication used when persistent asthma not controlled with other drugs • Prototype drug: montelukast (Singulair) • Mechanism of action: prevents airway edema and inflammation by blocking leukotriene receptors in airways • Primary use: for prophylaxis of persistent, chronic asthma • Adverse effects: headache, nausea, diarrhea

Role of the Nurse: Leukotriene Therapy for Asthma

• Monitor vital signs -Respiratory and pulse rates, respiratory effort, lung sounds -Skin color, oxygen saturation level • Monitor C B C and periodic liver function tests • Closely monitor prothrombin time (P T) and international normalized ratio (I N R) in patients taking warfarin (Coumadin) • Closely monitor phenytoin level with concurrent phenytoin therapy -Reduce theophylline dose; monitor zileuton levels • Assess for signs and symptoms of infection, especially in elderly • Advise patients not to use leukotriene modifiers during acute asthma attack

Role of the Nurse: Corticosteroid Therapy for Asthma- Monitor

• Monitor vital signs -Respiratory and pulse rates, respiratory effort, lung sounds -Skin color, oxygen saturation level, body weight

Beta-Adrenergic Agonists

• Most effective drugs for relieving acute bronchospasm • Activate beta2 receptors in bronchial smooth muscle to cause bronchodilation • Fewer cardiac side effects than older nonselective beta-adrenergics • Range from ultrashort to long-acting

Corticosteroids

• Most potent natural anti-inflammatory drugs • Inhaled, are drugs of choice for long-term prophylaxis of asthma -Must be taken daily -Systemic side effects rarely observed • Oral drugs used for short-term therapy of severe, acute asthma -Limit therapy to under 10 days

Role of the Nurse: Corticosteroid Therapy for Asthma

• Not recommended for pregnant or breast-feeding women • Primary purpose of inhaled corticosteroids is to prevent respiratory distress -Do not use this medication during acute asthma attack • Patients should watch for signs and symptoms of simple infections -Rinse mouth after using steroid inhalers -Closely monitor blood glucose levels

Pharmacotherapy of Chronic Obstructive Pulmonary Disease

• Obstructed airflow -Commonly caused by: chronic bronchitis, asthma -Progressive; end stage emphysema • Pharmacotherapy goals -Relieve symptoms -Avoid complications • Drug classes -Bronchodilators -Mucolytics and expectorants -Oxygen therapy -Antibiotics -Roflumilast (Daliresp)

Respiration

• Process of bringing O2 into body and moving carbon dioxide out • Involves two main processes -Ventilation moves air into and out of lungs -Perfusion is flow of blood through lungs

Bronchodilators—Beta-Adrenergic Agonists

• Prototype drug: albuterol (ProAir H F A, Proventil H F A, Ventolin H F A) • Mechanism of action: selectively binds to beta2 -adrenergic receptors in bronchial smooth muscle to cause bronchodilation • Primary use: for the termination of acute bronchospasm • Adverse effects: headaches, throat irritation, nervousness, restlessness, tachycardia, chest pain, allergic reactions

Anti-Inflammatory Agents—Corticosteroids

• Prototype drug: beclomethasone (Q V A R) • Mechanism of action: acts by reducing inflammation • Primary use: to decrease frequency of asthma attacks -Also for allergic rhinitis -Should not be used to terminate asthma attacks in progress • Adverse effects: oropharyngeal candidiasis

Bronchodilators—Anticholinergic

• Prototype drug: ipratropium (Atrovent) • Mechanism of action: causes bronchodilation by blocking cholinergic receptors in bronchial smooth muscle • Primary use: relief of acute bronchospasm -Sometimes combined with beta-agonists or glucocorticoids -Also prescribed for chronic bronchitis and for symptomatic relief of nasal congestion • Adverse effects: cough, drying of nasal mucosa, hoarseness, bitter taste

Aerosol Therapy

• Suspension of droplets or particles in a gas • Onset of action almost immediate • Drugs administered for local effect -Immediate relief of bronchospasm -Loosens thick mucus • Side effects are reduced; systemic effects can still occur

Lower Respiratory Tract

• The respiratory tree ends in dilated sacs called alveoli • Gases move between blood and inspired air • A semipermeable membrane allows: -Oxygen to enter the blood -Carbon dioxide and cellular waste products to leave the lungs