Asthma and COPD Drugs Overview

• Asthma and COPD drugs overview

Asthma Statistics (2022)

• 1 in 11 children (4.9 million) had asthma.
• 1 in 12 adults (23 million) had asthma.
• Morbidity/Mortality:
  • Predicted indirect cost over 20 years: $900 billion (includes missed days and medical costs).
  • About 10 people die from asthma daily.
  • Lower respiratory diseases are the third leading cause of death in the U.S.

Pathophysiology of Asthma

• Characteristic signs and symptoms: breathlessness, chest tightness, wheezing, dyspnea, cough.
• Treatment goals: Reduce impairment (decrease symptoms to maintain normal pulmonary function) and reduce risk (prevent recurrent exacerbations).
• Management of Chronic Asthma:
  • Non-pharm measures: Reduce exposure to allergens and triggers like house dust mites, pets, tobacco smoke, and household sprays.

Chronic Obstructive Pulmonary Disease (COPD)

• Definition: Irreversible, progressive disorder mainly from smoking and air pollution.
• Characteristics: airflow restriction & inflammation.
• 150,000 people die each year
• Two pathologic processes:
  • Chronic bronchitis: chronic cough and excessive sputum production due to hypertrophy of mucus-secreting glands.
  • Emphysema: enlargement of air spaces within bronchioles and alveoli caused by deterioration of the walls.
• Characteristic signs and symptoms: chronic cough, excessive sputum production, wheezing, dyspnea, poor exercise tolerance.
• Treatment goals: Reduce symptoms and risks, improve health status and exercise tolerance, prevent disease progression and exacerbations.

Pharmacologic Treatment: Reactive Airway Disease

• Anti-inflammatory agents: Glucocorticoids.
• Bronchodilators: Beta2 agonists.

Anti-Inflammatory Drugs: Glucocorticoids

• Prototypes: Beclomethasone [Qvar] (inhaled) and Prednisone/prednisolone (oral).
• MOA: Decrease synthesis and release of inflammatory mediators, reduce infiltration and activity of inflammatory cells.
• Therapeutic Use: Prophylaxis of chronic asthma and COPD, not used for ongoing attacks (effects develop slowly).

Anti-Inflammatory Drugs: Inhaled Glucocorticoids

• Prototype: Beclomethasone [Qvar]
• First-line therapy for managing inflammatory component of asthma and COPD and is generally used daily.
• Very effective and safer than systemic glucocorticoids.
• Advantages to inhalant administration: enhanced therapeutic effects, minimized systemic effects, rapid relief for acute attacks (for bronchodilators).
• Delivery devices: Metered-dose inhalers (MDIs), Respimats, Dry-powder inhalers (DPIs), Nebulizers.

Anti-Inflammatory Drugs: Inhaled Glucocorticoids - Adverse Effects

• Adverse effects: adrenal suppression, bone loss, oropharyngeal candidiasis and dysphonia.
• Minimize risk by rinsing and gargling after use and using a spacer.
• Slows growth in children but does not decrease overall adult height.

Anti-Inflammatory Drugs: Oral Glucocorticoids

• Use: Moderate to severe persistent asthma, management of acute exacerbations of asthma or COPD. Treatment should be as brief as possible.
• Adverse effects:
  • Short-term: few issues.
  • Long-term: adrenal suppression (most concerning), osteoporosis (most common).
• Suppression of intestinal calcium absorption and inhibition of bone formation, peptic ulcer disease, growth suppression in young patients.

Anti-Inflammatory Drugs: Glucocorticoids - Adrenal Suppression

• Adrenal suppression decreases the adrenal cortex's ability to produce endogenous glucocorticoids, which can be life-threatening during stress or trauma.
• Discontinuation or switching to inhaled glucocorticoids requires titration of oral dose.

Glucocorticoids: Nursing Implications

• Inhaled: For long-term suppression of inflammation. Teach proper device use. Minimize adverse effects by rinsing and gargling. Monitor risk of adrenal suppression and bone loss (Vitamin D/calcium, weight-bearing exercise).
• Oral: Short-term use only, no abrupt discontinuation. Additional glucocorticoids may be needed in times of stress or trauma. Monitor risk of adrenal suppression and bone loss (Vitamin D/calcium, baseline bone density).

Other Anti-inflammatory Agents

• Leukotriene modifiers (Montelukast).
• Mast cell stabilizers (cromolyn).

Anti-Inflammatory Drugs: Leukotriene Modifiers

• Second-line agents.
• Suppress effects of leukotrienes.
• Generally well tolerated.
• Daily oral administration.
• Prototype: Montelukast [Singulair].

Anti-Inflammatory Drugs: Leukotriene Modifiers - Montelukast [Singulair]

• MOA: Blocks receptor activation by leukotrienes, suppressing inflammatory response and smooth muscle constriction.
• Therapeutic indication: treatment and prophylaxis of asthma and COPD, exercise-induced bronchospasm, allergic rhinitis, but is not used for quick relief.
• Adverse effects (post-marketing): depression, mood changes, suicidality (rare).

Anti-Inflammatory Drugs: Mast Cell Stabilizers

• Prototype: cromolyn sodium [Cromolyn].
• MOA: Stabilizes mast cell membranes, preventing release of histamine and other mediators to suppress inflammation.
• Therapeutic use (prophylaxis): Second-line choice for chronic asthma, exercise-induced bronchospasm, allergic rhinitis.

Anti-Inflammatory Drugs: Cromolyn

• Route: Inhalation via metered-dose inhaler or nebulizer.
• Adverse effects: Safest of all antiasthma medications but not as effective as glucocorticoids; may cause cough or bronchospasm.

Nursing Implications: Cromolyn

• Patient education: drug is for acute and long-term prophylaxis of asthma, education on nebulizer use.
• Administer 15 minutes prior to exercise for EIB.
• Several weeks for therapeutic effect to develop if using for long-term prophylaxis

Bronchodilators

• Provide symptomatic relief but do not alter the underlying disease process (inflammation).
• Conjunctive therapy with a glucocorticoid for long-term suppression of inflammation.

Bronchodilators: Beta2-Adrenergic Agonists

• Principal bronchodilators.
• MOA: Activation of beta2 receptors in the smooth muscle of the lung to promote bronchodilation.
• Beta2 receptors locations: Lungs, heart, smooth muscle vasculature, uterus, liver, kidneys.
• Normally activated by epinephrine.

Bronchodilators: Beta2-Adrenergic Agonists - Types

• Types:
  • Short-acting beta2 agonists (SABAs): Immediate effects lasting 30-60 minutes.
  • Long-acting beta2 agonists (LABAs): Prolonged effect over 12 hours.
  • Oral agents/systemic: All are long acting and used for prophylaxis, not ongoing attacks.

Bronchodilators: Short-acting beta2 agonists (SABAs)

• Prototype: Albuterol [Proventil].
• “Rescue inhalers” for PRN use.
• MOA: Mimics catecholamines to activate beta2 receptors, promoting bronchodilation.
• Indications/administration: Acute/ongoing attack, EIB (prior to exercise), acute attack (nebulizer most effective).

Bronchodilators: Short-acting beta2 agonists (SABAs) - Adverse Drug Reactions

• ADRs (generally systemic): Tachycardia, angina, tremor.
• Excess use may cause: Tachycardia, angina, seizures, cardiac arrest death.
• If a patient is using a SABA more than twice weekly, asthma is not well managed.

Bronchodilators: Long-acting beta2 agonists (LABAs)

• Prototype: Salmeterol [Serevent].
• Use in asthma and COPD: Long-term control in patients with frequent attacks.
• Dosing is on a fixed schedule.
• Preferred treatment in stable COPD.
• When used to treat asthma, must always be combined with a glucocorticoid
• Monotherapy is contraindicated in patients with asthma due to increased mortality; ok to use in COPD.

Bronchodilators: Beta2-Adrenergic Agonists - Adverse Effects

• Inhaled preparations: Can have systemic effects if used excessively (tachycardia, angina, tremor).
• Oral preparations (terbutaline, albuterol): Non-selectivity can cause activation of Beta 1 & 2 receptors causing angina (beta1), tachydysrhythmias (beta1), tremor (beta2), uterine relaxation (beta2).

Nursing Implications: Beta2-Adrenergic Agonists

• Patient education: Teach proper device use with emphasis on hand/breath coordination and 1 minute between doses.
• LABA is not for aborting an attack.
• Adverse effects: SABAs-minimal, LABAs (inhaled and oral)-increased risk of severe attack/death.
• Report symptoms of tachydysrhythmias and/or angina pain.

Bronchodilators: Methylxanthines

• Prototype: Theophylline
• MOA: Produces bronchodilation by relaxing smooth muscle of the bronchi.
• General characteristics: Prolonged effect compared with beta2 agonists.
• Oral theophylline is used for maintenance therapy of chronic stable asthma, IV available for emergency use.
• Theophylline is no longer recommended for treatment of COPD.
• Narrow therapeutic range and toxicity is dose-dependent.

Bronchodilators: Methylxanthines - Toxicity

• Therapeutic Plasma levels (< 20 mcg/mL): Adverse effects uncommon.
• Plasma levels = 20-25 mcg/mL: Nausea, vomiting, diarrhea, insomnia, restlessness.
• Plasma levels > 30 mcg/mL: Severe dysrhythmias and convulsions. Death may result from cardiorespiratory collapse.
• Toxicity treatment: Stop theophylline and use activated charcoal with a cathartic.

Bronchodilators: Methylxanthines - Interactions

• Methylxanthines are metabolized by the liver and rate is highly individualized.
• Caffeine competes with the same metabolic enzymes, increasing risk for toxicity.
• P450 Inducers (Tobacco and marijuana, second-hand smoke) reduce theophylline levels.
• P450 Inhibitors (Cimetidine [Tagamet], Fluoroquinolone antibiotics [Cipro]) raise theophylline levels.

Nursing Implications: Theophylline

• Use with caution in patients with heart disease, liver/kidney dysfunction, severe hypertension, or smokers.
• Patient Education:
  • Minimize adverse effects and educate about caffeine interactions, smoking and second-hand smoke
  • Regular screening of plasma levels

Anticholinergic Drugs: Ipratropium

• MOA: Blocks muscarinic receptors in the bronchi, thereby reducing bronchoconstriction.
• Therapeutic effects begin within 30 seconds and persist about 6 hours
• Action and use: Fast-acting and inhaled to relieve bronchospasm.
• Indications: FDA approved for COPD; off-label use for asthma.
• Adverse effects: Dry mouth and irritation of the pharynx.

Management of Acute Severe Exacerbation of Asthma

• Goals: Relieve airway obstruction and hypoxemia, and normalize lung function as quickly as possible.
• Initial therapy: Oxygen, a systemic glucocorticoid, a nebulized high-dose SABA, nebulized ipratropium.