Respiratory Disorders and Asthma

Respiratory Disorders

• Asthma is a chronic condition involving hyperreactive airways that lead to episodic obstruction
• Asthma is often underdiagnosed and undertreated
• COPD (Chronic Obstructive Pulmonary Disease) is a chronic and progressive airflow obstruction, and is eventually fatal
• Allergic Rhinitis is a chronic condition characterized by red, itchy, watery eyes, a runny nose, and a non-productive cough

Pathophysiology of Asthma

• Asthma involves airflow obstruction due to bronchoconstriction
• Contraction of bronchial smooth muscle and inflammation of the bronchial wall contributes to asthma
• Increased mucus production is a part of asthma pathophysiology
• Underlying inflammation leads to airway hyperresponsiveness and airflow limitation
• Respiratory symptoms are a consequence of these factors
• Asthma is a chronic condition
• Triggers can stimulate asthma attacks

Drugs Used to Treat Asthma - Goals of Therapy

• Reverse and prevent airway inflammation
• Decrease the frequency and intensity of asthma symptoms
• Prevent exacerbations
• Minimize limitations in activity for asthma patients

Drugs Used to Treat Asthma - Beta Agonists (Quick Relief)

• Short Acting Beta-2 Agonists are used for quick relief
• Onset of action: 5-30 minutes, Duration: 4-6 hours
• Used for symptomatic treatment of bronchospasm
• Monotherapy is used for mild or intermittent asthma, or exercise-induced bronchospasm
• Can be used as an adjunct in moderate persistent and severe persistent cases
• Adverse effects (ADEs) are limited with direct inhalation delivery
• Examples include Albuterol & Levalbuterol

Drugs Used to Treat Asthma - Beta Agonists (Long-Term Control)

• Long Acting Beta-2 Agonists are used for long-term control
• They offer prolonged bronchodilation for at least 12 hours
• Used as an adjunct to Inhaled Corticosteroids (ICS) in moderate and severe asthma
• Monotherapy using LABAs is contraindicated in asthma
• Examples include Salmeterol and Formoterol

Drugs Used to Treat Asthma - Corticosteroids

• Corticosteroids are the Drug of Choice (DOC) for long-term control of persistent asthma
• Mechanism of Action (MOA): inhibit phospholipase A2 to decrease the release of arachidonic acid
• Decreases inflammatory cascade
• Reduced hyperresponsiveness of airway smooth muscle
• Examples include Beclomethasone, Budesonide, Fluticasone, and Mometasone

Drugs Used to Treat Asthma - Corticosteroids Routes

• Inhalation reduces systemic ADEs
• Inhalation includes Beclomethasone, Budesonide, Fluticasone, Mometasone
• Inhalation technique is important
• Oral/systemic corticosteroids (Prednisone, Methylprednisolone) are used in severe exacerbations

Drugs Used to Treat Asthma - Corticosteroids ADEs

• With Inhaled Corticosteroids (ICS): Oropharyngeal candidiasis and hoarseness
• Systemic ADEs: Osteoporosis, hyperglycemia, hypokalemia, hypertension, peripheral edema, immunosuppression, increased appetite

Drugs Used to Treat Asthma - Leukotriene Modifiers

• Examples include Zileuton, Zafirlukast, and Montelukast
• They inhibit the production (Zileuton) or action (Zafirlukast, Montelukast) of Leukotrienes
• Result: Decreased inflammation, arteriolar constriction, and mucus production
• Use: Generally 2nd line
• Prevention of asthma symptoms
• Prevention of exercise-induced asthma
• ADEs: Increased liver enzymes, headache, and dyspepsia

Drugs Used to Treat Asthma - Cromolyn

• Cromolyn inhibits mast cell degranulation and histamine release
• Alternative for Mild Persistent Asthma
• Short Duration Of Action (DOA) limits use

Drugs Used to Treat Asthma - Cholinergic Antagonists

• Cholinergic Antagonists inhibit vagal effects on the airways
• Short Acting (Ipratropium) has a slower onset than Short Acting Beta Agonists (SABA)
• Used in Asthma-COPD Overlap Syndrome, with SABA in ER, and when SABA is not tolerated
• Long Acting (Tiotropium) is an Add-on in adults with severe asthma with a history of exacerbations
• ADEs: Xerostomia, bitter taste

Drugs Used to Treat Asthma - Theophylline

• Theophylline is a bronchodilator for chronic asthma
• Replaced by beta-2 agonists and ICS: Narrow Therapeutic Index (TI), requires drug level monitoring, poor ADE profile, numerous drug interactions

Drugs Used to Treat Asthma - Monoclonal Antibodies

• Used in severe persistent asthma poorly controlled on conventional therapy
• Omalizumab: Binds to and inhibits IgE
• Mepolizumab, Benralizumab, Reslizumab: Interleukin-5 antagonists
• Use is limited by cost, route of administration, and adverse effects (ADEs)

Pathophysiology of COPD

• COPD is chronic, irreversible obstruction of airflow
• It is a progressive disease characterized by persistent symptoms
• Treatment involves smoking cessation
• Pharmacologic therapy to relieve symptoms and slow progression, addressing cough, excess mucus production, chest tightness, breathlessness, difficulty sleeping, and fatigue

Drugs Used to Treat COPD - Bronchodilators

• Long Acting Bronchodilators are preferred first-line treatment for COPD
• LABA: Indacaterol, Olodaterol, Vilanterol (once daily) & Aformoterol, Formoterol, Salmeterol (twice daily)
• LAMA: Aclidinium, Tiotropium, Glycopyrrolate, Umeclidinium
• Short-acting bronchodilators okay for patients at low risk with fewer symptoms
• A combination of LABA and LAMA is recommended in high-risk patients with more symptoms
• May be used if an inadequate response to one agent alone

Drugs Used to Treat COPD - Corticosteroids

• ICS is only recommended in select situations
• Can be added to a long-acting bronchodilator if FEV1 < 60% predicted
• Can only be added to a long-acting bronchodilator if symptoms of both asthma and COPD
• Oral corticosteroids are only for acute exacerbations

Inhaler Technique

• Inhaler technique is critical and should be assessed regularly
• Metered Dose Inhaler (MDI): Have propellants that eject the medication from the canister
• Exhale first
• Begin to inhale as you press the canister
• Continue inhaling throughout actuation
• Dry Powder Inhaler (DPI) requires a puncture capsule
• Inhale quickly and deeply to deposit the drug in the lungs
• Rinse mouth after any inhaled steroid
• Spacers involve a large canister that attaches to an MDI
• Allows large drug particles to "drop out" in the canister; only smaller, aerosolized particles make it to the lungs
• Minimizes the amount of drug deposited in the mouth and pharynx
• Simplifies technique
• Masks can be attached to a spacer to allow for easy delivery to young children

Pathophysiology of Allergic Rhinitis

• Inflammation of the mucous membranes of the nose is typically caused by inhalation of an allergen
• Common allergens: Dust, Pollen, Animal dander
• The allergen interacts with mast cells coated with IgE, causing the release of pro-inflammatory mediators
• Including Histamine and Leukotrienes
• Symptoms: Sneezing, itchy nose and eyes, watery rhinorrhea, nasal congestion, non-productive cough

Drugs Used to Treat Allergic Rhinitis

• Antihistamines block H1 receptors to manage symptoms caused by histamine release
• rapid onset of action to treat symptoms
• most effective at preventing symptoms of mild or intermittent disease
• First-generation antihistamines cause sedation & anticholinergic ADEs
• Second-generation agents are preferred
• Delivery can be oral, intranasal, or ophthalmic

Drugs Used to Treat Allergic Rhinitis - Intranasal Corticosteroids

• Are the most effective agents for Allergic Rhinitis (AR)
• Symptom improvement occurs 3-36 hours after the first dose
• Targets sneezing, itching, rhinorrhea, and congestion
• ADEs are localized
• Avoid deep breathing while administering
• Examples include Beclomethasone, Budesonide, Fluticasone, Mometasone, and Triamcinolone

Drugs Used to Treat Allergic Rhinitis - Decongestants

• Alpha Agonists cause arteriole constriction in the nasal mucosa
• Intranasal: Phenylephrine, Oxymetazoline
• rapid onset of action
• limited to 3 days of use
• Oral: Pseudoephedrine
• longer duration of action
• increased systemic side effects
• is not recommended for long-term treatment of allergic rhinitis

Cough

• Cough due to an underlying infection should not be inhibited if possible
• Before treating a cough, identify its cause and treat the cause when possible
• Opioids include Codeine:
• decreases sensitivity of cough centers in the Central Nervous System (CNS)
• with addictive potential and poor ADE profile
• Dextromethorphan is a synthetic derivative of morphine with the same antitussive effects but a better ADE profile
• Benzonatate suppresses the cough reflex peripherally
• Do not break capsules
• ADEs include dizziness and numbness of tongue/mouth/throat