Asthma COPD Allergic Rhinitis Cough Colds Asthma n

Asthma, COPD, Allergic Rhinitis Cough, Colds

Asthma n n Chronic, obstructive airway disease Causes: • Reversible hyperreactivity of bronchi & bronchioles • Bronchoconstriction • Vasodilation • Edema • Mucous production • Progressive airway remodeling over time

Asthma symptoms n n n Cough, including at night Wheezing Chest tightness Shortness of breath Mucus plugging

Pathophysiology n n Allergens bind to Ig. E antibodies on mast cells Mast cells release inflammatory mediators (e. g. , histamines, leukotrienes, prostaglandins) Mediators cause inflammatory cells (e. g. , eosinophils, leukocytes) to infiltrate airway walls, releasing more inflammatory mediators End result: airway inflammation and edema, increased mucus, smooth muscle hypertrophy, bronchospasm, “ramped up” airway hyperreactivity

Cromolyn Anti. Cholinergic Anti Ig. E Leukotriene modifiers Beta 2 agonists Glucocorticoids Methylxanthines

Asthma Treatment Expert Panel Report 3 (EPR-3) 4 Components: n Assessment & Monitoring n Education n Control of environmental factors n Medications http: //www. nhlbi. nih. gov/guidelines/asthma/asthgdln. pdf

COPD n Chronic bronchitis – excessive mucous secretion in the bronchial tree • cough, sputum, & airflow obstruction • involves bronchospasm n Emphysema – distended, hyperinflated, less elastic alveoli • Air trapping

Global strategy for diagnosis, management, & Treatment of Obstructive Lung Disease (GOLD Criteria) n Stage n Based on FEV 1, determines Tx n n n 1 2 3 4 – – Mild Moderate Severe Very severe

Treatment: Control Symptoms COPD Treatments… n do not reduce mortality n do reduce symptoms and improve Qo. L

Medications – Asthma & COPD n n Address BOTH bronchoconstriction & inflammation Bronchodilators • beta 2 agonists • methylxanthines • anticholinergics n Anti-inflammatory • glucocorticoids (steroids) • cromolyn • leukotriene modifiers • Ig. E blockers

Quick relief vs Long-Term Quick n Short acting beta agonist (SABA) Long-term n n Anticholinergics IV & oral glucocorticoids n n Long acting beta agonists (LABA) Methylxanthines Inhaled GCs Cromolyn Anti-Ig. E Leukitriene modifiers

Medication Routes Route Medication Inhaled MDI – aerosol MDI - powder Nebulizer Beta-2 agonists (short & long acting) Anticholinergics Glucocorticoids Oral Methylxantines Leukotriene modulators Injection Glucocorticoids Beta-2 agonists

Inhalation Drug Therapy n Three obvious advantages • Therapeutic effects are enhanced • Systemic effects are minimized • Relief of acute attacks is rapid (SABA) n Three types • Metered-dose inhalers (MDIs) • Dry-powder inhalers (DPIs) • Nebulizers

Factors affecting adherence n n n Frequency of administration Difficulty of administration Side effects Cost / coverage for drug Perceived benefit of drug

Factors affecting efficacy n Inhaled medications: • Particle size • Specific equipment use • Delivery technique

Types of inhalation devices • metered-dose inhalers (MDIs) • dry-powder inhalers (DPIs) • nebulizers

Use of a Spacer

Bronchodilators for asthma: beta 2 -adrenergic agonists n n n Sympathomimetic drugs: activate beta 2 adrenergic receptors • Located where? • What effect? Inhaled and oral Inhaled: • nebulized, MDI, or dry powder • can be used as “rescue meds” or for prevention/control

Bronchodilators for asthma n Beta 2 -adrenergic agonists • inhaled, short-acting (SABA) n albuterol, bitolterol, levalbuterol, pirbuterol • inhaled, long acting (LABA) n salmeterol, formoterol • Oral, long acting n albuterol, terbutaline

Bronchodilators for asthma: Anticholinergics n Ipratropium (Atrovent) • promotes bronchodilation by blocking cholinergic receptors in airways smooth muscle relaxation • additive effects when used with beta 2 -agonists • MDI or nebulizer • Indications: COPD, (asthma) n Tiotropium (Spiriva) • Long-acting anticholinergic • Recently approved for use in COPD • Advantages over ipratripium

Bronchodilators for asthma: Methylxanthines n n Theophylline • Highly variable oral absorption • Multiple drug interactions • Toxicity can be fatal • Plasma levels must be monitored • Sustained release preparations preferred Aminophylline • Preferred form for IV use • Loading dose; slow infusion • Rectal preparations also available

Anti-inflammatory Drugs n Glucocorticoids • inhaled, IV, and oral • decrease inflammation, airway edema, mucus production • increase responsiveness to beta 2 agonists • chronic inhaled: first-line therapy for moderate to severe asthma n maintain control, NOT abort acute attacks

Inhaled Glucocorticoids: drugs and doses n n n Inhaled-MDI or dry-powder • beclomethasone, budesonide, flunisolide, fluticasone, triamcinolone Usual dose: 1 -2 puffs 2 -4 times per day MDIs-use a spacer All types - rinse mouth after use Possible SE: adrenal suppression, bone loss When used together which is first glucocorticoid or bronchodilator?

Systemic glucocorticoids for asthma n Oral: prednisone or prednisolone • Short-term therapy for acute exacerbations; chronic use if unable to control symptoms otherwise • Goal: once daily or QOD dosing, early afternoon n Consider Ig. E blockers if remains poorly controlled n IV: for acute attack needing emergency care, admission

Systemic glucocorticoids for asthma n n Systemic steroids (IV or oral) used in high-dose, short-term “pulses” to control acute exacerbations What are the adverse effects of chronic systemic steroid use?

Anti-inflammatory drugs for asthma n Cromolyn • stabilizes mast cells reduced release of mediators • inhibits proliferation of inflammatory cells • nebulized or MDI • first line drug for control of asthma n NOT effective in acute attacks

Anti-inflammatory drugs for asthma: Leukotriene Modifiers n n n Decrease eosinophil infiltration, mucus production, airway edema, bronchoconstriction Oral administration Prophylaxis/maintenance Zileuton (Zyflo), Zafirlukast (Accolate), Montelukast (Singulair) Singulair may be preferred because. .

Anti-inflammatory drugs for asthma: Ig. E Blockers n Omalizumab—Xolair Binds circulating Ig. E Inhibits binding of Ig. E to mast cells, preventing release of inflammatory mediators Down-regulates mast cell receptors for Ig. E n Drawbacks to use. . . n n n

Asthma Guidelines – EPR-3 Pattern Treatment Mild intermittent SABA PRN Mild persistent Low dose inhaled GC & SABA PRN Moderate persistent Inhaled GC and LABA OR inhaled GC and leukotriene modifier/methylxanthine SABA PRN Severe persistent Medium to high dose inhaled GC with LABA plus other meds (leukotriene modifier/methylxanthine/anti-Ig. E) May need short course oral GC SABA PRN

GOLD GUIDELINES CATEGORY SYMPTOMS THERAPY A (mild/ moderate) Less Short-acting bronchodilator - SABA - Anticholinergic B (mild/ moderate) More Add to short acting - LABA or - Anticholinergic C (severe/ very severe) Less Inhaled GC + LABA or Long acting anticholinergic D (severe/ very severe) More Inhaled GC + LABA and/or Long acting anticholinergic

Management of asthma: Acute exacerbation n n Inhaled beta 2 agonists for acute relief of bronchospasm (MDI with spacer or nebulized solution) IV or oral steroid therapy Supplemental oxygen to keep O 2 sats > 95% SQ epinephrine if unable to use inhaled May require hospitalization

Allergic Rhinitis, Cough and Colds n n n Allergic rhinitis-inflammation of the nasal mucosa in response to allergens Seasonal or perennial Sneezing, runny nose, itching, nasal congestion due to release of histamine and inflammatory mediators

Drugs used to treat allergic rhinitis Antihistamines • Oral; intranasal Intranasal glucocorticoids Intranasal cromolyn Sympathomimetics (decongestants) • Oral; topical Anticholinergics Subcutaneous omalizumab

Antihistamines (H 1 antagonist)* Therapeutic uses n Relieve allergic reactions n Motion sickness (Dramamine) n Sleep aid n Common cold (for anticholinergic effects) *H 2 antagonists – reduce stomach acid (famotidine, ranitidine)

Antihistamines – Side effects n n Sedation Paradoxical stimulation (esp. in young & old) GI symptoms (N/V/D or constipation) Anticholinergic • Dry mouth • Palpitations • Urinary retention • Confusion

Antihistamine meds n n First generation • Diphenhydramine (Benedryl), chlorpheniramine (Chlor Trimeton), doxylamine (Unisom) Second generation • fexofenadine (Allegra), cetirizine (Zyrtec), loratidine (Claritin) • “non-sedating” (don’t cross BBB well) • Some differences in metabolism & excretion n Nasal spray: azelastine (Astelin)

Intranasal glucocorticoids n Also first line therapy; most effective drugs for prevention & treatment of allergic rhinitis n Beneficial effects take 2 to 3 weeks n Pre-treat with nasal decongestant n n SE: nasal dryness, burning; potential for systemic absorption Dose: start with full dose then reduce when symptoms are under control

Intranasal Cromolyn n n Less effective than intranasal glucocorticoids Takes 2 – 3 weeks to establish benefit Continue use even if symptom-free Pre-treat with decongestant Dose: one spray 3 to 6 times daily

Decongestants n n n Sympathomimetics: • stimulate alpha 1 receptors on blood vessels in nose resulting in. . Only relieve stuffiness; not helpful for allergy symptoms Oral agents: • e. g. Sudafed, Neo-synephrine • CNS stimulation; abuse potential Topical: Afrin – rebound congestion Avoid phenylpropanolamine

Combination therapies to treat allergic rhinitis n Combination therapies are useful – antihistamines & sympathomimetics n Examples - Allegra-D; Claritin-D n Can also use: • Anticholinergic • Leukotrine modifiers • Omalizumab

Drugs for Cough n Antitussives • opioid • non-opioid n n Dextromethorphan Expectorants • guaifenesin n Mucolytics • mucomyst

Cold Remedies n n n Acute upper respiratory viral infection Multiple symptoms Multiple cold remedies--usually combination preparations. • choose a preparation that covers only the symptoms that need to be addressed • avoid phenylpropanolamine