COPD Medications. Mechanism Of Action Indication(s) Common Side Effects Comments
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1 Short-Acting Beta-2 Agonists (SABAs) Levalbuterol (Xopenex) Albuterol sulfate (ProAir; Ventolin; Proventil) Beta-2 agonists relax bronchial smooth muscle by stimulating beta-2 adrenergic receptors which increases camp and produces functional antagonism to bronchoconstriction. Long-Acting Beta-2 Agonists (LABAs) Treatment or prevention of bronchospasm in patients with reversible obstructive airway disease Decreased serum potassium, tremor, rhinitis, headache, nervousness, Tachycardia, excitement, Decreased serum potassium, tremor, headache, nervousness, -Little effect on heart rate Formoterol (Foradil; Performist) Arformoterol (Brovana) Indacaterol (Arcapta Neohaler) Salmerterol (Serevent Diskus) Beta-2 agonists relax bronchial smooth muscle by stimulating beta-2 adrenergic receptors which increases camp and produces functional antagonism to bronchoconstriction. bronchoconstriction in patients with COPD (including chronic Tachycardia, excitement, Decreased serum potassium, tremor, headache, nervousness -BBW for asthma-related death -Patients using SABAs should be instructed to discontinue routine use of these medications prior to beginning treatment with a LABA -Do not use for acute episodes of COPD. -Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Short-Acting Anticholinergics (SAMAs) Ipratropium bromide (Atrovent) Produce bronchodilation via competitive inhibition of cholinergic receptors in bronchial smooth muscles and thus blocking the bronchoconstrictor action bronchospasm in patients with COPD (including chronic Bronchitis, COPD exacerbation, sinusitis, UTI, back pain, dyspnea, cough, flu-like symptoms, URI, xerostomia -Use caution in patients with narrow-angle glaucoma, myasthenia gravis, and prostatic hyperplasia -Not indicated for the initial treatment of acute episodes of
2 of vagal efferent impulses. Inhibition of vagal tone results in dilation of the large central airways and small airways Long-Acting Anticholinergics (LAMAs) Aclidinium bromide (Tudorza Pressair) Tiotropium (Spiriva HandiHaler; Spiriva Respimat) Produce bronchodilation via competitive inhibition of cholinergic receptors in bronchial smooth muscles and thus blocking the bronchoconstrictor action of vagal efferent impulses. Inhibition of vagal tone results in dilation of the large central airways and small airways bronchospasm associated with COPD (including Combination Short-Acting Beta-2 Agonist Plus Anticholinergic Albuterol/Ipratropium (Combivent Respimat; Duoneb) See individual mechanisms of action for short-acting Beta-2 agonists and shortacting anticholinergics Treatment of COPD in patients who are on a bronchodilator but continue to have bronchospasms and require a second bronchodilator Headache, nasopharyngitis, cough, diarrhea Xerostomia, URTI, pharyngitis, sinusitis, chest pain, edema, headache, abdominal pain, dyspepsia, constipation, UTI, rhinitis Bronchitis, URTI, Headache, Lung disease, dyspnea, cough bronchospasm -Use caution in patients with narrow-angle glaucoma, myasthenia gravis, and prostatic hyperplasia -Not indicated for the initial treatment of acute episodes of bronchospasm -Not indicated for the initial treatment of acute episodes of bronchospasm -Do not use in patients with allergies to soy or peanut products (All trimesters) -Excessive use may result in tolerance.
3 Combination Long-Acting Beta-2 Agonist Plus Anticholinergic Vilanterol/Umeclidinium (Anoro Ellipta) Methylxanthines Aminophylline Theophylline (SR) (Theo-24) See individual mechanisms of action for long-acting Beta-2 agonists and longacting anticholinergics Relax bronchial smooth muscle and pulmonary blood vessels, stimulate central respiratory drive, and increase diaphragm contractility. airflow obstruction in patients with COPD (including chronic Treatment of symptoms and reversible airway obstruction due to chronic asthma, or other chronic lung diseases Diarrhea, limb pain, pharyingitis, pleuritic pain, sinusitis, UTI, vertigo, headache, arthralgia, nausea, toothache, abdominal pain Diarrhea, nausea, vomiting, dizziness, headache, insomnia, tremor, irritability, restlessness, diuresis, difficulty urinating Diarrhea, nausea, vomiting, dizziness, headache, insomnia, tremor, irritability, restlessness, diuresis, difficulty urinating -BBW for asthma-related death -Contraindicated in patients with severe hypersensitivity to milk proteins. -Paradoxical bronchospasm may occur -A dose-dependent increase in heart rate was reported in healthy subjects; use with caution in patients with cardiovascular disorders. -Not recommended for acute symptom relief (All trimesters) -Only available as IV solution -Aminophylline is approximately 79% anhydrous theophylline by weight -Children under 1 year of age and elderly over 60 years of age have reduced theophylline clearance and increased risk of severe and potentially fatal theophylline toxicity -Theophylline-induced nonconvulsive status epilepticus has been reported (rarely) and should be considered in patients who develop CNS abnormalities. -Elderly patients have reduced theophylline clearance and have an increased risk of
4 Inhaled Corticosteroids (ICSs) Beclomethasone (Qvar) Budesonide (Pulmicort Flexhaler) Fluticasone (Flovent) Improve lung function by acting on multiple cell types and mediators involved in inflammation and airflow obstruction. Off Label: Long term treatment with inhaled corticosteroids added to long-acting bronchodilators is recommended for patients with severe and very severe COPD and frequent exacerbations that are not adequately controlled by long-acting bronchodilators. Long-term monotherapy with inhaled corticosteroids is not recommended. Combination Long-Acting Beta-2 Agonist Plus Corticosteroids Headache, URTI, pharyngitis, rhinitis Headache, dyspepsia, nausea, arthralgia, weakness, back pain, nasopharyngitis, cough, rhinitis, fever -Fatigue, malaise, headache, oral candidiasis, arthralgia, arthritis, musculoskeletal pain, sinus infection, sinusitis, URTI, throat irritation, nasal congestion, nasopharyngitis, rhinitis, bronchitis, pain, voice disorder, nausea and vomiting, influenza, cough, hoarseness toxicity or overdose. -Bronchospasm may occur with wheezing after inhalation (possibly fatal) -Prolonged use of corticosteroids may increase the incidence of secondary infection -Candida albicans infections may occur in the mouth and pharynx; rinsing with water after inhaler use may decrease risk -Rare cases of vasculitis or other systemic eosinophilic conditions can occur -Orally-inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients -Inhaled budesonide is pregnancy Category B Formoterol/Budesonide (Symbicort) Formoterol/Mometasone (Dulera) Salmeterol/Fluticasone (Advair) See individual mechanisms of action for long-acting Beta-2 agonists and corticosteroids airflow obstruction associated with COPD (including chronic Headache, nasopharyngitis, URTI, abdominal distress, oral candidiasis, pharyngolaryngeal pain, LRTI, sinusitis, bronchitis See individual comments on long-acting Beta-2 agonists and corticosteroids
5 Vilanterol/Fluticasone (Breo Ellipta) Generic Systemic Corticosteroids Prednisone (PredniSONE Intensol; Rayos) Methylprednisone (Medrol; Solu-Medrol) Improve lung function by acting on multiple cell types and mediators involved in inflammation and airflow obstruction. Off-Label use only: Systemic corticosteroids given for acute exacerbation of COPD are effective and recommended in the management of this condition. Hypertension, emotional instability, headache, increased intracranial pressure, seizure, impaired wound healing, carbohydrate intolerance, Cushing s syndrome, diabetes mellitus, fluid retention, menstrual irregularities, potassium loss, sodium retention, peptic ulcer, tachycardia, arrhythmias, cardiomegaly, abnormal fat distribution, immune suppression, psychiatric disturbances -Adrenal suppression; especially at high doses for prolonged periods -Prolonged use associated with Kaposi s sarcoma -Acute myopathy has been reported with high dose corticosteroids -Prolonged use may cause cataracts or glaucoma -High doses/long-term use has been associated with increased bone loss and fractures -May affect growth velocity; growth, so use should be routinely monitored in pediatric patients -Pregnancy Category C (methylprednisolone) -Pregnancy category D (prednisone) Phosphodiesterase-4 (PDE4) Inhibitors Roflumilast (Daliresp) Roflumilast and its metabolite selectively inhibit PDE4 leading to an accumulation of camp within inflammatory and structural cells important in the pathogenesis of COPD, To reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic a history of exacerbations Headache, weight loss, diarrhea, nausea, influenza, back pain -Contraindicated in moderate to severe hepatic impairment -Systemic exposure may be increased in patients with mild hepatic impairment -Supraventricular arrhythmias including atrial fibrillation have
6 suppress cytokine release and inhibition of lung infiltration by neutrophils and other leukocytes, attenuate pulmonary remodeling and mucociliary malfunction been reported -Weight loss usually observed within 6 months of initiating therapy and diarrhea within 4 weeks -Use only as adjunctive therapy to bronchodilator therapy Antibiotics Aminopenicillins Amoxicillin/Clavulunate (Augmentin) Macrolides (Azithromycin) Doxycycline Inhibits bacterial cell wall synthesis by binding to one or more of the penicillinbinding proteins (PBPs) Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin. Inhibits RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation. Inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane. Treatment of COPD exacerbations in patients with 3 cardinal symptoms - increase in dyspnea, sputum volume, and sputum purulence (Evidence B); patients with 2 cardinal symptoms if increased sputum purulence is one (Evidence C); patients who require mechanical ventilation (Evidence B) Diarrhea, nausea, rash, urticaria Diarrhea, nausea, pruritis, rash, abdominal pain, vomiting Nausea, vomiting, abdominal cramps, hepatotoxicity, intracranial hypertension, photosensitivity -Hypersensitivity reactions - Use with caution in patients with renal impairment; dosage adjustment recommended -Pregnancy category B - Macrolides (especially erythromycin) have been associated with rare QT c prolongation and ventricular arrhythmias - Use with caution in patients with severe renal impairment -Pregnancy category B - May induce hyperpigmentation in many organs, including nails, bone, skin -Pregnancy category D
7 References: 1. Lexicomp [internet database]. Hudson, OH: Wolters Kluwer. Updated Periodically. Accessed 28 Apr Micromedex 2.0 Healthcare Series [internet database]. Greenwood Village, CO: Truven Health Analytics, Inc. Updated Periodically. Accessed 24 Apr Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (Updated 2014). Global Initiative for Chronic Obstructive Lung Disease, Inc. Updated 2014.
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