eMedicine Specialties > Pulmonology > Obstructive Airways Diseases
Chronic Obstructive Pulmonary Disease: Treatment & Medication
Updated: Oct 26, 2009
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Treatment
Medical Care
The goal of chronic obstructive pulmonary disease (COPD) management is to improve daily living and the quality of life by preventing symptoms and the recurrence of exacerbations by preserving optimal lung function. Once the diagnosis of COPD is established, it is important to educate the patient about the disease and encourage them to actively participate in therapy.
Smoking cessation continues to be the most important therapeutic intervention. Most patients with COPD have a history of smoking or are currently smoking tobacco products. A smoking cessation plan is an essential part of a comprehensive management plan. The success rates are low because of the addictive power of nicotine, the conditioned response to smoking-associated stimuli, and psychological problems, including depression, poor education, and forceful promotional campaigns by the tobacco industry. The process of smoking cessation must involve multiple interventions.
Oral and inhaled medications are used for patients with stable disease to reduce dyspnea and improve exercise tolerance. Most of the medications used are directed at 4 potentially reversible causes of airflow limitation in a disease state that has largely fixed obstruction. The following factors may be present: (1) bronchial smooth muscle contraction, (2) bronchial mucosal congestion and edema, (3) airway inflammation, and (4) increased airway secretions.
Smoking cessation, physical intervention
The transition from smoking to not smoking occurs in 5 stages: precontemplation, contemplation, preparation, action, and maintenance. Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs.
Setting a quit date may be helpful. Physicians and other healthcare providers should participate in setting the target date and follow-up with respect to maintenance.
Successful cessation programs usually use the following resources and tools: patient education, a quit date, follow-up support, relapse prevention, advice for healthy lifestyle changes, social support systems, and adjuncts to treatment (eg, pharmacological agents). Mottillo et al reported meta-analysis results that conclude intensive behavioral intervention, including individual counseling and telephone counseling, among other, offers considerable benefit for increasing smoking abstinence.20
According to the US Preventive Services Task Force (USPSTF) guidelines, clinicians should ask all adults about use of tobacco products and provide cessation interventions to current users. The guideline engages a "5-A" approach to counseling that includes the following21 :
- Ask about tobacco use.
- Advise to quit through personalized messages.
- Assess willingness to quit.
- Assist with quitting.
- Arrange follow-up care and support.
Smoking cessation, pharmacologic intervention
Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs.
Nicotine is the ingredient in cigarettes primarily responsible for the addiction. Withdrawal from nicotine may cause unpleasant adverse effects, including anxiety, irritability, difficulty concentrating, anger, fatigue, drowsiness, depression, and sleep disruption. These effects usually occur during the first several weeks.
Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms. If a smoker requires his or her first cigarette within 30 minutes of waking up, they most likely are highly addicted and would benefit from nicotine replacement therapy.
Several nicotine replacement therapies are available. Nicotine polacrilex is a chewing gum and has better quit rates than counseling alone. Nicotine replacement therapy chewing pieces are marketed in 2 strengths (ie, 2 mg, 4 mg). An individual who smokes 1 pack per day should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke less than 1 pack per day. Instruct the patient to chew hourly and also to chew when needed for their initial cravings for 2 weeks. Gradually reduce the amount chewed over the next 3 months.
Transdermal nicotine patches are available readily for replacement therapy. Long-term success rates are 22-42%, compared with 2-25% with a placebo. These agents are well tolerated, and the adverse effects are limited to localized skin reaction. Nicotine replacement therapy patches are sold under the following trade names: NicoDerm, Nicotrol, and Habitrol. Each of these products is dosed with a scheduled graduated decrease in nicotine over 6-10 weeks.
The use of the antidepressant bupropion (Zyban) is also effective for smoking cessation. This nonnicotine aid to smoking cessation enhances central nervous nonadrenergic function. One study demonstrated that 23% of patients sustained cessation at 1 year, compared with 12% who sustained cessation with the placebo. Bupropion may also be effective in patients who not been able to quit smoking with nicotine replacement therapy.
The most recent drug to receive approval for smoking cessation is varenicline (Chantix). Varenicline is a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to result from activity at a nicotinic receptor subtype, where its binding produces agonist activity while simultaneously preventing nicotine binding. Agonistic activity is significantly lower than nicotine.
Bronchodilators
The use of bronchodilators is guided by some very important concepts. In some patients, the change in forced expiratory volume in 1 second (FEV1) may be small; however, benefit may be seen by some other mechanism, such as decreased hyperinflation (hence, lack of a bronchodilator response on pulmonary function testing should not preclude their use if clinically warranted). Furthermore, some patients may have difficulty achieving effective delivery of the medication using a metered-dose inhaler; hence, use of a spacer may be of benefit to the patient. Finally, inhaled delivery of medications is preferred over the oral route to help minimize potential adverse effects. Further, generally speaking, long-acting bronchodilators are more beneficial than short-acting ones.6,12,22
Beta-agonists
Inhaled beta2-agonist bronchodilators activate specific B2-adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cyclic adenosine monophosphate (AMP) and smooth muscle relaxation. Patients, even those who have no measurable increase in expiratory flow, may benefit from treatment using beta2 agonists.
In COPD, beta2 agonists produce less bronchodilatation compared with asthma. Patients primarily use beta2 agonists for relief of symptoms of COPD. In patients with mild intermittent symptoms, it is recommended to use a short-acting beta2 agonist for symptomatic relief. In patients with more persistent symptoms, a long-acting beta agonist should be used. Long-acting beta agonists have been shown to increase exercise endurance, prevent nocturnal dyspnea, and improve quality of life. See Staging for specific treatment recommendations.
Anticholinergic agents
Anticholinergic drugs compete with acetylcholine for postganglionic muscarinic receptors, thereby inhibiting cholinergically mediated bronchomotor tone, resulting in bronchodilatation. They block vagally mediated reflex arcs that cause bronchoconstriction. The clinical benefit is gained through a decrease in exercise-induced dynamic hyperinflation.
Short-acting anticholinergics such as ipratropium bromide in patients with stable COPD have been shown to have equivalent or superior activity when compared with a beta2 agonist. However, in combination with a beta2 agonist, synergistic effect on bronchodilatation occurs. This medication has slower onset and a longer duration than a beta2 agonist and is less suitable for use on an as-needed basis.
Typically, ipratropium bromide is administered 2-4 puffs every 6-8 hours. Tiotropium is a once-daily, long-acting anticholinergic medication that has been shown to have significant clinical benefit and is a first-line therapy in patients with persistent symptoms (see Staging). Although the results of the Understanding Potential Long Term Impacts on Function With Tiotropium trial (UPLIFT) did not show a change in the rate of decline of FEV1 or mortality when compared with placebo, it did show a significant reduction in frequency of COPD exacerbations and hospitalizations and an improvement in quality of life.23,24,25,26
Phosphodiesterase inhibitors
Methylxanthines (ie, theophylline) are nonspecific phosphodiesterase inhibitors that increase cyclic AMP within the airway smooth muscle of the airways. Additionally, they may improve diaphragm muscle contractility and stimulate the respiratory center.
Adding theophylline to the combination of bronchodilators can result in further benefit in stable COPD patients. However, the narrow therapeutic index of theophylline has caused a decline in its popularity. Patients metabolize theophylline primarily by the hepatic enzyme system, a process affected by age, the heart, and liver abnormalities. Serum levels of theophylline need to be monitored because of the potential for toxicity. Adverse effects include anxiety, tremors, insomnia, nausea, cardiac arrhythmia (particularly multifocal atrial tachycardia), and seizures. Hence, the previously recommended target range of 15-20 mg/dL has now been reduced to 8-13 mg/dL.
Second-generation specific phosphodiesterase IV inhibitors include cilomilast and roflumilast. They cause a reduction of the inflammatory process (macrophages and CD8+ lymphocytes) in patients with COPD. Cilomilast is completely absorbed following oral administration and its elimination half-life is approximately 6.5 hours. A dose of 15 mg twice daily has been found to be clinically effective. Nausea, presumably of central origin, is the principal adverse reaction. Preliminary clinical studies suggest a favorable clinical effect in COPD; however, these need to be confirmed in larger trials.
Roflumilast, a phosphodiesterase-4 inhibitor currently under investigation for use in the United States, exhibits anti-inflammatory effects, including reduced airway inflammation and improved lung function in patients with COPD. To analyze the impact of roflumilast on the incidence of COPD exacerbations requiring corticosteroids, Calverley et al performed 2 randomized, double-blind, placebo-controlled multicenter trials. Patients with COPD were randomly assigned to receive roflumilast or placebo for 52 weeks. Both studies revealed increased FEV1 in patients who received roflumilast compared with placebo (P <.0001). In addition, the rate of COPD exacerbations was reduced by 17% in patients who received roflumilast compared with placebo (P <.0003).27
Anti-inflammatory medications
Steroids
Corticosteroids are potent anti-inflammatory medications that affect the inflammatory cascade at multiple points. In the oral form, their primary role is for the treatment of exacerbations. The goal, however, is to wean from the steroid as soon as the patient can clinically tolerate it because of the concern for potential well-known systemic adverse effects. However, a small portion of patients may require long-term corticosteroid use to keep their symptoms under control. Note that oral steroids are not as effective in treating COPD exacerbations as they are for bronchial asthma exacerbations.
Inhaled corticosteroids provide a more direct route of administration to the airways. Consequently, aside from the development of thrush, the systemic adverse effects of these medications at standard doses are negligible. Although inhaled corticosteroids have not been shown to significantly reduce the rate of loss of lung function, in past studies they have been shown to reduce the frequency of exacerbations and slow the rate of loss of health-related quality of life. The Towards a Revolution in COPD Health (TORCH) trial, however, showed that a combination of an inhaled corticosteroid and a long-acting beta-agonist was more beneficial than inhaled corticosteroids alone.28 Additionally, those treated with inhaled corticosteroids were noted to have an increased rate of pneumonia. These data suggest that in patients with COPD, inhaled corticosteroids should only be used in conjunction with a long-acting beta-agonist.
Debate continues regarding use of inhaled corticosteroids and the risk for pneumonia in patients with COPD. Sin et al analyzed data from 7 large clinical trials (n = 7042) of patients with stable COPD who used inhaled budesonide (n = 3801) or a control regimen (placebo or formoterol alone). No significant difference was recorded for pneumonia occurrence between the budesonide group (3%; n = 122) and the control group (3%; n = 103). Increasing age and decreasing percent of predicted FEV1 were the only variables that were significantly associated with pneumonia occurrence.29
Nonsteroidal anti-inflammatory medications
Nonsteroidal anti-inflammatory medications have not been conclusively shown to have any benefit in COPD. Medications targeting interleukin 8 and tumor necrosis factor-alpha did not show any response. Leukotriene inhibitors commonly used in asthma have also not proven to be beneficial in COPD.
Macrolide antibiotics, however, have been shown to have anti-inflammatory effects in the airways of COPD patients. More specifically, azithromycin has been shown to improve phagocytic function of pulmonary macrophages and be a potent anti-inflammatory.16 Azithromycin is clinically used for its anti-inflammatory effects in patients with cystic fibrosis and in lung transplantation patients with chronic rejection. Furthermore, one study showed that erythromycin reduced the frequency of exacerbations in 109 patients with COPD treated over 12 months.30 These results, however, need to be validated in a larger study before such therapy can be recommended.
Antibiotics
In patients with COPD, chronic infection or colonization of the lower airways is common from Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In patients with chronic severe airways obstruction, Pseudomonas aeruginosa infection also may be prevalent.
Empiric antimicrobial therapy is recommended in patients with an acute exacerbation (as evidenced by an increase in baseline dyspnea and/or a change in the quantity or quality of cough) and evidence of an infectious process, such as fever, leukocytosis, or an infiltrate on chest radiograph. The antibiotic choice must be comprehensive and should cover all likely pathogens in the context of the clinical setting and local resistance patterns.1
Mucolytic agents
These agents reduce sputum viscosity and improve secretion clearance. Viscous lung secretions in patients with COPD consist of mucous-derived glycoproteins and leukocyte-derived DNA.
The oral agent N -acetylcysteine has antioxidant and mucokinetic properties and is used to treat patients with COPD. However, the efficacy of mucolytic agents in the treatment of COPD remains controversial, as they have also been shown to elicit bronchospasm.
Proton pump inhibitors
Sasaki et al conducted a randomized, observer-blind, controlled trial to determine if proton pump inhibitors (PPIs) reduce the incidence of common colds in patients with COPD. Patients (n = 100) were assigned to conventional therapy (control group) or conventional therapy plus PPI (lansoprazole 15 mg/d). The frequency of common colds and COPD exacerbations was measured, and the number of exacerbations per person over 12 months was significantly lower in the PPI group compared with the control group (P <.001). No significant difference in the numbers of common colds was observed between the PPI group and the control group. The authors concluded that although lansoprazole showed a significant decrease in COPD exacerbations, more definitive clinical trials are required.31
Oxygen therapy
COPD commonly is associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favorable effects on pulmonary hemodynamics.
Two landmark trials, the British Medical Research Counsel (MRC study) and the National Heart, Lung, Blood Institutes Nocturnal Oxygen Therapy Trial (NOTT), showed that long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD. Hypoxemia is defined as PaO2 of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used from 15-19 h/d.
Specialists recommend long-term oxygen therapy, therefore, for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythemia, or cor pulmonale. Reevaluate these patients 1-3 months after initiating therapy because some patients may not require long-term oxygen.
Many patients with COPD who are not hypoxemic at rest worsen during exertion. Home supplemental oxygen commonly is prescribed for these patients. Oxygen supplementation during exercise can prevent increases in pulmonary artery pressure, reduce dyspnea, and improve exercise tolerance. However, a study from 2008 demonstrated that patients with COPD-related hypoxemia and exertional desaturation who completed a program of pulmonary rehabilitation failed to show any benefit in domestic activity, health-related quality of life, or time spent outside of home in those treated with oxygen compared with placebo.32 Hence, the benefits of home ambulatory oxygen for this subset of patients remain controversial.
Oxygen therapy generally is safe. Oxygen toxicity from high-inspired concentrations (ie, >60%) is well recognized. Little is known about the long-term effects of low-flow oxygen. The increased survival and quality-of-life benefits of long-term oxygen therapy outweigh the possible risks. PaCO2 retention from depression of hypoxic drive has been overemphasized. PaCO2 retention is more likely a consequence of ventilation/perfusion mismatching rather than respiratory center depression. While this complication is not common, it is best avoided by titration of oxygen delivery to maintain PaO2 at 60-65 mm Hg.
The major physical hazards of oxygen therapy are fires or explosions. Patients, family, and other caregivers must be warned not to smoke. Overall, major accidents are rare and can be avoided by good patient and family training.
Oxygen delivery systems
The continuous flow nasal cannula is the standard means of oxygen delivery for the stable hypoxemic patient. It is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fraction of inspired oxygen (FiO2). Nasal oxygen delivery also is beneficial for most mouth-breathing patients. Humidification generally is not beneficial when the patient receives oxygen by nasal cannula at flows of less than 5 L/min.
Oxygen conserving devices function by delivering all of the supplemental oxygen during early inhalation. These devices improve the portability of oxygen therapy and may reduce overall costs. Three distinct oxygen-conserving devices exist—reservoir cannulas, demand pulse delivery devices, and transtracheal oxygen delivery.
Transtracheal oxygen delivery involves the insertion of a catheter percutaneously between the second and third tracheal interspace. Transtracheal oxygen delivery is invasive and requires special training by the physician, the patient, and the caregiver. The procedure has risks as well as medical benefits but has limited application.
Noninvasive positive-pressure ventilationNoninvasive positive-pressure ventilation (NIPPV), as the name suggests, allows the delivery of positive-pressure ventilation without the use of an endotracheal tube. In place of the tube is a tight-fitting nasal or facial mask, which is then attached to a continuous positive airway pressure (CPAP) or a bilevel positive airway pressure (BiPAP) machine. The positive pressure is beneficial in hypercapneic respiratory failure by decreasing the work of breathing, allowing a larger tidal volume for a given respiratory effort, hence improving alveolar ventilation.
NIPPV has been shown to have significant benefit in select patients with acute hypercapneic respiratory failure due to COPD, including a reduction in the need for endotracheal intubation, reduced hospital stay, and a mortality benefit.33,34 This modality should not be used in patients who are unable to protect their airway, are hemodynamically unstable, have significant secretions, are uncooperative, or have an Acute Physiology and Chronic Health Evaluation (APACHE) score of greater than 29.35
One study also suggests that in patients with chronic hypercapneic respiratory failure who are undergoing pulmonary rehabilitation, nocturnal NIPPV may improve quality of life, daytime PaCO2, and exercise tolerance.36
Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
Chronic obstructive pulmonary disease (COPD).
Chronic obstructive pulmonary disease (COPD). Bilevel positive airway pressure (BiPAP).
Surgical Care
Over the past 50-75 years, researchers have described a variety of surgical approaches to improve symptoms and restore function in patients who have emphysema. The following are the most commonly used:
- Bullectomy
- Removal of giant bullae has been a standard approach in selected patients for many years.
- The bullae in patients with emphysema generally range from 1-4 cm in diameter; however, on occasion, bullae can occupy more than 33% of the hemithorax (eg, giant bullae).
- Giant bullae may compress adjacent lung tissue, thereby reducing the blood flow and ventilation to the healthy tissue. Removal of these bullae may result in the expansion of compressed lungs and improved function.
- Patients who are symptomatic and have an FEV1 of less than 50% of the predicted value have a better outcome after bullectomy. This surgery is performed through midline sternotomy, a lateral incision, or by video-assisted thoracoscopy. Postoperative bronchopleural air leak is the major potential complication.
- Giant bullectomy can produce subjective and objective improvement in selected patients—in those who have bullae that occupy at least 30%, and preferably 50%, of the hemithorax and compress adjacent lung, who have FEV1 of less than 50% of the predicted value, and who otherwise have relatively preserved lung function.
- Lung volume reduction surgery
- Nearly 40 years ago, Brantigan et al first reported resectional surgery for diffuse emphysema in 33 patients. They resected 20-30% of each lung that appeared most diseased. Brantigan hypothesized that removal of a portion of the emphysematous lung increased the radial traction on the airways in the remaining lung, improving expiratory airflow and mechanical function of the respiratory system, thereby reducing symptoms.
- The surgical approach uses a midline sternotomy with stapling of the lung margins. Surgeons generally resect 20-30% of each lung from the upper zones. The lung volume reduction surgery procedure has a mortality rate of 0-18%. Several complications, including pneumonia and prolonged air leaks, have been observed.
- Several studies, including the large multicenter National Emphysema Treatment Trial (NETT), have demonstrated significant benefit in spirometry, exercise tolerance, dyspnea, health-related quality of life, and mortality in select patients.37 Those who benefit most are patients with heterogeneous (upper lobe) disease and a low exercise capacity despite optimal medical therapy and cardiopulmonary rehabilitation. Patients with an FEV1 of less than 20% predicted and either homogenous disease or diffusing capacity of the lung for carbon dioxide (DLCO) of less than 20% predicted are considered high risk for this procedure.
- Lung transplantation
- Lung transplantation is a relatively new therapy for advanced lung disease. Lung transplantation is performed only at select tertiary care centers around the world. Patients with COPD are the largest single category of patients who undergo the procedure.
- When evaluating a potential candidate, several factors need be taken into account, including symptomatology, comorbid conditions, and projected survival without transplantation (the BODE index is commonly used for this purpose). Generally speaking, most centers set an age limit of 65 years.
- The mean survival after lung transplantation is 5 years. The survival at 1 year is 80-90%.38,39 Whether or not this procedure has any effect on the survival of COPD patients is controversial; however, the main purpose is to improve symptomatology and quality of life.
Diet
Inadequate nutritional status associated with low body weight in patients with COPD is associated with impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rates. Nutritional support is an important part of their comprehensive care.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Additionally, the Medscape COPD Resource Center may be helpful.
Bronchodilators
These agents act to decrease muscle tone in both small and large airways in the lungs, thereby increasing ventilation. Category includes subcutaneous medications, beta-adrenergics, methylxanthines, and anticholinergics.
Tiotropium (Spiriva), a bronchodilator similar to ipratropium, is approved by the US Food and Drug Administration. Tiotropium is a quaternary ammonium compound. It elicits anticholinergic/antimuscarinic effects with inhibitory effects on M3 receptors on airway smooth muscles, leading to bronchodilation. Tiotropium is available as a capsule dosage form containing a dry powder for oral inhalation via the HandiHaler inhalation device. For adults, the contents of one capsule (18 mcg) are inhaled every day via the HandiHaler device. Contraindications, drug interactions, and adverse effects are similar to those of ipratropium.
Albuterol (Proventil, Ventolin)
Beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta agonists are prescribed initially as needed. May increase frequency. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, metered-dose inhalers, and dry-powder inhalers.
Adult
MDI: 2 puffs q3-4h
Nebulizer: 0.2-0.3 mL of 5% albuterol solution diluted to 2.5 mL with NS tid/qid; unit dose vials are available
Pediatric
MDI:
<12 years: Not recommended
>12 years: Administer as in adults
Nebulizer:
Infants and children: 0.01-0.02 mL of 5% solution diluted in 2-3 mL NS q4-6h
Adolescents: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Documented hypersensitivity; preexisting cardiac arrhythmia associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia; caution in hyperthyroidism, diabetes mellitus, hypertension, ischemic heart disease, seizures, and pheochromocytoma
Metaproterenol (Alupent)
Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta agonists initially are prescribed as needed. Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who are still symptomatic. Available as liquid for nebulizer, metered-dose inhalers, and dry-powder inhalers.
Adult
MDI: 2 puffs q3-4h
Nebulizer: 0.2-0.3 mL of 5% solution diluted to 2.5 mL with NS tid/qid
Pediatric
MDI:
<12 years: Not recommended
>12 years: Administer as in adults
Nebulizer:
Infants and children: 0.01-0.02 mL of 5% solution diluted in 2-3 mL NS q4-6h
Adolescents: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Documented hypersensitivity; cardiac arrhythmias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, diabetes mellitus, pheochromocytoma, and cardiovascular disorders; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia
Ipratropium (Atrovent)
Chemically related to atropine. Has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Used on a fixed schedule with beta agonist.
Adult
MDI: 2-4 puffs q4-6h
Nebulizer: 250 mcg diluted with 2.5 mL NS q4-6h
Pediatric
MDI: 1-2 puffs tid; not to exceed 6 puffs per d
Nebulizer: 250 mcg tid
Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol may increase effects
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction
Theophylline (Aminophylline, Theo-24, Theo-Dur, Slo-bid)
Potentiates exogenous catecholamines. Stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which stimulates bronchodilation.
Popularity has decreased because of narrow therapeutic range and frequent toxicity. Bronchodilation may require near toxic (>20 mg/dL) levels. However, clinical efficacy is controversial, especially in the acute setting.
Shown to increase exercise capacity, decrease dyspnea, and improve gas exchange. A longer-acting agent is used qd or bid.
Target concentration is 10 mcg/mL. Dosing = (target concentration - current level) X 0.5 (ideal body weight). Alternatively, 1 mg/kg results in approximately 2-mcg/mL increase in serum levels.
Adult
Initial: 10 mg/kg/d PO divided q8-12h
Maintenance: 10 mg/kg/d PO divided qd or bid; adjust dose in 25% increments to maintain serum theophylline level of 5-15 mcg/mL; not to exceed 800 mg/d
Pediatric
Children: 10 mg/kg/d PO divided doses q8-12h initial; 10 mg/kg/d PO qd or bid maintenance; adjust dose in 25% increments to maintain serum theophylline level of 5-15 mcg/mL; not to exceed 16 mg/kg/d
Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects of theophylline; theophylline effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon
Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution faster than 25 mg/min; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance; adverse effects include nausea, vomiting, tremor, seizures, coma, esophageal reflux, and atrial and ventricular arrhythmias
Salmeterol (Serevent)
By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. Effect also may facilitate expectoration.
Shown to improve symptoms and morning peak flows. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents.
When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts >12h. Used on a fixed schedule in addition to regular use of anticholinergic agents.
Adult
2 puffs bid
Pediatric
<4 years: Not established
4-12 years: 1 inhalation (50 mcg) bid at least 12h apart
>12 years: Administer as in adults
Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with salmeterol
Documented hypersensitivity; angina; cardiac arrhythmias associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia
Formoterol (Oxis, Foradil)
By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, formoterol can relieve bronchospasms. Effect also may facilitate expectoration.
Shown to improve symptoms and morning peak flows. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents.
When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts >12h. Used on a fixed schedule in addition to regular use of anticholinergic agents.
Adult
12-25 mcg bid
Pediatric
Not established
Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists such as salmeterol; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with salmeterol
Documented hypersensitivity; angina; cardiac arrhythmias associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia
Corticosteroids
A meta-analysis of 16 controlled trials in stable COPD found that approximately 10% of patients respond to these drugs. The responders should be identified carefully. An increase in FEV1 >20% is used as surrogate marker for steroid response. In acute exacerbation, steroids improve symptoms and lung functions. Inhaled steroids have fewer adverse effects compared with oral agents. Although effective, these agents improve expiratory flows less effectively than oral preparations, even at high doses. These agents may be beneficial in slowing rate of progression in a subset of patients with COPD who have rapid decline.
Fluticasone (Flovent)
Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak HPA axis inhibitory potency when applied topically. Effectiveness is not established.
Adult
Initial: 250-500 mcg bid
Previous therapy:
Bronchodilator alone: 88 mcg bid; may titrate to 440 mcg bid prn
Inhaled corticosteroids: 88-220 mcg bid; may titrate to 440 mcg bid prn
Oral steroids: 880 mcg bid; not to exceed 880 mcg bid
Pediatric
Not established
None reported
Documented hypersensitivity; viral, fungal, and bacterial infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use, application over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria; adverse effects include oral thrush, hoarseness, adrenal suppression, glaucoma, skin bruising, and alteration in bone metabolism
Budesonide (Pulmicort Turbuhaler)
Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak HPA axis inhibitory potency when applied topically. Effectiveness is not established.
Adult
Previous therapy:
Bronchodilator alone: 200-400 mcg bid; may titrate to 400 mcg bid prn
Inhaled corticosteroids: 200-400 mcg bid; may titrate to 800 mcg bid prn
Oral steroids: 400-800 mcg bid; may titrate to 800 mcg bid
Pediatric
Not established
None reported
Documented hypersensitivity; viral, fungal, and bacterial infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use, application over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria; adverse effects include oral thrush, hoarseness, adrenal suppression, glaucoma, skin bruising, and alteration in bone metabolism
Prednisone (Sterapred)
Conduct steroid trial to identify responders. Start corticosteroid therapy at 0.5-1 mg/kg of prednisone daily for 2-3 wk. If the FEV1 increases by 20% or more, taper dose to the minimum to maintain improvement.
Adult
0.5-1 mg/kg/d PO qd, gradually taper to minimum 10-20 mg/d, the dose that maintains improvement is continued long-term
Pediatric
Not established
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Smoking cessation therapies
Work best when used in conjunction with a support program, such as counseling, group therapy, or behavioral therapy. Nicotine replacements may be used to decrease physical withdrawal symptoms.
Antidepressants (eg, bupropion) are used as a nonnicotine aid to smoking cessation. One study demonstrated 23% sustained cessation with bupropion tablets at 1 year, compared to a 12% sustained cessation with placebo. Bupropion also may be effective in patients for whom nicotine replacement therapy is ineffective.
The most recent drug to receive approval for smoking cessation is varenicline (Chantix), a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors.
Nicotine patches (Habitrol, NicoDerm CQ) or nicotine polacrilex (Nicorette)
Nicotine patches: Individuals who smoke >1 pack/d initially need a 21-mg patch, followed by 14- and 7-mg patches.
Nicotine polacrilex: Nicotine is absorbed through the oral mucosa. Is absorbed quickly and closely approximates time course of plasma nicotine levels observed after cigarette smoking.
Available as 2- or 4-mg gum in a box containing 96 pieces. Careful adherence to chewing instructions is important for effective use. Manufacturer recommends that the gum not be used l>6 mo.
An individual who smokes 1 pack/d should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke <1 pack/d. Instruct the patient to chew hourly and for initial cravings for 2 wk, then gradually reduce amount chewed over 3 mo.
Adult
Habitrol/NicoDerm CQ: One 21-mg patch qd for 3-4 wk, then one 14-mg patch qd for 3-4 wk, followed by one 7-mg patch qd for 3-4 wk
Nicotrol: One 15-mg patch qd for 6 wk, then one 10-mg patch qd for 2 wk, followed by one 5-mg patch qd for 2 wk
Nicotine polacrilex: 1 piece of gum (2 mg) per h as needed to abstain from smoking; not to exceed 30 mg/d
Pediatric
Not established
May decrease diuretic effects of furosemide and decrease cardiac output; may decrease absorption of glutethimide; may increase circulating cortisol and catecholamines; not for use in patients who continue to smoke, use snuff, chew tobacco, or use other nicotine products because it may increase toxicity of nicotine
Documented hypersensitivity; nonsmokers; children; pregnancy; life-threatening arrhythmias; severe or worsening angina pectoris
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in peptic ulcer, coronary artery disease, angina, hypertension, peripheral arterial disease, diabetes, severe renal dysfunction, and hepatic dysfunction; may cause skin irritation
Bupropion (Zyban)
Used in conjunction with a support group and/or behavioral counseling. Inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake.
Adult
150-mg tab qd for 3 d, then increase to 150 mg bid with at least 8 h between each dose for 7-12 wk
Pediatric
Not established
Carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; toxicity increases with concurrent administration of levodopa and MAOIs
Documented hypersensitivity; seizure disorder; anorexia nervosa; concurrent use with MAOIs
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic insufficiency; doses >450/d significantly decrease seizure threshold; adverse effects include pruritus, angioedema, dyspnea, and insomnia; delusions and/or hallucinations may occur in patients who are depressed
Varenicline (Chantix)
Partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to be the result of activity at a nicotinic receptor subtype, where its binding produces agonist activity while simultaneously preventing nicotine binding. Agonistic activity is significantly lower than nicotine. Also elicits moderate affinity for 5-HT3 receptors. Maximum plasma concentrations occur within 3-4 h after oral administration. Following regular dosing, steady state is reached within 4 d.
Adult
Initiate 1 wk before date chosen to stop smoking
Days 1-3: 0.5 mg PO qd pc
Days 4-7: 0.5 mg PO bid pc
Day 8 to end of treatment: 1 mg PO bid pc
Continue treatment for 12 wk; if successfully stopped smoking at end of 12 wk, an additional course of 12 wk treatment is recommended; take after meals with full glass of water
Severe renal impairment (ie, CrCl <30 mL/min): Not to exceed 0.5 mg PO bid
ESRD with hemodialysis: Not to exceed 0.5 mg PO qd
Pediatric
<18 years: Not established
Data limited; coadministration with nicotine replacement therapy may increase incidence of nausea, headache, vomiting, dizziness, and dyspepsia compared with nicotine replacement therapy alone
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include nausea, headache, vomiting, flatulence, insomnia, abnormal dreams, and dysgeusia; decrease dose with severe renal impairment (ie, CrCl <30 mL/min) or ESRD undergoing hemodialysis
Serious neuropsychiatric symptoms have been reported during postmarketing surveillance and may include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide; these adverse events have been exhibited in patients without preexisting psychiatric illness, and patients with preexisting psychiatric illness have reported worsening symptoms during varenicline treatment; for more information, see the FDA MedWatch Safety Information at www.fda.gov/medwatch/safety/2008/safety08.htm#Varenicline
Beta-adrenergic agonist and anticholinergic agent combinations
Combine the benefits of the rapid onset of a beta-adrenergic agonist with the prolonged action of an anticholinergic agent.
Ipratropium and albuterol (DuoNeb)
Ipratropium is chemically related to atropine, Has antisecretory properties, and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa.
Albuterol is a beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.
Adult
3-mL vial administered qid via nebulization with up to 2 additional 3-mL doses allowed per d, if needed
Pediatric
Not established
Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects of ipratropium; beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Cefuroxime (Zinacef)
Second-generation cephalosporin. Maintains gram-positive activity that first-generation cephalosporins have. Adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis.
Condition of patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration.
Adult
2 g IV q6-8h
Pediatric
80-160 mg/kg/d IV divided q4-6h
Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patient receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Administer half dose if CrCl is 10-30 mL/min and one quarter dose if CrCl <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy
Azithromycin (Zithromax)
Replacing erythromycin as therapy for community-acquired pneumonia. Cover most potential etiologic agents, including Mycoplasma. Newer macrolides offer decreased GI upset and potential for improved compliance through reduced dosing frequency. Improved action against H influenzae.
Adult
Day 1: 500 mg PO
Days 2-5: 250 mg PO qd
Alternatively, administer 500 mg IV qd
Pediatric
<6 months: Not established
> 6 months:
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Documented hypersensitivity; hepatic impairment; do not administer with pimozide, sudden death may occur
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzyme levels and cause cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients
Clarithromycin (Biaxin)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Initial therapy in otherwise uncomplicated pneumonia.
Adult
500 mg PO bid for 10 d
Pediatric
Not established
Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Documented hypersensitivity; coadministration of pimozide
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies
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Further Reading
Keywords
chronic obstructive pulmonary disease, COPD, chronic bronchitis, emphysema, chronic obstructive airway disease, COAD, airflow obstruction, centriacinar emphysema, panacinar emphysema, distal acinar emphysema, paraseptal emphysema
