COPD; Alpha-1 antitrypsin deficiency; Bronchitis - chronic; Chronic bronchitis; Emphysema
Anticholinergic medications relax the bronchial muscles. They are generally inhaled and act as a bronchodilator over time. Bronchodilation does not have much effect on lung function and does not change the overall course of the disease. However, the medication helps improve breathlessness, ability to exercise, and quality of life.
Brands and Benefits. Anticholinergics used for COPD include short-acting ipratropium (Atrovent) and long-acting tiotropium (Spiriva). They are considered standard maintenance medications for COPD.
A single inhaler containing both ipratropium and the common beta2-agonist albuterol (Combivent) may prove to be better than either medication alone. Anticholinergics target the central airways, and beta-agonists target the smaller airways, which explains the possible additive benefits of the combination.
Other combinations are being explored. Long-acting anticholinergic medications are being given along with inhaled corticosteroids and long-acting beta-agonists. Although the combination may not reduce the number of exacerbations, it improves lung function and quality of life, and reduces hospitalizations.
Side Effects. Studies suggest that anticholinergics have few severe side effects. They are less likely to interfere with sleep than the other standard inhaled medications. The side effects of respiratory anticholinergic agents include mild cough and dry mouth.
However, two recent studies suggest that anticholinergics may pose serious heart risks. In one study, using an inhaled anticholinergic medication for more than a month was linked to an almost 60% increase in COPD patients' risk of heart attack, stroke, or death. Another study found that ipratropium increased the risk of cardiovascular death by more than 30%, particularly in men who were recently diagnosed with COPD. More research is needed to learn whether the medication was actually responsible for these poor outcomes.
When anticholinergics are no longer enough -- and sometimes in place of an anticholinergic -- health care providers will prescribe a beta2-agonist. GOLD guidelines recommend that all patients with COPD stages II - IV take a long-acting beta2-agonist.
Short-Acting Beta2-agonists. Short-acting bronchodilators are the primary medications for most COPD patients. Albuterol (Proventil, Ventolin) is the standard short-acting beta2-agonist. Others include:
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the older medications. Most are inhaled and are effective for 3 - 6 hours.
Long-Acting Beta2-Agonists. Long-acting beta2-agonists salmeterol (Serevent) and formoterol (Foradil) are proving to be particularly effective as long-term maintenance therapy for COPD. Major analyses of studies suggest they reduce exacerbations by 20 - 25%. They may help prevent bacteria from building up on the airways and may offer real improvements in lung function. Unlike short-acting forms, these beta2-agonists may even have anti-inflammatory properties. In 2007, the FDA approved a nebulized formulation of formoterol for the treatment of COPD. Until recently, only short-acting nebulizers were available.
Inhalers that combine a long-acting beta2-agonist and a corticosteroid (such as Advair, Seretide, and Symbicort) are more effective than either drug alone -- reducing exacerbations by 35% and improving exercise endurance.
Side Effects. Side effects of both long- and short-acting beta2-agonists include anxiety, tremor, restlessness, and headaches. Patients may experience fast and irregular heartbeats. A physician should be notified immediately if such side effects occur, particularly in people with existing heart conditions. Such patients face an increased risk of sudden death from heart-related causes. This risk is higher with medications taken by mouth or through nebulizers, but there have also been reports of heart attacks and chest pain (angina) in some patients using inhaled beta2-agonists.
Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists may become less effective when taken regularly over time, increasing the risk of overuse. The degree to which this affects the airways is uncertain. In some studies, these drugs became less effective with longer use. However, the peak effect appears to remain, making these drugs still useful for attacks. Regular use of long-acting beta2-agonists may reduce the effectiveness of short-acting forms.
A major concern is that patients who perceive beta2-agonists as being less effective may overuse them. Overdose can be serious and, in rare cases, even life threatening, particularly in patients with heart disease or asthma.
Corticosteroids are powerful anti-inflammatory drugs.
Oral Corticosteroids. Oral corticosteroids are reserved for treating COPD exacerbations, and research finds that they are better than inhaled corticosteroids for this purpose. They speed the time to recovery and reduce the length of the hospital stay, but they do not reduce mortality or affect the long-term progression of the disease. They shouldn't be regularly used for stable disease because of the increased risk of side effects.
Inhaled Corticosteroids. Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. However, their use in COPD is controversial. During the first 6 months of use, ICS may improve lung function. After 6 months, lung function begins to decline again. There is also evidence that ICS increases the risk of developing and dying from pneumonia in patients with COPD. ICS should be reserved for patients with severe COPD and frequent exacerbations.
Methylxanthines (primarily slow-release theophylline) are also bronchodilators, which relax the airways of the lungs. These drugs are used in patients with more severe exacerbations that do not respond completely to corticosteroids, oxygen, or antibiotics.
These drugs do not significantly improve lung function, symptoms, or overall outcomes when used for acute exacerbations. Some experts believe that the modest benefits do not outweigh the risk of toxic side effects from these drugs. Side effects are generally related to the amount of theophylline in the blood, and can include:
Many COPD drugs are inhaled using metered dose inhalers, dry powder inhalers, or nebulizers.
Metered-Dose Inhaler. The standard device for delivering COPD medication is the metered-dose inhaler (MDI). This device allows precise doses to be delivered directly to the lungs. A holding chamber, or spacer, improves delivery by giving the patient more time to inhale the medication.
Breath-Activated Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of the drug directly into the lungs. DPIs are as effective as MDIs and are easier to manage. Humidity or extreme temperatures can affect DPI performance, so these devices should not be stored in humid places (such as bathroom cabinets) or locations with high temperatures (such as glove compartments during summer months).
Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.
Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. Nebulizers are often used in hospitals or when the patient cannot use an inhaler.
Patients with persistent coughing and phlegm often use medications that loosen secretions and help move them out of the lungs.
Expectorants. Expectorants, such as guaifenesin (found in common cough remedies), stimulate the flow of fluid in the airways and help move secretions using the motion of cilia (the hair-like structures in the lung) and coughing. Expectorants have not been shown to benefit patients with COPD.
Mucolytics. Mucolytics contain ingredients that make phlegm more watery and easier to cough up. One of these ingredients, acetylcysteine, also acts as an antioxidant, which could provide additional benefit to people with COPD. The most effective mucolytic is stopping smoking. Anticholinergics appear to decrease the production of mucus. Beta2-agonists and theophylline improve mucus clearance.
Selective Phosphodiesterase-4 Inhibitors. Cilomilast (Ariflo) and roflumilast (Daxas) are selective phosphodiesterase-4 (PDE4) inhibitors. These medications block PDE4, an enzyme that is produced in excess amounts in people with COPD and asthma. It causes inflammation in the airways. The FDA has approved cilomilast for the treatment of COPD and asthma. Roflumilast is still in development. One study of cilomilast found that the drug significantly decreased exacerbations and increased quality of life. In other research, rofumilast significantly improved lung function in patients with severe, stable COPD.
Treating Acute Bronchitis or Pneumonia in COPD Patients. People with COPD are at increased risk for pneumonia, but any lung infection can worsen symptoms and speed deterioration of lung function. Patients with acute bronchitis or pneumonia who have signs of bacterial infection, such as green or yellow phlegm, usually need antibiotics.
Streptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis are the most common causes of pneumonia or exacerbations in people with COPD. The choice of antibiotic depends on the bacteria being treated and bacterial resistance to common antibiotics in the area. Giving preventive antibiotics to patients with frequent exacerbations is not recommended because this practice contributes to the development of bacterial resistance.
Beta-lactam antibiotics include penicillins, cephalosporins, and some newer medications. They share common chemical features, and all interfere with bacterial cell walls.
Penicillins. Penicillin was the first antibiotic. Many forms of this still-important drug are available today:
Many people have a history of allergic reaction to penicillin, but some evidence suggests the allergy may not return in a significant number of adults. Skin tests are available to help determine whether someone with a history of penicillin allergies could tolerate these important antibiotics.
Cephalosporins. Most of these antibiotics are not very effective against bacteria that have developed resistance to penicillin, and are used for more severe exacerbations. They are classified according to their generation:
Fluoroquinolones ("quinolones") interfere with the bacteria's genetic material to prevent them from reproducing. These antibiotics are used for more severe exacerbations.
S. pneumoniae strains that are resistant to the respiratory quinolones are uncommon in the U.S., but resistance is increasing.
Many quinolones cause side effects, including sensitivity to light and nervous system (neurologic), psychiatric, and heart problems. Pregnant women should not take this class of drugs. Quinolones also enhance the potency of oral anti-clotting drugs.
When it comes to treating acute exacerbations of chronic bronchitis, so-called second-line antibiotics (amoxicillin, clavulanate, macrolides, second- or third-generation cephalosporines, and quinolones) appear to be more effective than -- and just as safe as -- first-generation antibiotics (ampicillin, doxycycline, and trimethoprim/sulfamethoxazole).
Macrolides, Azalides, and Ketolides
Macrolides and azalides also affect the genetics of bacteria. These drugs include:
These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. All but erythromycin are effective against H. influenzae. Macrolides and azalides are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these medicines. Macrolide resistance rates doubled between 1995 and 1999, as more and more children were being treated with these antibiotics.
Ketolides. Ketolides are a new class of antibiotics. They are derived from erythromycin and were developed to combat organisms that have become resistant to macrolides. The FDA approved telithromycin (Ketek), the first antibiotic in the ketolide class, in 2004 for treating CAP, acute bacterial exacerbations of chronic bronchitis, and acute sinusitis. However, in February 2007, the FDA withdrew its approval of Ketek for acute bacterial sinusitis. The agency decided that the serious risks of Ketek outweighed its benefits for sinusitis treatment. The decision followed several 2006 reports of deaths from severe liver damage. Telithromycin is approved only for the treatment of CAP. The drug carries a strong "black box" warning noting its potentially serious or deadly side effects, including liver failure, vision problems, loss of consciousness, and nerve/muscle (neuromuscular) problems.
Tetracyclines inhibit the growth of bacteria. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include skin reactions to sunlight, burning in the throat, and tooth discoloration.
Trimethoprim-sulfamethoxazole (such as Bactrim, Cotrim, and Septra) is less expensive than amoxicillin and particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people who are allergic to sulfa drugs. Allergic reactions can be very serious.
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