MedicationsAnticholinergic AgentsAnticholinergic agents relax the bronchial muscles. They are generally inhaled and act as abronchodilator over time. Although bronchodilation does not have much effect on lung functionand does not change the overall course of the disease, the medication helps improvebreathlessness, 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 maintenancemedications 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 thecentral airways, and beta-agonists target the smaller airways, which explains the possibleadditive benefits of the combination.Other combinations are being explored. Long-acting anticholinergic medications are beingadministered along with inhaled corticosteroids and long-acting beta-agonists. While thecombination may not reduce the number of exacerbations, it improves lung function and qualityof life, and reduces hospitalizations.Side Effects. Anticholinergics have few severe side effects. They are less likely to impair sleepthan the other standard inhaled medications. The side effects of respiratory anticholinergic agentsinclude mild cough and dry mouth.Beta2-AgonistsWhen anticholinergics are no longer enough -- and sometimes in place of an anticholinergic --the doctor will prescribe a beta2-agonist. GOLD guidelines recommend that all patients withCOPD stages II - IV take a long-acting beta2-agonist.Short-Acting Beta2-agonists. Short-acting bronchodilators are the primary medications for mostCOPD patients. Albuterol (Proventil, Ventolin) is the standard short-acting beta2-agonist. Othersinclude: Bitolterol (Tornalate) Isoetharine (Bronkometer, Bronkosol), which is available in nebulizers Isoproterenol (Isuprel, Norisodrine, Medihaler-Iso) Metaproterenol (Alupent, Metaprel) Pirbuterol (Maxair) Terbutaline (Brethine, Brethaire, Bricanyl)Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than thestandard agents. 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 suggest they reduce exacerbations by 20 - 25%. They may help prevent bacteriafrom 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, theFDA 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 agent alone -- reducing exacerbations by 35% andimproving 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 physicianshould be notified immediately if such side effects occur, particularly in people with existingheart conditions. Such patients face an increased risk for sudden death from heart-related causes.This risk is higher with oral or nebulized agents, but there have also been reports of heart attacksand 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 ofoveruse. The degree to which this affects the airways is uncertain. In some studies, the durationof action has declined with use, but the peak effect appears to be preserved, making these drugsstill useful for acute attacks. Regular use of long-acting beta2-agonists may reduce the effect ofshort-acting forms.A major concern is that patients who perceive beta2-agonists as being less effective may overusethem. Overdose can be serious and, in rare cases, even life threatening, particularly in patientswith heart disease or asthma.CorticosteroidsCorticosteroids are powerful anti-inflammatory drugs.Oral Corticosteroids. Oral corticosteroids are reserved for the treatment of COPD exacerbations,and research finds that they are preferable to inhaled corticosteroids for this purpose. They speedthe time to recovery and reduce the length of the hospital stay, but appear to have no long-termbenefit. They shouldnt be regularly used for stable disease because of the increased risk of sideeffects.Inhaled Corticosteroids. Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. Theiruse in COPD is controversial. During the first 6 months of use, ICS may improve lung function.After 6 months, lung function resumes its decline. There is also evidence that ICS increases therisk of dying from pneumonia in patients with COPD. ICS should be reserved for patients withsevere COPD and frequent exacerbations.
Combining a long-acting bronchodilator (salmeterol) with a corticosteroid (fluticasone) appearsto improve survival and reduce exacerbations in patients with severe COPD compared to single-drug treatment. However, further studies are needed to determine whether this combinationmight increase the number of adverse side effects.Theophylline and Other MethylxanthinesMethylxanthines (primarily slow-release theophylline) are also bronchodilators. These drugs areused in patients with more severe exacerbations when there is an incomplete response tobronchodilators, corticosteroids, oxygen, or antibiotics.These agents do not significantly improve lung function, symptoms, or overall outcomes whenused for acute exacerbations. Some experts believe that the modest benefits do not outweigh therisk of toxic effects commonly associated with these agents. These side effects are generallyrelated to the amount of theophylline in the blood, but can include: Abdominal pain Anxiety Diarrhea Excess urination (diuresis) Irregular heartbeat (arrhythmia) and palpitations Headache Heartburn Insomnia Loss of appetite Nausea Reflux Restlessness Seizures Tremor VomitingAdministering Inhaled DrugsMany COPD drugs are inhaled using metered dose inhalers, dry powder inhalers, or nebulizers.Metered-Dose Inhaler. The standard device for COPD medication is the metered-dose inhaler(MDI). This device allows precise doses to be delivered directly to the lungs. A holdingchamber, 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 ofdrug directly into the lungs. DPIs are as effective as MDIs and are easier to manage. Humidity orextreme temperatures can affect DPI performance, so these devices should not be stored inhumid places (such as bathroom cabinets) or locations subject to high temperatures (such asglove compartments during summer months).
Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing theliquid 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 patientbreathes in. Nebulizers are often used in hospital settings or when the patient cannot use aninhaler.This metered-dose inhaler is a quick way of administering medicine directly into the bronchialpassageways to promote clearer breathing.Medicines That Loosen Lung SecretionsPatients with persistent coughing and sputum often use agents that loosen secretions and helpmove them out of the lungs.Expectorants. Expectorants, such as guaifenesin (found in common cough remedies), stimulatethe flow of fluid in the airways and help move secretions using the motion of cilia (the hair-likestructures in the lung) and coughing. Expectorants have not been shown to benefit patients withCOPD.Mucolytics. Mucolytics contain ingredients that make sputum more watery and easier to coughup. One of these ingredients, acetylcysteine, also acts as an antioxidant, which could provideadditional benefit to people with COPD. The most effective mucolytic is stopping smoking.Anticholinergics appear to decrease the production of mucus. Beta2-agonists and theophyllineimprove mucus clearance.Other Medications
Selective Phosphodiesterase-4 Inhibitors. Cilomilast (Ariflo) and roflumilast (Daxas) areselective phosphodiesterase-4 (PDE4) inhibitors. These medications block PDE4, an enzymeoverproduced in COPD and asthma that causes inflammation in the airways. The FDA hasapproved cilomilast for the treatment of COPD and asthma. Approval of roflumilast is pending.One study of cilomilast found that the drug significantly decreased exacerbations and increasedquality of life. In other research, rofumilast significantly improved lung function in patients withsevere, stable COPD.Statins. Patients with COPD are at an increased risk of death from coronary artery disease. Somestudies have found an association between statin use and COPD. The anti-inflammatoryproperties of statin medications might help slow lung function decline or help in the survival ofan exacerbation, especially in longtime smokers and people who have recently quit. Theseeffects have yet to be explained or proven.AntibioticsTreating Acute Bronchitis or Pneumonia in COPD Patients. People with COPD are atheightened risk for pneumonia, but any lung infection can worsen symptoms and speeddeterioration of lung function. Antibiotics are usually called for when acute bronchitis orpneumonia occurs, and the patient has signs of bacterial infection, such as green or yellowsputum.The most common organisms causing pneumonia or exacerbations in people with COPD includeStreptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis. The choice ofantibiotic depends on the bacteria being treated and the local rate of bacterial resistance tocommon antibiotics. Preventive antibiotic therapy for patients with frequent exacerbations isdiscouraged, since this practice contributes to the development of bacterial resistance.Antibiotic OptionsBeta-LactamsBeta-lactam antibiotics include penicillins, cephalosporins, and some newer medications. Theyshare common chemical features, and all interfere with bacterial cell walls.Penicillins. Penicillin was the first antibiotic. Many forms of this still-important drug areavailable today: Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is inexpensive, and at one time was highly effective against S. pneumoniae . Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar, but requires more doses and has more severe gastrointestinal side effects than amoxicillin.
Amoxicillin-clavulanate (Augmentin) is known as an augmented penicillin that works against a wide spectrum of bacteria and is used for more severe exacerbations. An extended release form is also available.Many people have a history of allergic reaction to penicillin, but some evidence suggests theallergy may not return in a significant number of adults. Skin tests are available to helpdetermine whether someone with a history of penicillin allergies could tolerate these importantantibiotics.Cephalosporins. Most of these agents are not very effective against bacteria that have developedresistance to penicillin, and are used for more severe exacerbations. They are classifiedaccording to their generation: Second generation: cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid) Third generation: cefpodoxime (Vantin), cefdinir (Omnicef), cefditoren (Spectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These antibiotics are effective against a wide range of Gram-negative bacteria. Cefditoren has also been shown to be 85% effective against Haemophilus influenzae and 90% effective against penicillin-resistant strains of S. pneumoniae.Fluoroquinolones (Quinolones)Fluoroquinolones ("quinolones") interfere with the bacterias genetic material to prevent themfrom reproducing. These antibiotics are used for more severe exacerbations. "Respiratory quinolones" are currently the most effective drugs available against a wide range of bacteria. These drugs include levofloxacin (Levaquin), sparfloxacin (Zagam), and gemifloxacin (Factive). Levofloxacin was the first drug approved specifically for penicillin-resistant S. pneumoniae. Some of the newer fluoroquinolones need to be taken only once a day. The fourth-generation quinolones moxifloxacin (Avelox) and clinafloxacin (which is still under development) are proving effective against anaerobic bacteria.S. pneumoniae strains resistant to the respiratory quinolones are uncommon in the U.S., butresistance is dramatically increasing.Many quinolones cause side effects, including sensitivity to light and neurologic, psychiatric,and heart problems. Pregnant women should not take this class of drugs. Quinolones alsoenhance the potency of oral anti-clotting drugs.When it comes to treating acute exacerbations of chronic bronchitis, so-called second-lineantibiotics [amoxicillin, clavulanate (Augmentin), macrolides, second- or third-generationcephalosporines, and quinolones] appear to be more effective than -- and just as safe as -- first-generation antibiotics (ampicillin, doxycycline, and trimethoprim/sulfamethoxazole).
Macrolides, Azalides, and KetolidesMacrolides and azalides also affect the genetics of bacteria. These drugs include: Azithromycin (Zithromax, Zmax) Clarithromycin (Biaxin) Erythromycin Roxithromycin (Rulid)These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. Allbut erythromycin are effective against H. influenzae. They 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 - 1999, as more and more children were beingtreated with these antibiotics. Some research suggests these agents may reduce the risk of a firstheart attack in some patients by reducing inflammation in the blood vessels.Ketolides. Ketolides are a new class of antibiotics. They are derived from erythromycin and weredeveloped to combat organisms that have become resistant to macrolides. Telithromycin (Ketek),the first antibiotic in the ketolide class, was approved by the FDA in 2004 for the treatment ofCAP, acute bacterial exacerbations of chronic bronchitis, and acute sinusitis. However, inFebruary 2007, the FDA withdrew approval of Ketek for acute bacterial sinusitis. The agencydecided that the serious risks of Ketek outweighed its benefits for sinusitis treatment. Thedecision followed several 2006 reports of deaths from severe liver damage. Telithromycin isapproved only for the treatment of CAP. The drug carries a strong "black box" warning noting itspotentially serious or deadly side effects, including liver failure, vision problems, loss ofconsciousness, and neuromuscular problems.TetracyclinesTetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline.They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant topenicillin are also often resistant to doxycycline. The side effects of tetracyclines include skinreactions to sunlight, burning in the throat, and tooth discoloration.Trimethoprim-SulfamethoxazoleTrimethoprim-sulfamethoxazole (such as Bactrim, Cotrim, and Septra) is less expensive thanamoxicillin and particularly useful for adults with mild bacterial upper respiratory infections whoare allergic to penicillin. The drug is no longer effective against certain streptococcal strains. Itshould not be used in patients whose infections occur after dental work, or in people who areallergic to sulfa drugs. Allergic reactions can be very serious