1. Medications
Anticholinergic Agents
Anticholinergic agents relax the bronchial muscles. They are generally inhaled and act as a
bronchodilator over time. Although bronchodilation does not have much effect on lung function
and does not change the overall course of the disease, 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
administered along with inhaled corticosteroids and long-acting beta-agonists. While the
combination may not reduce the number of exacerbations, it improves lung function and quality
of life, and reduces hospitalizations.
Side Effects. Anticholinergics have few severe side effects. They are less likely to impair sleep
than the other standard inhaled medications. The side effects of respiratory anticholinergic agents
include mild cough and dry mouth.
Beta2-Agonists
When 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 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:
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 the
standard agents. Most are inhaled and are effective for 3 - 6 hours.

2. 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 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 agent 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 for sudden death from heart-related causes.
This risk is higher with oral or nebulized agents, but there have also been reports of heart attacks
and 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, the duration
of action has declined with use, but the peak effect appears to be preserved, making these drugs
still useful for acute attacks. Regular use of long-acting beta2-agonists may reduce the effect 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
Corticosteroids 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 speed
the time to recovery and reduce the length of the hospital stay, but appear to have no long-term
benefit. 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. Their
use 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 the
risk of dying from pneumonia in patients with COPD. ICS should be reserved for patients with
severe COPD and frequent exacerbations.

3. Combining a long-acting bronchodilator (salmeterol) with a corticosteroid (fluticasone) appears
to improve survival and reduce exacerbations in patients with severe COPD compared to single-
drug treatment. However, further studies are needed to determine whether this combination
might increase the number of adverse side effects.
Theophylline and Other Methylxanthines
Methylxanthines (primarily slow-release theophylline) are also bronchodilators. These drugs are
used in patients with more severe exacerbations when there is an incomplete response to
bronchodilators, corticosteroids, oxygen, or antibiotics.
These agents 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 effects commonly associated with these agents. These side effects are generally
related 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
Vomiting
Administering Inhaled Drugs
Many 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 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
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 subject to high temperatures (such as
glove compartments during summer months).

4. 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 hospital settings or when the patient cannot use an
inhaler.
This metered-dose inhaler is a quick way of administering medicine directly into the bronchial
passageways to promote clearer breathing.
Medicines That Loosen Lung Secretions
Patients with persistent coughing and sputum often use agents 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 sputum 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.
Other Medications

5. Selective Phosphodiesterase-4 Inhibitors. Cilomilast (Ariflo) and roflumilast (Daxas) are
selective phosphodiesterase-4 (PDE4) inhibitors. These medications block PDE4, an enzyme
overproduced in COPD and asthma that causes inflammation in the airways. The FDA has
approved 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 increased
quality of life. In other research, rofumilast significantly improved lung function in patients with
severe, stable COPD.
Statins. Patients with COPD are at an increased risk of death from coronary artery disease. Some
studies have found an association between statin use and COPD. The anti-inflammatory
properties of statin medications might help slow lung function decline or help in the survival of
an exacerbation, especially in longtime smokers and people who have recently quit. These
effects have yet to be explained or proven.
Antibiotics
Treating Acute Bronchitis or Pneumonia in COPD Patients. People with COPD are at
heightened risk for pneumonia, but any lung infection can worsen symptoms and speed
deterioration of lung function. Antibiotics are usually called for when acute bronchitis or
pneumonia occurs, and the patient has signs of bacterial infection, such as green or yellow
sputum.
The most common organisms causing pneumonia or exacerbations in people with COPD include
Streptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis. The choice of
antibiotic depends on the bacteria being treated and the local rate of bacterial resistance to
common antibiotics. Preventive antibiotic therapy for patients with frequent exacerbations is
discouraged, since this practice contributes to the development of bacterial resistance.
Antibiotic Options
Beta-Lactams
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:
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.

6. 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 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 agents 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:
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 bacteria's genetic material to prevent them
from 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., but
resistance 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 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 (Augmentin), 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).

7. Macrolides, Azalides, and Ketolides
Macrolides 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. All
but 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 being
treated with these antibiotics. Some research suggests these agents may reduce the risk of a first
heart 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 were
developed 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 of
CAP, acute bacterial exacerbations of chronic bronchitis, and acute sinusitis. However, in
February 2007, the FDA withdrew 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 neuromuscular problems.
Tetracyclines
Tetracyclines inhibit bacterial growth. 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
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