Chronic Obstructive Pulmonary Disease Medication
- Author: Zab Mosenifar, MD; Chief Editor: Zab Mosenifar, MD more...
Medication Summary
Oral and inhaled medications are used for patients with stable chronic obstructive pulmonary disease (COPD) to reduce dyspnea, improve exercise tolerance, and prevent complications. Most of the medications used in COPD treatment are directed at the following 4 potentially reversible mechanisms of airflow limitation:
- Bronchial smooth muscle contraction
- Bronchial mucosal congestion and edema
- Airway inflammation
- Increased airway secretions
Bronchodilators act to decrease muscle tone in small and large airways in the lungs, thereby increasing ventilation. The category includes subcutaneous medications, beta-adrenergics, methylxanthines, and anticholinergics.
Additionally, opioids have been shown in multiple studies to relieve dyspnea, particularly near the end of life. Dosage is very patient specific. Currow et al used a low, once-daily dose of sustained-release morphine for chronic refractory dyspnea.[80]
Beta2-Adrenergic Agonists, Short-Acting
Class Summary
Beta2 -agonists activate specific B2 -adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cyclic adenosine monophosphate (cAMP) and smooth muscle relaxation. Beta2 -agonists produce less bronchodilatation in COPD than in asthma. Patients use beta2 -agonists primarily for relief of symptoms of COPD. In patients with mild, intermittent symptoms, short-acting beta2 -agonists is recommended for symptomatic relief.
Albuterol (Proventil HFA, Ventolin HFA
Albuterol is a short acting beta-agonist used for bronchospasm refractory to epinephrine. It 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.
Metaproterenol
Metaproterenol 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.
Levalbuterol (Xopenex)
Levalbuterol is a selective beta2-agonist agent used for the treatment or prevention of bronchospasm. Albuterol is a racemic mixture, while levalbuterol contains only the active R- enantiomer of albuterol. The S-enantiomer does not bind to beta2-receptors, but it may be responsible for some adverse effects of racemic albuterol, including bronchial hyperreactivity and reduced pulmonary function during prolonged use.
Pirbuterol (Maxair)
Pirbuterol acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Beta2-Adrenergic Agonists, Long-Acting
Class Summary
Beta2 -agonist bronchodilators activate specific beta2 -adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cyclic adenosine monophosphate (cAMP) and smooth muscle relaxation. 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. Long-acting beta-agonists include salmeterol, formoterol, arformoterol, and indacaterol. They all require twice-daily dosing, except for indacaterol, which is administered once daily.[81]
Salmeterol (Serevent)
By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. The effect also may facilitate expectoration. It is shown to improve symptoms and morning peak flows. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts more than 12 hours. It is used on a fixed schedule in addition to regular use of anticholinergic agents.
Formoterol (Oxis, Foradil)
Formoterol relaxes the smooth muscles of the bronchioles and relieves bronchospasms. This effect also may facilitate expectoration. It is shown to improve symptoms and morning peak flows. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. Bronchodilating effect lasts more than 12 hours. It is used in addition to anticholinergic agents.
Arformoterol (Brovana)
Arformoterol is a selective, long-acting beta-2 adrenergic receptor agonist that has 2-fold greater potency than racemic formoterol. Pharmacologic effects of arformoterol are from the stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in intracellular cyclic AMP levels in turn cause relaxation of bronchial smooth muscles.
Indacaterol, inhaled (Arcapta Neohaler)
Long-acting beta2-agonist (LABA) indicated for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. LABAs act locally in the lungs as bronchodilators. Stimulates intracellular adenyl cyclase, causing conversion of ATP to cyclic AMP; increased cyclic AMP levels cause relaxation of bronchial smooth muscle. Not for use as initial therapy in patients with acute deteriorating COPD.
Anticholinergic Agents
Class Summary
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. Clinical benefit is gained through a decrease in exercise-induced dynamic hyperinflation. These agents are poorly absorbed systemically and are relatively safe. Reported adverse effects include dry mouth, metallic taste, and prostatic symptoms.
Ipratropium (Atrovent)
Short-acting anticholinergics, such as ipratropium bromide (Atrovent), have been shown to have equivalent or superior activity in patients with stable COPD when compared with a beta2 agonist. When combined with a beta2 agonist, a synergistic effect on bronchodilatation occurs. Typically, 2-4 puffs of ipratropium bromide are administered every 6-8 hours. This medication has a slower onset and a longer duration than a beta2 agonist and is less suitable for use on an as-needed basis.
Tiotropium (Spiriva)
Tiotropium, a bronchodilator similar to ipratropium, is a once-daily, long-acting anticholinergic medication that has been shown to have significant clinical benefit. A quaternary ammonium compound, it elicits anticholinergic/antimuscarinic effects, with inhibitory effects on M3 receptors on airway smooth muscles, leading to bronchodilation. Tiotropium is the only long-acting muscarinic agent available at this time and has become a first-line therapy in patients with persistent symptoms. Tiotropium is more effective than salmeterol in preventing exacerbations.[47]
Xanthine Derivative
Class Summary
Xanthine derivatives such as theophylline relax the smooth muscles of the bronchi and pulmonary blood vessels. Inhibition of phosphodiesterase by these agents causes an increase in cyclic adenosine monophosphate (cAMP), causing the relaxation of bronchial smooth muscles.
Theophylline (Aminophylline, Theo-24, Theo-Dur, Slo-bid)
Theophylline is a nonspecific phosphodiesterase inhibitor and is now limited to use as an adjunctive agent. Theophylline has a narrow therapeutic window with significant adverse effects, including anxiety, tremors, insomnia, nausea, cardiac arrhythmia (particularly multifocal atrial tachycardia), and seizures. It is reserved for patients with hard-to-control COPD or for individuals who are not able to use inhaled agents effectively. Theophylline is metabolized primarily via the hepatic cytochrome P450 system, a process affected by age, cardiac status, and liver abnormalities. Serum levels of theophylline need to be monitored because of the potential for toxicity. The previously recommended target range of 15-20 mg/dL has now been reduced to 8-13 mg/dL.
Phosphodiesterase Type 4 (PDE-4) Inhibitors
Class Summary
Roflumilast, a phosphodiesterase type 4 inhibitor, may reduce exacerbations, improve dyspnea, and increase lung function for patients with COPD on concomitant long-acting beta-agonists.[82]
Roflumilast (Daliresp)
Roflumilast is a selective phosphodiesterase 4 (PDE4) inhibitor. The specific mechanism of action is not well defined but is thought to be related to the effects of increased intracellular cyclic AMP in lung cells. It is indicated to decrease the frequency of exacerbations or worsening of symptoms from severe COPD.
Corticosteroids, Inhalant
Class Summary
In acute exacerbations, steroids improve symptoms and lung function. Inhaled corticosteroids provide a more direct route of administration to the airways and, similar to other inhaled agents, are only minimally absorbed. Inhaled steroids have fewer adverse effects than do oral agents, although they improve expiratory flows less effectively, even at high doses. These agents may be beneficial in slowing the rate of progression in a subset of patients with COPD who have rapid decline.
Fluticasone inhaled (Flovent)
Fluticasone inhibits bronchoconstriction producing direct smooth muscle relaxation. It may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. Effectiveness in COPD is not established. Inhaled corticosteroids have a lesser role in the management of chronic bronchitis. Several studies demonstrate no benefit, although approximately half of patients who respond to oral steroids may benefit from inhaled agents.
Budesonide inhaled
Budesonide inhibits bronchoconstriction, producing direct smooth muscle relaxation. It may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It has extremely potent vasoconstrictive and anti-inflammatory activity, and it alters the level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators. It also decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Effectiveness is not established in COPD.
Corticosteroids, Oral
Class Summary
The use of oral steroids in the treatment of acute exacerbations is widely accepted and recommended, given their high efficacy. Note that oral steroids are not as effective in treating COPD exacerbations as they are in treating bronchial asthma exacerbations.
Prednisone (Sterapred)
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Methylprednisolone (Solu-Medrol, Medrol)
Methylprednisolone is usually given in IV form for initiation of corticosteroid therapy, although the oral form is theoretically equally efficacious. The 2 forms are equal in potency, time of onset, and adverse effects. Inhaled corticosteroids are probably equally efficacious and have fewer adverse effects.
Beta-Adrenergic Agonist and Anticholinergic Agent Combinations
Class Summary
These agents combine the benefits of the rapid onset of a beta-adrenergic agonist with the prolonged action of an anticholinergic agent.
Ipratropium and albuterol (Combivent, DuoNeb, Combivent Respimat)
Ipratropium is chemically related to atropine, and it has antisecretory properties. Albuterol is a beta agonist for bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta2 receptors with little effect on cardiac muscle contractility.
Metered-dose inhalers that contain chlorofluorocarbons (CFCs) are currently being phased out in the US; alternate inhalers without CFCs are available (Combivent Respimat)
Beta2-Adrenergic Agonist and Corticosteroid Combinations
Class Summary
Combination therapy is recommended when COPD patients are uncontrolled with bronchodilator monotherapy. Agents that use a long-acting beta agonist and an inhaled corticosteroid are commonly used in asthma and COPD and show increased clinical benefits.
Budesonide/formoterol (Symbicort)
Formoterol relieves bronchospasms by relaxing the smooth muscles of the bronchioles in conditions associated with asthma. Budesonide is an inhaled corticosteroid that alters the level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.
Fluticasone and salmeterol (Advair Diskus)
Fluticasone inhibits bronchoconstriction mechanisms, producing direct smooth muscle relaxation. It may decrease number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It also has vasoconstrictive activity. Salmeterol relaxes the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis and can relieve bronchospasms. Its effect may also facilitate expectoration.
Antibiotics
Class Summary
In patients with COPD, chronic infection or colonization of the lower airways is common from S pneumoniae, H influenzae, and M catarrhalis. In patients with chronic severe airway obstruction, P aeruginosa infection may also be prevalent. The use of antibiotics for the treatment of acute exacerbations is well supported.
Amoxicillin (Amoxil, Trimox, Moxatag)
Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Doxycycline (Doryx, Monodox, Doxy, Adoxa)
Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, it concentrates in bile, and it is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Trimethoprim/sulfamethoxazole (Co-Trimoxazole, TMP-SMZ)
Sulfamethoxazole and trimethoprim inhibit bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, resulting in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. Like tetracycline, it has in vitro activity against Bartonella pertussis. It is not useful in mycoplasmal infections.
Cefuroxime (Zinacef)
Cefuroxime is a second-generation cephalosporin and maintains gram-positive activity of first-generation cephalosporins; it adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. It binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. The condition of the patient, the severity of infection, and the susceptibility of the microorganism determine proper dose and route of administration. It also resists degradation by beta-lactamase.
Azithromycin (Zithromax)
Azithromycin acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used to treat acute bacterial exacerbations of chronic obstructive pulmonary disease caused by S pneumoniae, H influenzae, and M catarrhalis. They cover most potential etiologic agents, including Mycoplasma. The newer macrolides offer decreased GI upset as well as potential for improved compliance through reduced dosing frequency. They also afford improved action against H influenzae.
Clarithromycin (Biaxin)
Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.
Smoking Cessation Therapies
Class Summary
Smoking cessation continues to be the most important therapeutic intervention for COPD. Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs. Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms.
Nicotine transdermal system (Nicotrol, Habitrol, NicoDerm CQ)
Transdermal nicotine patches are readily available for replacement therapy. Long-term success rates are 22-42%, compared with 2-25% for placebo. These agents are well tolerated, and the adverse effects are limited to local skin reactions. Nicotine replacement therapy patches are sold under the trade names NicoDerm, Nicotrol, and Habitrol. Each of these products is dosed with a scheduled graduated decrease in nicotine over 6-10 weeks.
Nicotine polacrilex (Nicorette)
Nicotine polacrilex is a chewing gum and has better quit rates than does counseling alone. Nicotine-replacement-therapy chewing pieces are marketed in 2 strengths (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 patients 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.
Bupropion (Zyban)
The use of the antidepressant bupropion (Zyban) is also effective for smoking cessation. This non-nicotine aid to smoking cessation enhances central nervous system nonadrenergic function. Bupropion may also be effective in patients who have not been able to quit smoking with nicotine replacement therapy. It is used in conjunction with a support group and/or behavioral counseling. It inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake.
Varenicline (Chantix)
Varenicline is a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Its 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.
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