COPD bronchodilators

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

The two major types of bronchodilators are the sym-padiomimetics and die xantiiine derivatives. The anticholinergic drug ipratropium bromide (Atrovent) is used for bronchospasm associated witii COPD, chronic bronchitis, and emphysema. Ipratropium is included in die Summary Drug Table Bronchodilators. Chapter 25... 

Bronchodilators are the mainstay of treatment for symptomatic COPD. They reduce symptoms and improve exercise tolerance and quality of life. 

Theophylline is a non-specific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle resulting in bronchodilation. It has a modest bronchodila-tor effect in patients with COPD, and its use is limited due to a narrow therapeutic index, multiple drug interactions, and adverse effects. Theophylline should be reserved for patients who cannot use inhaled medications or who remain symptomatic despite appropriate use of inhaled bronchodilators. 

Leukotriene modifiers (e.g., zafirlukast and montelukast) have not been adequately evaluated in COPD patients and are not recommended for routine use. Small, short-term studies showed improvement in pulmonary function, dyspnea, and quality of life when leukotriene modifiers were added on to inhaled bronchodilator therapy.27,28 Additional long-term studies are needed to clarify their role. 

Tashkin DP, Cooper CB. The role of long-acting bronchodilators in the management of stable COPD. Chest 2004 125 249-259. 

Patients experiencing a COPD exacerbation may have worsening dyspnea, increase in sputum volume, or increase in sputum purulence. Other common features of an exacerbation include chest tightness, increased need for bronchodilators, malaise, fatigue, and decreased exercise tolerance. 

Methylxanthines are no longer considered first-line therapy for COPD. Inhaled bronchodilator therapy is preferred over theophylline for COPD because of theophylline s risk for drug interactions and the interpatient variability in dosage requirements. Theophylline may be considered in patients who are intolerant or unable to use an inhaled bronchodilator. A methylxanthine may also be added to the regimen of patients who have not achieved an optimal clinical response to an inhaled anticholinergic and [i2-agonist. 

As with other bronchodilators in COPD, parameters other than objective measurements such as FEVj should be monitored to assess efficacy. Subjective parameters, such as perceived improvements in dyspnea and exercise tolerance, are important in assessing the acceptability of methylxanthines for COPD patients. 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all early pulmonary drug-delivery devices, it delivered small-molecule compoimds (bronchodilators or inhaled corticosteroids) to the airways (not necessarily the deep limg) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems used for asthma and COPD the energy somces in these devices were mechanical and patient inspiration. 

Hansel TT, Barnes PJ, Tiotropium bromide A novel once-daily anticholinergic bronchodilator for the treatment of COPD, Drugs Today (Bare) 38 585-600, 2002. 

Bronchospasm (solution and aerosol) Used alone or in combination with other bronchodilators (especially beta-adrenergics) as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. 

Bronchospasm Use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm and require a second bronchodilator. 

AminophyUine [Bronchodilator/Xanthine Derivative] Uses Asthma, COPD bronchospasm Action Relaxes smooth muscle (bronchi, pulm... 

Albuterol Ipratropium (Combivent, DuoNeb) [Bronchodilator/Adrenergic, Anticholinergic] Uses coPD ... 

Reversibility tests to bronchodilators are recommended at all stages of obstructive airways diseases. They are helpful in differentiating patients with COPD with those of asthma. Many patients with COPD and even those with severe airflow obstruction can demonstrate (partial) reversibility. Patients with a positive bronchodilator response i.e. reversibility are more likely to respond to a trial of oral or inhaled corticosteroids. 

Although a variety of interpretations have been issued, reversibility to bronchodilators is considered to be present when the FEV i increases by 200 ml and 12% of the pre-bronchodilator value. Although in the latest GINA guidelines this issue is no longer addressed, the same criteria have been used for evaluation of the response to corticosteroids. A corticosteroid trial compared spirometric tests before and at the end of oral prednisolone (e.g. 30 mg/d) taken for two weeks or a course of inhaled steroid (e.g. beclomethasone 500 pg twice daily or equivalent) taken for six weeks. A positive response to corticosteroids justified prescription of regular inhaled steroid. Subjective improvement as a single efficacy parameter is not considered to be a satisfactory end point. Objective improvement is seen in 10-20% of patients with COPD. 

COPD is a chronic, slowly progressive disorder characterized by airways obstruction (FEVi < 80% predicted FEViA C ratio < 70%) which does not change markedly over several months. The airways obstruction is largely fixed but may be partially reversible by bronchodilator therapy. Unlike asthma, airflow limitation in COPD can never be returned to normal values. The diagnosis of COPD is usually suggested by symptoms. A firm diagnosis can only be made by objective measurement of airways obstruction with spirometric tests, which may be enhanced by radio diagnostic techniques (Table 4). 

Bronchodilators play an important role in the longterm control of symptoms, but they do not alter the progression of COPD. In all current guidelines there is consensus that bronchodilators are the cornerstone... 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

While the treatment of infections can be of beneflt in COPD patients a Cochrane systematic review concludes that bronchodilators produce only modest short-term improvement in clinical scores in patients with bronchitis. This small beneflt must be weighed against the costs of these agents. 

Mapel DW, Nelson LS, Lydick E, Soriano J, Yood MU, Davis KJ et al. Survival among COPD patients using fluticasone/sahneterol in combination versus other inhaled steroids and bronchodilators alone. COPD 2007 4(2) 127-34. 

Bronchodilator of choice for COPD Patient/Famiiy Education... 

COPD is characterized by airflow limitation that is not fully reversible with bronchodilator treatment. The airflow limitation is usually progressive and is believed to reflect an abnormal inflammatory response of the lung to noxious particles or gases. The condition is most often a consequence of prolonged habitual cigarette smoking, but approximately 15% of cases occur in nonsmokers. 

Albuterol Selective B2 agonist Prompt, efficacious bronchodilation Asthma, chronic obstructive pulmonary disease (COPD) drug of choice in acute asthmatic bronchospasm Aerosol inhalation duration several hours also available for nebulizer and parenteral use Toxicity. Tremor, tachycardia t overdose arrhythmias... 

Theophylline Uncertain phosphodiesterase inhibition t adenosine receptor antagonist Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm) Asthma, COPD Oral duration 8-12 h but extended-release preparations often used Toxicity. Multiple (see text)... 

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