Chronic obstructive pulmonary disease (COPD) is a major public health problem, with inhaled anticholinergic agents being the treatment of choice. The disadvantage of currently approved therapies for the treatment of COPD is that agents such as ipratropium (Atrovent, Boehringer Ingelheim) must be administered numerous times daily. Tiotropium (Spiriva, Pfizer/Boehringer Ingelheim) is a new, recently FDA-approved, long-acting anticholinergic drug that requires only once-daily dosing. Tiotropium displays selective receptor kinetics by dissociating more slowly from M1 and M3 receptors than M2 receptors. In patients with COPD, tiotropium 18 mcg inhaled once daily results in significant improvement in lung function. Furthermore, improvements appear sustained for up to 3 weeks after discontinuing tiotropium. Tiotropium is well tolerated with minimal systemic absorption resulting in a favorable adverse effect profile. The most common adverse effect associated with tiotropium is dry mouth. Given the longer duration of action, once-daily dosing, minimal adverse effects, and documented improvements in lung function, tiotropium is poised to replace ipratropium as the inhaled anticholinergic of choice. (Formulary. 2004;39:203-212.)
Chronic obstructive pulmonary disease (COPD) is expected to become the third-leading cause of death and fifth-leading cause of disability by 2020 and represents a significant public health concern both now and in the future. (1,2) COPD is a nonreversible airway disease characterized by airflow obstruction and a chronic persistent inflammatory process. Mucus hypersecretion is common as is a lack of airway hyperreactivity. The lack of airway hyperreactivity is in stark contrast to the findings of most asthmatic patients who exhibit a robust response to bronchodilators. For most COPD patients, symptomatic relief is achieved with a combination of bronchodilators, such as long and short-acting beta[.sub.2]-agonists and anticholinergic agents. Approximately 10% of patients with COPD may also have asthma and therefore corticosteroids can provide some additional symptom relief. (3) However, the majority of patients with COPD experience little benefit with the addition of either oral or inhaled corticosteroids. (3)
The vast majority of patients develop COPD secondary to smoking; therefore the first goal in managing COPD patients is to ensure smoking cessation. (3-6) Currently the only therapies shown to improve survival in COPD patients are smoking cessation and oxygen therapy. (3-6) In light of this, a tremendous demand exists for pharmaceutical manufacturers to develop successful pharmacologic interventions that will help reduce the morbidity and mortality associated with COPD. Most treatment guidelines for managing COPD recognize anticholinergic agents as first-line agents. (3-6) Until February 2004, ipratropium (Atrovent, Boehringer Ingelheim) was the only FDA-approved anticholinergic agent available for COPD in the United States. The approval of tiotropium (Spiriva, Pfizer/Boehringer Ingelheim), a long-acting, once-daily, inhaled anticholinergic bronchodilator, added another therapy to the COPD armamentarium.
CHEMISTRY AND PHARMACOLOGY
Anticholinergic agents have long been used for the treatment of airway diseases. For example, the inhaled smoke from alkaloid-containing botanical preparations such as Datura stramonium (jimson weed) evolved into inhaling atropine cigarettes to the inhalation of nebulized solutions of atropine. (7,8) The development of N-quaternary congeners of atropine (eg, ipratropium) helped minimize systemic anticholinergic side effects by creating a molecule that...
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