Tiotropium bromide

Abstract

Therapy with bronchodilators forms the pharmacologic foundation of the treatment of patients with COPD. Bronchodilators can significantly lessen dyspnea, increase airflow, improve quality of life, and enhance exercise performance. While bronchodilators decrease airway resistance and lessen dynamic hyperinflation in patients with COPD, they have not been shown to alter the rate of decline in FEV1 over time, or improve patient survival. Fairly recently, a long-acting, once-daily anticholinergic medication, tiotropium bromide, has been developed which may improve symptom management in COPD patients. This paper reviews anticholinergic pharmacologic therapy for patients with COPD focusing on tiotropium bromide, and discusses treatment strategies based on disease stage. It is important to recognize that while bronchodilators improve symptoms, a multimodality treatment approach including respiratory and rehabilitative therapy, nutrition services, psychosocial counseling, and surgical care, is often necessary for the best possible care of patients with COPD.

Figure 1

Pulmonary muscarinic cholinergic receptors. M₁ and M₃ receptors mediate bronchoconstriction and mucus production in the lung. M₂ receptors inhibit M₁ and M₃ receptors via negative feedback. Ipratropium inhibits all three muscarinic receptors. Tiotropium quickly dissociates from the M₂ receptor but continues to antagonize the M₁ and M₃ receptor. Thus, tiotropium blocks bronchoconstriction and allows inhibition of bronchoconstriction to continue. The slow dissociation of tiotropium from the M₁ and M₃ receptors accounts for its long half-life.

Figure 2

Chemical structure of ipratropium.

Figure 3

Tiotropium bromide. Note the similarity to ipratropium (Figure 2) and the presence of the quaternary nitrogen group, which is responsible for its efficacy.

Figure 4

Tiotropium improves lung volumes compared with placebo. Reproduced from Celli B, ZuWallack R, Wang S, et al. 2003. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest, 124:1743–8. Copyright © 2003, with permission from CHEST. Abbreviations: FRC, functional residual capacity; IC, inspiratory capacity; SVC, slow vital capacity.

Figure 5

Treatment of COPD by stage. Reproduced from Lipson DA. 2004. Redefining treatment in COPD: new directions in bronchodilator therapy. Treat Respir Med, 3:89–95. Erratum in Treat Respir Med, 3:181. Copyright © 2004, with permission from Adis International Ltd. Abbreviations: LVRS, lung volume reduction surgery.