Beta-adrenoceptor agonists: basic pharmacology
COPD is a disease state characterised by airflow limitation that is not fully reversible. The limitation of airflow develops progressively and is usually associated with an abnormal inflammatory response of the lungs to noxious particles or gases. COPD is characterised by inflammation throughout the respiratory system, including bronchial and bronchiolar airways, parenchyma and pulmonary vasculature. Increased numbers of inflammatory cells [macrophages, T-lymphocytes (predominantly CD8+) and neutrophils] in the airways is also a feature of this disease [1,2]. Activation of inflammatory cells releases a variety of mediators, including leukotriene B4 (LTB4), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), that in turn contribute to widespread degenerative changes to the structure of the respiratory tract and promote neutrophilic inflammation [2-6]. An imbalance between proteases that digest elastin and other structural proteins and antiproteases that protect against this damage is thought to contribute to the progression of this disease . Oxidative stress may also be involved in the pathogenesis of COPD. It is likely that cigarette smoke and other factors associated with COPD can initiate an inflammatory reaction in the airways that leads to this disease. The airflow obstruction seen in COPD patients is usually accompanied by airway hyperresponsiveness. This chronic airflow obstruction especially affects small airways, with lung elasticity also lost due to enzymatic destruction of the lung parenchyma, resulting in progressively worsening emphysema. COPD is characterised by shortness of breath, cough, sputum production and exercise limitation, with acute exacerbations resulting in worsening of symptoms. Inhaled bronchodilators, including β2-adrenoceptor agonists, have been shown to ameliorate respiratory symptoms and improve the quality of life for COPD patients and are recommended in the management of acute exacerbations of this disease. Unfortunately, β2-adrenoceptor agonists fail to provide lasting improvements in the deteriorating lung function seen in COPD.