![]() 23 Formoterol is metabolized primarily in the liver by CYP450 enzymes and undergoes glucuronidation and O-demethylation. The cytochrome P450 (CYP) isoform 3A4 is responsible for aliphatic oxidation of salmeterol base, which is extensively metabolized by hydroxylation, with the major metabolite being alpha- hydroxysalmeterol and with subsequent elimination predominantly in the feces. The xinafoate moiety has no discernable pharmacological activity, is highly protein bound, and has a long elimination half-life of about 12 to 15 days in healthy individuals. These two compounds are then absorbed, distributed, metabolized, and excreted independently. Salmeterol xinafoate dissociates in solution to salmeterol and 1-hydroxy-2-naphthoic acid. 22 Secondly the intrinsic efficacy of the drugs varies-formoterol is a full agonist whilst salmeterol is a partial agonist hypothetically this implies formoterol should provide better bronchodilation. There is also some evidence to suggest that salmeterol binds to an additional exosite within the receptor, potentiating the longer effect of the drug. 21 Both drugs have adequate lipophilic properties that allow them to remain in the airway tissues in close vicinity to B 2AR, explaining the longer duration of action. 20 Salmeterol’s onset of action is, at least 20 minutes, significantly longer. Both are lipophilic, with salmeterol being far more so than formoterol the relative water solubility of formoterol enables it to diffuse rapidly to the B 2AR and cause bronchodilation in between 1 to 3 minutes, similar to that of SABAs. ![]() 17 Salmeterol and formoterol have some important differences which can be explained by their physicochemical properties. Despite these characteristics, it appears to be inferior to salmeterol in terms of health related quality of life (HRQoL) scores and its ability to reduce exacerbations, albeit in indirect comparisons only. Formoterol’s potency and speed of action make it effective in both quick relief and for prolonged effect. Salmeterol and formoterol are LABAs with extended duration of action maintained 12 hours after inhalation of a single dose, 19 which has led to their twice daily dosing. This review outlines the pharmacological management of stable COPD. 7 The main goals in management of COPD are improving health status, reducing symptoms, preserving lung function decline, preventing exacerbations, and reducing mortality. 6 These co-morbidities interact to increase the risk of hospitalization and mortality in COPD patients, especially as the airway obstruction becomes more severe. The most widely recognized manifestations include the presence of concomitant cardiovascular disease, skeletal muscle dysfunction, osteoporosis, and clinical depression/anxiety. What is unclear at present is whether these manifestations are directly related to COPD or are just an independent consequence of the exposure to common causal effects such as tobacco smoking and inactivity. 5 Although mainly categorized by airflow limitation, in many patients the disease seems to be associated with several extra-pulmonary manifestations. 3 Frequent exacerbations are associated with more rapid decline of lung function 4 and are one of the greatest costs to the health economy, partly through hospital admissions, and partly through loss of work days. Acute exacerbations are defined by increased cough, dyspnea, or increased sputum purulence from baseline, 2 and punctuate the disease process with a deleterious impact on patients’ daily activities and well-being. In affected individuals lung function deteriorates progressively over several years, with increasing symptoms such as cough, sputum production, and dyspnoea. ![]() 1 COPD is associated with an enhanced chronic inflammatory response which is responsible for the airway abnormalities and architectural distortion of the lung parenchyma. ![]() 1ĬOPD is characterized by airflow limitation that is progressive and not fully reversible the latest severity categorization also includes exacerbation frequency and symptom burden as key features. 1 Globally the burden of disease is projected to increase in the coming decades due to continued exposure to COPD risk factors and an ageing population. It is currently the fourth leading cause of death worldwide and predicted to be the third by 2020. Chronic obstructive pulmonary disease (COPD) is a multi-component disease which is both preventable and treatable.
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