Beta-2
adrenergic agonists are
sympathomimetic agents that stimulate bronchodilation by activation of
adenyl cyclase to produce cyclic 3'5'
adenosine monophosphate (
AMP). Short-acting beta-agonists (SABAs) have a 3- to 6-hour duration of action, and the duration of action of long-acting beta-agonists (LABAs) exceeds 12 hours. Because of their rapid onset of action, SABAs are effective for rescue from symptoms of
chronic obstructive pulmonary disease (
COPD). LABAs-
salmeterol and
formoterol-have been shown to significantly improve lung function, health status, and symptom reduction, compared with
ipratropium. Despite safety concerns over the use of LABAs as monotherapy in
asthma the use of these medications in
COPD has generally been described as safe. Novel
bronchodilators for
COPD in late-stage development include the beta-agonists indacterol and
carmoterol. Parasympathetic activity in the large and medium-size airways is mediated through the
muscarinic receptors and results in airway smooth-muscle contraction, mucus secretion, and possibly increased ciliary activity. Although short-acting
ipratropium has been used as monotherapy or in combination with
albuterol the use of long-acting
antimuscarinics is superior in improving health outcomes. The use of
tiotropium results in improved health status,
dyspnea, and exercise capacity, and reduced hyperinflation and
COPD exacerbation rate in patients with moderate to severe
COPD. Analysis of prospective clinical trial data shows a mortality reduction in subjects treated with
tiotropium, despite retrospective review of insurance claims that show an enhanced mortality.
Theophylline is a nonselective
phosphodiesterase inhibitor that acts as both a weak
bronchodilator and a
respiratory stimulant. Novel approaches include using the inhalation route to reduce side effects and combination with inhaled
corticosteroids (ICS). However, because of its potential adverse effects and narrow therapeutic index, it should only be used when symptoms persist despite optimal
bronchodilator therapy. Current guidelines highlight that for
COPD patients uncontrolled by
bronchodilator monotherapy, combination
therapy is recommended. These include LABA/ICS and LAMA/LABA combinations.
Bronchodilators and their combination with ICS are central to the management of
COPD. The choice of agents is based primarily on disease stage, individual response, cost, side effect profile, and availability.