ABSTRACT
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 β-agonists (SABAs) have a 3- to 6-hour duration of action, and the duration
of action of long-acting β-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 β-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.
KEYWORDS
COPD - bronchodilator - inhaled corticosteroid - combination therapy - disease modification
end points - FEV1 decline
REFERENCES
Available from http://www.goldcopd.org Bronchodilator therapy of airway disease . In: Chung KF, Barnes PJ Pharmacology and Therapeutics of Airway Disease. New York,
NY; Informa Healthcare USA 2009: 198-225
jdonohue@med.unc.edu
