Journal of Allergy and Clinical Immunology
Nonrespiratory EffectsAdverse effects of β-agonists☆
Section snippets
Cardiac effects
Mild tachycardia is common when patients are first exposed to β-agonists, even the most recent highly β2AR-specific agents. In part, tachycardia may result from dilation of peripheral vasculature that reduces venous return, resulting in sympathetic nervous system reflexes and increased inotropic and chronotropic effects. β-Agonists may also stimulate β2ARs in the cardiac muscle itself, in both the left ventricle and the right atrium, increasing heart rate directly.
The early adrenergic agents,
Pharmacologically predictable effects of SABAs in unusual physiologic circumstances
Several research groups have quite extensively studied the effects of hypoxia in an acute episode of asthma on the response of cardiac muscle and the intact cardiac function as evaluated by electrocardiography. Such effects, which could exaggerate the adverse effects of β-agonists, imply that hypoxemia and hypercapnia should be aggressively treated when high doses of β-agonists are required in acute situations and that perhaps β-agonists should be used with caution in patients with chronic
Increased nonspecific airway responsiveness
Several carefully conducted studies have confirmed that the regular or frequent use of the classic SABAs fenoterol, albuterol, and terbutaline can result in a small increase in AHR, measurable after the drug is withheld for some hours. Responsiveness to nonspecific bronchoconstrictor agents such as histamine or methacholine was increased between 0.5 and 1 doubling dilution by regular use of β-agonist in the majority of studies reviewed.
Animal studies have shown AHR to histamine after treatment
Consequences of adverse effects of SABAs
There seems to be little doubt that the epidemics of both mortality and morbidity (as reflected in hospitalizations and emergency room visits) associated with β-agonists are related to adverse effects on airway responsiveness and not to cardiac or metabolic adverse effects. Increased severity of asthma during regular β-agonist treatment has been manifested as lower lung function as well as increased symptoms, nocturnal symptoms, need for short course of prednisone, and other indicators of a
Pharmacologically predictable effects of LABAs
The pharmacologically predictable effects of LABAs are similar to those seen with SABAs but overall are less substantial.
Nonpharmacologically predictable effects of LABAs
Neither salmeterol nor formoterol has been shown to increase airway responsiveness to either specific stimuli (allergen or exercise) or nonspecific stimuli (histamine, methacholine, saline), except in children, in whom the use of salmeterol as monotherapy led to deterioration of lung function and to AHR.69, 70 Tolerance to the bronchoprotective effects of both salmeterol and formoterol has been repeatedly demonstrated,71, 72 but rebound AHR has not been shown.73 There is no epidemiologic
Conclusions
In summary, the pharmacologically predictable effects of both SABAs and LABAs are not problematic, except perhaps in the presence of hypoxia or comorbidity, and tolerance to these effects occurs readily. LABAs overall show fewer pharmacologically predictable effects than SABAs. Adverse effects on airway responsiveness and inflammation have been shown with regular SABAs but not with LABAs.
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Reprint requests: Malcolm R. Sears, MB, Firestone Institute for Respiratory Health, St Joseph's Healthcare and Master University, 50 Charlton Ave East, Hamilton, Ontario, L8N 4A6, Canada.