Risks Versus Benefits of Inhaled ??2-Agonists in the Management of Asthma

Abstract

The therapeutic goal for the treatment of asthma should be to suppress bronchial mucosal inflammation with preventive drugs such as inhaled corticosteroids, and to relieve symptoms of wheezing and breathlessness with bronchodilator drugs. The lower recommended doses of inhaled beta 2-agonists produce rapid effective bronchodilatation without systemic adverse effects; higher doses may produce substantial improvements in airway response which may help patients with more severe airflow obstruction. Higher doses of inhaled beta 2-agonists also cause dose-related systemic adverse beta 2 effects including tremor, tachycardia, hypokalaemia and associated electrocardiographic sequelae. In this respect, although fenoterol appears to cause greater extrapulmonary beta 2-mediated adverse effects at higher doses, there is no evidence to suggest that it is any less beta 2-selective. There is also some evidence to suggest that use of regular inhaled beta 2-agonists may cause increased bronchial hyperreactivity and possibly deterioration in disease control. Patients who require such regular use should therefore be given additional anti-inflammatory therapy with inhaled corticosteroids. The recent availability of novel, longer-acting inhaled beta 2-agonists such as salmeterol and formoterol will also make necessary a careful reappraisal of their long term use in patients with asthma.

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

“…This has been the subject of much basic and clinical research. [120][121][122][123][124][125] Although downregulation of beta 2 adrenoceptors has been demonstrated in laboratory studies, most large clinical trials of LABAs have shown that tolerance to the bronchodilator effects of LABAs is not a significant clinical problem. 115 Tolerance to the bronchoprotective effects of LABAs against bronchoconstrictor stimuli such as methacholine challenge or exercise has been demonstrated in clinical studies.…”

Tolerance with beta 2‐adrenoceptor agonists: time for reappraisal.

“…The issue of safety and increased mortality in relation to the use of 02-adrenoceptor agonists has been extensively reviewed elsewhere and will only be referred to here in the context of tolerance [1][2][3][4][5][6][7]. The facilitatory effects of disease modifying agents such as corticosteroids on 02-receptors and tachyphylaxis will also be discussed, as this has implications in clinical situations where the two therapies are often used concurrently.…”

The Use of Bronchodilators in Stable Chronic Obstructive Pulmonary Disease

“…15 Also an increase in the dose of these drugs is modest and oral and intravenous -agonists do reach 2 -receptors limited to a small population of COPD patients, with on vascular smooth muscle, with consequent pula lack of reproducibility for any given individual, and monary vasodilatation at rest, and may further reduce pulmonary artery pressure by lowering airways reis at the expense of various side effects including tremor, tachycardia and hypokalemia. 25 sistance. 34 The resulting increase in cardiac output is by an after load reduction mechanism.…”