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Inhaled corticosteroids and β agonists are the most frequently prescribed drugs in the management of chronic asthma. Current guidelines emphasise their complementary role. Inhaled corticosteroids are the treatment of choice for all but the mildest of disease. Short acting β agonists are recommended for “as required” relief of asthma symptoms, whereas long acting agents are indicated as a supplement to anti-inflammatory therapy if breakthrough symptoms persist.1 Thus, co-prescribing is commonplace. However, despite dynamic interactions between endogenous glucocorticoids and catecholamines in vivo, it is only recently that interest in the possibility of drug interactions has developed. Two topical and clinically relevant questions arise. Firstly, do positive interactions occur, thus providing theoretical justification for current trends to use combination products incorporating a long acting β agonist and a corticosteroid? Secondly, do negative interactions occur which might explain the apparent paradox that, despite increasing use of the two therapies over the last 30 years, the overall burden of asthma morbidity in most western countries has continued to increase?2
Effects of glucocorticoids on β receptor function
Endogenous adrenal glucocorticoids have an important facilitatory effect on β receptor function in vivo. In animals adrenalectomy results in a generalised loss of responsiveness to catecholamines.3 4 Conversely, the presence of glucocorticoids enhances β receptor mediated responses: myocardial contractility, hepatic and voluntary muscle glucose metabolism, and bronchial smooth muscle relaxation have been shown to increase.4 These actions occur at physiological concentrations of glucocorticoid.
At least two mechanisms are proposed whereby glucocorticoids modify β receptor function. The first is by regulating the coupling of β receptors to G proteins and hence adenyl cyclase activation (fig 1). The degree of coupling determines cell responsiveness to β receptor stimulation.5 Following exposure to exogenous β agonist, uncoupling occurs rapidly by phosphorylation of the receptor (desensitisation). There are a number of phosphorylation pathways, including β …
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