No abstract

This study was designed to determine whether resistance to the airway effects of the beta-agonist, salbutamol, would develop in three groups of subjects while taking large doses of inhaled salbutamol. Six normal non-atopic, six atopic non-asthmatic, and eight atopic asthmatic subjects were studied by an identical technique. The development of resistance was assessed from salbutamol dose-response studies in which the airway response was measured as specific airway conductance (sGaw). Further evidence was sought in the atopic and asthmatic subjects by measuring the airway response to a standard histamine inhalation challenge and the protective effect of 100 f4g salbutamol on this challenge, and by six-hourly peak flow recordings. Subjects were assessed before and during four weeks in which they took inhaled salbutamol regularly in doses increasing to 500 /g qid in week 4. Normal subjects showed a progressive reduction in the bronchodilator (sGaw) response to salbutamol during the four weeks, indicating the progressive development of resistance. The atopic subjects, both asthmatic and non-asthmatic, showed no reduction in the response to salbutamol during the four weeks, nor any change in the response to histamine challenge or in regular peak flow readings. These results demonstrate that asthmatic patients do not develop bronchial beta-adrenoceptor resistance easily and suggests that they and atopic non-asthmatic subjects are less susceptible to its development than normal subjects.

1. Airway, metabolic and cyclic nucleotide responses to intravenous salbutamol were measured in five patients with mild asthma who had taken no medication in the week before the study. The studies were repeated after the patient had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 2000 micrograms daily in week 4. 2. The pretreatment airway, metabolic and cyclic nucleotide responses to salbutamol were similar to those previously reported in normal subjects. These patients therefore did not show evidence of partial beta-adrenoceptor blockade. 3. After 4 weeks' salbutamol therapy the airway response to intravenous salbutamol was unchanged. 4. The glucose, pyruvate and adenosine 3':5'-cyclic monophosphate (cyclic AMP) responses to intravenous salbutamol were depressed after regular salbutamol administration. The dose-response curve for non-esterified fatty acids and insulin, though displaced downwards, did not indicate an impaired response to salbutamol since the shape was unchanged. There was no significant change in the lactate, glycerol and total ketone response. 5. This study confirms that tissues differ in the ease with which they develop resistance to beta-adrenoceptor agonists. Asthmatic airways appear to be relatively protected from developing assistance when compared with other tissues in asthmatic patients and when compared with the airways of normal subjects.

No abstract

Tiaramide hydrochloride is a new non-steroidal anti-inflammatory agent previously shown to inhibit allergic responses both in vitro and in vivo. Clinical studies in asthmatic adults and children have also shown benefit. We report a double blind cross-over study in 35 adult asthmatic patients comparing oral tiaramide 200 mg four times daily with oral salbutamol 4 mg four times daily and placebo. Symptoms and bronchodilator inhaler usage were recorded in diary cards and morning and evening peak expiratory flow rates were also monitored. Both tiaramide and salbutamol had a significant therapeutic effect compared with placebo. More patients preferred tiaramide than salbutamol and there were fewer side effects during treatment with tiaramide. Tiaramide may be a useful oral therapy in asthma particularly for those patients intolerant of oral beta-adrenergic agonists.