Resistance to -adrenoceptor stimulants (a possible explanation for the rise in ashtma deaths)

1. Resistance to isoprenaline has been produced in man and dog by prolonged exposure to the same, or the pharmacologically similar compounds, terbutaline and isoetharine.2. In guinea-pigs, pretreatment with these agents increases asthma mortality provoked by histamine which suggests that this resistance may reduce the effectiveness of endogenous sympathetic drive to the bronchi.3. Possible mechanisms by which the asthma death rate could be increased are discussed.4. It is suggested that a drug-induced cross resistance to endogenous sympathetic stimulation could have led to a deterioration of the asthmatic state in patients using the pressurized aerosols of sympathomimetic bronchodilators and that this might account for the rise in asthma death rate.