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. 1975 Dec;55(4):547–554. doi: 10.1111/j.1476-5381.1975.tb07431.x

Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo.

C J Benoy, M S El-Fellah, R Schneider, O L Wade
PMCID: PMC1666729  PMID: 1212562

Abstract

1 Pretreatment of the guinea-pig subcataneously three times daily with either 5 mug/kg isoprenaline or adrenaline reduced the response of the isolated perfused histamine-constricted lung when challenged with either the same or a different sympathomimetic bronchodilator. The longer the animals were pretreated and the higher the dose of bronchodilator the greater was the degree of tolerance developed. 2 Tolerance was developed to aminophline in the same preparation when the guinea-pig had been pretreated with aminophyline or isoprenaline. Cross-tolerance also developed adrenaline when the guinea-pig had been pretreated with aminophyline. 3 Tolerance was still persistent in guinea-pigs one and two weeks after pretreatment three times daily with either isoprenaline of adrenaline (5 mu/kg s.c.) for seven days in the same preparation. Only after three weeks was the tolerance diminished. 4 These results suggest that asthmatic patients who use bronchodilators excessively may become refractory to the bronchodilator effect of these drugs. They also support the hypothesis that induced cross-resistance to endogenous sympathetic stimulation could lead to a deterioration of the asthmatic state in patients using the sympathomimetic bronchodilators and that this may explain the increase in asthma mortality rate. 5 A mechanism of tolerance to sympathomimetic bronchodilators is postulated.

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Selected References

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