Development of tolerance to oral salbutamol in the third trimester of pregnancy: a study of circulatory and metabolic effects.

1 The purpose of the study was to investigate whether a development of tolerance does occur or not to salbutamol-induced cardiovascular and metabolic effects after oral long term treatment in pregnancy. 2 Twenty-three women in late pregnancy were given an oral dose of 4 mg salbutamol in the morning after an overnight fast. Ten of the women had not been exposed to beta-adrenoceptor agonists earlier in their pregnancy (group A). Thirteen of the women had been treated with salbutamol in a dose of 4 mg four times a day for 12 to 33 days preceding the study (group B). 3 Blood samples were collected every 30 min for 120 min and analyzed for cyclic AMP, insulin, C-peptide, glucose, lactate, glycerol, non-esterified fatty acids (NEFA) and 3-hydroxybutyrate (3-HB). Heart rate and blood pressure were recorded simultaneously. 4 In group A there was significant increase in plasma cyclic AMP and increased glycogenolysis, lipolysis and insulin secretion. In this group there were also significant cardiovascular effects, that is, an increase of heart rate and decrease of diastolic blood pressure. 5 In group B the effects of salbutamol were significantly less pronounced, indicating a development of tolerance. 6 We conclude that the metabolic side-effects are not sufficient reason to withhold beta-adrenoceptor agonists to healthy pregnant women with threatened premature labour, since tolerance rapidly develops to these actions.