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

Abstract

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 /3-adrenoceptor agonists earlier in their pregnancy (group A). Thirteen of the women had been treated with oral 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 -adrenoceptor agonists to healthy pregnant women with threatened premature labour, since tolerance rapidly develops to these actions.

Does tachyphylaxis occur to the non‐pulmonary effects of salmeterol?

“…Tachyphylaxis has been observed previously to the hyperglycaemic response observed after other P2-adrenoceptor agonists [5,6,16] so the results in the present study with salmeterol are consistent with these findings.…”

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

“…Some data suggest that beta-2-agonists promote lipolysis (Goldberg et al, 1975). However, tolerance to beta-2stimulated FFA release does occur (Wager et al, 1981). In conclusion, the possibility cannot be excluded that beta-agonist treatment contributes to the increase in lipolysis in our patients.…”

The effects of long‐term infusion of salbutamol, diltiazem and nifedipine on uterine contractions in the ovariectomized, post‐partum rat

“…Such tolerance is likely to have a pharmacodynamic rather than a pharmacokinetic basis as similar observations have been made on several cell types both in vivo and in vitro. These tissues have OJ included smooth muscles other than uterus, leucocytes, glioma cells, cardiovascular tissues and adipocytes (Wager et al, 1981;Frederich et al, 1983;Harden, 1983;Berg et al, 1984;Stiles et al, 1984). Some of the biochemical changes associated with tolerance to P-adrenoceptor agonists such as decreased production of cyclic AMP and decrease in number of binding sites for P-adrenoceptor agonists on repeated challenge with the agonist have been described in the myometrium of rat and human uterus (Johansson & Andersson, 1980;Berg et al, 1985).…”