Growth, adrenal steroids reducing

Long-term use of adrenal steroids in children presents essentially the same problems as in adults except that growth is retarded approximately in proportion to the dose. This is unlikely to be important unless therapy exceeds 6 months there is a spurt of growth after withdrawal. Intermittent dosage schedules (alternate day) may reduce the risk (rarely, corticotropin may be preferred, see p. 675). 

The first inhaled glucocorticoid, beclomethasone dipropionate, revolutionized asthma therapy, when it was found that topical delivery to the lung resulted in reduced systemic side-effects (adrenal suppression, oseteoporosis and growth inhibition) typically seen with oral steroid treatments. Interestingly, a further reduction in systemic exposure was achieved with the introduction of fluticasone propionate (1). The evolution of this drug stemmed from observations with the steroid 17-carboxylates that showed that these esters were active topically when esterified, while the parent acids were inactive. Thus it was realized that enzymatic hydrolysis of the ester would lead to systemic deactivation. SAR studies led to a series of carbothioates, which were very active in vivo when topically applied to rodents, but were inactive after oral administration. It was shown that fluticasone propionate (1) underwent first pass metabolism in the liver to the corresponding inactive 173-carboxylic acid (la) (Scheme 1). This observation was... 

Cloned mouse adrenal cortex tumor cells respond to ACTH with an increased output of steroids which is independent of the growth phase T. v fithin 5 minutes the cells retract from the surface of the vessel and from each other and within 1 hour a rounded-up morphology is seen. This cell line is unable to hydroxylate position 21 but has a high ability to reduce the 20-keto group. 

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