Steroids Concept for NEET/AIIMS/USMLE/FMGE/PLAB
Development of steroids:
The endogenous steroid hydrocortisone is taken as a reference steroid, which has equal glucocorticoid and mineralocorticoid effect taken as 1. Its duration of action is 8-12 hours. The structure of hydrocortisone contains four rings A, B, C and D and selective changes were made to these rings to synthesize new and better steroids.
• An addition of a double bond in ring A increased the glucocorticoid effect by 4 times and slightly decreased mineralocorticoid effect. There was an increased duration of action to 12-36 hours as well. These steroids are prednisone and prednisolone.
Methylation of prednisolone (Methyl prednisolone) increased the glucocorticoid effect by 5 times with duration of action unchanged i.e. 12-36 hours.
• Addition of fluorine at ring B increased glucocorticoid effect by 15 times and mineralocorticoid effect by 150 times. This steroid is a mineralocorticoid called as fludrocortisone. Aldosterone has only mineralocorticoid effect which is 500 times that of hydrocortisone. However the affinity of mineralocorticoid receptors is higher with fludrocortisone as compared to aldosterone.
• Addition of both double bond at ring A and fluorine at ring B increased the glucocorticoid effect by 30 times (betamethasone and dexamethasone) and 5 times (triamcinolone). However this lead to zero mineralocorticoid effect. Hence these steroids are called as pure glucocoriticoids. The increase in half life for dexamethasone and betamethasone was to 36-72 hours and triamcinolone was to 12-36 hours. .
• However the glucocorticoid with maximum affinity for glucocorticoid receptors is dexamethasone more than betamethasone.
• Further steroids were added with functional groups like valerate, propionate and butyrate that increased the lipid solubility. This is essential for topical use of steroids in cream and ointment form.
• Addition of functional group like dipropionate to beclomethasone made it inactive and it is activated in lungs by esterase where they produce anti-inflammatory effect in bronchial asthma. The benefit is a lesser incidence of oropharyngeal candidiasis.