Mifepristone (RU-486) is used for medical abortion and also for Cushing's syndrome. The mechanism by which mifepristone treats hypercortisolaemia is different from its abortifacient action. In Cushing's syndrome it acts as:

• A An inhibitor of 11-beta-hydroxylase, reducing adrenal cortisol synthesis
• B A CRH receptor antagonist at the hypothalamus, reducing ACTH release
• C A glucocorticoid receptor antagonist, blocking cortisol action at peripheral tissues without reducing cortisol levels ✓
• D A mineralocorticoid receptor antagonist, reducing fluid retention in Cushing's syndrome

Explanation

Mifepristone is a competitive antagonist at glucocorticoid receptors (Type II) and progesterone receptors. In Cushing's syndrome, it blocks the glucocorticoid receptor (GR) in peripheral tissues — muscles, liver, adipose, immune cells — reducing the systemic effects of excess cortisol (hyperglycaemia, hypertension, muscle wasting) without lowering circulating cortisol levels (which typically rise further due to loss of negative feedback). It is approved for Cushing's syndrome with type 2 diabetes. Its abortifacient action is via progesterone receptor antagonism. It does not inhibit steroidogenesis directly (unlike metyrapone or ketoconazole).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.