Mifepristone RU 486

Mifepristone is a progesterone receptor antagonist that has a high affinity for glucocorticoid receptors and little agonist effect. This drug has recently been approved for use in the United States for the treatment of hypercor-tisolism. At high doses, mifepristone blocks negative feedback of the hypothalamic-pituitary axis, thereby increasing endogenous corticotrophin and cortisol levels. Because mifepristone exerts its effects at the receptor level and not by altering glucocorticoid production, elevated serum cortisol and corticotrophin levels may not accurately reflect the effectiveness of the therapeutic regimen. Mifepristone does not inhibit cortisol binding to the mineralocorticoid receptor, so that the resulting corticotrophin disinhibition may cause potassium depletion. Thus, administration of a mineralocorticoid receptor antagonist such as spironolactone may be indi cated with mifepristone. Hypoadrenalism, nausea, and drowsiness have been reported during prolonged administration of mifepristone.

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