Mifepristone (RU-486) is a progesterone and glucocorticoid receptor antagonist. When used as an abortifacient in early pregnancy, why is it always combined with a prostaglandin (misoprostol) rather than used alone?

• A Prostaglandins reduce the risk of mifepristone-induced hyperkalemia
• B Misoprostol prevents the anti-glucocorticoid effect of mifepristone causing adrenal insufficiency
• C Prostaglandins provide analgesia that mifepristone cannot offer alone
• D Mifepristone alone causes decidual breakdown but its efficacy (complete expulsion) is ~64–80%; misoprostol adds uterotonic contractility to ensure complete expulsion of products of conception, increasing efficacy to >95% ✓

Explanation

Mifepristone acts as a competitive antagonist at progesterone receptors, causing decidual breakdown (loss of uterine lining support for the pregnancy) and sensitizing the myometrium to prostaglandins. However, mifepristone alone achieves complete abortion in only ~64–80% of cases — incomplete expulsion occurs without adequate uterine contractility. Misoprostol (a synthetic PGE1 analogue) stimulates uterine contractions via FP and EP prostaglandin receptors, expelling the products of conception. The combination achieves >95% efficacy. Misoprostol also softens and dilates the cervix (cervical ripening). The anti-glucocorticoid effect of mifepristone is a separate pharmacodynamic concern managed by timing (short-course use).

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

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Written and medically reviewed by the StethoPrep medical team.