What is the mechanism of action of mifepristone (Generic name) in a medical abortion?

Mechanism of Action of Mifepristone in Medical Abortion

Mifepristone works in medical abortion primarily as a selective antagonist of the progesterone receptor, blocking the action of progesterone which is necessary to sustain pregnancy, leading to uterine contractions and increased sensitivity to prostaglandins. 1, 2

Primary Mechanism

• Mifepristone has high affinity for the progesterone receptor, competitively binding to it and preventing progesterone from exerting its pregnancy-maintaining effects 1
• By blocking progesterone action, mifepristone causes:
  • Decidual breakdown (deterioration of the uterine lining) 3
  • Cervical softening and dilation 4
  • Increased uterine sensitivity to prostaglandins 5
  • Induction of uterine contractions 2

Molecular Action

• Mifepristone binds to the cytosolic progesterone receptor and prevents gene transcription by blocking recruitment of coactivators, rendering the receptor complex inactive 3
• The drug demonstrates a mixture of antagonistic effects on progesterone receptors, with the relative strength of these effects related to the proportions of PR-A and PR-B receptors in the specific tissue 3, 6
• At higher doses, mifepristone also blocks glucocorticoid receptors (GR-II), though this action is less relevant to its abortifacient properties 1

Clinical Application in Medical Abortion

• In medical abortion protocols, mifepristone (typically 200-600 mg) is followed 24-48 hours later by a prostaglandin analog such as misoprostol 5, 2
• This combination achieves complete abortion in 92-95% of pregnancies up to 49 days of amenorrhea 7
• The effectiveness is related to:
  • The type and dose of prostaglandin used 5
  • Route of administration (vaginal misoprostol is more effective than oral) 5
  • Gestational age and parity 5

Pharmacokinetics

• After oral administration, mifepristone reaches peak plasma concentrations between 1-2 hours for single doses 1
• The drug is highly bound to alpha-1-acid glycoprotein and albumin in plasma (approximately 99.2%) 1
• Mifepristone is metabolized by cytochrome P450 3A4 in the liver, producing three active metabolites 1
• The half-life of mifepristone is approximately 85 hours with multiple dosing 1
• Excretion occurs primarily (approximately 90%) via the fecal route 1

Important Clinical Considerations

• Food significantly increases plasma levels of mifepristone, so consistent administration with meals is recommended for predictable drug concentrations 1
• Mifepristone interferes with the effectiveness of hormonal contraceptives, so non-hormonal contraception is recommended during treatment and for one month afterward 1
• Common side effects include abdominal pain, while serious complications can include incomplete abortion, endometritis, and bleeding requiring medical intervention 7

Historical Context

• Mifepristone was originally discovered during a search for synthetic ligands of the glucocorticoid receptor, but was found to have more potent antiprogesterone effects 3
• It was initially developed and commercialized specifically for pregnancy termination 3
• In countries where medical abortion has been widely available for extended periods (France, Scotland, Sweden), approximately 60-70% of eligible women choose this method 5

Medical abortion using mifepristone represents a non-surgical option for early pregnancy termination with efficacy comparable to vacuum aspiration at the same gestational age 5, 4.