Misoprostol

Mechanism

Mechanism of Action

Misoprostol is a synthetic analogue of prostaglandin E1 (PGE1). It acts as a selective agonist of prostaglandin type E receptors (specifically EP3 and EP4) in myometrial smooth muscle cells and cervical stroma.

Physiology of Cervical Maturation and Contraction

1. Myometrial Contraction (EP3 Pathway): By binding to the Gi/Gq protein-coupled EP3 receptor, misoprostol inhibits adenylate cyclase (reducing cAMP) and increases intracellular calcium flux. This generates a tonic and sustained contraction of the gravid uterus, independent of gestational age.
2. Cervical Maturation (Pathway EP4): In the cervix, binding to EP4 receptors stimulates the release of collagenase matrix metalloproteinases (collagenase and elastase), which degrade collagen fibrils and increase the concentration of glycosaminoglycans (hyaluronic acid). This process of dissolution of the extracellular matrix disorganizes the cervix, inducing its effacement and dilation.

Indicators and dose

Indications

• Cervical ripening and induction of labor at term (especially with unfavorable cervix, Bishop scale < 6).
• Prevention and treatment of postpartum hemorrhage due to uterine atony (of choice when parenteral uterotonics are not available).
• Treatment of delayed, incomplete or avoidable abortion.
• Induction of medical abortion in the first and second trimester (in sequential combination with mifepristone).
• Gynecological Use: Previous ripening of the cervix before a diagnostic or surgical hysteroscopy, or the insertion of an IUD.

Pharmacokinetics by Route of Administration

After absorption, misoprostol (a methyl ester) is rapidly deesterified by plasma esterases to its main active metabolite: misoprostol acid. It is 90% bound to serum albumin. Its elimination half-life is short, 20 to 40 minutes, and it is excreted mainly through the kidneys (80%).

Dosing and Precision Adjustment

• Cervical ripening and term induction: 25 µg vaginally every 4 to 6 hours (maximum dose 150 µg in 24 hours), or specific oral formulation of 25 µg every 2 hours in fractions.
• Treatment of Postpartum Hemorrhage (Atony): 600 to 800 µg sublingually or rectally in a single dose.
• Missed or incomplete abortion (< 12 weeks): 800 µg vaginally every 24 hours for a maximum of 2 or 3 doses, or 600 µg sublingual.
• Pre-hysteroscopy cervical ripening: 200 to 400 µg vaginally or orally 4 to 12 hours before the procedure.

Pregnancy and Breastfeeding

FDA Category X (outside obstetric indications for delivery or termination of pregnancy). It is a powerful teratogenic agent; If pregnancy continues after a failed exposure, it is associated with serious anomalies such as Moebius Syndrome (congenital palsy of the VI and VII cranial nerves with bilateral facial paralysis) and defects due to limb reduction secondary to transplacental vascular ischemia. In lactation, misoprostol acid is excreted in milk at minimal but self-limiting levels; It is recommended to discard the first dose after high doses.

Security

Contraindications

Absolute

• Hypersensitivity to misoprostol or other prostaglandins.
• History of previous cesarean section or transmural uterine surgery (when used for induction of labor at term due to high risk of uterine rupture).
• Active acute fetal distress.
• Suspected placenta prior or placental abruption.

Relative

• Active bronchial asthma or history of severe bronchospasm.
• Uncontrolled glaucoma.
• Moderate kidney or liver failure.
• Presence of a single segmental uterine scar (evaluate risk/benefit in second trimester abortions).

Adverse Effects (ADR)

• Fever and Chills: ADR of dose-dependent central origin (stimulation of prostaglandin receptors in the hypothalamic thermostat). Very common after sublingual or oral administration at high doses (> 400 µg).
• Uterine hyperstimulation / Tachysystole: May trigger fetal bradycardia due to transient hemodynamic compromise.
• Gastrointestinal Effects: Transient osmotic diarrhea (due to increased secretion of water and electrolytes in the colon) and abdominal cramping pain.