Methylergometrine

Mechanism

Mechanism of Action

Methylergometrine is a semisynthetic ergot alkaloid (ergotamine) with selective action on the myometrium. It acts as a partial agonist of α₁-adrenergic, serotonergic (5-HT₂) and dopaminergic receptors of uterine smooth muscle cells.

Physiology of Sustained Tetanic Contraction

Unlike the rhythmic pattern induced by oxytocin, methylergometrine continuously activates ligand-independent calcium ion channels and inhibits intraneuronal reuptake of catecholamines. This induces a generalized, intense and sustained tetanic uterine contraction, with a marked increase in basal myometrial tone. This contraction compresses the intrametral sinusoidal vessels (the "physiological ligatures of Pinard"), mechanically stopping the hemorrhage immediately.

Pharmacokinetics

Pharmacokinetics

• Routes of administration: Deep intramuscular and intravenous (exclusively in critical hemorrhagic emergencies and administered slowly in no less than 60 seconds due to the risk of hypertensive crisis), oral (for maintenance).
• Absorption: Rapid after IM injection (onset of action after 2-5 minutes); Orally it is absorbed by 60%, with onset of action after 10 minutes.
• Distribution: Wide tissue diffusion. It binds strongly to plasma plasma proteins. It temporarily crosses the blood-brain barrier.
• Metabolism: Extensive first-pass hepatic metabolism by oxidation mediated predominantly by the isoenzyme CYP3A4.
• Half-life (t_1/2): Biphasic, with a terminal elimination phase of about 1.5 to 2 hours.
• Excretion: Biliary-fecal 90% in the form of conjugated metabolites; the remaining 10% is eliminated through the urine.

Indicators and dose

Indications

• Treatment of postpartum or postabortion hemorrhage due to uterine atony or hypotonia refractory to oxytocin.
• Adjunctive treatment of puerperal uterine subinvolution and locometry.

Dosage and Adjustment

• Acute treatment of PPH: 0.2 mg (1 ampoule of 1 mL) by slow IM or IV route (diluted in 5 mL of saline) every 2 to 4 hours if necessary (maximum cumulative dose of 1.2 mg in 24 hours).
• Postpartum oral use: 0.125 to 0.25 mg orally 3 times a day for up to 5 days to control uterine subinvolution.

Pregnancy and Breastfeeding

Absolutely contraindicated during pregnancy. In lactation, it is demonstrably excreted in breast milk and can inhibit prolactin secretion due to dopaminergic stimulation. Repeated use for more than 1-2 days may cause ergothymic intoxication syndrome in the infant (characterized by vomiting, diarrhea, hypothermia, cardiovascular instability, and seizures). Breastfeeding should be discontinued if prolonged treatment is required.

Security

Contraindications

Critical Safety Warning: Vascular Pathologies

Due to its potent agonist effect on peripheral vascular α₁-adrenergic receptors, methylergometrine induces generalized arterial vasoconstriction. It is strictly contraindicated in patients with:

• Preeclampsia or Eclampsia (imminent risk of hypertensive encephalopathy or intracranial hemorrhage).
• Gestational or chronic arterial hypertension of any degree.
• Coronary heart disease or history of vasospastic angina (risk of coronary artery spasm and acute myocardial infarction).
• Occlusive peripheral arterial disease of any etiology.
• Severe sepsis or active septic shock.

Adverse Effects (ADR)

• Acute arterial hypertension: Common after intravenous administration or in patients with increased vascular reactivity.
• Throbbing headache, dizziness and tinnitus: Associated with transient blood pressure spike.
• Ergotism: Peripheral ischemia in extremities (coldness, tingling, pain) if administered continuously or prolonged.
• Chest tightness or dyspnea.

Interactions

The combination with potent CYP3A4 inhibitors (macrolides such as erythromycin or clarithromycin, azole antifungals such as ketoconazole or voriconazole, protease inhibitor antivirals) drastically delays its clearance, raising serum levels of methylergometrine and precipitating severe generalized vasospasm and coronary ischemia. peripheral.