What is the mechanism of action of magnesium sulfate in preeclampsia?

Mechanism of Action of Magnesium Sulfate in Preeclampsia

Magnesium sulfate prevents or controls convulsions in preeclampsia primarily by blocking neuromuscular transmission and decreasing acetylcholine release at the motor nerve end-plate, while also acting as a vasodilator to improve cerebral blood flow and protect the blood-brain barrier. 1

Primary Mechanisms of Action

Magnesium sulfate works through several complementary mechanisms:

1. Neuromuscular Effects

   • Blocks neuromuscular transmission by decreasing acetylcholine release at motor nerve endings 1
   • Creates a depressant effect on the central nervous system without adversely affecting the mother, fetus, or neonate when used as directed 1
   • Acts as an anticonvulsant by raising the seizure threshold 2

2. Vascular Effects

   • Produces peripheral vasodilation 1
   • Lowers blood pressure at higher doses 1
   • May relieve cerebral vasoconstriction, improving cerebral blood flow 2
   • Decreases peripheral vascular resistance 2

3. Blood-Brain Barrier Protection

   • Protects the blood-brain barrier integrity 2
   • Limits cerebral edema formation, which is a key pathologic finding in eclampsia 2
   • May decrease cerebral perfusion pressure, preventing cerebral barotrauma 3

Pharmacokinetics and Therapeutic Levels

• Onset of Action:

  • Immediate with IV administration, lasting about 30 minutes
  • With IM administration, onset occurs in about one hour and persists for 3-4 hours 1

• Distribution:

  • Approximately 40% of plasma magnesium is protein-bound
  • Unbound magnesium diffuses into extravascular-extracellular space, bone, across the placenta, and into amniotic fluid 4
  • In pregnant women, apparent volume of distribution reaches constant values between 3-4 hours after administration (0.250-0.442 L/kg) 4

• Therapeutic Levels:

  • Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/L 1
  • For treatment of eclamptic convulsions: 1.8 to 3.0 mmol/L 4
  • Target plasma level should be >0.6 mmol/L (>1.5 mg/dL) 5

• Elimination:

  • Exclusively excreted by the kidneys at a rate proportional to plasma concentration and glomerular filtration 1
  • 90% of the dose is excreted during the first 24 hours after IV infusion 4

Clinical Monitoring and Toxicity

Magnesium toxicity correlates directly with serum concentration:

• Loss of deep tendon reflexes: First warning sign at 3.5-5 mmol/L 4
• Respiratory depression/paralysis: Occurs at 5-6.5 mmol/L 4
• Cardiac conduction alterations: At levels >7.5 mmol/L 4
• Cardiac arrest: Can occur when concentrations exceed 12.5 mmol/L 4

Monitoring should include:

• Deep tendon reflexes
• Respiratory rate
• Urine output
• Level of consciousness 5

Clinical Application in Preeclampsia

The use of magnesium sulfate is well-established for:

• Preeclampsia with severe hypertension
• Preeclampsia with neurological signs or symptoms
• HELLP syndrome with co-existing severe hypertension
• As a neuroprotective agent for preterm preeclampsia if delivery is required before 32 weeks' gestation 5

Important Considerations and Caveats

• Calcium chloride (10%) 5-10 mL or calcium gluconate (10%) 15-30 mL should be immediately available to counteract magnesium toxicity 5
• Magnesium sulfate should be continued for 24 hours postpartum to prevent eclampsia 5
• Patients with impaired renal function require dose adjustments due to the renal excretion of magnesium 5
• Continuous maternal administration beyond 5-7 days can cause fetal abnormalities 5
• The benefit-to-risk ratio must be considered based on the severity of preeclampsia - routine use in mild preeclampsia is not supported, while it is justified in severe preeclampsia 3

While the exact mechanism of action remains not fully understood, the effectiveness of magnesium sulfate in preventing eclamptic seizures is likely multi-factorial, combining its effects on the neuromuscular junction, cerebral vasculature, and blood-brain barrier protection.