Question 4

Outline the pharmacology of intravenously administered magnesium sulphate.

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College Answer

Overall answers were well structured. However, a lack of detail and inaccurate pharmacokinetics was common. Better answers included a discussion of the mechanism of action of Mg++ including Ca++ antagonism, presynaptic cholinergic effects and NMDA receptor antagonism. Adverse effects were not discussed in detail by many candidates and contraindications were commonly omitted.


Class Electrolyte replacement
Chemistry Divalent cation salt
Routes of administration IV, orally, or as a neb
Absorption 30% oral bioavailability (depends on body magnesium levels - more is absorbed in states of systemic magnesium depletion)
Solubility pKa -3.0; good water solubility
Distribution VOD =0.25-0.442 L/kg; 40% protein-bound
Target receptor Numerous pharmacodynamic targets, including NMDA receptors, L-type calcium channels,
Metabolism Not metabolised, but is a cofactor in numerous metabolic processes
Elimination Renally excreted; reabsorption mainly by thick ascending lmb and distal convoluted tubule. Supraphysiological plasma concentrations result in decreased reabsorption
Time course of action Half life of around 4 hours
Mechanism of action Multiple mechanisms of action, including:
- Smooth muscle relaxation by increasing the uptake of intracellular calcium into the sarcoplasmic reticulum
- skeletal muscle relaxation due to inhibition of acetylcholine release from the neuromuscular junction
- CNS depressant effects by inhibition of NMDA receptors
- Decreased AV node conduction due to calcium channel blocker effects
- co-factor in electrolyte homeostasis, including Na+/K+ ATPase function
Clinical effects,  Bronchodilation, areflexia, muscle weakness, paralysis, smooth muscle relaxation, vasodilation, hypotension, anticonvulsant effects
Contraindications Neuromuscular junction disease; bradycardia; poor AV node function
Single best reference for further information Connolly & Worthley (1999)


Connoley & Worthley: "Intravenous Magnesium" Critical Care and Resuscitation 1999; 1: 162-172

Fazekas, Tamás, et al. "Magnesium and the heart: antiarrhythmic therapy with magnesium." Clinical cardiology 16.11 (1993): 768-774.

José R Weisinger, Ezequiel Bellorín-Font Magnesium and phosphorus Review Article The Lancet, Volume 352, Issue 9125, 1 August 1998, Pages 391-396