Outline the pharmacology of intravenously administered magnesium sulphate.
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