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.
|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