Describe the pharmacology of magnesium sulphate.
The standard “pharmacology template” approach would have served well to cover this question. Answers were generally lacking in detail and focussed on extraneous physiology rather than pharmacology. Toxicity and side-effects were important to emphasise, especially in the context of infusions for treatment of asthma and/or pre-eclampsia.
|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