Describe the pharmacology of magnesium sulphate.
This was a repeat question and very poorly answered for such a commonly used agent. A structured approach to describing any drugs pharmacology was often not used. Most answers were lacking depth and detail. The questions asked the pharmacology NOT physiology of magnesium sulphate. This was best answered with a standard template addressing: Presentation, Uses, Main actions, Pharmacodynamics, Pharmacokinetics, Mode of Action, Toxicity, and any Special Points
|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, neuromuscular junction|
|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 (anticonvulsant) 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, smooth muscle relaxation, vasodilation, anticonvulsant effects,|
|Single best reference for further information||Connolly & Worthley (1999)|
Lu JF. Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles. Clinical Pharmacokinetics. 38(4):305-14, 2000 Apr.
José R Weisinger, Ezequiel Bellorín-Font Magnesium and phosphorus Review Article The Lancet, Volume 352, Issue 9125, 1 August 1998, Pages 391-396
Keith W. Muir, MD, MRCP; ;Kennedy R. Lees, MD, FRCP Dose Optimization of Intravenous Magnesium Sulfate After Acute Stroke Stroke. 1998; 29: 918-923
Mackenzie Walser, Ann A. Browder ION ASSOCIATION. III. THE EFFECT OF SULFATE INFUSION ON CALCIUM EXCRETION Published in Volume 38, Issue 8 J Clin Invest. 1959; 38(8):1404–1411 doi:10.1172/JCI103916
Mohammed, S., and S. Goodacre. "Intravenous and nebulised magnesium sulphate for acute asthma: systematic review and meta-analysis." Emergency Medicine Journal 24.12 (2007): 823-830.
Vu, M. K., et al. "The osmotic laxative magnesium sulphate activates the ileal brake." Alimentary Pharmacology and Therapeutics 14.5 (2000): 587-596.
Agarwal, Anil, et al. "Vein pretreatment with magnesium sulfate to prevent pain on injection of propofol is not justified." Canadian Journal of Anesthesia 51.2 (2004): 130-133.
Roth, Paul, and Eckhard Werner. "Intestinal absorption of magnesium in man." The International journal of applied radiation and isotopes 30.9 (1979): 523-526.
Blancquaert, Laura, Chris Vervaet, and Wim Derave. "Predicting and testing bioavailability of magnesium supplements." Nutrients 11.7 (2019): 1663.
Gröber, Uwe, et al. "Myth or reality—transdermal magnesium?." Nutrients 9.8 (2017): 813.
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.