Question 20

Describe the pharmacology of magnesium sulphate.

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College Answer

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

Discussion

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, 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)

References

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.