Question 10

Describe the pharmacology of magnesium sulphate.

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College Answer

Magnesium is a commonly administered agent within Intensive Care practice. Candidates performed poorly because of a lack of sufficient knowledge and a failure to structure their answer. For a good answer candidates were expected to mention that Magnesium comes as an inorganic sulphate, acts as a cofactor for a vast number of reactions, can be given orally (poor absorption) as well as intravenously, renal excretion with a low threshold. 

Recommended sources: Rang and Dale Pharmacology Pg 388; Katzung Basic and Clinical Pharmacology, Pg 244.

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,
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)

References

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