Outline the pharmacology of intravenous magnesium sulphate.
The best answers appropriately addressed the pharmacology of magnesium sulphate, rather than diverting into physiology. They noted that the question concerned intravenous magnesium sulphate and did not discuss other routes. They included pharmaceutics, important examples of the wide-ranging indications, listed potential modes of action and considered the full range of body systems affected including potential adverse effects. Drug interactions, such as potentiation of neuromuscular blocking agents, and pharmacokinetics (including stating that magnesium is not metabolised) were described.
|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