Magnesium (pharmaceutical preparation)

Magnesium, as a pharmaceutical preparation, is used to treat conditions including magnesium deficiency and hypomagnesemia, as well as eclampsia.^[1] Magnesium is important to health.

Usually in lower dosages, magnesium is commonly included in dietary mineral preparations, including many multivitamin preparations.

Types of preparations

In practice, magnesium is given in a salt form together with any of several anionic compounds serving as counter-ions, such as chloride or sulfate ('sulphate' in British English). Nevertheless, magnesium is generally presumed to be the active component. An exception is the administration of magnesium sulfate in barium chloride poisoning,^[2] where sulfate binds to barium to form insoluble barium sulfate.

Magnesium is absorbed orally at about 30% bioavailability from any water soluble salt, such as magnesium chloride or magnesium citrate. The citrate is the least expensive soluble (high bioavailability) oral magnesium salt available in supplements, with 100 mg and 200 mg magnesium typically contained per capsule or tablet.

Magnesium aspartate, chloride, lactate, citrate and glycinate each have bioavailability 4 times greater than the oxide form and are equivalent to each other per amount of magnesium, though not in price.^[3][4]

The ligand of choice for large-scale manufacturers of multivitamins and minerals containing magnesium is the magnesium oxide due to its compactness, high magnesium content by weight, low cost, and ease-of-use in manufacturing. However it is insoluble in water. Insoluble magnesium salts such as magnesium oxide or magnesium hydroxide (milk of magnesia) depend on stomach acid for neutralization before they can be absorbed, and thus are relatively poor oral magnesium sources, on average.

Magnesium sulfate (Epsom salts) is soluble in water. It is commonly used as a laxative, owing to the poor absorption of the sulfate component. In lower doses, they may be used as an oral magnesium source, however.

Magnesium l-threonate is a new magnesium preparation that in preclinical animal studies has shown great promise as a treatment of mild cognitive impairment.^[5] Its efficacy and safety has now been replicated in the first double-blind placebo controlled human trial.^[6]

Intravenous or intramuscular magnesium is generally in the form of magnesium sulfate solution. Intravenous or intramuscular magnesium is completely bioavailable, and effective. It is used in severe hypomagnesemia and eclampsia.

Indications

Indications and uses for administering magnesium include:

• Magnesium deficiency and hypomagnesemia.
• Eclampsia. Empirical and clinical evidence supports the effectiveness of magnesium for this use.^[1] For this purpose, magnesium may act as a vasodilator, with actions in the peripheral vasculature or the cerebrovasculature, to decrease peripheral vascular resistance or relieve vasoconstriction.^[1] Additionally, magnesium may also protect the blood–brain barrier and thereby limit formation of cerebral edema, or it may act as a central anticonvulsant.^[1] The preparation usually used for this purpose is magnesium sulfate.
• Laxative use, particularly magnesium citrate and magnesium hydroxide
• Antiarrhythmic agent for torsades de pointes in cardiac arrest. Magnesium sulfate is the first-line agent for such use under the 2005 ECC guidelines and for managing quinidine-induced arrhythmias.^[7]
• As a bronchodilator after beta-agonist and anticholinergic agents have been tried, e.g. in severe exacerbations of asthma.^[8] Recent studies have revealed that magnesium sulfate can be nebulized to reduce the symptoms of acute asthma.^[8] It is commonly administered via the intravenous route for the management of severe asthma attacks.
• Anti-contraction medication: Magnesium sulfate can also delay labor in the case of premature labor, to delay preterm birth.^[9][10]
• Mild cognitive impairment. Magnesium l-threonate is able to deliver high amounts of magnesium to the central nervous system and has in preclinical animal studies as well as human trials shown remarkable results, even reversing full-blown dementia in some of the animal studies.^[11][12] The results of these studies are well in line with systematic reviews showing that Alzheimer’s patients have lower magnesium status when compared to healthy controls.^[13] Despite its apparent simplicity, just replenishing the brains stores of a vital mineral, this study parallels recent findings in other domains of neurobiology, for example the finding that a new copper formulation is able to halt the progression of amyotrophic lateral sclerosis.^[14]

Side effects

More common side effects from magnesium include upset stomach and diarrhea, and calcium deficiency if calcium levels are already low.^[15]

Overdose

Overdose of magnesium (hypermagnesemia) is only possible in special circumstances. It can cause nausea, vomiting, severely lowered blood pressure, confusion, slowed heart rate, respiratory paralysis.^[15] In very severe cases, it can cause coma, cardiac arrhythmia, cardiac arrest and death.^[15]

Magnesium overdose can be counteracted by administering calcium gluconate.^[16]

References

1. Euser, A. G.; Cipolla, M. J. (2009). "Magnesium Sulfate for the Treatment of Eclampsia: A Brief Review". Stroke 40 (4): 1169–1175. doi:10.1161/STROKEAHA.108.527788. PMC 2663594. PMID 19211496.
2. "BARIUM CHLORIDE DIHYDRATE 4. First Aid Measures". Jtbaker.com. Retrieved 2009-07-06.
3. Firoz M, Graber M: "Bioavailability of US commercial magnesium preparations.", Magnesium Research 2001 Dec;14(4):257-62.
4. Lindberg JS, Zobitz MM, Poindexter JR, Pak CY: "Magnesium bioavailability from magnesium citrate and magnesium oxide.",J Am Coll Nutr. 1990 Feb;9(1):48-55.
5. Li W, Yu J, Liu Y, Huang X, Abumaria N, Zhu Y, Huang X, Xiong W, Ren C, Liu XG, Chui D, Liu G (2014). "Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model". Molecular Brain 7 (65): 1–20. doi:10.1186/s13041-014-0065-y. PMID 25213836.
6. Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S (2015). "Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial". Journal of Alzheimer's disease 49 (4): 971–990. doi:10.3233/JAD-150538. PMID 26519439.
7. "When clicking citation, it is listed under ''Other medicinal and home uses''". Disabled-world.com. 2007-01-04. Retrieved 2009-07-06.
8. Blitz M, Blitz S, Hughes R, Diner B, Beasley R, Knopp J, Rowe BH. Aerosolized magnesium sulfate for acute asthma: a systematic review. Chest 2005;128:337-44. PMID 16002955.
9. "Magnesium sulfate for preterm labor". Webmd.com. 2007-01-19. Retrieved 2009-07-06.
10. Lewis DF (September 2005). "Magnesium sulfate: the first-line tocolytic". Obstet. Gynecol. Clin. North Am. 32 (3): 485–500. doi:10.1016/j.ogc.2005.03.002. PMID 16125045.
11. Li W, Yu J, Liu Y, Huang X, Abumaria N, Zhu Y, Huang X, Xiong W, Ren C, Liu XG, Chui D, Liu G (2014). "Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model". Molecular Brain 7 (65): 1–20. doi:10.1186/s13041-014-0065-y. PMID 25213836.
12. Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S (2015). "Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial". Journal of Alzheimer's disease 49 (4): 971–990. doi:10.3233/JAD-150538. PMID 26519439.
13. Veronese N, Zurlo A, Solmi M, Luchini C, Trevisan C, Bano G, Manzato E, Sergi G, Rylander R (2016). "Magnesium Status in Alzheimer's Disease: A Systematic Review". American journal of Alzheimer's disease and other dementias 31 (3): 208–213. doi:10.1177/1533317515602674. PMID 26351088.
14. Williams JR, Trias E, Beilby PR, Lopez NI, Labut EM, Bradford CS, Roberts BR, McAllum EJ, Crouch PJ, Rhoads TW, Pereira C, Son M, Elliott JL, Franco MC, Estévez AG, Barbeito L, Beckman JS (2016). "Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.". Neurobiology of disease 89 (4): 1–9. doi:10.1016/j.nbd.2016.01.020. PMID 26826269.
15. Magnesium at University of Maryland Medical Center (UMMC). Reviewed last on: 6/17/2011 by Steven D. Ehrlich
16. Omu AE, Al-Harmi J, Vedi HL, Mlechkova L, Sayed AF, Al-Ragum NS (2008). "Magnesium sulphate therapy in women with pre-eclampsia and eclampsia in Kuwait". Med Princ Pract 17 (3): 227–32. doi:10.1159/000117797. PMID 18408392.