Magnesium: competition to lithium?

Magnesium: competition to lithium?

The element magnesium (Mg) is a silvery-white and lightweight metal. It is protected by a thin oxide layer, which is very difficult to remove but at the same time removes the need to store it in an oxygen-free environment (see alkali metals). Magnesium reacts with water but much more slowly than its neighbouring earth alkaline metal calcium. Magnesium is a highly flammable metal, and once ignited it burns with a characteris-tic bright white flame. There are three stable isotopes of magnesium, namely ²⁴Mg (79% occurrence), ²⁵Mg and ²⁶Mg. ²⁸Mg is radioactive with a half-life of 21 h .

Most magnesium salts are soluble in water, and given in large amounts they work as a laxative in the human body. Aqueous magnesium ions are sour in taste. Magnesium hydroxide (MgOH₂) has only limited solubility in water and the resulting suspension is called milk of magnesia, which is commonly used as an antacid and is known to be a mild base. Magnesium is extracted on a large scale using a Down’s cell  or the ferrosilicon process with seawater being the main source. Mg²⁺ stands in a so-called diagonal relationship to Li⁺, which explains why these ions have similar properties and biological activity.

Biological importance

Mg²⁺ is an essential ion in the human body and is a crucial constituent in numerous enzymatic processes. Indeed, Mg²⁺ is essential to most living cells as a signalling molecule and is involved in nucleic acid bio-chemistry dealing with the manipulation of ATP (adenosine triphosphate), DNA, RNA and related processes. For example, ATP has to be coordinated to a magnesium ion in order to become biologically active. Mg²⁺ also stabilises DNA and RNA structures, which can be seen in their increased melting points.

Mg²⁺ ions form the redox-active centre in chlorophyll, which facilitates the process of photosynthesis and the connected carbon fixation in green plants. Therefore, green vegetables, as well as milk, whole grain and nuts, are good sources of magnesium. It has to be kept in mind that most magnesium salts are water soluble and therefore processed vegetables, mainly cooked in water, are low in magnesium ion content.

In the human body, Mg²⁺ is the fourth most abundant cation and the second most abundant ion in the interstitial fluid. Mg²⁺ is an essential co-factor dealing with more than 300 cellular enzymatic processes.

On average, the human body contains about 24 g of magnesium ions, with half of it being incorporated into bones and the other half being present in muscles and soft tissue. The majority of Mg²⁺ is absorbed in the ilium and colon, and the kidneys are the major excretory organ. Mg²⁺ is filtered at the glomerulus, and 10–15% is re-absorbed at the proximal tubule, 60–70% at the thick part of the ascending limb of the loop of Henle and 10–15% at the distal tubule .

Nevertheless, magnesium salts are generally not well absorbed from the gastrointestinal (GI) tract and therefore are often used as osmotic laxatives. The kidneys regulate the magnesium ion levels in plasma, and as a result high levels of Mg²⁺ are retained when the patient has renal failure. The resulting hypermagnesia can cause muscle weakness and arrhythmia, but it is a rare condition. Hypomagnesia, defined as low magne-sium levels in the blood plasma, can be the result of losses in the GI tract, for example, excessive diarrhoea. Magnesium imbalances can also be a result of alcoholism or secondary to treatment with certain drugs. Hypo-magnesia is often followed by hypocalcaemia (low calcium ion plasma levels) as well as hypokalaemia and hyponatraemia.

Clinical applications and preparations

Magnesium ion imbalances can manifest in a variety of conditions such as hypo- and hypermagnesaemia. Magnesium ion preparations are also used as antacids, mostly in combination with aluminium-based salts. Additionally, magnesium salts are involved in the treatment of arrhythmia (irregular heart beat) and eclampsia, a life-threatening hypertensive disorder in pregnant women.

Symptomatic hypomagnesaemia is associated with plasma serum Mg²⁺ levels of <0.5–1 mmol/kg for a period of 5 days or more. Mg²⁺ ions are initially given as intravenous (i.v.) or intramuscular injection; the latter is fairly painful and consisting of magnesium sulfate (MgSO₄). MgSO₄ can also be used as emergency treatment for very serious arrhythmias, a disorder of the heart rate (pulse). In an emergency treatment, it is usually given intravenously as one single dose or with one repeat (Figure 3.5) .

Note that the plasma magnesium concentration should be monitored, and the dose has to be reduced in patients with renal impairment as Mg²⁺ is excreted via the kidneys. Magnesium ions can also be given orally to the patient, for example, in the form of magnesium glycerophosphate tablets.

Magnesium hydroxide [Mg(OH)₂] is present in antacids because of its laxative properties and is also the main ingredient of the ‘milk of magnesia’. The ‘milk of magnesia’ is a suspension of Mg(OH)₂ in water, which has a milk-like appearance because of the low aqueous solubility of Mg(OH)₂. It is considered as a strong electrolyte and a weak base and is given to the patient for indigestion and heartburn. The alkaline suspension neutralises any excess stomach acid and therefore works as an antacid. It also stimulates intestinal movement, as the magnesium ions increases the water content in the intestines through its osmotic effect and as a result softens any faeces present.

Magnesium trisilicate (Mg₂Si₃O₈) can also be used in antacid preparations especially in the treatment of peptic ulcers. The mode of action includes the increase of the pH of the gastric fluid together with the formation of a colloidal silica precipitate, which forms a protection for the GI mucosa. Most antacids contain a mixture of aluminium hydroxide [Al(OH)3] and magnesium and/or calcium preparations. Therefore, the mode of action will be further discussed in the chapter on aluminium-based drugs  (Figure 3.6).

Unfortunately, orally taken magnesium salts can show interactions with other drugs taken simultaneously. Magnesium trisilicate reduces the absorption of iron products, certain antibiotics (such as Nitrofurantoin) or antimalarial drugs (such as Proguanil). Magnesium salt preparations, which form part of antacids, are not recommended to be taken at the same time as a variety of drugs such as ACE inhibitors, aspirin and peni-cillamine. In most cases, antacids reduce the absorption of the simultaneously taken drug. Therefore, before any treatment with antacids, the full medical history of the patient should be taken and possible interactions assessed .