Chemical structure of magnesium trisilicate (Mg2Si3O8)

Chemical structure of magnesium trisilicate (Mg2Si3O8)
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 (see Section 4.3.5) (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 penicillamine. 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 [4].
3.4 Calcium: the key to many human functions
Calcium is the most abundant inorganic element in the human body and is an essential key for many physiological processes. Ca2+ has numerous intra and extracellular physiological roles, for example, a universal role
as messenger and mediator for cardiac, skeletal and smooth muscle contractions. Calcium ions are a critical
factor in several life-defining biochemical processes as well as in the endocrine, neural and renal aspects of
blood pressure homeostasis.
Calcium has the symbol Ca and atomic number 20 and is a soft grey alkaline earth metal. Calcium has
four stable isotopes (40Ca and 42Ca–44Ca) and the metal reacts with water with the formation of calcium
hydroxide and hydrogen.
2Ca + 2H2O → 2CaOH + H2 (3.3)
Calcium salts can be found in everyday life. Limestone, cement, lime scale and fossils are only a few
examples where we encounter Ca2+. They also have a wide spectrum of applications spanning from
insecticides to clinical applications. Calcium arsenate [Ca3(AsO4)2] is extremely poisonous and is used in
insecticides. Calcium carbonate (CaCO3) can be found in clinical applications such as antacids, but note
that an excessive intake can be hazardous. Calcium chloride (CaCl2) is used in ice removal and dust control
on dirt roads, as a conditioner for concrete and as an additive in canned tomatoes. Calcium cyclamate
[Ca(C6H11NHSO4)2] is used as a sweetening agent, and calcium gluconate [Ca(C6H11O7)2] is used as a
food additive in vitamin pills. Calcium hypochlorite Ca(OCl)2 can be found in swimming pool disinfectants,
in bleaching agents, in deodorants and in fungicides. Calcium permanganate [Ca(MnO4)2] is used in textile
production, as a water-sterilising agent and in dental procedures. Calcium phosphate [Ca3(PO4)2] finds
56 Essentials of Inorganic Chemistry
applications as a supplement for animal feed, as a fertiliser, in the manufacture of glass and in dental
products. Calcium sulfate (CaSO4⋅2H2O) is the common blackboard chalk.
3.4.1 Biological importance
Calcium ions play important roles in the human body in a variety of neurological and endocrinological
processes. Calcium is known as a cellular messenger and it has a large intra- versus extracellular gradient (1 : 10 000), which is highly regulated by hormones. This gradient is necessary to maintain the cellular
responsiveness to diverse extracellular stimuli. Calcium ions are also involved in the formation of bones and
teeth, which act also as a reservoir for calcium ions.
A normal adult body contains ∼1000 g of calcium, of which around 99% are extracellular and most of
which is stored in bones and teeth. Bones actually serve as a dynamic store for Ca2+. The remaining 1%
of Ca2+ can be found in the extracellular space, such as plasma, lymph and extracellular water. The intra
and extracellular Ca2+ concentration is extremely important to many physiological functions and is therefore
rigorously controlled (Figure 3.7) [6].
Calcium ions are regulated within the gut, skeleton and kidneys. The Ca2+ homeostasis is normally in equilibrium, which means that the amount of Ca2+ enters the body is equal to the amount of Ca2+ leaving the body.
Calcium ion levels are regulated by hormones that are not regulated by the Ca2+ level, called noncalciotropic
hormones, for example, sex hormones and growth factors. In contrast, there are hormones that are directly
related to Ca2+, for example, PTH (parathyroid hormone), which are called calciotropic hormones. PTH controls the serum plasma level of Ca2+ by regulating the re-absorption of Ca2+ in the nephron, stimulating the
uptake of Ca2+ from the gut and releasing Ca2+ from the bones which act as a reservoir.
Modified hydroxylapatite, also frequently called hydroxyapatite and better known as bone mineral, makes
up ∼50% of our bones. Hydroxylapatite is a natural form of the mineral calcium apatite, whose formula is
Dietary calcium
Dietary habits,
supplements
1000 mg
Extracellular space
300 mg
900 mg
500 mg
500 mg 990 g
PTH
Calcitonin
Estrogens Kidney
175 mg
1,25(OH)2D 25(OH)2D
1-α hydroxylase
825 mg
Small
intestine
Bone
9825 mg
125 mg
Vit D-R
Vit D 10 000 mg
Figure 3.7 Calcium homeostasis [6] (Reproduced with permission from [6]. Copyright © 2005, John Wiley &
Sons, Ltd.)
Alkaline Earth Metals 57
usually denoted as Ca10(PO4)6(OH)2. Modifications of hydroxylapatite can also be found in the teeth, and a
chemically identical substance is often used as filler for replacement of bones, and so on. Nevertheless, despite
similar or identical chemical compositions, the response of the body to these compounds can be quite different.
3.4.2 How does dietary calcium intake influence our lives?
It is believed that an optimal dietary calcium intake can prevent chronic diseases. In the Stone Age, the average
calcium intake was 2000–3000 mg Ca2+/day per adult, whereas now-a-days it has decreased to an average of
600 mg/day [7]. This means that we are living in permanent calcium deficiency, and it is believed that there
are linkages to various chronic diseases, such as bone fragility, high blood pressure and colon cancer [8].
Ca2+ is an essential nutrient, and the required amount varies throughout a person’s life time depending on
the stage of life. There have been three stages of life identified when the human body needs an increased level
of Ca2+. The first one is childhood and adolescence because from birth to the age of ∼18 the bones form
and grow until they reach their maximum strength. Pregnancy and lactation has also been identified as a time
when the human body is in need of an increased level of Ca2+. A full infant accumulates around 30 g of Ca2+
during gestation and another 160–300 mg/day during lactation. Ageing has been identified as the third period
of life in humans when increased calcium intake is required. This has been associated with several changes
to the calcium metabolism in the elderly (Table 3.2).
3.4.3 Calcium deficiency: osteoporosis, hypertension and weight management
Osteoporosis is most commonly associated with calcium deficiency, but an adequate calcium intake should
not only be considered as a therapy for bone loss. It should be seen as an essential strategy for the maintenance
Table 3.2 Optimal daily calcium intake
according to NIH Consensus Conference [6]
Age mg/d
Neonates
0–6 mo 400
6–12 mo 600
Children
1–5 yr 800
6–10 yr 800–1200
Adolescents
11–24 yr 1200–1500
Male adults
25–65 yr 1000
Elderly 1500
Female adults
20–25 yr 1000
Pregnant and nursing 1200–1500
Postmenopausal (>50 yr) 1500
Elderly (>65 yr) 1500
Source: Reproduced with permission from [6]. Copyright ©
2005, John Wiley & Sons, Ltd.
58 Essentials of Inorganic Chemistry
of health in the ageing human. Ninety-nine percent of Ca2+ is found in the bones, as they function as a reservoir. Osteoporosis is known to be the major underlying cause on bone fractures in postmenopausal women.
Calcium uptake and plasma concentrations are closely regulated by hormones, as outlined in Section 3.4.1.
Nevertheless, there has been no clear and direct relationship between Ca2+ intake and bone health established
until now. It is believed that a high Ca2+ concentration and vitamin D level is essential in the first three decades
of life in order to establish an optimum bone density level. These also modify the rate of bone loss, which is
associated with ageing.
Studies support the hypothesis that calcium supplementation can reduce blood pressure, being more beneficial to salt-dependent hypertension. The regulation of the cellular calcium metabolism is central to blood
pressure homeostasis. It is believed that the higher the level of cytosolic-free calcium ions, the greater the
smooth muscle vasoconstrictor tone, which in turn has an effect on the sympathetic nervous system activity
and thus on the blood pressure. Nevertheless, studies do not justify the use of calcium supplementation as the
sole treatment for patients with mild hypertension.
It has been hypothesised that there exists a link between dietary calcium and weight management in humans.
It has been proposed that a low-calorie, high-Ca2+ diet helps in supporting the fight against obesity and
increase the energy metabolism. The recommended Ca2+ intake should be around 1200 mg/day as previously
mentioned depending on the age. Available evidence indicates that increasing the calcium intake may substantially reduce the risk of being overweight, although long-term, large-scale prospective clinical trials need
to be conducted to confirm or better clarify this association.
3.4.4 Renal osteodystrophy
Renal osteodystrophy, also called renal bone disease, is a bone mineralisation deficiency seen in patients with
chronic or end-stage renal failure.
Vitamin D is usually activated in the liver to the pro-hormone calcidiol and then in the kidney to calcitriol,
which is the active form of vitamin D. Both activation steps are based on a hydroxylation reaction. Pro-vitamin
D is hydroxylated in the 25 position in the liver (calcidiol) and then in the kidney at the 1α-position (calcitriol).
Calcitriol helps the body to absorb dietary Ca2+ (Figure 3.8).
In patients with renal failure, the activation to calcitriol is depressed, which results in a decreased concentration of Ca2+ in the blood plasma. Furthermore, the plasma phosphate level increases as a result of the
kidney impairment. This, in turn, reduces the amount of free Ca2+ in the blood even more, as the phosphate
complexes the free Ca2+. The pituitary gland senses the low levels of plasma Ca2+ and releases PTH. As
previously outlined, PTH increases the re-absorption of Ca2+ in the nephron and absorption in the gut, and
promotes the release of Ca2+ from the bones. In turn, this leads to a weakening of the bone structure.
Vitamin D
Liver
Calcidiol Calcitriol
Level too low
Release of
PTH
Promotes
dietary
uptake of
Ca2+
Kidney
Figure 3.8 Activation of vitamin D
Alkaline Earth Metals 59
Patients can be treated with phosphate binders in order to avoid excess phosphate absorption from the gut.
Dialysis will also be helpful in removing excess phosphate from the blood. Furthermore, the patient can be
given synthetic calcitriol and potentially calcium supplements.
3.4.5 Kidney stones
Around 20–40% of all kidney stones are associated with elevated Ca2+ level in the urine. For a long time,
it has been suggested that low dietary calcium intake would be the best method to prevent the recurrence of
kidney stones. More recent studies involving patients who suffered from recurring calcium oxalate stones
showed that a low calcium diet did not prevent the formation of kidney stones. It was actually found that
a higher calcium intake of around 1200 mg/day resulted in a significant reduction of the recurrence of kidney stones by around 50%. It is believed that the restriction of calcium leads to an increase in absorption
and excretion of oxalate in the urine and therefore promotes the formation of calcium oxalate stones. Currently, the conclusion is that kidney stone formation in healthy individuals is not associated with calcium
supplementation [4].
3.4.6 Clinical application
Calcium supplements are usually required only if the dietary Ca2+ intake is insufficient. As previously mentioned, the dietary requirements depend on the age and circumstances; for example, an increased need can
be seen in children, in pregnant women and in the elderly where absorption is impaired. In severe acute
hypocalcaemia, a slow i.v. injection of a 10% calcium gluconate has been recommended. It has to be kept
in mind that the plasma Ca2+ level and any changes to the electrocardiogram (ECG) have to be carefully
monitored [5].
A variety of calcium salts are used for clinical application, including calcium carbonate, calcium chloride,
calcium phosphate, calcium lactate, calcium aspartate and calcium gluconate. Calcium carbonate is the most
common and least expensive calcium supplement. It can be difficult to digest and may cause gas in some
people because of the reaction of stomach HCl with the carbonate and the subsequent production of CO2
(Figure 3.9).
Calcium carbonate is recommended to be taken with food, and the absorption rate in the intestine depends
on the pH levels. Taking magnesium salts with it can help prevent constipation. Calcium carbonate consists
of 40% Ca2+, which means that 1000 mg of the salt contains around 400 mg of Ca2+. Often, labels will only
indicate the amount of Ca2+ present in each tablet and not the amount of calcium carbonate

You May Also Like