4.2 Current use of metals in medicine: an overview
Take a look at Table 4, in which you’ll see examples of where metals may be found in therapeutic and other health care applications. This is certainly not a comprehensive list; it has just been included to give you a feel for the topic. A quick look at of the table reveals applications ranging from cancer treatment to over-the-counter medication and personal care.
| Metal | Form (common/trade name) | Use/treatment |
|---|---|---|
| Li | carbonate (Camcolit®) | bipolar disorders |
| Na | bicarbonate (Alka-Seltzer®) | heartburn |
| Mg | sulfate (Epsom salts) | constipation |
| hydroxide (milk of magnesia) | heartburn | |
| Al | hydroxide (Gaviscon®) | heartburn |
| silicate (kaolin) | diarrhoea | |
| Ca | carbonate | heartburn, peptic ulcer, diarrhoea |
| Ga | Ga(III) complex | cancer |
| As | organic arsenic compound (Melarsoprol®) | sleeping sickness |
| Sr | 89Sr complex | bone cancer |
| Sb | sodium stibogluconate | leishmaniasis |
| Bi | bismuth subsalicylate, C7H5BiO4 (Pepto-Bismol®) | heartburn, diarrhoea |
| tripotassium dicitratobismuthate (De-nol®) | peptic ulcer | |
| Ti | oxide | sunblock |
| V | complex | diabetes |
| Fe | Na2[Fe(CN)5(NO)].2H2O | hypertension |
| Cu | histidine complex | Menkes disease |
| Zn | oxide | sunblock |
| oxide with 0.5% Fe2O3 (calamine lotion) | antimicrobial agent | |
| Y | 90Y complex | bone and liver cancer |
| Zr | Zr(IV) glycinate | antiperspirant |
| Ru | Ru(III) complex | cancer parasitic disease |
| Ag | silver sulfadiazine | burns |
| Ag/Hg amalgam | dental amalgams | |
| Pt | Pt(II) complex | cancer |
| Pt(IV) complex | cancer | |
| Au | Au(III) complex | cancer |
| Au(I) complex | arthritis | |
| Re | 186Re, 188Re complex | bone cancer |
| Ti | Ti alloy | hip and knee replacement |
| Sm | 153Sm complex | bone cancer |
You should note from Table 4 that many of the metal complexes listed are used in the treatment of cancer and this will be the main focus of the next sections. However, before you look at metal complexes used in cancer therapy, you will briefly consider a few examples where metals are used in medical treatments for more common ailments, including those available ‘over the counter’.
Gold complexes have been used in the treatment of rheumatoid arthritis; the most recent drug to be used is aurofin which is taken orally. The active component is Au(I), the ligands in the complex conferring the necessary absorption and transport properties to the pharmaceutical agent.
NO plays a number of important roles in the body, in particular in the dilation of blood vessels in the cardiovascular system. Complexes, such as Nitropress® (Na2[Fe(CN)5(NO)].2H2O, which release NO can be used to alleviate acute hypertension; a series of Ru complexes have been investigated in this regard.
Lithium, taken orally as Li2CO3 tablets, is used for the treatment of bipolar affective disorders. The mode of action is unclear; however, the active ingredient is believed to be .
Two vanadium complexes have completed clinical trials for the treatment of Type II (insulin-resistant) diabetes. The complexes are prodrugs (see below), dissociating to release vanadyl ions which are believed to enhance the effect of insulin in controlling glucose levels. The key role for the ligands in the complexes appears to be to aid absorption and to provide sufficient stability to the complex so that it only dissociates when required.
Metal alloys have long been used as bone replacements in both hip and knee replacement surgery; such alloys need to be biocompatible, must be able to withstand the corrosive environment in the body and have a high strength and resistance to fatigue. Biomaterials such as hydroxyapatite, Ca10(PO4)6(OH)2, the mineral component of bones and teeth, are also undergoing study for this application. Metal alloys are also used in dentistry as implants and in amalgams.
Peptic ulcers, of which the most common are gastric (stomach) and duodenal, are associated with the bacterium Helicobacter pylori, which thrives in the acidic environment of the stomach. The bacterium causes inflammation by preventing the regulation of acid in the gastrointestinal tract. These ulcers can be very painful, especially when stimulated by gastric and duodenal acids.
The active ingredient in one treatment for peptic ulcers is tripotassium dicitratobismuthate.
The acidic environment present in the stomach results in the precipitation of bismuth oxychloride and/or bismuth citrate polymers. These precipitates coat the ulcer site, isolating it from the gastric and duodenal acids and allowing it to heal. Bismuth may also have an antibacterial action, and given in combination with antibiotics is particularly successful at treating stomach ulcers.
Magnesium and aluminium hydroxides are examples of antacids sold commercially to treat heartburn, an unpleasant sensation which arises from the regurgitation of gastric acid up the oesophagus.
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Suggest why these compounds might be used as antacids.
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These compounds are bases. The hydroxide ions neutralise the stomach acid. For the same reason, sodium bicarbonate and calcium carbonate are also antacids.
Magnesium hydroxide can also be used as a laxative (as can a range of other magnesium compounds). is not readily absorbed by the body and remains in the intestines in faeces, where it will absorb water from the surrounding tissue. This results in softening of the faeces as well as encouraging excretion as the increase in volume stimulates the intestines.
The laxative effect of when given as an antacid can be neutralised by the addition of aluminium hydroxide, which is also an antacid but also can cause constipation. In this case, the aluminium absorbs water from the faeces.
Zinc oxide is commonly used to treat a variety of skin conditions and is a key ingredient in calamine lotion, barrier and nappy creams to sooth itching and irritation. It is also occasionally used as a sunblock, although TiO2 is more common; particles of the oxide act as a physical block, reflecting and/or scattering harmful UV radiation.
In the next section, you will start to look at the use of metal complexes in cancer treatment, beginning with the molecule that started it all – cisplatin.