Drugs

The ideal drug should be effective on anyone and should have no side effects.

The ideal drug should only contain the active substance, at most diluted in definitely harmless media as, for example, water.

Unfortunately, the ideal drug does not exist.

Pharmakon (

The activity of a drug depends on a great number of variables, one of which is the extreme complexity of the animal man together with the far-from-negligible difference there is between individual and individual and also in the same individual over time. So, a drug can be more or less occasionally beneficial for one, indifferent for someone else and harmful for a third subject. Let us just take as an easy example - caffeine, a very common natural compound used also in many medicaments: there is someone who takes large amounts of it every day without showing any particular effect; others who have a headache if they abuse it; others who are kept awake the whole night if they only take a drop of coffee and, finally, people who can’t sleep if they do not drink their cup before bedtime. But of substances which behave in a very different way, as is the case of caffeine, there are many. In fact, almost all of them, although in most cases the differences are not so extreme, with the due exceptions of allergic reactions.

Paradoxical effects are very well known by pharmacologists and toxicologists. A paradoxical effect or paradoxical reaction is the result of the administration of a medical drug, opposite to the effect which would normally be expected - for example, pain caused by a pain relief medication, suicidal compulsions from anti-depressants or the so-called Eagle effect [5-9].a

So, what is currently considered to be a good drug is one which is statistically effective (and beneficial) to a majority of subjects.

It should be added that side effects may occur any time, and it is not so rare that they become evident only after a long time: odds which are particularly critical for those who take the same drug in a chronic way. In fact, however long and accurate a trial is, it will never cover all the possibilities which a drug encounters, and, like it or not, after all, to a greater or lesser extent, anyone taking a drug is a guinea pig.

It can also be interesting to remember how not too seldom a placebo has a better effect than a drug aimed to treat a certain disease. The reason for this apparent oddity is easily explained considering the concept of homeostasis, that is, the self-regulating processes by which man, as well as any living being, tends to maintain biological stability while adjusting to conditions which are the best possible for the continuation of life in a state of well-being. At the same time, it must be remembered that all pharmaceuticals are also poisons (see their Greek etymology) and, as such, are potentially harmful as well as hopefully beneficial. It may happen that the damage outweighs the benefit, and therefore, in those cases, it is much more convenient to let the organism intervene according to the homeostasis just mentioned. In short, it may happen that letting nature work is more advantageous than replacing her.

’The effect originally referred to the reduced antibacterial effect of penicillin at high doses, a paradoxical effect because the effectiveness of an antibiotic generally rises with increasing drug concentration.

To make matters more complicated, there is the crossover effect of drugs, something which, especially when the medicaments administered to the same patient are relatively numerous, is very hard, if not utterly impossible, to predict.

Nowadays, drugs are not prepared on the spot, immediately and on request. The use of galenic preparations is also rapidly declining, and almost all of today's medicaments are industrial products which are made to be manageable for the caregiver and for those who take them; which must be movable and storable for a long-enough time, maintaining unchanged their characteristics; and which must be the least possible sensitive to environmental conditions, for example, those relating to temperature and humidity. In addition to that, the drug should not be too unpleasant for those who use it. So, a lot of substances which have nothing to do with the active ingredient but are necessary to accomplish all those results are added, and it is not impossible that those substances exert some side effect.

A practical problem concerning drugs is the presence of the same active ingredient in products with different commercial names. So, it happens that the same patient takes too high doses of the same drug, believing that it is something different This occurs frequently when the patient turns to several specialists who do not know about each other and who prescribe the same active ingredient or the set of the same active ingredients with different brand names. Just to give an example relating to an active ingredient used and abused, having to write a book on the subject, we found that in Italy paracetamol is present 470 times.

Anyone taking drugs as tablets necessarily takes substances as micro- and nanoparticles added on purpose to dilute the active ingredient, to ensure that the drug does not break before being taken but disintegrates once it has entered the body, to make the product pleasant to the eye and so on. Also gelatin capsules and syrups may contain particulate excipients as an addition. Thus, particles such as those of talc or titanium dioxide are swallowed together with the active ingredient.

To our knowledge, a study has never been conducted showing that the amount of excipients taken is equivalent to that in any way eliminated. Therefore, it is not known whether something remains in the organism, where and how much. As a rule, the excipients in the form of particles are evaluated exclusively from a chemical point of view, and according to this criterion, their reactivity is negligible or, in practical terms, zero. But if one looks at them from the nanopathological point of view, it is clear that those particles are foreign bodies which necessarily behave as such. And the fact becomes particularly important for those who must take a drug in a chronic or, in any case, in a prolonged way over time. But now micro-and nanoparticles are also used in many sunscreens to block UVA and UVB rays. In the cosmetics industry, they are used in toothpaste, lipsticks, creams, ointments and powders, and there are many industrial foods which contain them as a deliberate addition, if not as ignored pollutants. Though the Food and Drug Administration (FDA) has approved titanium dioxide particles for food, drugs and cosmetics, there is no actual evidence about their safety.

On top of it, a number of drugs, or, at least, a substantial number among those we had a chance to check, are polluted by solid, inorganic particles whose effects depend on many variables, the most important of which are due to the class the medicament belongs to. Particles in a cream to be spread on the skin may prove to be not particularly dangerous but not so, as just mentioned, for particles polluting a medication taken orally. Much more dangerous are the particle-polluted medicaments taken by aerosol and, to the maximum of dangerousness, those administered as an injectable solution. Of course, since they are pollutants, they cannot be expected to be listed in the technical data sheet prepared by the manufacturer. In short, they are there but they are ignored.

We have no idea where those particles polluting drugs come from, be it h orn the raw materials used, h orn the technical procedures or from a production environment which is not perfectly clean. To be able to give an answer and, maybe, suggest solutions, we should be permitted to inspect the producer’s facilities, something which we have never been allowed to do. What is certain is that the checks which should be carried out by the manufacturers and, a fortiori, by the relevant public bodies are, to say the least, insufficient.

The following three figures (Figs. 5.15, 5.16 and 5.17) show electron microscopy images of particulate matter contained in the drugs rafton, torvast and lansoprazole, respectively.

(a)

(b)

Figure 5.15 Rafton is a corticosteroid drug (budesonide) in the form of capsules used as a symptomatic against chronic diarrhea and in mild forms of Crohn's disease. Regardless of the presence of particles used as an excipient without knowing their actual fate, that of almost usual steel and non-unusual titanium, the most notable presence is the uranium component in some particles.

Torvast is a statin administered as tablet which is used to lower blood lipid levels

Figure 5.16 Torvast is a statin administered as tablet which is used to lower blood lipid levels. The particles found are calcium-based with dimensions ranging from the fraction of a micron to a hundred microns. Being a drug which is taken orally, it must be considered that the gastrointestinal system is permeable to large particles, and it is not known whether those we detected are biodegradable and, if so, in how long. If the particle takes a relatively long time to degrade, it may have time enough to trigger the inflammatory reaction.

Lansoprazole, sold under the commercial name of Lansox, is a medication which reduces stomach acid. Talc (Mg-Si) is used as an excipient

Figure 5.17 Lansoprazole, sold under the commercial name of Lansox, is a medication which reduces stomach acid. Talc (Mg-Si) is used as an excipient.

Appendix: Why Chelation Therapy Is Ineffective with Nanoparticles

A relatively high number of large molecules (e.g. proteins, polysaccharides and polynucleic acids) called ligands, due to certain chemical characteristics of theirs, can bind a metal ion in a cyclic or ring structure in a kind of pincer action. Chelatingagents, particularly, though not exclusively, salts of ethylenediaminetetraacetic acid (EDTA), are widely used in medical practice to treat metal poisoning. Their administration, although currently used without too many precautions, is quite critical and not easy to dose correctly Chemical selectivity as to the element meant to be eliminated is not particularly high, so, in addition to affecting the toxic cation to be removed, medical chelation involves elements which, in trace or in larger quantities, are beneficial to the organism, such as calcium, iron, zinc, magnesium and selenium, which, except in the case of poisoning by one of those elements, should remain undisturbed. Side effects, the quickest of which to become manifest is in general a feeling of fatigue, are therefore numerous; some of them are even very serious, and the use of chelation agents should be reserved to strict necessity and limited as much as possible in time.

It must be added that chelating agents cannot negotiate the lipophilic cellular membrane, and therefore, they cannot act against intracellular poisoning. For example, in a biological environment (e.g. the blood), organic mercury is lipophilic and can easily enter the cells, settling in the cytoplasm and then in the mitochondria as Hg2*. Hydrophobic agents are sometimes added to chelators to have them enter the cell, but their efficacy is controversial.

In any case, chelators are useless against inorganic, solid, insoluble particles. In fact, they can sequester only ions, while the metallic and non-metallic elements composing particles are generally part of alloys or crystals or are amorphous structures. Furthermore, a particle is generally stable and, however, is much bigger than an atom. To make an easily understandable example, trying to hook a particle with a chelating agent is like trying to grab an elephant with eyelash tweezers. So, considering their actual efficacy and their long list of contraindications and side effects, before administering a chelation therapy it is mandatory to understand the nature of the intoxication meant to be treated. Then, once the chelation therapy has started, it is essential to check the patient about the chemical balance of the trace elements present in his/her body to avoid the risk of stealing something indispensable.

Regardless of actual chelation, several different remedies which have nothing to do with that chemical process are proposed to free the body h orn inorganic pollutants, even particulate ones. Zeolite, a family of microporous, alumino-silicate minerals, is one of them (Fig. 5.18). Of the more than 200 different formulas existing, about 40 are of natural geological origin and they are capable of accommodating in their structure a wide variety of cations. On their

‘purifying” properties, at least for some of them, there is a certain episodic literature, but in fact, there is no evidence relating to their effectiveness, especially as for micro- and nanoparticles. And nothing can be found in the literature to demonstrate that all the product ingested is actually eliminated and how.

Zeolites are microporous, alumino-silicate minerals of volcanic origin with a structure which somehow recalls that of activated carbon

Figure 5.18 Zeolites are microporous, alumino-silicate minerals of volcanic origin with a structure which somehow recalls that of activated carbon. The large surface in relation to their volume suggests an ability to trap substances harmful to the body. There is a relatively large amount of episodic literature which reports success in cases of the most diverse pathologies. To our knowledge, however, not enough extensive studies exist over time to check whether the benefits have been preserved and whether side effects have occurred if not all the zeolite introduced into the body was then eliminated in the stool or in any other way. In that case, zeolite would be a solid, inorganic and non-biodegradable foreign body.

In our experience, getting rid of micro- and nanoparticles when they have been captured by tissues is something which no drugs have shown to be able to do.

References

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