We live in a hypermedicalized society in which health is managed as another consumer good more accessible to anyone. So much so that it seems normal to take that yellow pill to sleep, that other pink to go to the bathroom and the white one to mitigate the headache after a night of partying.
According to Joan-Ramón Laporte, professor of pharmacology at the Autonomous University of Barcelona, the consumption of medicines in Spain is 50% times higher than the European average. Laporte criticizes that, too often, it is society itself that generates the “need” to consume them.
The worst thing is that this excessive desire to consume medicine does not come free. We often pay a heavy price in the form of adverse drug reactions or drug interactions. Without forgetting the other side of the coin: therapeutic ineffectiveness. Due in large part to that not all people benefit in the same way from the drugs.
Same drug, different reactions
It is evident that not all of us respond the same dose of, for example, paracetamol or ibuprofen. “This sleeping pill doesn’t do anything to me and when you take it you sleep like a log” or “I haven’t taken this pain medication for a long time, it doesn’t work for me” are phrases that we hear relatively frequently at home or in a conversation between friends. The fact is that, for the same dose, we observe different responses in the population, from the expected efficacy, to the lack of it in some cases, or even adverse effects in others.
Why does this happen? It must be borne in mind that for a drug to produce its therapeutic or toxic effects, it must reach certain concentrations at its place of action (biophase). Until that happens, it goes through a series of stages:
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Absorption: the entry of the drug into the body from the place of administration. The journey begins!
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Distribution: the drug transits through the blood to the tissues and organs where it has to act and from which it has to be eliminated. Depending on the drug, this trip can be done alone or together with proteins present in the blood and tissues.
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Elimination: the concentrations of the drug in the body are decreasing as a consequence of its metabolism and / or excretion.
Almost all drugs are metabolized in the liver, thanks to the activity of enzymes that transform them chemically to facilitate their elimination.
As a consequence of this enzymatic biotransformation, some drugs become active, others lose activity and there are some that generate toxic metabolites, responsible for adverse effects.
Finally, thanks to the excretion processes, the drug is permanently eliminated from the body. The end of the trip!.
Absorption, distribution, metabolism and excretion are the so-called pharmacokinetic processes. Something like “what the body does to the drug.” And we know that there are inter-individual differences in these processes that largely condition the different response to drugs.
This means that variations in absorption (alterations in gastrointestinal pH, blood flow, gastric emptying …), or in distribution (differences in drug-transporting proteins or in blood flow), or in metabolism (biotransforming enzymes with more or less activity), and even in excretion (kidney function) are very often responsible for observing individual responses to such different drugs.
In addition, the response to medications depends on pharmacodynamics, which studies the actions and effects of drugs (“what the drug does to the body”).
Question of genes
The variability in the response to a treatment between different people may be due to the age, sex, pathologies of the patient and the intensity of the symptom to be treated. But, above all, to the genetic differences between individuals.
This is where the third element comes into play, pharmacogenetics, which is the discipline that investigates the link between the genetic makeup of people and their response to drugs. To be exact, it analyzes how the so-called genetic polymorphisms (variations in the structure of genes between individuals) affect the response of drugs.
Between 20% and 95% of the variability between individuals in the response to drugs is explained by genetic differences. Specifically, differences in the rate of drug metabolism, transport across cell membranes, and the susceptibility of targets with which drugs interact to trigger the response. It has been proposed that the lack of response to some antidepressant and antiepileptic drugs lies in genetic polymorphisms that affect pharmacokinetic and / or pharmacodynamic processes.
Personalized medicine
What seems indisputable is that integrating knowledge of the sources of variability in the response to drugs would facilitate the selection of the right drug, the right dose and for a particular person. This is what is known as “personalized medicine”.
The alchemist Paracelsus (1493-1541) uttered the famous phrase: “single dose facit venenum”(“only the dose makes the poison”). Allow us, Mr. Paracelsus, to add: “…differently in different people“
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