What is individualized therapy?
And how does smoking affect the selection of medicines
The term "personalized therapy" is associated with high technology and expensive tests, but in fact it means taking into account the characteristics of the patient — for example, how old he is and whether he has concomitant diseases. Although, of course, more complex methods can be used in such therapy. Pharmacologist Yuri Kiselyov tells about what factors should be considered when individualizing treatment, why monitor the concentration of drugs in the blood and how pharmacogenetics helps treat depression.
Personalization of medicine or individualization of treatment is taking into account the individual characteristics of the patient when prescribing and conducting drug therapy. Such an individual feature may be gender: the male and female bodies differ quite strongly not only anatomically, but also physiologically. In particular, women have the potential for pregnancy, and this should be taken into account: for example, in a pregnant woman, medications will be distributed, metabolized and excreted from the body somewhat differently. In addition, it is necessary to take into account the potential teratogenic effect of the drug, that is, the likelihood that it can lead to defects, to disorders of fetal development.
In addition, age should be taken into account during therapy. In young children, for example, the metabolism of drugs in the liver occurs completely differently than in older children or in adults. Elderly people are more sensitive to many medications than young people: in most cases, the elderly have slightly or significantly reduced renal function, which means that it is difficult to remove the drug.
In addition to gender and age, behavioral and environmental factors need to be taken into account — for example, smoking. Certain components of tobacco smoke affect not only the development of lung cancer, but also liver enzymes that process drugs. Suppose we have identical twins who have schizophrenia, and they both receive the same antipsychotic — but one smokes and the other does not. In a smoker with a high probability, the concentration of the drug in the blood will be lower due to the fact that the components of tobacco smoke thus affect liver enzymes. Another example is alcohol: it not only interacts with a number of medications, but also can simply lead to the patient forgetting to take the medicine, and this will change the effect of drug therapy.
The factor of the presence of concomitant diseases is very important, because a medicine that helps with one disease can have a negative effect on the course of another. In addition, with several diseases, we naturally take several medications, and we need to take into account possible drug interactions that can be very serious and potentially fatal.
Pharmacogenetics
Pharmacogenetics is a subsection of pharmacology that studies the interaction of the human genome and drug therapy. For example, liver enzymes that provide drug metabolism are synthesized on the basis of certain genes, and if these genes differ in different people, then their metabolism will be different. As an example, we can name metoprolol, which belongs to the group of beta-blockers: it is a very widely used remedy for the treatment of coronary heart disease, arterial hypertension, and chronic heart failure. Metoprolol is metabolized in the liver, and the more active the enzymes are, the faster the drug disappears from the body.
In the European population, several subgroups can be distinguished: 50-60% of Europeans have some standard variant of the gene responsible for metoprolol metabolism, but about 10-15% metabolize metoprolol slowly, that is, their drug will be excreted from the body slower than the average person — which means it can accumulate and lower blood pressure and heart rate more. At the same time, 2-5% of the European population belong to the group of rapid metabolizers: their gene variant provides very rapid processing of metoprolol in the liver and its very rapid disappearance from the blood. Such pharmacogenetic variability is relevant not only for metoprolol, but for a huge number of other drugs, and it may be associated not only with hepatic metabolism.
What does this mean for us in practice? Suppose a patient receives a good antidepressant at the right dose, but nevertheless we cannot get the effect. In this situation, the appointment of pharmacogenetic tests is justified when we check which gene variants are carried by this particular patient. Maybe the antidepressant is processed very quickly in the liver, the concentration of the drug drops very quickly, and the dose or frequency of administration is insufficient. There is still a possibility that the drug does not penetrate sufficiently into the brain: this is also often determined by genes. In such situations, we use pharmacogenetic panels, which include a number of analyses for certain genetic variants relevant to drugs used in the treatment of depression. Similarly, there is, for example, a statin panel, an antipsychotic panel, a panel of drugs that affect blood clotting — and so on. Such panels are widely used in clinical practice in Western countries and are now included in clinical use and in Of Russia.
Therapeutic drug observation
Another important method in individualized therapy is therapeutic drug monitoring, in which the concentration of drugs in blood, saliva or other biological fluids is measured. This is important, because only by measuring the concentration of the drug in the blood, we can find out exactly whether it has been absorbed and in what quantities. For example, in Norway, a study was conducted of elderly patients who received gabapentin for the treatment of chronic pain: in many patients, it proved ineffective. It turned out that in 90% of patients, the concentration of the drug in the blood was extremely low, partly due to the fact that gabapentin, in principle, is poorly absorbed in the intestine, and in elderly people it is especially bad: they needed a large dose.
There is another example. The Oslo University Hospital and the National Epilepsy Center conducted a study of valproate, a drug for the treatment of, in particular, epilepsy. In 200 people who received the same dose of valproate daily, the concentration of the drug in the blood was measured at the same time point. It turned out that the spread of the drug concentration at the same dose is plus or minus 3000%. On the one hand, this is a very alarming finding, but on the other hand, it is very valuable, because now we at least know about this problem and can implement therapeutic drug surveillance in practice.
Prospects of individualized therapy
So, the effect of drugs on individual individuals can be very different, and there may be many reasons for this: this may be a genetic feature, it may be related to age or gender, lifestyle features, concomitant diseases and many other factors. Therefore, individualization of therapy is very important, and today we have tools for true individualization — for example, pharmacogenetics and therapeutic drug surveillance. Of course, they are not cheap and not easy to use, but they are getting cheaper, and I really hope that their use will spread to even the smallest hospitals and polyclinics in our country.
About the author: Yuri Kiselyov – Ph.D., Associate Professor at Oslo Metropolitan University
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