What is Pharmacogenetics?

Pharmacogenetics is the discipline that studies the genetic variations that affect the individual response to drugs, its final objective being the personalization of treatments. Thanks to this, we can:

1) Anticipate inadequate responses to treatment: Until now, these differences in response to a drug could only be identified after undergoing exposure. Pharmacogenetics offers an alternative to this situation.

2) Unalterable information: The pharmacogenetic analysis provides very valuable information since a single pharmacogenetic analysis will give us information about our metabolization profile throughout our entire life.

What does this Pharmacogenetic Panel study?

This Panel studies the risk of an individual to suffer an abnormal metabolization of the most frequently used drugs (see list of drugs in ANNEX). This abnormal metabolism of the drug means that its rate of elimination from the body is faster or slower than normal. But how does this whole process take place?

When a drug is administered, it goes through different processes such as absorption, distribution to its site of action, metabolism and excretion. In each of these steps there could be a genetic variation with a different clinical result. Of all these processes, the best studied is drug metabolism. The cytochrome P450 enzymatic system is one of the most relevant in Pharmacogenetics, specifically the enzymes CYP2D6, CYP2C19, CYP2C9 and CYP3A5. These genes have a multitude of alleles (each of the variant forms of a gene) responsible for Abnormal Metabolism:

-Ultrafast Metabolizer (UM): Enzymes metabolize the drug very quickly, reducing its effect on the body. The genotype is made up of more than two active alleles (gene duplication), giving rise to a greater enzymatic endowment.
Solution: An increase in the dose of the drug is usually required, due to the high rate of metabolization, to achieve an optimal therapeutic response .

-Normal Metabolizer (EM): Medications are processed correctly. The genotype consists of two active alleles, giving rise to a functional enzyme.
Solution: Unless there are other factors that prevent it, standard doses of the drug can be used.

-Intermediate Metabolizer (IM): These are individuals with a metabolism of intermediate drug. The genotype is made up of an active and an inactive allele, so that its functional enzymatic endowment is diminished.Solution: Pharmacological interactions should be avoided, that is, drug treatments that further decrease the body's metabolizing capacity. (PM): The genotype is made up of two inactive alleles, resulting in the loss of functional enzyme Solution: A decrease in the dose of the drug is usually required due to a lower elimination rate that increases the risk of side effects.

How are the results interpreted?

It can be assumed that genetic factors, on which Pharmacogenetics focuses, are responsible for between 20 and 95% (depending on the drug) of the variability observed in the effects of the drug; but these are not the only ones that contribute to the different response to treatment since it is also affected by environmental factors such as the duration of treatment, the interaction with other drugs, kidney and liver function, age, diet, smoking or alcohol .

The analysis in the context in which the patient finds himself and the joint assessment of all these factors, both environmental and genetic, is what will determine the choice of the most suitable drug for each patient, avoiding both adverse pharmacological reactions and the loss of efficacy of the drug. treatment.

Taking into account the previous premises and the genetic result of the patient, the list of drugs that appears in the ANNEX can be consulted.In the event that the patient presents any genetic variation in any of the genes studied, it means that ESA ENZYME does not work within the “normality” and therefore, the drugs metabolized by ESA ENZYME will present an abnormal metabolism (Ultrafast Metabolizer or Slow Metabolizer). Finally, it should be noted that the dose of any drug should NOT be altered without first consulting with your doctor.
Laboratory EUROESPES