Symptoms and Treatment of Limited Personality Disorder

All the medications we take interact with our body in a certain way, and there are peculiarities in how each of us reacts to certain medications. Certain characteristics of the patient, such as, for example, age, lifestyle or the presence of any diseases, as well as their treatment, can affect the reaction of an individual to a particular medicine. In this sense, from a biological point of view, one of the determining factors of the effectiveness and toxicity of a drug is our genetic material.

DNA, Molecule Inherited

Deoxyribonucleic acid or DNA is the molecule that makes up our genetic material, which means our heredity. Certain regions in our DNA are formed by genes that contain information about the formation of proteins, which, combining together with other chemical compounds, form our cells, tissues and organs.

For proteins to work properly, they must have the appropriate shape. This is what DNA serves for, carrying information for our cells so that they can build proteins correctly, at the right time and in the right place.

Genes and Drugs

When we take a medicine, it must go through various stages inside our body before reaching the organ where its help is needed. If the medication is taken orally, it is first absorbed, then integrated into the metabolic process, and then distributed throughout the body, and eventually it will be removed from our body. Certain changes in the DNA sequence, in the genes in which the proteins that control these processes are encoded, create a special protein that will interact with the drug in a slightly different way, thereby causing a different reaction.

Pharmacogenetics is a field in which genetics and pharmacology are combined, and the relationship between changes in the sequence of our DNA and the reaction to a certain drug treatment is investigated.

Through the study of certain changes in DNA, pharmacogenetics can help prevent the risk of adverse effects and lack of effectiveness of a certain drug, as well as determine the most appropriate dosage in each individual case. Thus, pharmacogenetics is a valuable tool for optimizing treatment at the individual level, acting one step ahead for safer and more effective personalized treatment.

Genetic Variability in Drug Response

Personalized medicine takes into account these and other individual characteristics of each person to create the most personalized course of treatment. Pharmacogenetics is a part of personalized medicine, analyzing a patient’s genetic profile based on a DNA sample, a molecule of heredity that each of us has inside our cells.

The DNA sequence of two different people is 99.9% identical. The remaining 0.1% accounts for genetic diversity, most of the differences between people are “recorded” in it, and it is this small segment that is the subject of the study of pharmacogenetics.

If we analyze a group of people taking the same doses of a certain medication, we will find that some will have a good response to treatment, while others will not show the expected effect, and some will even develop adverse effects.

One of the reasons for this variability is the differences in the process of drug exchange within our body. For most people, this process proceeds normally or in the expected way. But in some people, the metabolism is disrupted, they cannot remove the drug from the body or its excretion is very slow, which creates problems in the reaction or contributes to the development of adverse reactions.

On the other hand, in a small group of people, the drug exchange process occurs extremely quickly, therefore, despite taking the medicine at the indicated dose, due to the speed of excretion from the body, they do not get the desired effect. A certain percentage of these differences in the rate of exchange is due to certain changes in the DNA sequence, and this can be easily detected by taking a human DNA sample.

Similarly, there are certain genetic changes, usually localized in the genes that encode the “target” for the effects of drugs, or mechanisms for their activation, which is associated with the effectiveness of drugs or the risk of developing certain types of adverse effects associated with the course of treatment. Thus, identifying these options for the patient can also help to choose the most appropriate treatment.

Precursors of Pharmacogenetics

The history of pharmacogenetics goes back to 510 BC, when Pythagoras discovered that the use of legumes in some people caused a severe and potentially fatal reaction. Currently, we know that such people suffer from favism, hemolytic anemia, which is caused by an “inherited” deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6FD).

But this was not known until the beginning of the XX century, when the English doctor Archibald Garrod conducted his research on the nature of heredity of diseases related to metabolism, introducing the concept of “chemical individualism”. In his work Innate errors of metabolism, published in 1909, Garrod writes that “a certain dose of medicine, harmless to most people, has toxic effects for some patients, while other people may show exceptional tolerance to the same drug.”

In 1959 Friedrich Vogel first coined the term “pharmacogenetics” to denote the study of the role played by changing individual genes for drug response.

Over the following years, new examples of excessive reactions were published, expressed both in the ineffectiveness of drugs and in the manifestation of hereditary models. But the reason for them was not clear until the late 80s, when studies began to be published concerning the molecular basis for certain hereditary models.

In recent decades, the rapid development of new DNA analysis technologies, together with the publication of the decoding of the human genome, has given impetus to the rapid evolution of pharmacogenetics.

Advantages of Pharmacogenetics

Traditionally, it was believed that the reaction to a particular drug depended on physiological factors such as age, weight or gender, as well as external factors such as diet, bad habits or concomitant diseases. Currently, it has been known for several years that genetic factors play a key role in the variability of reactions to drugs, giving in some cases 50% of such dependence.

As already noted, not all the drugs are completely effective for all patients. This indicator is estimated in the range from 25 to 80% of satisfactory reactions of patients, depending on the course of treatment, while the rate of reactions to most drugs ranges from 50 to 70%. Moreover, except for the lack of an absolute response to treatment, drugs can give severe adverse reactions.

In the specific case of drugs used in the field of psychiatry, up to 60% of patients with depression do not fully respond to antidepressants, and up to 30% do not receive any reaction. In addition, the adverse effects of antidepressant treatment are frequent, and their occurrence cannot be predicted a priori.

Similarly, although antipsychotic drugs have revolutionized the treatment of schizophrenia, the remission rate is about 35–40%. Moreover, it is estimated that about 25% of patients undergoing long-term treatment with antipsychotic drugs develop distant dyskinesia, an adverse effect related to the motor system, which is potentially irreversible.

Also in the event of treatment of epilepsy, a similar phenomenon is observed: therapy with the use of antiepileptic drugs is characterized by effectiveness, adverse reactions and unpredictable individual dosage. Moreover, 20% of patients with epilepsy are resistant to antiepileptic drugs.

In the event of attention deficit hyperactivity disorder (ADHD), it is described that about 20–30% of patients do not respond or show intolerance to treatment.

Personalized medicine based on pharmacogenetics provides potential advantages in various areas of therapy compared to classical methods, because it allows you to more accurately select medications and learn about the possibility of certain adverse reactions. Such information provided by pharmacogenetics increases the likelihood of successful treatment and can result in overall savings for the healthcare system, because the number of intermediate stages of treatment and possible costs associated with them are reduced.