Ruy Miranda
Social Anxiety Shyness Info

The side effects of drugs used in the treatment of Social Phobia, as is the case with those used in connection with other health problems, depend on a number of factors that are related to the chemical characteristics of the drug on the one hand and to the characteristics of the organism on the other. Over the last few years, we have received a steady flow of good news in relation to questions related to the organism, more specifically with regard the role of genes in this field. Indeed, in many cases there is a connection between some genetic characteristics and the appearance of side effects.

To better understand this subject, it is necessary to first understand the role of certain biological substances in the metabolism of these drugs.

Any substance, including prescription medication, that enters the organism is subject to a series of reactions in order to adapt to the biological characteristics of that organism. The substance is then metabolized. The purpose of these reactions is to make good use of the substance. Enzymes play an essential role in living organisms by promoting these reactions.

The metabolization of drugs used in the treatment of Social Phobia/Social Anxiety Disorder, as is the case with various other drugs (and also foods), occurs as a result of the interference of enzymes known collectively as Cytochrome P450. This is treated as a family of proteins.

Proteins are biological substances formed by the fusion of dozens or hundreds or thousands of other tiny organic molecules known as amino acids. Each protein has a specific function in the organism, whether in the organism of an ameba or that of an elephant. Proteins of the Cytochrome P450 family have an enzymatic function in the metabolization of various substances.

Should an enzyme present some kind of change in its chemical structure, it will not perform its function correctly. For example, the change could render the reactions more sluggish. Consequently, the drug accumulates progressively in the organism, once it has been administered daily, and this can lead to the appearance of side effects. At other times, the change may cause a total incapacity of the organism to process the drug, in which case its level increases rapidly in the blood stream and the side effects could be serious.

Nowadays it is possible to predict and avoid these undesirable conditions through examinations that indicate the genetic profile of the person for many enzymes. The genetic profile, in this case, is the description of certain characteristics of the genes responsible for the production of the enzymes that process these drugs.

Some enzymes belonging to the Cytochrome P450 family located in cells of the liver, are specialized in processing various substances, such as almost all of the drugs used in the treatment of Social Aniety/Phobia (most of them are also used in depressions and obsessive-compulsive disorders). The main enzymes of the family are known by the abbreviations CYP2C9, CYP2C19 and CYP2D6. Of these, the CYP2D6 is the one that figures prominently in the metabolization of the greatest number of drugs, which is the most important in this theme. The prediction of how an enzyme will act is made through the study of genes responsible for its synthesis - therefore, it is an indirect assessment.

Genes permanently influence the maintenance of life and not just in the transmission of hereditary traits of the organism. They are present in around one hundred trillions of cells in the adult human organism, springing into action when necessary. The reactions for the maintenance of life are processes in each one of these cells. Consequently, by examining what happens within one cell, it is possible to generalize for all the others.

A cell is composed of various structures, but, for the purposes of this article, it will be presented as having two structures: the nucleus and the cytoplasm. Inside the nucleus are the chromosomes, and within the chromosomes is DNA, the genes responsible for controlling what happens in the cytoplasm. Physical, chemical, and physio-chemical reactions take place in the cytoplasm that are responsible for the maintenance of cellular life. How do the genes control what happens within the cytoplasm?

The control occurs more or less in the following manner. A section of DNA (a gene), inside the nucleus, serves as a pattern for the production of another biological substance called RNA (ribonucleic acid). Once synthesized, this is diffused through the membrane of the nucleus and reaches the cytoplasm. In specific areas of the cytoplasm, the RNA serves as a pattern for the production of proteins.

Therefore, each protein has a gene that is responsible for its origin. If there is a need for a certain enzyme within the cell, the gene then produces the RNA, which passes to the cytoplasm, and from there promotes the production of the necessary enzyme.

If a gene presents a change in its chemical structure, it will generate changes in the chemical structure of the enzyme. As there is the probability of diverse changes in the genes, there can be various forms of the same enzyme. This is known as genetic polymorphism.

Changes in the genes are known as mutations. Therefore, mutation is nothing more than a change in the chemical structure of the gene. A certain mutation might cause the CYP2D6 enzyme, for example, to process an antidepressant or other drugs more slowly.

Modifications in the genes are just one of the many reasons why an antidepressant, or any other drug, produces side effects. Furthermore, depending on the present conditions and other individual characteristics, these effects can be serious. However, this can also occur with other drugs that pass through the same metabolic circuit.

Any biological or non-biological substance is potentially capable of producing undesirable effects, even toxic and lethal ones, depending, among other things, on how it is metabolized. Predicting undesirable effects, avoiding them, and optimizing treatment are the aims of any physician. It is possible to choose the best drug from the genetic map as well as to avoid the drugs that can cause undesirable effects.

It has been estimated that close to fifty percent of the medication consumed by Americans is either ineffective or produces mild to serious undesirable effects as a consequence of the individual genetic traits. Most appear to be linked to the activity of the CYP2D6 enzyme. Listed below are some of the data relative to this enzyme:

-- 10 % of the Caucasian population experiences a mild action from this enzyme. Consequence: the dose to be used should be one-half or less then the normal dose.

-- 7% of the Caucasian population experiences an extra quick action of the enzyme. Consequence: look for other drugs that pass through a different metabolic circuit.

A number of research studies have consistently shown that there are great genetic variations among ethnic groups. The following experience ultra-quick action of the enzyme: 29% of Ethiopians, 1% of Chinese and Japanese, and 4.8% of sub-continental Indians.

What really matters is the individual, each individual - whether Caucasian, Ethiopian, or any other ethnic group. Seeing that the genetic profile of the enzymes belonging to the Cytochrome P450 family can contribute to individualized therapy and, therefore, optimized, it is possible to predict that within two years these exams will be routine in the United States and within five years, worldwide. It is possible that before 2015, this profile, by then uniting a greater range of metabolic circuits, will also be part of the metabolic profile of newborns.

April, 2005

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