|Side Effects Caused
by Genetic Changes
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
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
Enzyme Relationships and Side Effects
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.
Differences in Metabolism
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.
Changes in the Enzyme and Genetic Traits
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.
Antidepressants and Side Effects
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.
Genetic Differences of Ethnic Origin
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
-- 7% of the Caucasian population experiences an extra quick action of the
enzyme. Consequence: look for other drugs that pass through a different
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.
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