This elementary unit represent of itself a regulationary-structural system
which consist of: element of structure (a ferment either a receptor, or component of a membrane,
etc.), and element of regulation (a gene, system of hormonal synthesis, etc.) and also transport
element (blood, etc.), - that opportunity of considering it is as a "elementary addictive unit"
of organism, i.e. the most simple model, allowing to explain of itself principles of origin and
development of narcotic dependence (narcomanogenesis).
It turns out that in a basis of molecular mechanisms a formation the drug of
dependence (narcomania) lay (it is necessary and enough) four general-metabolic the phenomena:
physical and chemical interaction, functional limitary, inertia of processes regulation, and psychic
ability to project.
This has allowed to prove and offer some new approaches to understanding
pathogenesis of alcoholism, to its biochemical diagnostics, to its pathogenesis of treatment
and it an opportunity of preventive measures.
Keywords: abstinence abusing, adaptation, addiction,
alanine aminotransferase, alcohol, alcoholism, aspartate aminotransferase, biochemical
diagnostics,
carbohydrate, diagnostic, drug dependence, drug addictions, elemental unity of narcomanogenesis,
elemental unity of toxicomanogenesis, elementary addictive unit, euphoria, fatty liver, functional
limited, gamma-glutamyltransferase, hypothesis, inertia, inertial system, limiting, limiting,
medicinal dependence, mental, metabolism, molecular mechanisms, narcomania, narcomanogenesis,
narcotic dependence, narcotics, objectivization of diagnostics, pathogenesis of alcoholism,
pathogenetic treatment, psychic, readaptation, regulation, social, system analysis, system,
therapeutic, toxicomania, toxicomanogenesis, transferases, treatment.
- The sum and substance:
Deductions (Part 1)
1._ The highest nervous system of
the person in the presence of narcotic substances appears
"switched off", that is why and - not capable to adequate
participation in elimination of the metabolic disbalance
caused by presence in an organism of narcotics;
2._ Endogenous functional (or metabolic)
insufficiency of an organism can quite serve as that favorable
background for which - the use of narcotic substances becomes
more preferable;
3._ Teenagers (namely, what name "difficult"),
as well as a "morbid" part of the population of a society,
of course, require the help; but not substitutes of type of alcohol,
tobacco, narcotics or ideological abstraction, and - in social adaptation
(anticipating, preventive and, the main thing, socially oriented),
as well as - in possibility of the intellectual development
(education, culture);
4._ The structural-regulationary system
which has aggregated in: (ferment, either a receptor, or
component of a membrane, etc.) and regulationary components
(a gene, system of hormonal synthesis, etc.), and also transport
(blood, etc.), it is possible to consider as "elementary addictive
unit" organism, i.e. - the most simple model, allowing to explain
principles of occurrence and development of narcotic dependence
(narcomanogenesis);
5._ Features of functioning of this,
"elementary addictive unit", are that, that in principle can
explain molecular mechanisms of occurrence of such clinical
phenomena of narcomanogenesis, toxicomanogenesis or drug addiction -
as: euphoria, tolerance, an inclination, an abstinent syndrome
(addiction) and a polynarcotism;
6._ The basic biological reason of
narcomanias, toxicomanias and drugs addiction (and, was
probably, and other addictions, including behavioural) is -
feature of processes of regulation existing in biological systems,
namely, their inertiaful;
7._ Dependence (alcoholic, narcotic,
or any another) forms, first of all, at that level of the biochemical
or neurophysiological organisation of an organism, where its is
regulationary-functional relations with substances (or factors),
causing dependence, develop most inertially;
8._ For formation of an inclination
to narcotic substance (or addictions) it is important, that
the mental projection (euphoria, a condition of comfort and
well-being), resulting the use of a narcotic - answered also
it, the person, to psychological preferences and personal
valuable orientations;
9._ General inertiaful of interactions
of an organism with narcotic substance can develop not
obligatoryly of one, but also from several factors making it,
of processes;
10._ Interaction of narcotic
substance with inertial component of biological system can
remain and "not noted" until then - while this inertial
system will not receive the intermediary (or the projection)
at level of mentality (at level of behaviour of all organism);
11._ - Participation of
nervous system in formation of "elementary addictive unit",
in principle, is important for clinical implications of
narcomanogenesis, but not obligatoryly - for formation
narcotic or drug addiction, as such;
12._ Any uninertial system (separate
component, sequence of components or more difficult biological
organization), basically, shouldn't be capable to formation
"in itself" neither toxicomanias, nor drug addiction, - and
in an overall picture of narcomanogenesis will play a passive,
"buffer" role;
13._ Only directional influences and,
first of all, on regulatory components and processes - towards
reduction of their inertiaful - can provide efficiency of a
readaptation of biological systems to their existence
"without narcotics";
14._ Search of ways of maintenance
of a condition of the reduced inertiaful (during the moments of
presence of a narcotic in an organism), - is one of probable
paths to achievement as conditions of steady remission, and -
"abilities to live with narcotics" without occurrence of
dependence on them;
15._ If, all told above to summarise,
it is possible to assert, that - at the heart of mechanisms
of formation of addiction (any, including narcotic) four
biological phenomena (or the factor) lay all only:
1) physics-chemical interaction (in our case - "narcotic interaction",
i.e. ability of narcotic psychotropic substance to cause the answer
at level of metabolic, physiologic or physical processes of an
organism);
2) a functional limited, i.e. - the most important
role in formation of addiction - limiting stages of sequence of
processes;
3) a mental capability of project on, i.e. the immediate
or mediated participation of narcotic, psychotropic substance in
functioning of "emotionally-motivational apparatus" brain; and,
at last,
4) regulatory inertiaful, i.e. slow enough
character of processes as adaptations, and
readaptatia (bad reversibility);
16._ As to two other factors:
physics-chemical interaction and a mental capability
of project on, - that intervention (controlling), in
principle, can be organised already and "now", through
preventive actions, - for example, strong-willed (the
psychotherapy, socially oriented advertising, etc.) or
organizational (restriction of access to narcotic
substances, toughening of the control, etc.);
17._ As a whole, for an exception of
the possibility of occurrence of a narcomania, toxicomania
or other dependences in biological system, basically, there
is enough organization of corresponding effective measures
in relation to one, any of four numbered requirements (or
factors) narcomanogenesis (toxicomanogenesis).
The bases of these statements can be seen here:
I.I. Goryushkin
"Molecular mechanisms of drug addictions, toxicomanias (regulationary-structural
relations)", 1986
// Zh Nevrol Psikhiatr Im SS Korsakova 1986;86(2):258-64. Russian
- The sum and substance:
Deductions (Part 2)
;1._ For an alcoholism, its 1st, an incipient state,
characteristicly primary increase in blood serum of activity
gamma-glutamyltransferase (GGT), with its yield for limits of borders of
normal, at remaining within high bounds of normal activity aspartate
aminotransferase (AST), alanine aminotransferase (ALT);
2._ For 2nd, centre stage, an alcoholism characteristicly
further increase in blood serum of activity of a GGT, and also - increase (with
a yield for limits of borders of normal) and AST, at - normal of activity of the
ALT remaining within high bounds;
3._ While for 3rd, final stage of an alcoholism,
increase for limits of borders of normal of activity of all three ferments
is characteristic: both a GGT, and AST, and the ALT (though, it is fair it
far not in all cases);
4._ An alcoholism as procedural disease, differs
sequence of involving of ferment systems in pathogenesis that finds the
reflexion in initial, or primary, increase in blood of activity of a GGT,
then - AST and, at last, the ALT;
5._ Complex of ferment indexes: GGT, AST and
ALT, - can be used with a view of objectivization of the clinical
diagnosis of disease of the person an alcoholism;
6._ And, for rising of objectivity and reliability
of the diagnostic inference positioned on the basis of a complex of yielded
ferments, repeated blood samplings are necessary for the analysis;
7._ At the same time, it is necessary to mean, that
3rd stage of an alcoholism (on A.A.Portnov's classification) on character of
changes of activity of the above-stated transferases of blood - nosologicaly
do not represent homogeneous group;
8._ The reason of increase of a GGT at abusing
of the person alcohol (the beginning of an alcoholism, its 1st stage) are
metabolic processes, namely, the adaptaion-regulatorial answer of an organism
to the use of alcohol;
9._ The hyperenzymatic of a GGT and AST
(in 2 stages of an alcoholism) is also - result of intensifying of
the general-metabolic adaptable-regulationary answer of an organism
on proceeding use (and abusing) alcohol;
10._ It, rising of activity of a GGT at an
alcoholism (1я and 2я stages), are result of "necessity" of maintenance
in an organism of conditions of "normal" passing of an exchange of alcohol
(in the conditions of abusing it) - by maintenance in an organism more high
speed of an exchange of a coenzyme A;
11._ As abusing alcohol is often accompanied by
deficiency of alimentary components, including, and proteins, and consequently,
and deficiency of irreplaceable amino acids, which participating and in
processes of an exchange of alcohol and lipids (such, for example, as
cysteine or methionine);
12._ The event at an alcoholism accumulation of
fat in a liver, instead of in faty depots, is caused mainly by a condition
of protein deficiency in an organism abusing alcohol and, consequently,
enrichment of a ration abusing-complete protein - should promote prevention
of processes and faty, and, following for it, a fibrous degeneration of a
liver (cirrhosis);
13._ Consequently, the adequate alimentary and
therapeutic measures referred on elimination of protein deficiency
and optimization of carbohydrate and faty exchanges at abusing alcohol, -
should promote prevention of processes of a faty degeneration of a liver;
14._ The mechanism of primary increase at an
alcoholism of AST, instead of the ALT, - consists as in substrate activate
of AST, and - substrate, but - limitation of the ALT;
15._ And, for primary increase at an alcoholism
of AST, instead of ALTs (in 2nd its stage) are responsible as processes of
domination of fat metabolism (initiated by the use of alcohol), and,
accompanying them, molecular braking mechanisms of carbohydrate metabolism.
16._ In a condition of an alcoholic abstinence the
organism of the patient urgently requires the enlarged quantities of a pyruvate
(or alcohol!?) - for elimination of deficiency in acetyl-KoA and oxaloacetate,
and also - for normalization of functioning of a cycle of tricarboxylic acids
and, bound to it, processes of breath;
17._ Thus, a carbohydrate foodstuff - natural,
(instead of refined, type: sugar, pure glucose, etc.), as well as adequate
pharmacological influences (thiamin, riboflavin, nicotinic acid, folic and
ascorbic acids, etc.), referred on normalization of carbohydrate metabolism
in an alcoholic abstinence, in principle, - should provide and the most
pathogenetic and, consequently, "softer" replacement of alcohol; as well as,
was probably, further and 'nonalcoholic existence'.
- The sum and substance:
Deductions (Part 3)
1._ The purpose of use of laboratory biochemical
methods in clinic of an alcoholism is - rising of efficiency of
medical-diagnostic process that is reached by means of definition in
blood serum of level of activity of transferases: gamma-glutamyltransferase
(GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT);
2._ If cases get to group of "practically healthy"
persons of "household drunkenness', or the beginning of disease by an
alcoholism, or conditions of remission of an alcoholism, - that use of
biochemical parameters and 'such normal' (for the purpose of specification
of the diagnosis an alcoholism) can turn out unproductive;
3._ The fact of fluctuation (that increases,
decreases) ferment indexes of blood serum: the GGT, AST, the ALT, -
found out during repeated researches of the patient, carries in itself
also acknowledgement of the diagnosis an alcoholism;
4._ It is important to understand always, that
enzymatic laboratory indexes, as well as results of any other clinical
research, of course, have real value only in a complex with symptoms.
- The sum and substance:
Deductions (Part 4)
1._ Alcoholism, on advantage - disease intoxicationful
and hepathologic (instead of purely narcological, or mental);
2._ An inclination (to alcohol, to a narcotic
or to an opposite sex) biologically - only the vital attribute referring
an organism on realization actual for it, at present, of the vital necessity;
3._ For a society the necessity for narcotic
substances is socially unacceptable necessity; to be exact, excessive
necessity, therefore as moderated is unacceptable: whether it be drunkenness
or, for example, a tobacco smoking, - while, as is known, does not meet
serious counteraction;
4._ If the purpose of treatment of an
alcoholism - to help the patient to recover, pathogenetic therapy is
necessary;
5._ An integral part of pathogenetic treatment
of the alcoholic is - its social adaptation (i.e. reprogramming of its
"consciousness") if I will, of course, be retried, as the purpose to
have - to help the patient to recover;
6._ Without knowledge of pathogenesis of
diseases to turn to it (medicine), even by means of statistical
calculations of "evidence-based medicine", - to system of scientific
knowledge, nothing will help; today (and not only in the theory, but also
in practice), - systems approach, systems analysis is necessary for medicine;
8._ Correct use of mathematical methods
(statistics) in medicine demands also ability to mathematical,
abstract thinking and derivation; without same, use of statistics -
and "the eaten away egg is not worthy";
9._ If, a problem of an alcoholism to consider
it is system, becomes obvious, that limiting processes in biological
systems "and find out themselves";
10._ And, consequently, increases of
levels of activity of transferases: gamma-glutamyltransferase (GGT) and
aspartate aminotransferase (AST) in blood serum of
alcoholics also are that other, as limiting components of alcoholic
pathogenesis finding out;
11._ And, therefore, pathogenetic
therapy of an alcoholism should be accompanied (first of all, or
including) by normalization of levels of activity of these transferases;
12._ And, consequently, only the adequate
measures referred on normalization of activity of these transferases,
can turn out sufficient and for "treatment" from an alcoholism;
13._ Measurement in blood of alcoholics, along
with a GGT and AST, - also an alanine aminotransferase (ALT), - it
is necessary to consider as
additional "agent" of the control over efficiency and pathogenestic of
made treatment (i.e. - the control over change of "parameters of a biochemical
condition" the patient);
14._ Without the social equipment on
abstention from abusing alcohol and on the healthy way of life,
which else and a society were approved and encouraged, - no "purely
pathogenetic treatment is able help the decision of a problem of an
alcoholism;
15._ If depression of level of transferases i
n blood does not occur, fault to it can be, as we already noted, only
two reasons: continuation (secret) use of alcohol or inadequate
medical influence;
16._ Thus, the biochemical estimation of
a condition of the patient (with use of transferases) can help and
in objectivization of the diagnosis of an alcoholism, and in specification
of a stage of this disease and makes therapy of this disease of more
effective - because the estimation of "biochemical state parameters"
patient - is always concrete and is always individual.
