The concept of cumulation, types (examples). Habituation and tachyphylaxis (examples); possible reasons for these manifestations. Cumulation of medicinal substances, types, meaning, examples Cumulation of medicinal substances

Cumulation I Cumulation (late Latin cumulatio accumulation, increase)

strengthening the effect of drugs and poisons when they are repeatedly administered in the same doses.

A distinction is made between material and functional K. By material K. we mean the accumulation of the active substance in the body, which is confirmed by direct measurement of its concentrations in the blood and tissues. Material K., as a rule, is characteristic of substances that are slowly metabolized and are not completely eliminated from the body. In this regard, with repeated administrations, if the intervals between them are not long enough, such substances gradually increase in the body, which is accompanied by an increase in their effect and can lead to the development of intoxication. Material coagulation often occurs when taking a number of cardiac glycosides (for example, digitoxin), alkaloids (atropine, strychnine), long-acting hypnotics (phenobarbital), indirect anticoagulants (syncumar, etc.), and salts of heavy metals (for example, mercury).

The development of material K. is facilitated by a decrease in the antitoxic function of the liver and excretory kidneys, which may be due not only to pathological changes in these organs in certain diseases (liver cirrhosis, nephritis, etc.), but also to age-related deviations in their functional activity, for example in children and individuals old age. Sometimes the ability of some drugs (digitalis cardiac glycosides, amiodarone, etc.) to produce material K is used for medicinal purposes, prescribing them in relatively high doses at the beginning of treatment to ensure rapid accumulation of active substances in the body in concentrations that have a therapeutic effect, and then they switch to so-called maintenance doses.

Functional K. is more characteristic of substances that affect the activity of the central nervous system, and, as a rule, indicates the high sensitivity of the body to such substances. A classic example of functional K. is mental disorders and personality changes in chronic alcoholism and drug addiction. Functional K. is also possible when taking antidepressants from the group of monoamine oxidase inhibitors, anticholinesterase drugs with irreversible action (phosphacol), etc. With functional K., the concentrations of active substances in the body media available for measurement do not exceed those after a single administration of the corresponding medications.

To prevent complications associated with the ability of drugs to cause cancer, the most important things are the correct selection of doses of drugs, the choice of the optimal regimen for their administration, and careful monitoring of the dynamics of functional changes in the body. To prevent possible negative consequences of material K., modern methods of quantitative determination of the content of drugs in the blood and tissues are used.

1. Small medical encyclopedia. - M.: Medical encyclopedia. 1991-96 2. First aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic Dictionary of Medical Terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what “Cumulation” is in other dictionaries:

- [lat. cumulatio increase, accumulation] 1) fin. in the insurance business: accumulation of insured objects in a limited space; 2) physical concentration of explosion energy in a certain direction. Dictionary of foreign words. Komlev N.G., 2006.… … Dictionary of foreign words of the Russian language

Accumulation, concentration, accumulation Dictionary of Russian synonyms. cumulation noun, number of synonyms: 5 concentration (23) ... Synonym dictionary

English cumulation, lat. cumulatio increase, accumulation of a large number of insured objects or objects with large insured amounts that may be affected by the same insured event (natural disaster, military ... Dictionary of business terms

- (from the medieval Latin cumulatio accumulation) accumulation in the body and summation of the effects of certain medicinal substances and poisons; may lead to poisoning... Big Encyclopedic Dictionary

CUMULATION, cumulation, female. (lat. cumulatio Accumulation) (med.). The accumulation of medicinal substances or poisons in the body from prolonged use, enhancing their effect. Ushakov's explanatory dictionary. D.N. Ushakov. 1935 1940 ... Ushakov's Explanatory Dictionary

cumulation- and, f. cumulation f., German Kumulation lat. cumulatio. 1. Finnish In the insurance business: a concentration of insured objects in one place (in one warehouse, on one ship, etc.). Krysin 1998. 2. med. The accumulation in the body of some is slow... ... Historical Dictionary of Gallicisms of the Russian Language

CUMULATION- (from Lat. cumulare accumulate), the summation of the action in the body of a certain medicinal substance or poison, resulting in a sharp increase in the pharmacological action characteristic of a given substance, and sometimes the appearance of new symptoms.… … Great Medical Encyclopedia

CUMULATION- in insurance, a set of risks in which a large number of insured objects or several objects with significant insured amounts can be affected by the same insured event, resulting in a very large... ... Legal encyclopedia

CUMULATION- (cumulative effect) concentration of action (see) in one specific direction, for example. under the action of a cumulative combat projectile, piercing the armor of tanks with a directed and concentrated stream of gases formed during its explosion (this ... ... Big Polytechnic Encyclopedia

- (Late Lat. cumulatio accumulation, from Lat. cumulo accumulate): Cumulation (literary criticism) is a way of constructing compositions of chronicle and multilinear narrative and dramatic plots. Cumulation (medicine) ... Wikipedia

AND; and. [from lat. cumulatio accumulation] Honey. Strengthening the effect of a drug upon repeated administration. ◁ Cumulative, oh, oh. K. effect. What are the properties of the medicine? * * * cumulation (from the Middle Ages. Lat. cumulatio accumulation), accumulation in ... ... encyclopedic Dictionary

I
(Late Latin cumulatio accumulation, increase)
strengthening the effect of drugs and poisons when they are repeatedly administered in the same doses.
A distinction is made between material and functional K. By material K. we mean the accumulation of the active substance in the body, which is confirmed by direct measurement of its concentrations in the blood and tissues. Material K., as a rule, is characteristic of substances that are slowly metabolized and are not completely eliminated from the body. In this regard, with repeated administrations, if the intervals between them are not long enough, the concentration of such substances gradually increases in the body, which is accompanied by an increase in their effect and can lead to the development of intoxication. Material coagulation often occurs when taking a number of cardiac glycosides (for example, digitoxin), alkaloids (atropine, strychnine), long-acting hypnotics (phenobarbital), indirect anticoagulants (syncumar, etc.), and salts of heavy metals (for example, mercury).
The development of material K. is facilitated by a decrease in the antitoxic function of the liver and the excretory ability of the kidneys, which can be caused not only by pathological changes in these organs in certain diseases (liver cirrhosis, nephritis, etc.), but also by age-related deviations in their functional activity, for example in children and elderly people. Sometimes the ability of some drugs (digitalis cardiac glycosides, amiodarone, etc.) to produce material K is used for medicinal purposes, prescribing them in relatively high doses at the beginning of treatment to ensure rapid accumulation of active substances in the body in concentrations that have a therapeutic effect, and then they switch to so-called maintenance doses.
Functional K. is more characteristic of substances that affect the activity of the central nervous system, and, as a rule, indicates the high sensitivity of the body to such substances. A classic example of functional K. is mental disorders and personality changes in chronic alcoholism and drug addiction. Functional K. is also possible when taking antidepressants from the group of monoamine oxidase inhibitors, anticholinesterase drugs with irreversible action (phosphacol), etc. With functional K., the concentrations of active substances in the body media available for measurement do not exceed those after a single administration of the corresponding medications.
To prevent complications associated with the ability of drugs to cause cancer, the most important things are the correct selection of doses of drugs, the choice of the optimal regimen for their administration, and careful monitoring of the dynamics of functional changes in the body. To prevent possible negative consequences of material K., modern methods of quantitative determination of the content of drugs in the blood and tissues are used.
Bibliography: Lepakhin V.E., Borisov Yu.B. and Moiseev V.S. Clinical pharmacology with international nomenclature of drugs, M., 1988; Kharkevich D.A. Pharmacology, p. 50, M., 1987.
II
(lat. cumulo, cumulatum to add up, accumulate)
in pharmacology and toxicology, the accumulation of a biologically active substance (material K.) or the effects it causes (functional K.) during repeated exposure to medicinal substances and poisons.

View value Cumulation in other dictionaries

Cumulation J.— 1. Accumulation in the body and summation of the effects of certain medicinal substances and poisons. 2. Concentration of explosive energy in a projectile, grenade, bomb, etc.
Explanatory Dictionary by Efremova

Cumulation- cumulations, w. (Latin cumulatio - Cluster) (med.). The accumulation of medicinal substances or poisons in the body from prolonged use, enhancing their effect.
Ushakov's Explanatory Dictionary

Cumulation- -And; and. [from lat. cumulatio - accumulation] Honey. Strengthening the effect of a drug upon repeated administration.
◁ Cumulative, -aya, -oe. K. effect. K-th properties of the medicine.
Kuznetsov's Explanatory Dictionary

Cumulation- English cumulation, lat. cumulatio - an increase, accumulation of a large number of insured objects or objects with large insured amounts that can be......
Economic dictionary

Cumulation of Insurance Risks— concentration of insurance objects or risks in a limited territory and insured persons in one insurance company.
Economic dictionary

Cumulation- - in insurance - a set of risks in which a large number of insured objects or several objects with significant insured amounts can.........
Legal Dictionary

Cumulation- (Latin cumulo, cumulatum to add, accumulate) in pharmacology and toxicology, the accumulation of a biologically active substance (material K.) or the effects caused by it (functional........
Large medical dictionary

Cumulation- (from medieval Latin cumulatio - accumulation) - accumulation in the body and summation of the effects of certain medicinal substances and poisons; can lead to poisoning.
Large encyclopedic dictionary

CUMULATION OF POLLUTION— CUMULATION OF POLLUTION (from Latin cumulatio - increase, accumulation), addition of a harmful effect, increase, collection, concentration of the active principle........
Ecological dictionary

MATERIAL CUMULATION— MATERIAL CUMULATION - an increase in the amount of a substance in the body with repeated exposure. Observed provided that the intake of the substance........
Ecological dictionary

FUNCTIONAL CUMULATION— FUNCTIONAL CUMULATION is a progressive increase in changes with repeated exposure to a substance.
Ecological dictionary

MATERIAL CUMULATION OF PESTICIDES— MATERIAL CUMULATION OF PESTICIDES - systematic accumulation of pesticides in the body.
Ecological dictionary

MATERIAL CUMULATION OF POISONS— MATERIAL CUMULATION OF POISONS, see Art. Chronoconcentration cumulative poisons.
Ecological dictionary

On the body.

Material cumulation(synonym - accumulation) is quantitatively characterized in the study of pharmacokinetics and toxicokinetics.

Functional cumulation is detected during a cumulation study, which is part of a routine experimental study of the general toxic effects of pharmacological substances and other toxicants. The study of general toxic effects includes:

• acute toxicity study - characterization of the amount of a substance that causes death of animals with a single exposure;
• cumulativeness study - characterization of the amount of a substance that causes death of animals with repeated exposures;
• chronic toxicity study - identifying the nature of poisoning during long-term exposure and determining safe doses.

The purpose of the cumulative study is to determine the nature of the effect of a substance on the body upon repeated administration and to select doses for chronic experiments. Selection is carried out on the basis of comparison of doses of the substance that cause death of animals with single and repeated exposure. By cumulative effect we mean gain effects of the poison upon repeated exposure.

Research methods

To study cumulativeness, various methods are used based on taking into account the death of animals upon repeated exposure to the substance under study. Preference is often given to the method of Lim et al., which allows one to evaluate in one study not only the cumulative properties of a substance during its effect on the body, but also the development of tolerance (addiction) to it.

Scheme for studying cumulation using the method of subchronic toxicity according to Lim

In the first four days, a dose of one tenth of the dose is administered daily. D.L. 50 (- the dose that causes the death of half in a group of animals; established during an acute toxicity study). Then the dose is increased by 1.5 times and administered for the next four days. (After administration of the substance for the eighth time, the accumulated dose is one semi-lethal dose.) If necessary, the study is continued further, every four days increasing the dose by 1.5 times the previous level until half the animals die (usually 5 out of 10). Calculate the cumulation coefficient:

where is the cumulation coefficient, is the average lethal dose accumulated with n-fold administration, is the average lethal dose with a single administration. When - they talk about cumulation (in the sense of increasing the effect of the poison), if - about tolerance. The resulting qualitative (ordinal at best) estimate is informally used when planning a chronic experiment. An alternative is to quantify the accumulation coefficient, which makes it possible to predict the probability of animal mortality when planning chronic toxicity studies.

Quantitative determination of the cumulation coefficient

Cumulation coefficient ( k) is defined as the proportion of a substance (or effect) that continues to exert its effect at the time of the next administration in such a way that the sequence of effective doses is represented as:

where is the actual dose administered, constant or variable as in Lim’s scheme. The probability of death of animals from a sequence of n+1 introductions are calculated as the probability of the occurrence of at least one of the set of events:

where is the probability of death of animals when exposed to a substance in an effective dose is determined from the relationship where is the normal distribution function, the parameters of which are determined by the probit analysis method during the study of acute toxicity. The cumulation coefficient in this definition acts as a measure of the relationship between successively administered doses. The numerical value of the cumulation coefficient is selected so that the sequence corresponds to the probability P obtained in an experiment to study cumulativeness.

Qualitatively, the value of the coefficient in the range from -1 to 0 can be interpreted as the development of tolerance, 0 - as the absence of dependence between repeated exposures to the substance, from 0 and above - as cumulation (more than 1 - cumulation in the narrow sense of the word). The resulting assessment can be used to determine the potential risk of death from the use of a substance in various doses and periods, or, by setting an acceptable probability, to determine the appropriate modes of administration of the test substance. It is obvious that the predictive power of the assessment is limited to a certain area around the point (dose, factor) at which the experimental value was obtained P when studying cumulativeness. For example, it is easy to imagine that having determined addiction to ethyl alcohol in a short-term experiment, one should not count on the stability of this quality when exposed to large doses in a long-term experiment.

Cumulation (Late Lat. cumulatio accumulation, increase) - enhancing the effect of drugs and poisons when they are repeatedly administered in the same doses.
A distinction is made between material and functional K. By material K. we mean the accumulation of the active substance in the body, which is confirmed by direct measurement of its concentrations in the blood and tissues. Material K., as a rule, is characteristic of substances that are slowly metabolized and are not completely eliminated from the body. In this regard, with repeated administrations, if the intervals between them are not long enough, the concentration of such substances gradually increases in the body, which is accompanied by an increase in their effect and can lead to the development of intoxication. Material coagulation often occurs when taking a number of cardiac glycosides (for example, digitoxin), alkaloids (atropine, strychnine), long-acting hypnotics (phenobarbital), indirect anticoagulants (syncumar, etc.), and salts of heavy metals (for example, mercury).
The development of material K. is facilitated by a decrease in the antitoxic function of the liver and the excretory ability of the kidneys, which may be due not only to pathological changes in these organs in certain diseases (liver cirrhosis, nephritis, etc.), but also to age-related deviations in their functional activity, for example in children and elderly people. Sometimes the ability of some drugs (digitalis cardiac glycosides, amiodarone, etc.) to produce material K is used for medicinal purposes, prescribing them in relatively high doses at the beginning of treatment to ensure rapid accumulation of active substances in the body in concentrations that have a therapeutic effect, and then they switch to so-called maintenance doses.
Functional K. is more characteristic of substances that affect the activity of the central nervous system, and, as a rule, indicates the high sensitivity of the body to such substances. A classic example of functional K. is mental disorders and personality changes in chronic alcoholism and drug addiction. Functional K. is also possible when taking antidepressants from the group of monoamine oxidase inhibitors, anticholinesterase drugs with irreversible action (phosphacol), etc. With functional K., the concentrations of active substances in the body media available for measurement do not exceed those after a single administration of the corresponding medications.
To prevent complications associated with the ability of drugs to cause cancer, the most important things are the correct selection of doses of drugs, the choice of the optimal regimen for their administration, and careful monitoring of the dynamics of functional changes in the body. To prevent possible negative consequences of material K., modern methods of quantitative determination of the content of drugs in the blood and tissues are used.

Bibliography: Lepakhin V.E., Borisov Yu.B. and Moiseev V.S. Clinical pharmacology with international nomenclature of drugs, M., 1988; Kharkevich D.A. Pharmacology, p. 50, M., 1987.