What is cumulation and why is it dangerous. Cumulation of medicinal substances, types, meaning, examples

On the body.

Material cumulation(synonymous with accumulation) is quantitatively characterized in the study of pharmacokinetics, toxicokinetics.

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

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

The purpose of the study of cumulativeness is to clarify the nature of the action of a substance on the body during repeated injections and the selection of doses for chronic experiments. The selection is carried out on the basis of a comparison of doses of a substance that causes the death of animals during a single and repeated exposure. By cumulative action we mean here gain the effect of the poison upon repeated exposure.

Research methods

To study cumulativeness, we use various methods based on accounting for the death of animals upon repeated exposure to the substance under study. Preference is often given to the method of Lim et al., which makes it possible to evaluate in one study not only the cumulative properties of a substance when it affects the body, but also the development of tolerance (addiction) to it.

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

For the first four days, a daily dose of one tenth of the DL 50 ( - dose that causes the death of half in the group of animals; is established during the study of acute toxicity). Then the dose is increased by 1.5 times and the next four days are administered. (After the eighth dose, the accumulated dose is one semi-lethal dose.) If necessary, the study is continued further, increasing the dose by 1.5 times the previous level every four days until half of 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, - the average lethal dose with a single injection. When - they talk about cumulation (in the sense of enhancing the action of the poison), if - about tolerance. The resulting quality (in best case ordinal) evaluation is informally used in the design of a chronic experiment. An alternative is to quantify the cumulation coefficient, which makes it possible to predict the probability of death of animals when planning studies of chronic toxicity.

Quantification of the cumulation factor

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

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

where - the probability of death of animals when exposed to a substance in an effective dose is determined from the dependence where - 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 the experiment on the study of 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 estimate can be used to determine the potential risk of death from the use of a substance in various doses and terms, or, by setting an acceptable probability, to determine the appropriate modes of administration of the test substance. Obviously, the predictive power of the estimate is limited to a certain area around the point (dose, multiplicity) at which the experimental value is obtained. P in the study of 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 Latin cumulatio accumulation, increase) is an increase in the effect of drugs and poisons when they are repeatedly administered in the same doses.

Distinguish between material and functional cumulation. By material cumulation is meant the accumulation of the active substance in the body, which is confirmed by direct measurement of its concentrations in the blood and tissues. Material cumulation, as a rule, is characteristic of substances that are slowly metabolized and not completely eliminated from the body. In this regard, with repeated injections, 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 cumulation often occurs when taking a number of cardiac glycosides (for example, digitoxin), alkaloids (atropine, strychnine), long-acting hypnotics (phenobarbital), indirect anticoagulants (syncumara, etc.), salts of heavy metals (for example, mercury).

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

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

For the prevention of complications associated with the ability of drugs to accumulate, the most importance have the correct selection of doses of drugs, the choice of the optimal scheme for their appointment, careful monitoring of the dynamics of functional changes in the body. To prevent possible negative consequences of material cumulation, modern methods of quantitative determination of the content of drugs in the blood and tissues are used.

When re-introduced medicinal substances their effect can both increase and decrease.

The increase in effect may be due to accumulation in the body or in individual bodies medicinal substances - cumulation . It is material and functional.

Material cumulation- the medicinal substance is slowly excreted from the body and accumulates in it with repeated injections, reaching toxic amounts. To avoid, re-introduction should be administered after a significant part of the elimination or destruction of the previous dose. Functional cumulation- when the originally introduced substance is removed from the body, and the function of the organ or system, changed by it, has not yet been restored. If at this time to introduce a second dose of the drug, then its effect is much more pronounced and longer.

addictive- decrease in effect with repeated use of the drug. It may be associated with a decrease in the absorption of a substance, an increase in the rate of its excretion from the body, a decrease in the sensitivity of receptors.

addiction (addiction)) - an irresistible desire for re-admission. People have mental and physical. Mental - emotional discomfort without medication

Physical - when the drug is discontinued, a serious condition occurs associated with a disorder in the functions of organs and systems.

Idiosyncrasy- genetically determined hypersensitivity to any drug. It happens after the use of iodine preparations by pets,

Question 25 of the ticket: addiction to medicinal substances with their repeated introduction:

addictive(tolerance, lat. tolerantis - patience) is a decrease in sensitivity to the drug after its repeated administration, which requires an increase in dose in order to cause an effect of the same intensity that occurred after administration of a lower dose. addictive- this is a partial or complete loss of the therapeutic (therapeutic) effect during prolonged use of the drug without the phenomena of drug dependence, that is, the development of addiction. For example, when administering laxatives plant origin containing antraglycosides (rhubarb root, buckthorn bark, hay leaves), after a few weeks the laxative effect decreases. Habituation is a general biological property that can also be observed in microorganisms after the use of small doses of chemotherapeutic drugs. It is possible to eliminate addiction both by increasing (within the available limits) the dose, and by replacing the drug or stopping its use for some time.

A rapid decrease in the effectiveness of a drug after repeated administration, which develops over a period of time from several minutes to one day, is called tachyphylaxis(from Greek tachys - fast and phylaxis - protection). An example of tachyphylaxis can be a decrease in the hypertensive effect of ephedrine. After the first injection of the drug, blood pressure rises; after repeated 2-3 injections with an interval of 20-30 minutes, the vasoconstrictive effect is significantly reduced. To a bowl accustoming to medicine develops slowly, within several weeks of constant reception. Sleeping pills (especially derivatives of barbituric acid), tranquilizers, narcotic analgesics, laxatives, etc. have the property of being addictive. chemical structure, addiction is also possible (promedol, morphine). Mechanisms of tolerance are different . A widely known fact arsenophagy- the ability of "trained" animals to take orally large quantities arsenic oxide without detrimental effects. Habituation in this case is due to the development inflammatory processes in the mucous membrane of the alimentary canal and a decrease in the absorption of the poison as a result. If arsenic oxide is administered parenterally to such an animal, even the smallest dose is lethal.

Most common cause addiction is the induction by the drug of microsomal liver enzymes and the acceleration of its own metabolism. This mechanism predominates in the development of addiction to barbiturates. Tolerance to organophosphorus compounds is due to a decrease in the sensitivity of cholinergic receptors to acetylcholine. The cause of habituation may also be the phenomenon of autoinhibition, similar to the well-known phenomenon in biochemistry of the inhibition of an enzyme by a substrate. The essence of the phenomenon lies in the fact that in the case of an excess in the body of the drug, not one, but several molecules bind to the receptor. The receptor is "overloaded" and pharmacological effect turns out to be much less. Tolerance should not be equated with drug dependence.

Dependence on drugs and other substances (addiction). According to the findings of the WHO Expert Committee, drug dependence is mental condition, sometimes even physical, which is the result of an interaction between a living organism and a medicinal substance with certain behavioral and other reactions, when the desire to take the drug is constant or occurs periodically in order to avoid the discomfort that occurs without taking it.

addiction- this is a strong, sometimes insurmountable requirement for the systematic use of certain drugs and other drugs that cause euphoria (Greek eu - pleasant and phero - endure), to improve mood, improve well-being, and also eliminate discomfort arising after the abolition of these funds.

Means that cause addiction can be divided into the following groups: alcohol-barbiturate (ethyl alcohol, phenobarbital); canabina (marijuana, hashish); cocaine; ethereal solvents (toluene, acetone, carbon tetrachloride); drugs that cause hallucinations (LSD, mescaline, psilocybin); drugs derived from opium (morphine, codeine, heroin) and their synthetic substitutes (promedol, fentanyl).

Dependence on several substances at the same time is possible.

Distinguish between mental and physical dependence on drugs. According to the WHO definition, mental dependence is "a condition in which a drug causes a feeling of satisfaction and mental exaltation - a state of euphoria that requires periodic or continuous administration of a drug in order to obtain a sense of satisfaction in order to avoid discomfort"; physical dependence - an adaptive state characterized by intense physical disturbances after the cessation of taking a particular drug. These disorders, i.e. withdrawal syndrome(lat. abstinentia - abstinence; synonymous with withdrawal syndrome, deprivation) - a complex of specific signs of mental and physical disorders characteristic of a particular narcotic analgesic.

The mechanism of this phenomenon is due to the fact that, as a result of systematic administration, the substance is included in the biochemical processes occurring in the body.

As a result, the metabolism and functioning of tissues are altered. The body gradually adapts to such a state, creating a new, different from the usual, metabolic homeostasis. In the event of discontinuation of the drug, the equilibrium biochemical processes is violated. There is a serious condition (abstinence) - various, often severe somatic disorders (possible death), which is eliminated only with the resumption of the introduction of the substance.

The brain cells are most sensitive to changing conditions, which is why drug dependence is caused by drugs that affect the central nervous system. The systematic use of narcotic analgesics with the development of dependence is called drug addiction. Changes in the functions of the brain lead to the sequential development of states of euphoric sleep and abstinence. With increasing dependence, the euphoric phase is reduced, the sleep phase almost disappears, the withdrawal phase changes and deepens. The most severe picture of drug dependence develops when physical, mental dependence and tolerance are combined.

Ticket question 26: drug addiction:

drug addiction- a syndrome that develops with repeated long-term use of drugs and is manifested by a sharp deterioration in health or well-being when the drug is discontinued. The most well-known dependence is on psychotropic drugs, often associated with withdrawal, for example, with the withdrawal of opiates or psychostimulants. However, dependence on many other drugs, such as glucocorticosteroids, is known. In persons with neurotic, somatoform and anxiety-depressive disorders, with persistent insomnia, after prescribing sedatives and sleeping pills dependence is formed (in about 10% of cases) - an attempt to stop taking leads to an exacerbation of symptoms. Drug dependence is widespread when taking benzodiazepines, primarily due to the unreasonable duration of their intake: with their short-term use, the risk of dependence is reduced.

The withdrawal syndrome of psychopharmacological drugs can be considered as a variant of the withdrawal syndrome in drug addiction, but it has a number of significant differences. Closest to the withdrawal syndrome is the syndrome of tranquilizer withdrawal: in this case, manifestations of physical and mental dependence are observed, although mental dependence in the form of craving for the drug rarely occurs - more often there is a so-called psychological attachment. With the abolition of antidepressants, only physical dependence is present: a characteristic vegetative symptom complex takes place, and with the abolition of antipsychotics, physical dependence is also observed (vegetative symptom complex and extrapyramidal disorders) without mental dependence. Long-term use of antipsychotics and antidepressants usually also does not cause changes in drug tolerance.

Drug dependence is overcome by abrupt (in the case of mental dependence) or gradual withdrawal of the drug or by replacing the drug with a less addictive one. Addiction(English) addiction- dependence, addiction, addiction), in a broad sense, - an obsessive need felt by a person for a certain activity. The term is often used for phenomena such as drug dependence, drug addiction, but is now more applied to non-chemical, as well as psychological addictions, for example, behavioral, examples of which are: Internet addiction, gambling, shopaholism, psychogenic overeating, fanaticism, etc.

In a medical sense, addictiveness is obsessive the need to repeat certain actions, accompanied, in case of violation of the patient's usual schedule, clearly expressed physiological and psychological deviations, non-trivial behavior and other mental disorders.

Ticket question 27: the phenomenon of synergism and antagonism of medicinal substances:

synergy is a type of interaction in which the effect of a combination exceeds the sum of the effects of each of the substances taken separately. i.e. 1+1=3 . Synergism can relate to both desired (therapeutic) and unwanted effects medicines. The combined administration of the thiazide diuretic dichlothiazide and ACE inhibitor enalapril leads to an increase in the hypotensive effect of each of the drugs, which is used in the treatment of hypertension. However, the simultaneous administration of aminoglycoside antibiotics (gentamicin) and the loop diuretic furosemide causes a sharp increase in the risk of ototoxicity and the development of deafness.

SYNERGISM OF MEDICINES (from the Greek synergia - cooperation, assistance), simultaneous action in one direction of two or more. substances that provide a higher overall effect than the action of each of them separately. Medicines. Substances can act on the same elements (direct S. l. s.) or on different ones (indirect S. l. s.). An example of direct S. l. with. can serve as a drug. the action of chloralhydrite and alcohol, indirect - the expansion of the pupil with atropine and adrenaline. As a result of the joint action of synergists pharmacological. the effect happens unequal force that depends on properties of substances, their doses and features patol. state of the body. S. l is most fully expressed. with. with a combination of substances in small doses, as well as with a combination of substances acting on different systems.

With a combination of certain drugs. substances, you can get an increase in the action of one of them (for example, an increase in the narcotic effect of chloral hydrate with chlorpromazine). Such a phenomenon is called potentiation. When both substances affect the same body systems and in the same direction (for example, potentiation of barbiturate anesthesia with chlorpromazine), potentiation of cash. true. In contrast, with false potentiation, it will help. substance has no active pharmacological. action, but only weakens the decay or slows down the release of the main. substances (eg, prolongation of barbiturate anesthesia with chloracizine). Therefore, false potentiation is one of the forms of prolongation (long-term action)

The effect of the summation of the action of drugs is used in practical medicine to reduce the possible manifestation of undesirable side effects, since the lower the dose, the less likely development of adverse events.

Antagonism(from the Greek anti-against, agon- fight) of drugs in combinations manifests itself in the weakening or complete disappearance of their pharmacotherapeutic action. In medicine, antagonism as a type of pharmacological incompatibility can be conditionally divided into physicochemical and physiological. Physico-chemical include the so-called competitive, physical and chemical antagonisms (pharmaceutical incompatibility); to physiological - direct and indirect (pharmacological incompatibility).

Physical antagonism in pharmacology is possible between adsorbents (activated carbon, proteins, bentonite) and active medicinal substances, the effect of which is excluded due to their adsorption on adsorbents.

In practice, physical and chemical antagonists are more often used as antidotes, or antidotes (from the Greek antidotos - antidote). So, in case of barium chloride poisoning, sodium sulfate can be used as an antidote; heavy metals are strongly bound and rendered harmless by unithiol, etc.

With the simultaneous use of several medicinal substances, it is possible to completely turn off or weaken the action of some substances by others.

This phenomenon is called pharmacological antagonism. It is considered to be based on the presence of competitive relations or changes in the background for the action of substances.

Like synergy, antagonism can be direct or indirect. In the first case, medicinal substances have the same object of action, and in the second, the objects are different.

For example, a pupil constricted by arecoline can be dilated with atropine or epinephrine.

Atropine and arecoline act through the same object (cholinergic nerves) and hence their antagonism is direct.

The opposite effect of arecoline and adrenaline is obtained due to the impact on different objects (adrenergic and cholinergic nerves), but directly related to the same function (pupil size), so their antagonism is indirect. Antagonists can act to the same extent (two-way antagonism) or in different, when the influence of one of them prevails over the other (one-sided antagonism).

Since the final stage pharmacological action- paralysis, insofar as paralyzing substances are unilateral antagonists in any combination. Exciting and depressing substances can act antagonistically either bilaterally or unilaterally, depending on the properties of the antagonists.

28 ticket question:sources of drugs :

These include minerals, vegetable raw materials, raw materials of animal origin, waste products of microorganisms, synthetic compounds

Mineral springs are purified various chemical compounds: iron, copper, iodine, manganese, bismuth, cobalt, sodium, etc.

Animal origin- These are preparations obtained from organs and tissues of animals: adrenaline, insulin, hormonal preparations of the adrenal glands, pituitary gland, enzyme preparations, poisons of snakes, spiders, bees (antibiotics of animal origin).

Herbal medicinal substances Sources of medicinal substances can be fruits, flowers, leaves, bark, roots, rhizomes. various plants. According to the chemical structure, these are different compounds:

Alkaloids (alcalos - alkali). These are nitrogenous alkali-like substances that can contain oxygen and be oxygen-free - caffeine, nicotine, atropine, strychnine, etc.

Glycosides are ester-like substances, which include the non-sugar content of aglycone and the sugar glycone. These drugs are obtained from various kinds foxglove, lily of the valley, Montenegrin, strophanthus, etc.

Resins are compounds insoluble in water (soluble in organic solvents). With alkalis, they form soap-like compounds - sabur.

gums - These are mucus and mucus-like substances containing carbohydrates. Hydrolysis gives sugars. In water, mucus acts envelopingly.

Fixed oils- castor, sunflower, linseed, etc.

Essential oils - volatile aromatic compounds: dill, caraway, mustard, cloves, mint, etc. (expectorant, emetic).

Tannins- nitrogen-free compounds with local action (oak bark, blueberries, sage).

Ticket question 29: Medication dosing sources:

Age. The body's sensitivity to drugs changes with age. Children and the elderly over 60 are more sensitive to the effects of drugs than middle-aged people.

Body mass. Children are given a lower dose than adults medicinal product due to their lower body mass. And the greater the body weight of a person, the greater the dosage they are prescribed.

individual sensitivity. On the different people the same l / n can act differently, even if it is the same dosage. The action of l / n may vary depending on pathological condition organism. Some pharmacological agents, show their effect only in pathological conditions (for example, acetylsalicylic acid, lowers body temperature only in case of its increase, cardiac glycosides clearly stimulate the activity of the heart only in case of heart failure)

30 ticket question: complications drug therapy:

Complications of drug therapy are called drug-induced changes in the properties and functions of organs and systems of the body, accompanied by unpleasant subjective sensations or objectively threatening the health or life of the patient. They are caused by side, toxic or non-specific effects of drugs.

A side effect is considered to be the action of a drug that has the same mechanism of occurrence as the main one, but is not desirable from a therapeutic point of view. There is no drug that does not have side effect. So, the appointment of an adrenomimetic adrenaline hydrochloride as a bronchodilator causes tachycardia, an increase in blood pressure. A frequent side effect of chemotherapeutic agents is the suppression of the vital activity of not only the pathogen infectious disease, but also commensal microorganisms. When the vital activity of microorganisms sensitive to the drug is suppressed, species insensitive to it (cocci, bacteria, fungi) multiply intensively (drug dysbacteriosis, candidiasis).

Phytoncides - antibiotics of plant origin (onion, garlic, wild garlic, bird cherry, nettle, etc.)

Microorganisms are the producers of many medicinal substances: antibiotics, enzyme preparations, etc. Preparations of fungal origin are also widely used - antibiotics.

Synthetic medicinal substances are drugs that are obtained in the laboratory by chemical reactions: FOS, HOS, carbamates, antibiotics, sulfonamides, hormonal, enzymatic, etc.

Side effects become complications if they cause complaints of the patient or pose a threat to health or life. For example, in the treatment of bronchial asthma with atropine, dry mouth caused by it can reach such an extent that swallowing and/or speech becomes difficult. Such a degree of side effect is assessed as a complication of drug therapy and requires the adoption of measures aimed at eliminating this complication, in particular, drug withdrawal. These complications are dose-dependent, easily predictable, and their manifestations, most often, are of little severity. In order to prevent them, it is necessary, firstly, to use drugs with maximum selectivity of action. For example, relief of bronchospasm with a mixed adrenomimetic adrenaline is accompanied by an increase in blood pressure and tachycardia, but the non-selective beta-agonist izadrin causes only tachycardia, and the selective beta2-agonist fenoterol (berotec) does not cause either an increase in blood pressure or significant tachycardia.

Complications of a toxic nature, most often, have a different mechanism of occurrence than the main action. For example, the inhibition of hematopoiesis that occurs during treatment with butadione is not due to the blockade of COX. Toxic complications are often the result of an overdose of drugs, including those due to material or functional cumulation with prolonged use of even therapeutic doses (chronoconcentration effect.). In this case, a predominant toxic lesion of one or a group of organs (systems) is usually observed, in connection with which neurotoxic, cardiotoxic, etc. are distinguished. LV action.

Among adverse reactions when using drugs, the most common effects are due to their pharmacological properties when using the drug in a therapeutic dose. For example, redness of the skin when applying nicotinic acid a common and normal reaction, although an adverse one, or tricyclic antidepressants and chlorpromazine not only affect the central nervous system, but also cause dry mouth and double vision.

For some drugs, toxic complications cannot be avoided at all. For example, cytostatics not only inhibit the growth of tumor cells, but also damage all rapidly dividing cells and inhibit the bone marrow. Therefore, in addition to their direct effect, they naturally lead to leukopenia.

With an increase in the dose of drugs, the risk of adverse reactions increases, for example, leukopenia develops from taking cytostatics, and the sedative effect of antihistamines increases.

Diseases of cardio-vascular system are the leading cause of death in humans, and hypertension plays a primary role in this. Therefore, millions of people are being treated for hypertension and coronary disease hearts. Beta-blockers and blockers are primarily used for therapy. calcium channels. During therapy, there are several options clinical forms adverse reactions associated with the pharmacological activity of the drug. Beta-blockers, reserpine, methyldopa, clonidine cause depression. Therefore, propranolol (Inderal), which is especially often accompanied by depression, should not be used by people suffering from depression or who have suffered from it in the past. Atenolol and nadolol are less likely to lead to such side effects. Fatigue is often caused by beta-blockers, reserpine, methyldopa, and clonidine. Beta-blockers, methyldopa and a number of other drugs in the treatment of pathology of the cardiovascular system cause impotence and other types of sexual dysfunction. Often, when taking antihypertensive drugs, especially guanitidine, prazosin and methyldopa, dizziness is observed and, as a result, orthostatic hypotension with a sharp rise from a sitting or lying position. This can lead to falls and fractures. Among beta-blockers, labetalol most often causes dizziness, decreased blood pressure, which makes it a second-line drug in the treatment of uncomplicated hypertension. Beta-blockers can cause bronchospasm and provoke asthma attacks, so they should not be used by patients bronchial asthma, chronic bronchitis or emphysema.

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Cumulation(accumulation) - the accumulation of biologically active substance(material cumulation) or the effects it causes (functional cumulation) with repeated exposure to medicinal substances and poisons on the body.

• A positive point is the prolonged action of the drug (reducing the frequency of administration).
• Negative - increased risk of symptoms of intoxication and drug poisoning.

There are material (accumulation of the drug) and functional (accumulation of the effect).

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

This is typical for long active drugs, which are slowly released or persistently bound in the body (for example, some cardiac glycosides from the digitalis group). The accumulation of the substance during its repeated appointments can be the cause of toxic effects. In this regard, it is necessary to dose such drugs taking into account cumulation, gradually reducing the dose or increasing the intervals between doses of the drug.

Functional cumulation is detected when the effect "accumulates", and not the substance. So, with alcoholism, increasing changes in the function of the central nervous system can lead to the development of delirium tremens. In this case, the substance (ethyl alcohol) is rapidly oxidized and does not linger in the tissues. Only its neurotropic effects are summarized. Functional cumulation also occurs with the use of MAO inhibitors.

addictive to medicines (tolerance to medicines) - weakening of the effects (decreased effectiveness) of drugs with their repeated use.

There is congenital and acquired.

Tachyphylaxis – special kind addictive, characterized by rapid development (possible after the first dose)

Rapid addiction to drugs (after 2-4 injections) is referred to as "tachyphylaxis". Drug addiction may be pharmacokinetic and/or pharmacodynamic in nature.

Reasons for purchasing:

1. Pharmacokinetics:

• malabsorption.
• enzyme induction

The basis of pharmacokinetic devices for the development of addiction is a decrease in the concentration of pharmaceuticals in the region of receptors sensitive to them due to a change in the repeated administration of some characteristics of the pharmacokinetics of drugs, for example, their absorption, distribution, decrease in bioavailability due to increased biotransformation, acceleration of hepatic, renal and other types of clearance . Pharmacokinetic mechanisms are of primary importance in the development of addiction to products from the group of barbituric acid derivatives, benzodiazepine tranquilizers and some other pharmaceuticals.

2. Pharmacodynamic:

• desynthesis
• temporary loss of receptor sensitivity
• decrease in the number of receptors, with prolonged use of antagonists; there is a decrease in the number of receptors on the membrane surface.
• decreased choice of neurotransmitters
• loss of receptor sensitivity

With the pharmacodynamic type of addiction to pharmaceuticals, their concentration in the region of the corresponding specific receptors does not change, but there is a decrease in the sensitivity of organs and tissues to products. The reasons for this kind of adaptive response of the body to drugs are a decrease in the density of specific receptors, a decrease in their sensitivity to pharmaceuticals, and a change in the process of conjugation of the function of receptors of their intracellular mediators and effector molecular systems. Pharmacodynamic mechanisms are characteristic of addiction to narcotic analgesics, adrenomimetics, sympathomimetics, adrenoblocking agents, etc.