Psychological encyclopedia. Terminology of addiction

Drug tolerance and drug dependence

Substances that act on the central nervous system usually have the greatest effect when first used. Their regular use leads to the development of drug tolerance or psychological and physical

depending on them.

The degree of tolerance to the various effects of the drug may vary. Thus, if a patient no longer receives the desired therapeutic effect from a toxic drug administered at a low dose, increasing the dose may result in greater toxic effects. On the other hand, tolerance may provide some benefit in cases where the patient becomes accustomed to the side effects of the drug, but the therapeutic effect does not wane.

DEVELOPMENT OF TOLERANCE

The mechanisms by which drug tolerance develops are not fully understood. In some cases, this resistance is explained by adaptation of nerve cells - a process in which they become accustomed to the drug and lose the ability to respond to its presence. Alternatively, the drug may stimulate the liver to increase production of enzymes involved in breaking down the drug. For example, nicotine and phenobarbital have this effect. This leads to an increase

▼ Over time, the patient may develop tolerance to the therapeutic effect of the drug. Increasing the dose may increase toxicity without achieving the desired effect.

the rate of destruction of the drug substance and, accordingly, reduces its effectiveness.

CROSS TOLERANCE_

The development of tolerance to one drug can lead to resistance to other similar drugs. Thus, an increase in enzyme activity caused by exposure to a drug can contribute to cross-tolerance - a decrease in the effect of drugs that are eliminated by the same enzymes.

▲ The body may develop tolerance to the prescribed drug if it is taken continuously. Over time, increasing the dose is necessary to achieve the desired effect.

For most drugs, the risk of developing tolerance can be reduced by starting treatment at the lowest effective dose of the drug and avoiding repeated doses. If tolerance does develop, sensitivity can sometimes be restored by temporarily stopping the drug.

Tolerance, or addiction to a drug, is a condition in which the effect of a drug becomes less pronounced over time or in which increasingly larger doses must be taken to achieve the desired effect. For example, nicotine in cigarettes when first used can cause vomiting, a burning sensation in the mouth, and dizziness, but if smoking continues, these effects become much less noticeable. Tolerance often develops with the use of opiates, barbiturates and other drugs that have a stimulating or depressant effect on the central nervous system.

▲ Alcohol has a depressant effect on the central nervous system. A person who is addicted to alcohol may be tolerant to other sedatives.

Amphetamine tolerance

Amphetamines are drugs that have a stimulating effect on the central nervous system. They relieve fatigue, cause a feeling of euphoria and excitement, and promote increased alertness and physical activity. Tolerance to all these effects develops rather slowly.

At the same time, amphetamines cause loss of appetite and stimulate some functions of the autonomic nervous system.

system, which leads to an increase in blood pressure and inhibition of motor activity of the gastrointestinal tract. Tolerance to these effects develops quickly; symptoms disappear within a few days. Amphetamines were used as an appetite suppressant in the 1950s and 1960s, but their use was subsequently banned due to the risk of addiction and abuse.

Although the development of tolerance begins after the first dose of an opioid, it usually does not become clinically apparent until after 2 to 3 weeks of frequent administration of usual therapeutic doses. Tolerance develops to a greater extent when large doses are administered at short intervals and is less pronounced when small doses are administered with long intervals between administrations.

Depending on the substance and the observed effect, tolerance can lead to a 35-fold increase in the effective dose. Severe tolerance usually develops to the analgesic, euphoric effects and respiratory depression. For example, respiratory arrest in a normal patient without tolerance may occur with the administration of morphine at a dose of 60 mg, whereas in an opioid-tolerant addict, administration of morphine at a dose of 2000 mg at intervals of 2-3 hours may not cause noticeable respiratory depression .

Tolerance also develops to antidiuretic, emetic and antihypertensive drugs, but not to miotic, convulsive and obstipation effects.

Tolerance to the euphoric and respiratory effects of opioids decreases within a few days after discontinuation of the drug. The habituation to the emetic effect may last for several months. The rate at which tolerance develops and subsides, as well as the degree of tolerance to different opioid analgesics, may vary.

Cross-tolerance.(Cross tolerance). Is an important characteristic of opioids and implies that a patient who is tolerant to morphine will also be tolerant to other opioid agonists.

Tolerance also develops to the action of analgesics of the mixed agonist-antagonist group, but to a lesser extent than to the action of agonists. Effects such as hallucinations, lethargy, hypothermia and respiratory depression are reduced after repeated use. However, tolerance to agonist-antagonists is not usually combined with tolerance to agonist opioids. It is important to note that tolerance NOT developing To antagonistic effects neither mixed agonist-antagonists nor pure antagonists.

2. Physical dependence.

The development of physical dependence is an invariable accompaniment of tolerance to mu-type opioids after their repeated administration.

The inability to continue administration of the drug leads to a characteristic withdrawal syndrome - abstinence syndrome, which reflects exaggerated rebound effects of the basic pharmacological properties of opioids. Withdrawal symptoms and signs include:

1) runny nose, 8) mydriasis,

2) lacrimation, 9) muscle pain,

3) yawning, 10) vomiting,

4) chills, 11) diarrhea,

5) piloerection (goose bumps); 12) anxiety

6) hyperventilation, 13) hostility.

7) hyperthermia;

The number and intensity of signs and symptoms are determined by the degree of physical dependence. Administration of an opioid during this period suppresses withdrawal symptoms almost immediately.

The onset, duration and intensity of withdrawal depend on the drug and may be related to its biological half-life. For morphine and heroin, signs of withdrawal usually begin 6 to 10 hours after the last dose. The maximum is observed after 36-48

hours, after which the severity of most signs and symptoms gradually decreases. By the fifth day, most effects have disappeared, but some may persist for months.

For mixed agonist-antagonists, signs and symptoms of withdrawal may occur upon abrupt cessation of repeated administrations of pentazocine, cyclazocine, or nalorphine, but this syndrome is different from that caused by morphine and other agonists. This condition is characterized by anxiety, lack of appetite, weight loss, tachycardia, chills, fever and cramping abdominal pain.

Once the signs of withdrawal disappear, tolerance also disappears, which is manifested by the restoration of sensitivity to opioid agonists. However, despite the loss of physical dependence on the opioid, the craving for it may persist for many months.

Precipitated (stimulated) by antagonist– A transient and intense withdrawal syndrome may be induced in a subject with physical dependence to opioids following administration of naloxone or another antagonist. Within 3 minutes after injection of the antagonist, signs and symptoms appear similar to those observed after stopping the drug, the maximum is reached after 10-20 minutes, the syndrome weakens within an hour.

]

Substance abuse and drug dependence are extremely complex conditions that are influenced by many of the factors listed above. However, there are some pharmacological phenomena associated with long-term drug use that are independent of social and psychological factors. These include, first of all, changes in the body's response to the drug upon repeated administration. The most common of these changes is tolerance, which consists of a weakening of the response to the drug after repeated administration. In Fig. Figure 24.1 shows a typical dose-response curve: as the dose of a drug increases, its effects also increase. With repeated administration of the drug, the curve shifts to the right (tolerance develops). In this case, the same effect can be achieved only by introducing a higher dose. For example, diazepam usually has a sedative effect at a dose of 5-10 mg. However, when this drug is abused to obtain euphoria, tolerance develops and the dose increases to hundreds of milligrams (cases have been described when the dose of diazepam exceeded 1000 mg/day). From the table 24.3 shows that there are several forms of tolerance, each of which appears to be caused by specific mechanisms.

Figure 24.1. Shift of the dose-response curve in tolerance and sensitization. With tolerance, the curve shifts to the right (a larger dose is required to achieve the same effect), with sensitization - to the left

Tolerance develops more quickly to some effects of psychoactive drugs than to others. For example, tolerance to the euphoria caused by opioids (heroin, etc.) develops quickly, and therefore, to achieve a “high,” drug addicts constantly increase the dose. Tolerance to the gastrointestinal effects of opioids develops more slowly. A discrepancy between the rate at which tolerance is formed to euphoria and to the effects on vital functions (respiration and circulation) can lead to life-threatening consequences.

Innate tolerance(see above, “Physiological and psychological factors”) manifests itself already with the first use of the drug.

Acquired tolerance divided into pharmacokinetic, pharmacodynamic and mental. The latter includes behavioral tolerance, which, in turn, can be conditioned reflex.

At pharmacokinetic (metabolic) tolerance repeated use of a substance results in changes in distribution or metabolism such that its concentration in the blood (and therefore in target organs) is reduced. The most common mechanism of pharmacokinetic tolerance is acceleration of drug metabolism. For example, barbiturates induce liver microsomal enzymes, which accelerates their elimination (as well as the elimination of many other drugs also metabolized by liver microsomal enzymes). As a result, the serum concentration of these drugs decreases and the effect is weakened.

Pharmacodynamic tolerance develops as a result of adaptive changes in the system itself on which the substance acts. As a result, the reaction to a given substance at a given concentration is weakened. An example is a decrease in receptor density and the efficiency of coupling of receptors with intracellular signal transmission systems.

Mental tolerance- this is a decrease in some of the effects of the drug due to compensatory mechanisms that are developed during the learning process. An example would be behavioral tolerance. It involves developing skills to mitigate some of the effects of mild to moderate intoxication. Thus, alcohol abusers can learn to walk more or less straight even when highly intoxicated. Behavioral tolerance is ensured by both the acquisition of motor skills and more cautious behavior based on knowledge of the consequences of taking a given substance. With severe intoxication, behavioral tolerance is overcome and disturbances become noticeable.

A special form of behavioral tolerance is conditioned reflex. It is a set of adaptive reactions to conditioned reflex stimuli combined with the use of a psychoactive substance (type of drug, its smell or circumstances surrounding its use). Such substances often cause drowsiness, changes in blood pressure, heart rate, peristalsis, etc. In response to this, compensatory reactions develop in the body. If the circumstances accompanying the use of a psychoactive substance (the smell of the drug, the type of syringe, etc.) remain unchanged, then they acquire the character of signal (conditioned reflex) stimuli. As a result, compensatory reactions develop even before the psychoactive substance enters the body. Conditioned tolerance is based on classical (Pavlovian) conditioning. If a psychoactive substance is taken in new, unexpected circumstances, then tolerance decreases and the effects of the substance increase (Wikler, 1973; Siegel 1976).

Table 24.3. Forms of tolerance

Congenital (initial sensitivity or insensitivity)
Acquired
- Pharmacokinetic (metabolic)
- Pharmacodynamic
- Mental
  - Behavioral
    - Conditioned reflex
- Acute tolerance
- Sensitization (reverse tolerance)
- Cross tolerance

Acute tolerance develops with very frequent (“binge”) use of a psychoactive substance. For example, cocaine is sometimes used several times an hour for one or several hours (sometimes even a day). Moreover, each subsequent dose of cocaine has an increasingly weaker effect. Acute tolerance is the opposite of sensitization, which also occurs with periodic use of the drug.

Sensitization. Psychostimulants (eg, cocaine or amphetamine) may cause sensitization, or reverse tolerance. At the same time, the reaction to each subsequent dose increases. Sensitization is characterized by a shift of the dose-response curve to the left (Fig. 24.1). For example, when cocaine is administered daily to rats, each subsequent dose causes an increasing increase in motor activity. Part of sensitization to cocaine may be conditioned. Thus, placing a rat in a cage where it was usually given cocaine, or giving it a placebo after a few days of using cocaine, causes the same increase in motor activity. Sensitization, in contrast to acute tolerance, occurs with large intervals between doses, usually about a day.

Figure 24.2. Changes in dopamine concentration

In rats, using intravital microdialysis, extracellular fluid was obtained in the area of the nucleus accumbens and the content of dopamine in it was studied against the background of the development of sensitization (Kalivas and Duffy, 1990; Fig. 24.2). The very first intraperitoneal injection of cocaine at a dose of 10 mg/kg led to an increase in the concentration of dopamine in the dialysate. Next, cocaine was administered once a day. After the seventh injection, dopamine concentrations were significantly higher than after the first; This was consistent with more pronounced changes in behavior. In Fig. 24.2 also shows a conditioned reflex reaction: the administration of saline 3 days after the cessation of cocaine injections was accompanied by an increase in dopamine levels and an increase in behavioral activity. Data from a few studies suggest that sensitization also exists in humans. It is believed that it is precisely this that causes psychosis during long-term use of psychostimulants.

Description for fig. 24.2. Changes in the concentration of dopamine (determined by intravital microdialysis) in the extracellular fluid in the area of the nucleus accumbens in rats after daily intraperitoneal administration of cocaine (10 mg/kg). The increase in dopamine concentration after the 7th injection is significantly higher than after the 1st. Administration of saline prior to cocaine injection did not increase dopamine concentrations; administration 3 days after the 7th injection of cocaine led to a significant increase in this concentration, apparently as a result of a conditioned reflex reaction. cm - dopamine concentration, % of initial. Kalivas and Duffy, 1990.

Cross tolerance. Cross tolerance is called tolerance to substances that are similar to a long-term drug in structure and mechanism of action. It is important to remember about cross-tolerance when administering medication to patients suffering from drug dependence. One of the methods of treating addiction - detoxification - consists of gradually (to prevent withdrawal symptoms) reducing the dose of the substance that caused the addiction; eventually the substance is discontinued completely. During detoxification, you can temporarily prescribe a drug to which you have cross-tolerance. For example, heroin addicts develop cross-tolerance to all opioids, and any one can be used during detoxification.

See tolerance, cross.

View value Cross Tolerance in other dictionaries

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Dystopia Kidneys Heterolateral Crossed- (d. renis heterolateralis cruciata) congenital D. kidney with its location on the opposite side, next to the second kidney.
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Cross infection- (i. cruciata) I. as a result of mutual exchange of pathogens among persons (patients or convalescents) who are in close contact.
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Reactivation Cross— inclusion of loci of a bacteriophage inactivated by ultraviolet radiation into the progeny of a non-irradiated viable bacteriophage during mixed infection of a bacterial cell.
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Sensitization Cross— S. to antigens that have common determinants with the allergen that caused sensitization.
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Cross Modulation- mutual modulation of two or more oscillations due to their interaction in nonlinear devices or propagation in space with nonlinear properties.

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Tolerance- - tolerance for other people's opinions, beliefs, behavior.
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More meanings of the word and translation of CROSS TOLERANCE from English into Russian in English-Russian dictionaries.
What is and translation of CROSS TOLERANCE from Russian into English in Russian-English dictionaries.

More meanings of this word and English-Russian, Russian-English translations for CROSS TOLERANCE in dictionaries.

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X-REFERENCE - cross reference
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IMMUNOLOGICAL TOLERANCE
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CROSSREFERENCE — cross-reference crossreference wt. cross reference
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CROSS
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