Ticket 47

1. Changes in the body's reactions to medicinal substances during their repeated administration. The concept of addiction, drug dependence, tachyphylaxis, sensitization. Cumulation of medicinal substances. Social aspects of drug abuse. The harm of self-medication.

Repeated administrations of the same medicinal substance can lead to a quantitative (increase or decrease) and qualitative change in the pharmacological effects.

Among the phenomena observed with repeated administration of drugs, there are cumulation, sensitization, addiction (tolerance) and drug dependence.

Cumulation (from Lat. Cumulatio - increase, accumulation) is the accumulation of a medicinal substance in the body or the effects it causes.

Material cumulation - an increase in the concentration of a drug in the blood and / or tissues after each new administration in comparison with the previous concentration. Drugs that are slowly inactivated and slowly excreted from the body, as well as drugs that firmly bind to blood plasma proteins or are deposited in tissues, for example, some hypnotics from the barbiturate group, digitalis drugs, can accumulate with repeated injections. Material accumulation can cause toxic effects, which must be taken into account when dosing such drugs.

Functional cumulation is an increase in the effect of a drug with repeated injections in the absence of an increase in its concentration in the blood and / or tissues. This type of cumulation occurs with repeated intake of alcohol. With the development of alcoholic psychosis ("delirium tremens") in susceptible persons, delusions and hallucinations develop at a time when ethyl alcohol has already been metabolized and is not detected in the body. Functional cumulation is also characteristic of MAO inhibitors.

Sensitization. Many medicinal substances form complexes with blood plasma proteins, which acquire antigenic properties under certain conditions. This is accompanied by the formation of antibodies and sensitization of the body. Repeated administration of the same medicinal substances causes allergic reactions. Often such reactions occur with repeated injections of penicillins, procaine, water-soluble vitamins, sulfanilamides, etc.

Addiction (tolerance, from Lat. Tolerantia - patience) is a decrease in the pharmacological effect of a drug when it is repeated in the same dose. With the development of addiction, in order to achieve the same effect, it is necessary to increase the dose of drugs. Tolerance develops to both the therapeutic and toxic effects of drugs. For example, with prolonged use of morphine, tolerance arises not only to its analgesic effect, but also to the depressing effect on the respiratory center. So, the main reason for addiction to phenobarbital is considered to be the activation of its metabolism due to the induction of liver enzymes caused by phenobarbital itself. Drug addiction can develop over several days or months.

In the case of the development of addiction, a break is taken in the use of this substance, and if it is necessary to continue treatment, drugs with a similar effect, but from a different chemical group, are prescribed. When replacing one substance with another, regardless of its chemical structure, cross-addiction may occur (if these substances interact with the same receptors or enzymes).

A special case of addiction is tachyphylaxis (from the Greek tachys - fast, phylaxis - protection) - the rapid development of addiction with repeated injections of the drug at short intervals (10-15 minutes). Tachyphylaxis to ephedrine is well known due to depletion of norepinephrine reserves at the endings of synaptic nerve fibers. With each subsequent introduction of ephedrine, the amount of norepinephrine released into the synaptic cleft decreases, and the hypertensive effect of the drug (increased blood pressure) is weakened.

Another special case of addiction is mitridatism - the gradual development of insensitivity to the action of the drug and poisons, which arises during their prolonged use, first in very small, and then in increasing doses. According to ancient Greek legend, King Mithridates thus acquired insensitivity to many poisons.

With repeated administration of certain substances that cause extremely pleasant sensations (euphoria), drug dependence develops in predisposed individuals.

Drug addiction - an urgent need (irresistible urge) to constantly or periodically resume the intake of a certain drug or group of substances. First, the substance is taken to achieve a state of euphoria, well-being and comfort, eliminate painful experiences, test new sensations. However, after a certain time, the need for repeated admission becomes insurmountable, which is aggravated by the withdrawal syndrome: the emergence of a severe condition associated with mental and somatic disorders (dysfunctions of organs and body systems) when the drug is discontinued. This condition is designated by the term "abstinence" (from Latin abstinentia - abstinence).

Distinguish between mental and physical drug dependence. Psychic drug dependence is characterized by a sharp deterioration in mood and emotional discomfort, a feeling of fatigue when deprived of the drug. It occurs with the use of cocaine and other psychostimulants (amphetamine), hallucinogens (lyzergic acid diethylamide, LSD-25), nicotine, Indian hemp (marijuana, hashish, plan, marijuana). Physical drug addiction is characterized not only by emotional discomfort, but also the occurrence of withdrawal syndrome. Physical drug dependence develops to opioids (heroin, morphine), barbiturates, benzodiazepines, alcohol (ethyl alcohol).

Drug dependence is often combined with addiction, while increasing doses of the substance are required to obtain euphoria. The most severe drug dependence occurs in the case of a combination of mental dependence, physical dependence and addiction.

Substance abuse - the use of substances in order to obtain intoxicating effects. Drug addiction is a special case of substance abuse, when a substance referred to the list of substances causing drug dependence (narcotic substances) and subject to control is used as an intoxicating agent. Cancellation Phenomenon. It can be expressed in two (essentially opposite) versions. The first is less common, mainly with prolonged use of hormonal agents and consists in persistent suppression of the function of its own glands and the loss of the corresponding hormones from regulation. This option occurs especially easily and often with tragic consequences when treating with corticosteroids (hydrocortisone, prednisolone, dexametazone). A hormone (or its analogue) introduced from the outside makes the work of its own gland unnecessary, and it undergoes (as an inoperative organ) atrophy, the degree of which is proportional to the duration of treatment. Restoration of the structure and function, for example, of the adrenal glands after a course of cortisone therapy, may require up to six months or more. A sharp withdrawal of the hormone used causes acute corticoid insufficiency with a shock-like syndrome with severe stress, surgical interventions.

2. Non-steroidal anti-inflammatory drugs (non-narcotic analgesics). Classification. The mechanism of their anti-inflammatory, analgesic and antipyretic action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.

Classification:

1) Derivatives of salicylic acid: aspirin.

2) Derivatives of pyrazolone: ​​analgin.

3) Derivatives of indoleacetic acid: INDOMETACIN.

4) Derivatives of phenylacetic acid: DICLOFENAC.

5) Propionic acid derivatives: IBUPROFEN.

6) Derivatives of aniline: PARACETAMOL.

The mechanism of antipyretic drugs: Reduces the excitability of the thermal center, dilates blood vessels, increases sweating, inhibits the synthesis of prostaglandins.

The mechanism of anti-inflammatory action: reduces the activity of hyaluronidase and capillary permeability, stabilizes lysosomal membranes, decreases the production of ATP, decreases the synthesis of inflammatory mediators or increases their inactivation.

The mechanism of analgesic action is a peripheral component: they disrupt the synthesis of pain mediators, delaying their release and activation; disrupt the synthesis and release of histamine, serotonin, decrease the activity of proteolytic enzymes. Central component: they block the nuclei of the thalamic tubercles, prevent the transmission of pain impulses to the cortex.

Indications: headaches, dental pains, joint pains, muscle pains, neurological pains, acute rheumatism, arthritis, thrombophlebitis.

Side effects: Vomiting, abdominal pain, allergies, kidney damage.

Contraindications: gastric ulcer and duodenal ulcer, kidney disease and hematopoiesis.

Paracetamol - well tolerated, side effects are rare, does not affect the stomach and platelet aggregation.

Aspirin - reduces platelet aggregation, blood glucose, stimulates respiration, increases bile secretion. Analgin - greater analgesic effect.