Basic rules for taking antidotes. Poisons and their antidotes. Basic issues of antidote therapy. General information about antidotes for poisoning

Antidote is a medicine used in the treatment of poisoning and helping to neutralize the poison or prevent and eliminate the toxic effect they cause.

There are direct and non-direct antidotes. direct action.

(I) Direct action – there is a direct chemical or physico-chemical interaction between the poison and the antidote. The main options are sorbent preparations and chemical reagents. Sorbent preparations – the protective effect is carried out due to nonspecific fixation (sorption) of molecules on the sorbent. The result is a decrease in the concentration of poison interacting with biological structures, which leads to a weakening of the toxic effect. Sorption occurs due to nonspecific intermolecular interactions - hydrogen and van der Waals bonds (not covalent!). Sorption can be carried out from the skin, mucous membranes, from the digestive tract (enterosorption), from the blood (hemosorption, plasma sorption). If the poison has already penetrated the tissue, then the use of sorbents is not effective. Examples of sorbents: Activated carbon, kaolin (white clay), Zn oxide, ion exchange resins.

For cyanide poisoning (salts of hydrocyanic acid HCN), glucose and sodium thiosulfate are used, which bind HCN. Below is the reaction with glucose:

Intoxication with thiol poisons (compounds of mercury, arsenic, cadmium, antimony and other heavy metals) is very dangerous. Me2+). Such poisons are called thiol based on their mechanism of action - binding to thiol (-SH) groups of proteins:

The binding of the metal to the thiol groups of proteins leads to the destruction of the protein structure, which causes the cessation of its functions. The result is a disruption of the functioning of all enzyme systems of the body.
To neutralize thiol poisons, dithiol antidotes (SH-group donors) are used. Their mechanism of action is presented in bottom diagram. The resulting poison-antidote complex is removed from the body without causing harm to it.

Another class of direct-acting antidotes is antidotes - complexones ( complexing agents). They form strong complex compounds with toxic cations Hg, Co, Cd, Pb. Such complex compounds are excreted from the body without causing harm to it. Among complexones, the most common are ethylenediaminetetra salts. acetic acid(EDTA), primarily sodium ethylenediaminetetraacetate.

II)Indirect-acting antidotes.
Indirect antidotes are substances that do not themselves react with poisons, but eliminate or prevent disorders in the body that occur during intoxication (poisoning).
1) Receptor protection from toxic effects.
Poisoning with muscarine (fly agaric poison) and organophosphorus compounds occurs through the mechanism of blocking the enzyme cholinesterase. This enzyme is responsible for the destruction of acetylcholine, a substance involved in the transmission of nerve impulses from the nerve to the muscle fibers. When there is an excess of acetylcholine, random muscle contractions occur - cramps, which often lead to death. The antidote is atropine. Atropine is used in medicine to relax muscles. Anthropine binds to the receptor, i.e. protects it from the action of acetylcholine.
2) Restoration or replacement of a biological structure damaged by poison.
In case of fluoride and HF poisoning, and in case of poisoning with oxalic acid H2C2O4, Ca2+ ions bind in the body. The antidote is CaCl2.
3) Antioxidants. Poisoning with carbon tetrachloride CCl4 leads to the formation of free radicals in the body. Excess free radicals are very dangerous, they cause damage to lipids and disruption of the structure of cell membranes. Antidotes are substances that bind free radicals (antioxidants), for example alpha-tocopherol (vitamin E).

4) Competition with poison for binding to the enzyme. When poisoning with methanol, very toxic compounds are formed in the body - formaldehyde and formic acid. They are more toxic than methanol itself. This is an example of lethal fusion. Lethal synthesis– transformation in the org-me in the process of metabolism of less toxic compounds into more toxic ones.

Ethyl alcohol C2H5OH binds better to the enzyme alcohol dehydrogenase. This inhibits the conversion of methanol to formaldehyde and formic acid. CH3OH is excreted unchanged. Therefore, taking ethyl alcohol immediately after methanol poisoning significantly reduces the severity of poisoning.

Topic of the lesson: Medical means of prevention and assistance in case of chemical radiation injuries

Lesson objectives:

1. Give an idea of antidotes, radioprotectors and their mechanism of action.

2. To familiarize with the principles of emergency care for acute intoxication, for radiation injuries at the source and at the stages of medical evacuation.

3. Show the achievements of domestic medicine in the research and development of new antidotes and radioprotectors.

Questions for the practical lesson:

6. Means of preventing the general primary reaction to radiation, early transient

7. Basic principles of first aid, pre-medical and first aid medical care for acute poisoning and radiation injuries.

Questions to take notes in your workbook

1. Antidotes, mechanisms of antidote action.

2. Characteristics of modern antidotes.

3. General principles of emergency care for acute intoxication.

Procedure for using antidotes.

4. Radioprotectors. Indicators of the protective effectiveness of radioprotectors.

5. Mechanisms of radioprotective action. a brief description of and the procedure for application

nia. Means for long-term maintenance of increased radioresistance of the body.

7. Means of preventing the general primary reaction to radiation, early transient

total incapacity. Prehospital treatment of ARS.

Antidotes, mechanisms of antidote action

Antidote (from Greek. Antidotum- given against) are medicinal substances used in the treatment of poisoning and helping to neutralize the poison or prevent and eliminate the toxic effect caused by it.

A more expanded definition is given by experts from the WHO International Chemical Safety Program (1996). They believe that an antidote is a drug that can eliminate or weaken the specific effect of xenobiotics due to its immobilization (chelating agents), reducing the penetration of the poison to effector receptors by reducing its concentration (adsorbents) or counteraction at the receptor level (physiological and pharmacological antagonists).

Antidotes according to their action are divided into nonspecific and specific. Nonspecific antidotes are compounds that neutralize many xenobiotics through physical or physicochemical action. Specific antidotes act on specific targets, thereby neutralizing the poison or eliminating its effects.

Specific antidotes exist for small amount highly toxic chemicals and they differ in their mechanisms of action. It should be noted that their appointment is far from a safe undertaking. Some antidotes cause serious adverse reactions Therefore, the risk of their use must be weighed against the likely benefit of their use. The half-life of many of them is shorter than poison (opiates and naloxone), so after an initial improvement in the patient's condition, it may worsen again. It is clear from this that even after the use of antidotes it is necessary to continue careful monitoring of patients. These antidotes are more effective when used in the initial toxicogenic stage of poisoning than in more late period. However, some of them have an excellent effect in the somatogenic stage of poisoning (anti-toxic serum “anticobra”).

In toxicology, as in other areas of practical medicine, etiotropic, pathogenetic and symptomatic agents are used to provide assistance. The reason for administering etiotropic drugs is knowledge of the immediate cause of poisoning and the toxicokinetics of the poison. Symptomatic and pathogenetic substances are prescribed based on the manifestations of intoxication.

Antidotes are medicines or special compounds, the use of which in the prevention and treatment of poisoning is due to their specific antitoxic effect.

The use of antidotes underlies preventive or therapeutic measures to neutralize the toxic effects of chemicals. Because many chemicals have multiple mechanisms toxic effect, in some cases it is necessary to simultaneously introduce various antidotes and at the same time use therapeutic agents that eliminate not the causes, but only individual symptoms poisoning Moreover, since the underlying mechanisms of action of most chemical compounds are not well understood, treatment of poisoning is often limited to symptomatic therapy. The experience gained in clinical toxicology shows that some drugs, in particular vitamins and hormones, can be classified as universal antidotes due to the positive preventive and therapeutic effect that they have in various poisonings. This is explained by the fact that poisoning is based on common pathogenetic mechanisms. There is still no generally accepted classification of antidotes. The most rational classification system is based on the reduction of antidotes into main groups depending on the mechanism of their antitoxic action - physical, chemical, biochemical or physiological. Based on the conditions under which antidotes react with poison, a distinction is made between local antidotes, which react with the poison before it is absorbed by the tissues of the body, and resorptive antidotes, which react with the poison after it enters the tissues and physiological fluids.

It should be noted that antidotes of physical action are used exclusively for the prevention of intoxication, and antidotes of resorptive action are used both for the prevention and treatment of poisoning.

2.6.1. Physical antidotes

These antidotes have a protective effect mainly due to the adsorption of the poison. Due to their high surface activity, adsorbents bind solid molecules and prevent their absorption by the surrounding tissue. However, molecules of the adsorbed poison may later separate from the adsorbent and return to the stomach tissue. This separation phenomenon is called desorption. Therefore, when using physical antidotes, it is extremely important to combine them with measures aimed at the subsequent removal of the adsorbent from the body. This can be achieved by gastric lavage or the use of laxatives if the adsorbent has already entered the intestines. Preference here should be given to saline laxatives (for example, sodium sulfate), which are hypertonic solutions, stimulating the flow of fluid into the intestines, which virtually eliminates the absorption of solid matter by tissues. Fatty laxatives (eg. Castor oil) can promote the adsorption of fat-soluble chemicals, resulting in an increase in the amount of poison absorbed by the body. In cases where the exact nature of the chemical is unknown, the use of saline laxatives is recommended. The most typical antidotes in this group are activated carbon and kaolin. They have a great effect in acute alkaloid poisoning ( organic matter plant origin, for example, atropine) or salts of heavy metals.

2.6.2. Chemical antidotes

The mechanism of their action involves a direct reactionbetween poison and antidote. Chemical antidotes can be either local or resorptive.

Local action. If physical antidotes have a low-specific antidote effect, then chemical ones have a fairly high specificity, which is due to the very nature of the chemical reaction. Local action chemical antidotes is provided as a result of neutralization reactions, the formation of insoluble compounds, oxidation, reduction, competitive substitution and the formation of complexes. The first three mechanisms of action are of particular importance and are better studied than others.

A good example of neutralizing poisons is the use of alkalis to counteract strong acids accidentally ingested or on the skin. Neutralizing antidotes are also used to carry out reactions that result in the formation of compounds with low biological activity. For example, if strong acids enter the body, it is recommended to rinse the stomach with warm water to which magnesium oxide (20 g/l) has been added. In case of poisoning with hydrofluoric or citric acid, the patient is given a pasty mixture of calcium chloride and magnesium oxide to swallow. In case of contact with caustic alkalis, gastric lavage should be performed with a 1% solution of citric or acetic acid. In all cases of exposure to caustic alkalis and concentrated acids, it should be borne in mind that emetics are contraindicated. Vomiting causes sudden contractions of the stomach muscles, and since these corrosive fluids can attack the stomach tissue, there is a risk of perforation.

Antidotes that form insoluble compounds that cannot penetrate mucous membranes or skin have a selective effect, i.e. they are effective only in case of poisoning by certain chemicals. A classic example of this type of antidotes is 2,3-dimercaptopropanol, which forms insoluble, chemically inert metal sulfides. He gives positive effect in case of poisoning with zinc, copper, cadmium, mercury, antimony, arsenic.

Tannin (tannic acid) forms insoluble compounds with salts of alkaloids and heavy metals. The toxicologist must remember that tannin compounds with morphine, cocaine, atropine or nicotine have varying degrees of stability.

After taking any antidotes of this group, it is necessary to perform gastric lavage to remove the formed chemical complexes.

Of great interest are antidotes with combined action, in particular a composition that includes 50 g of tannin, 50 g of activated carbon and 25 g of magnesium oxide. This composition combines antidotes of both physical and chemical action.

In recent years, the topical use of sodium thiosulfate has attracted attention. It is used in cases of poisoning by arsenic, mercury, lead, hydrogen cyanide, bromine and iodine salts.

Sodium thiosulfate is used orally in the form of a 10% solution (2-3 tablespoons).

Local application antidotes for the above poisonings should be combined with subcutaneous, intramuscular or intravenous injections.

In cases of ingestion of opium, morphine, aconite or phosphorus, oxidation of the solid substance is widely used. The most common antidote for these cases is potassium permanganate, which is used for gastric lavage in the form of a 0.02–0.1% solution. This drug has no effect in case of poisoning with cocaine, atropine and barbiturates.

Resorptive action. Resorptive antidotes of chemical action can be divided into two main subgroups:

antidotes that interact with certain intermediate products formed as a result of the reaction between the poison and the substrate;

b) antidotes that directly interfere with the reaction between the poison and certain biological systems or structures. In this case, the chemical mechanism is often associated with the biochemical mechanism of antidote action.

Antidotes of the first subgroup are used in case of cyanide poisoning. To date, there is no antidote that would inhibit the interaction between cyanide and the enzyme system affected by it. After absorption into the blood, cyanide is transported by the bloodstream to the tissues, where it interacts with the ferric iron of oxidized cytochrome oxidase, one of the enzymes necessary for tissue respiration. As a result, oxygen entering the body stops reacting with the enzyme system, which causes acute oxygen starvation. However, the complex formed by cyanide with iron of cytochrome oxidase is unstable and easily dissociates.

Consequently, treatment with antidotes proceeds in three main directions:

1) neutralization of poison in the bloodstream immediately after it enters the body;

2) fixation of poison in the bloodstream in order to limit the amount of poison entering the tissues;

3) neutralization of the poison entering the blood after the dissociation of cyanomethemoglobin and the complex of cyanide and substrate.

Direct neutralization of cyanide can be achieved by introducing glucose, which reacts with hydrocyanic acid, resulting in the formation of slightly toxic cyanohydride. A more active antidote is ß-hydroxyethylmethylenediamine. Both antidotes should be administered intravenously within a few minutes or seconds after the poison enters the body.

The more common method is one in which the task is to fix the poison circulating in the bloodstream. Cyanides do not interact with hemoglobin, but actively combine with methemoglobin, forming cyanomethemoglobin. Although it is not highly stable, it can persist for some time. Therefore, in this case, it is necessary to introduce antidotes that promote the formation of methemoglobin. This is done by inhaling amyl nitrite vapor or intravenous injection of sodium nitrite solution. As a result, free cyanide present in the blood plasma binds to a complex with methemoglobin, losing much of its toxicity.

It must be borne in mind that antidotes that form methemoglobin can affect blood pressure: if amyl nitrite causes a pronounced, short-term drop in pressure, then sodium nitrite has a prolonged hypotonic effect. When administering substances that form methemoglobin, it should be taken into account that it not only takes part in the transfer of oxygen, but can itself cause oxygen starvation. Therefore, the use of methemoglobin-forming antidotes must follow certain rules.

The third method of antidote treatment is to neutralize cyanide released from complexes with methemoglobin and cytochrome oxidase. For this purpose, sodium thiosulfate is injected intravenously, which converts cyanides into non-toxic thiocyanates.

The specificity of chemical antidotes is limited because they do not interfere with the direct interaction between the venom and the substrate. However, the effect that such antidotes have on certain parts of the mechanism of toxic action has an undoubted therapeutic significance, although the use of these antidotes requires high medical qualifications and extreme caution.

Chemical antidotes that directly interact with a toxic substance are highly specific, allowing them to bind toxic compounds and remove them from the body.

Complexing antidotes form stable compounds with di- and trivalent metals, which are then easily excreted in the urine.

In cases of poisoning with lead, cobalt, copper, vanadium, disodium calcium salt of ethylenediaminetetraacetic acid (EDTA) has a great effect. The calcium contained in the antidote molecule reacts only with metals that form a more stable complex. This salt does not react with ions of barium, strontium and some other metals with a lower stability constant. There are several metals with which this antidote forms toxic complexes, so it should be used with great caution; in case of poisoning with cadmium, mercury and selenium, the use of this antidote is contraindicated.

For acute and chronic poisoning with plutonium and radioactive iodine, cesium, zinc, uranium and lead, pentamil is used. This drug is also used in cases of cadmium and iron poisoning. Its use is contraindicated for persons suffering from nephritis and cardiovascular diseases. Complexing compounds in general also include antidotes whose molecules contain free mercapto groups - SH. Of great interest in this regard are dimercaptoprome (BAL) and 2,3-dimercaptopropane sulfate (unithiol). The molecular structure of these antidotes is comparatively simple:

H 2 C – SH H 2 C – SH | |

HC – SH HC – SH

H 2 C – OH H 2 C – SO 3 Na

BAL Unithiol

Both of these antidotes have two SH groups that are close to each other. The significance of this structure is revealed in the example below, where antidotes containing SH groups react with metals and non-metals. The reaction of dimercapto compounds with metals can be described as follows:

Enzyme + Me → Me enzyme

HSCH 2 S – CH 2

HSCH + enzyme Me → enzyme + Me– S – CH

HOCH 2 OH–CH 2

The following phases can be distinguished here:

A) reaction of enzymatic SH groups and the formation of an unstable complex;

B) reaction of the antidote with the complex;

C) release of the active enzyme due to the formation of a metal-antidote complex, excreted in the urine. Unithiol is less toxic than BAL. Both drugs are used in the treatment of acute and chronic poisoning with arsenic, chromium, bismuth, mercury and some other metals, but not lead. Not recommended for selenium poisoning.

There are no effective antidotes for the treatment of poisoning by nickel, molybdenum and some other metals.

2.6.3. Biochemical antidotes

These drugs have a highly specific antidote effect. Typical for this class are antidotes used in the treatment of poisoning with organophosphorus compounds, which are the main components of insecticides. Even very small doses of organophosphates inhibit the function of cholinesterase as a result of its phosphorylation, which leads to the accumulation of acetylcholine in tissues. Since acetylcholine has great value for the transmission of impulses in both the central and peripheral nervous systems, its excessive amount leads to disruption nerve functions, and therefore to serious pathological changes.

Antidotes that restore the function of cholinesterase belong to hydroxamic acid derivatives and contain the oxime group R – CH = NOH. The oxime antidotes 2-PAM (pralidoxime), dipyroxime (TMB-4) and isonitrosine are of practical importance. Under favorable conditions, these substances can restore the function of the cholinesterase enzyme, weakening or eliminating Clinical signs poisoning, preventing long-term consequences and promoting successful recovery.

Practice, however, has shown that best results are achieved in cases where biochemical antidotes are used in combination with physiological antidotes.

2.6.4. Physiological antidotes

The example of poisoning with organophosphorus compounds shows that suppression of cholinesterase function leads, first of all, to the accumulation of acetylcholine in synapses. There are two possibilities to neutralize the toxic effect of the poison:

A) restoration of cholinesterase function;

B) protection of physiological systems sensitive to acetylcholine from the excessive action of this mediator of nerve impulses, which leads to

Diets initially to acute agitation and then to functional paralysis.

An example of a drug that suppresses sensitivity to acetylcholine is atropine. The class of physiological antidotes includes many drugs. In case of acute central nervous system excitation, which is observed in many poisonings, it is recommended to administer narcotics or anticonvulsants. At the same time, in case of acute suppression of the respiratory center, central nervous system stimulants are used as antidotes. To a first approximation, it can be argued that physiological (or functional) antidotes include all drugs that cause physiological reactions that counteract poison.

Therefore, it is difficult to make a clear distinction between antidotes and drugs used in symptomatic therapy.

Control questions

How are toxic substances classified according to purpose of use?
What types of poisoning do you know?
List the experimental parameters of toxicometry.
Name the derived parameters of toxicometry.
What is the essence of the toxicity receptor theory?
In what ways do harmful substances enter the body?
What is the biotransformation of toxic substances?
Ways to remove foreign substances from the body.
What are the features of acute and chronic poisoning?
List the main and additional factors that determine the development of poisoning.
Name the types of combined effects of poisons.
What are antidotes?

^ PART 3. COMPETITION AND PROFESSIONAL

Toxic substances that can poison you lie in wait at every step - they are found in plants, animals, medicines and various substances that surround people in everyday life. Most poisons are lethal. To neutralize their effects, antidotes for poisoning are used, a table with the classification of which is presented in this article.

General information about antidotes for poisoning

Like any strong medicine, antidotes given for poisoning have their own pharmacological properties, which evaluate different specific drugs. These include in particular:

time of receipt;
efficiency;
dose of application;
side effects.

Depending on the period and severity of the disease, the value of antidote therapy may vary. Thus, Treatment of poisoning with antidotes is effective only on early stage , called toxicogenic.

The duration of the stage varies and depends on the substance that caused the poisoning. The longest duration of this phase is 8-12 days and refers to the effect of heavy metals on the body. Least time refers to poisoning by cyanide, chlorinated hydrocarbons and other highly toxic and rapidly metabolized compounds.

Antidote therapy should not be used if there are doubts about the reliability of the diagnosis and the type of poisoning, since due to the certain specificity of this type of treatment, it is possible to cause double harm to the body, because often the antidote is no less toxic than the object of intoxication itself.

If the first stage of the disease is missed and severe disturbances in the circulatory system develop, then, in addition to antidote therapy, the effectiveness of which will now be reduced, urgent resuscitation measures are necessary.

Antidotes are indispensable in conditions of delayed or irreversible acute poisoning, but in the second phase of the disease, called somatogenic, they cease to have a therapeutic effect.

All antidotes can be divided into three groups according to their mechanism of action:

etiotropic – weaken or eliminate all manifestations of intoxication;
pathogenetic - weaken or eliminate those manifestations of poisoning that correspond to a specific pathogenetic phenomenon;
symptomatic - weaken or eliminate some manifestations of poisoning, such as pain, convulsions, psychomotor agitation.

Thus, effective antidotes, which are most helpful in case of poisoning, have high level toxicity. And vice versa - the safer the antidote, the less effective it is.

Classification of antidotes

Types of antidotes were developed by S. N. Golikov– it is his version of the classification that is often used by modern medicine:

local action of antidotes, in which the active substance is absorbed by the body tissue and the poison is neutralized;
the general resorptive effect is based on the effect of a chemical conflict between the antidote and the poison;
competitive action of antidotes, in which the poison is displaced and bound by harmless compounds based on the chemical identity between the antidote and enzymes, as well as other elements of the body;
the physiological effect is based on the opposition between the behavior of poison and antidote in the body, which makes it possible to remove disturbances and return to a normal state;
The immunological effect consists of vaccination and the use of specific serum that is effective for a specific poisoning.

Antidotes are also classified and divided according to their nature. Antidotes are distinguished separately:

from animal/bacterial poisoning;
from mushroom toxins;
from plant and alkaloid;
in case of drug poisoning.

Depending on the type of poison, poisoning can be food or non-food. Any poisoning that leads to a deterioration in the patient’s condition must be neutralized with antidotes. They prevent the spread and poisoning of poisons in organs, systems, biological processes, and also inhibit functional disorders caused by intoxication.

Food poisoning

A condition with acute digestive upset that occurs after eating poor-quality foods or drinking is called food poisoning. It occurs when eating spoiled food that is contaminated with harmful organisms or contains dangerous chemical compounds. The main symptoms are nausea, vomiting, diarrhea.

There are infectious and toxic poisonings: the sources of the former are all kinds of bacteria, microbes, viruses and protozoan single-celled organisms that enter the body with food. Toxic poisoning refers to the poisons of heavy metals, inedible plants and other products with a critical content of toxins that have entered the body.

Manifestations of the disease develop within 2-6 hours after infection and are characterized by a sharp development of symptoms. Among infectious poisonings, the greatest danger for infection is represented by meat and dairy products, which, if they are contaminated and have undergone insufficient heat treatment, can cause serious harm, since they represent an ideal environment for the proliferation of bacteria and other organisms.

Methods for identifying hazardous products

An externally fresh and tasty product can also be dangerous, since the microorganisms that initially entered it multiply gradually, but their very presence threatens to spoil the functionality of the gastrointestinal tract. That's why The first and most important rule of food consumption is safety control. Food products can only be purchased in specially designated places; they must be sold by people who have medical books. Food must be kept in premises that have passed a sanitary inspection, are registered in the system and have the right to operate accordingly. Of course, various eateries with shawarma, street pies and other dubious food outlets are not included in this list.

Infectious poisonings are extremely dangerous for others and can lead to infection.. Freshly prepared foods have minimal chance of being contaminated, but leftover food becomes potentially dangerous after just a few hours.

In addition to the expiration date, which should always be checked, even if the purchase is made in a large retail chain, signs that may indicate that the food has been stored for longer than expected include the following:

damaged packaging, traces of defects on the package that led to a violation of its integrity;
an atypical, too strong odor or, conversely, its absence;
stratification of consistency, its heterogeneity;
any bubbles when stirring, if it is not mineral water;
the color and smell are not what they should be - especially if it is meat, eggs, milk;
the presence of sediment, opacity, any suspicious changes in the usual appearance of the product.

The presence of these characteristics should stop you from purchasing a similar product and choose the one that does not raise doubts.

Symptoms

A toxin or microbe that enters the body can act in different ways, but there are characteristic general symptoms which occur most frequently. This temperature, general weakness, disruption of the gastrointestinal tract. Doctors also often note a patient’s loss of appetite, nausea, pain and bloating in the abdomen. The patient is weakened, looks pale, may break out in a cold sweat and have low blood pressure.

At toxic poisoning symptoms and disorders are more serious: the patient shows signs of dehydration, vision is impaired - he sees objects in two, and temporary blindness may occur. Possible salivation, hallucinations, paralysis, loss of consciousness, convulsions, coma.

Risk groups include young children, pregnant women and the elderly. For them, the symptoms may be more severe, and the disease has a poor prognosis.

Primary symptoms of poisoning with some toxins can appear within an hour and increase over several days. It is important to identify the disease as early as possible and begin treatment.

Treatment

It is necessary to immediately call an ambulance and begin providing first aid to the victim. emergency assistance: gastric lavage with soda or potassium permanganate, use of enterosorbents, intake of large amounts of fluid. In this condition, you must wait for an ambulance and not undertake other treatment. Antibiotics, bifidobacteria, any antiemetic or alcohol-containing drugs, as well as any medications that are given without a confirmed diagnosis and if poisoning is suspected, can have a detrimental effect on a person and significantly complicate treatment.

All further measures should be carried out in a hospital under the supervision of specialists. With timely treatment, the prognosis is often favorable.

Antidotes used for acute poisoning

At the first signs of acute poisoning, it is first necessary to diagnose the nature of intoxication. To do this, you will need medical history data, various physical evidence - the remains of containers with traces of the use of a toxic liquid, etc. It is also worth paying attention to the presence of a specific odor, which can determine the nature of the substance that caused the poisoning. All data on clinical manifestation symptoms of a poisoned person.

The toxicogenic phase of poisoning is the very first stage of intoxication, in which the poison has not yet had time to affect the entire body, and its maximum concentration in the blood has not yet been reached. But already at this stage the body is damaged by toxins with characteristic manifestations of toxic shock.

It is important to start treatment as quickly as possible. As a rule, the doctor will apply assistance in the first toxicogenic phase on the spot, before the patient is hospitalized. Since it is at this stage of providing or not providing assistance that the entire further prognosis is decided.

First of all, gastric lavage is used, enterosorbents and laxatives are administered, then antidotes are administered.

For certain types of poisoning, the stomach should only be rinsed through a tube, so such questions should be discussed with your doctor.

Symptomatic treatment consists of maintaining and monitoring a person’s life support functions. If the airway is obstructed, it should be cleared in the necessary manner. Analgesics are used for pain relief, but only before the gastric lavage process, glucose and ascorbic acid are administered.

Table of the most common poisonings with antidotes

In case of acute poisoning, urgent hospitalization is required to the intensive care and resuscitation department. The doctor continues to rinse the gastrointestinal tract, artificial ventilation lungs, treatment with diuretics, antidotes and antagonists.

But the most effective results are achieved with the help of artificial detoxification, consisting of hemosorption, hemodialysis, plasmapheresis, and peritoneal dialysis. With these steps, poisons and toxins are eliminated more intensively.

General table of antidotes for poisoning by toxins and poisons

It is necessary to take antidotes, not only to prevent the body from being damaged by toxic substances, but also to stop certain symptoms that develop against the background of poisoning. It is necessary to develop and apply the correct scheme, which will be effective in each individual case, to prevent intoxication. Some types of poisoning have a delayed onset and their manifestations can be sudden and immediately develop into a clinical picture.

Group of toxins	Antidotes
Cyanides, hydrocyanic acid	Amyl nitrite, propyl nitrite, anthicyanin, dicobolt salt EDTA, methylene blue, sodium nitrite, sodium thiosulfate
Iron salts	Desferrioxamine (desferal)
Narcotic analgesics	Naloxone
Copper sulfate	Unithiol
Iodine	Sodium thiosulfate
Opiates, morphine, codeine, promedol	Nalmefene, naloxone, levarphanol, nalorphine
Arsenic	Unithiol, sodium thiosulfate, cuprenil, disodium salt
Silver nitrate	Sodium chloride
Mercury vapor	Unithiol, cuprenil, sodium thiosulfate, pentacin
Ethanol	Caffeine, atropine
Potassium cyanide	Amyl nitrite, chromospan, sodium thiosulfate, methylene blue
Hydrogen sulfide	Methylene blue, amyl nitrite

Mode of application, dosage forms and the dosage of antidotes for poisoning should be agreed with the attending physician; it is also necessary to confirm the diagnosis using tests in order to properly conduct therapy.

Any antidote is the same chemical substance, careless handling of which can also harm the body. The effect of the antidote is achieved through a chemical reaction that occurs when it interacts with the source of poisoning.

Table of antidotes for poisoning with substances of different nature

From animal/bacterial intoxication

In case of drug poisoning

Plant and alkaloid antidotes

Antidotes for mushroom toxins

Details of therapy for some poisonings

Let us consider antidote therapy for the most common and dangerous poisonings in detail:

Chlorine. Its vapors can reflexively stop breathing, cause chemical burn and pulmonary edema. In severe poisoning, death occurs within a few minutes. If the toxin damage is moderate or light form severity, prescribed effective therapy. First of all, the victim is taken out to Fresh air , in severe cases, they do bloodletting, wash the eyes with novocaine, give antibiotics penicillin group, cardiovascular drugs. Treat with morphine, atropine, ephedrine, calcium chloride, diphenhydramine, hydrocortisone.
Salts of heavy metals. Plenty of fluids, diuretics, and enterosorbents are required. When washing the stomach, use a tube and introduce unithiol through it. Use a laxative.
Organophosphorus compounds. These are household and medical pesticides that are used everywhere as a class of OPs. When poisoned by these toxins, the skin and mucous membranes are primarily affected. Calcium gluconate and lactate serve as antidote. A mixture of egg white and milk is suitable. It is necessary to rinse the stomach with saline or soda solution.

Conclusion

To date, developed urgent measures for timely response in case of poisoning varying degrees to effectively eliminate all consequences. In addition to the use of an antidote, measures aimed at preventing and treating intoxication are classified as follows:

Emergency measures, which include washing the gastrointestinal tract, mucous membranes, skin.
Accelerated measures that use various kinds of diuretics that absorb toxins, sorbents and other processes aimed at removing toxins from the body.
Restorative measures aimed at treating the vital functions of body systems and individual organs.
The process of oxygenation necessary for a poisoned organism.

Subject to hygiene rules, careful attention to the food and water consumed, vigilance regarding chemicals and household utensils, poisoning prevention is most effective. But if poisoning does occur, it is necessary to take immediate action, the first of which is calling an ambulance. It should be remembered that the effectiveness of treatment increases significantly with a timely and competent approach.

Antidotes or antidotes These are medicinal drugs that, when introduced into the body under conditions of intoxication, are capable of neutralizing (inactivating) a poison circulating in the bloodstream or even already associated with some biological substrate, or eliminating the toxic effect of the poison, as well as accelerating its elimination from the body. Antidotes also include those that can prevent poison from entering the body.

By mechanism therapeutic effect existing antidotes can be divided into the following main groups.

1. Physico-chemical- the action is based on physical and chemical processes (adsorption, dissolution) in the alimentary canal. These include adsorbents, which are, if not universal, then polyvalent. The most common antidote of this type is activated carbon, which, having large surface, is able to adsorb poison that enters the stomach. However, its activity is limited by the fact that it is able to take the poison “captive” only before its resorption. Therefore, such antidotes can only be used orally.

2. Chemical- the action is based on a specific chemical interaction with the poison, as a result of which the latter is inactivated. In this case, the antidote, by binding, precipitation, displacement and competitive or other reactions, converts the poison into a harmless substance excreted in urine or feces from the body.

3. Physiological or functional- the action is aimed at eliminating the toxic effect of the poison. Unlike previous ones, such antidotes do not react directly with the poison and do not change its physicochemical state, but interact with the biological substrate, which is negatively affected by the poison. The action of physiological antidotes is based on the principle of functional antagonism.

The division of antidotes into these groups is arbitrary, since many of them can be mixed-type drugs, the action of which is more complex than each of the given groups separately. An antidote can also be a mixture of several therapeutic agents, administered in a certain sequence or simultaneously. At the same time, while providing a therapeutic effect in various directions, individual ingredients complement each other or enhance the effect by summing up or potentiating the anti-dote effect. The most effective antidotes are those that are able to deactivate the poison at the points of its application.

An important circumstance ensuring the high activity of the antidote is the timing of its administration after poisoning. The earlier the antidote is applied, the more effective its positive effect is.

Currently, medical practice for combating various poisonings still has a small number of therapeutic agents with antidote action. For the treatment of poisoning with various arsenic compounds - organic and inorganic, 3-, 5-valent (arsenic anhydride, arsenites and arsenates of sodium and calcium, Paris greens, osarsol, novarsenol), as well as heavy metals, including radioactive ones (mercury, copper , polonium, cadmium, etc.), mercapto compounds have widely proven themselves, for example, the domestic drug unithiol(A.I. Cherkes, V.E. Petrunkin et al., 1950).

In structure, it is a dithiol, that is, a compound containing two sulfhydryl groups, and belongs to the chemical type of antidotes.

Unithiol has a wide range of therapeutic effects; it can be administered parenterally, through the mouth. The drug is stable when stored both in the crystalline state and in the form of solutions. The creation of this antidote was made possible by revealing the mechanism of the toxic action of arsenic-containing compounds. The toxic effect of the latter is due to the blocking effect on the mercapto groups of thioproteins of enzyme systems that play a vital role. In this case, the sulfhydryl groups of enzymes, easily interacting with thiol poisons, form a strong toxic complex (protein - poison), as a result of which thio-proteins lose their reactive ability.

Unithiol When entering an organism poisoned by arsenic- and metal-containing substances, due to the high reactivity of sulfhydryl groups, it easily reacts with arsenic or metal, thereby preventing the binding of poisons to the mercapto groups of enzyme proteins. In this case, dithiols with arsenic or metal form low-toxic, water-soluble complex compounds - cyclic thioarsenites or metal mercaptides, which are then excreted in the urine from the body. Thioarsenites are stronger than those formed during the interaction of poisons. with 5H-groups of enzymes, and are inferior in toxicity to the latter. Therefore, when treated with unithiol, more arsenic or metal is found in the urine of victims than in untreated patients. These antidotes are used as active funds elimination of poisons, which is important for both acute and chronic poisoning.

It should be noted that unithiol reacts not only with free arsenic and metal-containing compounds, but also with poison, which has already reacted with thioenzymes. Therefore, the antidote is capable of not only protecting enzymes from the blocking effects of poisons, but also reactivating the mercapto groups of enzyme systems already inhibited by poison. Thiol drugs have both preventive and pronounced therapeutic effects.

The drug has the same effect as unithiol and is recommended for poisoning with thiol poisons, in particular lead and mercury. Succimer removes them from the body more evenly and affects the removal of microelements from the body less than unithiol (O. G. Arkhipova et al., 1975).

Oxathiol(L.A. Ilyin, 1976), which is an analogue of unithiol, turned out to be a more effective eliminator of radioactive polonium. Oxathiol reduces the degree of internal irradiation of the body by this emitter.

Known from monothioya penicillamine, which has complexing properties and is therefore recommended for mercury and lead poisoning(with saturnism) and their salts (S.I. Ashbel et al., 1974).

The complexing properties of penicillamine depend not only on the presence of an active sulfhydryl group, but are also associated with the stereochemical structure of its molecule, as well as the presence of a nitrogen atom and a carboxyl group, which provide the possibility of forming coordination bonds. Due to this, penicillamine forms stable complexes with lead, which cannot be said about unithiol.

The latter, being a powerful antidote for a number of thiol poisons, turned out to be ineffective against arsenic hydrogen. This is due to the fact that the mechanism of the toxic action of this arsine differs from that of other arsenic-containing substances.

The joint efforts of chemists and toxicologists resulted in the creation of an antidote mecaptida, which turned out to be effective against arsenic hydrogen poisoning.

Lipoidotropic properties, as well as high capillary activity, contribute to the penetration of the antidote into erythrocytes. Being easily oxidizable, the drug forms compounds containing disulfide groups that oxidize arsenic hydrogen and its metabolites - arsenic hydrates. The then reduced dithiol and the oxidation products of arsenous hydrogen form low-toxic cyclic thioarsenites, which are excreted from the body in the urine.

Unithiol, being a water-soluble dithiol and having reducing properties, cannot oxidize arsenic hydrogen. Therefore, applied in early dates intoxication with the latter, it even worsens the course and outcome of poisoning. In more late dates(5-7 days after poisoning), when the process of arsine oxidation has basically ended and arsenic-containing substances have formed, unithiol can be recommended as an eliminator that accelerates the removal of arsenic from the body.

For poisoning with many metals Along with thiol drugs (unithiol, succimer), complexons ( chelating agents) - a group of compounds capable of forming stable, low-dissociation complexes with many heavy metals, which are relatively quickly eliminated from the body. Of these, the most common thetacine-calcium(calcium disodium salt of ethylenediamine tetraacetic acid, EDTA), pentacin, etc.

Thetacine-calcium 20 ml of 10% solution is administered intravenously (in isotonic solution sodium chloride or in a 5% glucose solution), as well as orally in tablets of 0.5 g. Single dose 2 g, daily dose - 4 g.

Complexons are more often used in medical practice as eliminators of many toxic metals, alkaline and rare earth elements, as well as radioactive isotopes from the body.

In case of iron poisoning(iron sulfate, gluconate and lactate), the most effective is deferoxamine (desferol), a derivative of hydroxamic acid. This complexing agent is able to remove iron from the body in urine without affecting the content of other metals and trace elements. Consequently, thiol antidotes are not the only active detoxifying agents against arsenic-containing compounds and some heavy metals.

Taking into account that the neutralization of many halohydrocarbon derivatives in the body occurs mainly through their conjugation with mercapto groups of biosubstrates (glutathione, cysteine), monothiols such as cysteine and acetylcysteine.

Cysteine is an effective specific treatment for intoxication with aliphatic monohalocarbons; methyl bromide, metall chloride, ethyl chloride, methyl iodide, epichlorohydrin and other drugs (I. G. Mizyukova, G. N. Bakhishev, 1975).

It is important to note that cysteine has a positive effect when taken orally. This makes it possible to use it as a prophylactic agent, which is of great practical importance when carrying out fumigation work with toxic substances such as methyl bromide, methylallyl chloride, etc.

The mechanism of the therapeutic effect of cysteine in case of monohaloalkyl poisoning is considered mainly as a result of the competitive action of sulfhydryl groups of the drug and proteins, as well as amino acids of the body in relation to the haloalkyl as a highly reactive alkylating agent. As a result, low-toxic compounds are formed in the form of precursors of mercapturic acids (5-methylcysteine and 5-methylglutathione), which are excreted from the body in the urine.

Cysteine has an antidote effect against poisoning with many aliphatic monohalocarbons. With an increase in the number of halogen atoms in the molecule of a substance (for example, dichloroethane, dibromoethane, carbon tetrachloride), the effect of cysteine decreases or disappears.

Acetylcysteine- a highly effective therapeutic agent not only for poisoning with monohalide derivatives of aliphatic hydrocarbons, but also with dihalide derivatives. Thus, the detoxifying ability of acetylcysteine in case of poisoning with dichloro- and dibromoethane was shown for the first time (I. G. Mizyukova, M. G. Kokarovtseva, 1978). In this case, mainly toxic metabolites of dichloroethane (chloroethanol, monochloroacetic aldehyde, monochloroacetic acid), which are formed in the body, are neutralized.

The therapeutic effect of acetylcysteine is carried out in two ways: chemical conjugation of a toxic substance or its metabolites with cysteine (formed in the body from acetylcysteine), as well as an increase in the volume of enzymatic conjugation with reduced liver glutathione.

Acetylcysteine is more stable than cysteine, which is found both in the crystalline state and in the form of solutions.

An example of complex antidote therapy is specific agents used for poisoning with hydrocyanic acid and cyanide compounds.

Antidote therapy for cyanide poisoning consists of the sequential use of methemoglobin formers and sulfur-containing compounds, as well as carbohydrates.

Methemoglobin-forming drugs(amyl nitrite, propyl nitrite, sodium nitrite, etc.) convert hemoglobins into methemoglobin by oxidizing ferrous iron into ferric iron. The cyan ion, in turn, quickly and strongly reacts with the ferric iron of methemoglobin and forms cyanmethemoglobin, preventing the interaction of the poison with cntochrome oxidase, that is, preventing the blockade of the enzyme.

The resulting cyanmethemoglobin is an unstable compound, and the elimination of the cyan group can again have a toxic effect. But this process is already proceeding slowly. Therefore, along with methemoglobin formers, it is necessary to use agents that can react with cyanion. These include sulfur-containing substances (sodium thiosulfate) and carbohydrates (chromosmon or glucose).

Antidotes are used as antidotes, especially in cases where, when exposed to a particular chemical agent under the body’s conditions, the oxidation of the poison results in the formation of more toxic products than the original substance. The stabilizing effect of antioxidants lies in the fact that they enter into a competitive relationship with the oxidizing agent or together with the latter for enzymes involved in oxidation processes.

In the first option, the antioxidant prevents the oxidation of the poison and thereby reduces the amount of toxic products of its transformation circulating in the body.

For example, ethyl alcohol prevents the oxidation of methanol and, therefore, inhibits the formation of formaldehyde and formic acid, which cause the toxic effect of methyl alcohol.

In the second option, antioxidants, by breaking the oxidative chain, can suppress the formation of free radicals or direct the conversion of peroxides towards the formation of stable products.

Some vitamins and amino acids can be used as antioxidants. Thus, in an experiment on animals we obtained positive results when using tocopherol acetate in conditions of intoxication with organochlorine pesticides such as heptachlor and the gamma isomer of hexachlorane, as well as cystine, cystamine and methionine in benzene poisoning.

Along with antidotes aimed at neutralizing or binding poison, they are widely used in medical practice. medicinal preparations, the purpose of which is to prevent or eliminate the harmful manifestations of the action of poisons, are physiological or functional antidotes.

For the first time, it was used as a physiological antidote. atropine sulfate for fly agaric poisoning. It was found that the drug eliminates the effects of various cholinomimetic (acetylcholine, carbacholine, pilocarpine hydrochloride, arecoline, muscarine, etc.) and anticholinesterase substances (physostigmine salicylate, proserine, galantamine hydrobromide, organophosphorus compounds). Other anticholinergic drugs (scopolamine hydrobromide, platiphylline hydrotartrate, aprofen, diprofen, tropacin, etc.) have the same effect, but to a lesser extent than atropine sulfate.

A study of the mechanism of antagonism between cholinomimetic and anticholinergic substances showed that the latter have a greater affinity for cholinergic receptors compared to cholinomimetic substances. Thus, atropine sulfate can remove the effect of even several lethal doses of cholinomimetic and anticholinesterase substances, while the latter do not eliminate all the symptoms of atropine sulfate poisoning.

It is known that organic phosphorus compounds, which are used in many industries National economy, including agricultural ones, as pesticides (thiophos, metaphos, chlorophos, methylmercaptophos, karbofos, methylnitrophos, etc.), are strong cholinesterase inhibitors.

Due to phosphorylation, cholinesterase is inactivated and the ability to hydrolyze acetylcholine is lost. As a result of this, there is an excessive accumulation of acetylcholine in the places of its formation, which causes the toxic effect of organophosphorus compounds (OPC), which manifests itself in excitation of the nervous system, spastic state of smooth muscles, and convulsions of striated muscles.

In the mechanism of toxic action of FOS inhibition of cholinesterase plays an important and sometimes decisive role, but this process is not the only one. Along with it, there is a direct effect of the poison on a number of important systems and organs.

The use of anticholinergic drugs has become the basis for antidote therapy for poisoning with organophosphorus substances. Of these, the most widely used is atropine sulfate, which blocks the M-cholinoreactive systems of the body, and they become insensitive to acetylcholine. Being an antagonist of acetylcholine, the drug enters into a competitive relationship with it for the possession of the same receptor and removes the muscarinic-like effect of FOS (in particular, bronchospasm, reduces glandular secretion and salivation).

Atropine sulfate is more effective when administered for prophylactic purposes. For treatment it must be used in large doses and repeatedly, because the effect of the drug disappears faster than the effect of FOS. Under conditions of FOS intoxication, the tolerance of catropine sulfate increases sharply, so it can be administered in large quantities (20 mg or more per day).

Poisoning with FOS is also accompanied by a number of nicotine-like phenomena. Due to the fact that atropine sulfate has more pronounced properties to eliminate the muscarinic-like effect, other anticholinergic drugs (tropacin, aprofen, antispasmodic) that can reduce nicotine-like effects were subsequently proposed. To enhance the antidote effect of atropine sulfate as a peripheral anticholinergic, it is recommended to use central anticholinergics (amizil, etc.). This combination of anticholinergics has found practical use in the treatment of poisoning with organophosphate insecticides.

When FOS interacts with cholinesterases, the serine hydroxyl of the esterase center of the enzyme is phosphorylated by the same mechanism by which its acetylation occurs when interacting with acetylcholine. The difference is that dephosphorylation is much slower than deacetylation. This suggested the possibility of accelerating the dephosphorylation of inhibited cholinesterase using nucleophilic agents.

The process of reactivation of cholinesterase, inhibited by organophosphorus compounds, occurs under the influence of hydroxamic acid derivatives. These data made it possible to use reactivators capable of restoring the activity of cholinesterase inhibited by the poison as specific treatments for OP poisoning.

Reactivators displace FOS from compounds with cholinesterase and thereby restore its activity. As a result of this effect, cholinesterase is activated, the enzymatic hydrolysis of acetylcholine is resumed and, consequently, the process of chemical transmission of nerve impulses is normalized.

Currently, more active reactivators than hydroxamic acids have been obtained - TMB-4, which in the Soviet Union was called dipyroxime (isonitrosine), as well as salts 2-PAM (prali-doxime), MINA (monoisonitrosoacetone) and toxagonin (obidoxime). The drugs are capable of not only reactivating inhibited choline esterase, but also directly reacting with FOS, thereby forming non-toxic hydrolysis products. Unfortunately, the widespread use of cholinesterase reactivators in medical practice is largely hampered by their high toxicity.

Further research made it possible to obtain less toxic and more effective reactivators - diethixime, which is close in structure to acetylcysteine (V. E. Krivenchuk, V. E. Petrunkin, 1973; Yu. S. Kagan et al., 1975; N. V. Kokshareva, ^1975), as well as dialcob - a complex compound of cobalt (V.N. Evreev et al., 1968).

Hence, antidote therapy for FOS poisoning carried out in two directions - the use of anticholinergics and the use of cholinesterase reactivators. It is most effective to combine cholicolytics with reactivators.

To others example of physiological antagonism, used for therapeutic purposes, can also serve as competitive relationship between carbon monoxide and oxygen. Carbon monoxide has a much greater affinity for hemoglobin compared to oxygen. Therefore, when there are lower concentrations of carbon monoxide in the air compared to oxygen in the blood, a gradual accumulation of carboxyhemoglobin occurs and the content of oxyhemoglobin decreases.

For the successful use of oxygen in conditions of carbon monoxide poisoning, its concentration in the air must be thousands of times higher than the concentration of the poisonous gas. Oxygen at high concentrations can displace CO from the formed carboxyhemoglobin Hbco. The use of oxygen for carbon monoxide intoxication is considered as a specific therapy.

Bemegride, nalorphine hydrochloride and protamine sulfate act on the principle of functional antagonism.

Bemegrid is an antagonist of barbiturates, therefore it is used in the treatment of acute poisoning with these substances and hypnotics. Nalorphine hydrochloride is used as an antidote in conditions of acute poisoning with analgesic drugs (morphine hydrochloride, promedol, etc.).

Protamine sulfate- heparin antagonist, used as an antidote for poisoning with this anticoagulant.

Treatment of various chemical poisonings cannot be limited to the use of only specific antidotes, although in many cases they play a decisive role.

Only complex therapy using methods of enhancing natural and artificial detoxification of the body, existing antidotes, as well as pathogenetic and symptomatic agents aimed at protecting those organs and functions of the body that are selectively affected by a toxic substance, will contribute to the fastest recovery of the victim.

Treatment of acute poisoning, 1982