Chemical antidotes. Types of antidotes, their use

Events emergency care in case of acute poisoning, they are based on general principles:

1. Stopping further entry of “poison” into the body.

2. Use of antidotes.

3. Restoration and maintenance of impaired vitality important functions(breathing, blood circulation).

4. Detoxification.

5. Relief of leading intoxication syndromes.

When characterizing measures aimed at stopping the entry of a toxicant into the body during an emergency, one should certainly keep in mind the use of technical means of protection (gas masks, protective suits) and special (sanitary) treatment. The speedy evacuation of those affected from the outbreak also serves the purpose of stopping further exposure to the toxicant.

In addition, it should be remembered that a toxic substance can remain in the gastrointestinal tract for quite a long time. Therefore, measures aimed at stopping the further entry of a toxic substance into the blood should also include methods for removing non-absorbed toxicant from gastrointestinal tract. Among these therapeutic measures include tube gastric lavage with the introduction of a sorbent, high siphon enema, intestinal lavage.

Antidote (from anti dotum - “given against”) - (1) a drug used in the treatment of acute poisoning that is capable of (2.1) neutralizing a toxic substance, (2.2) preventing or (2.3) eliminating the toxic effect caused by it.

Conditions for classifying a medicine as an antidote.

1) therapeutic effectiveness medicine in the treatment of acute poisoning due to

2) mechanisms of antidote action, the main ones are

2.1) the ability to “neutralize” a toxic substance directly in internal environments body;

2.2) the ability of the antidote to protect the target structure from the action of the toxicant;

2.3) the ability to stop (eliminate) or reduce the severity of the consequences of damage to the target structure, which manifests itself more light current intoxication.

Conventionally, the following can be distinguished mechanisms of action of antidotes(according to S.A. Kutsenko, 2004):

1) chemical,

2) biochemical,

3) physiological,

4) modification of metabolic processes of a toxic substance (xenobiotic).

Chemical mechanism of action of antidotes is based on the ability of the antidote to “neutralize” the toxicant in biological media. Antidotes directly contact the toxicant and form non-toxic or low-toxic compounds that are quickly eliminated from the body. Antidotes bind not only to a toxicant “freely” located in biological media (for example, circulating in the blood) or located in a depot, but can displace the toxicant from its connection with the target structure. Such antidotes include, for example, complexing agents used for salt poisoning heavy metals, with which they form water-soluble, low-toxic complexes. The antidote effect of unithiol for lewisite poisoning is also based on a chemical mechanism.

Biochemical mechanism of antidote action can be roughly divided into the following types:

I) displacement of the toxicant from its connection with target biomolecules, which leads to the restoration of damaged biochemical processes (for example, cholinesterase reactivators, used for acute poisoning with organophosphorus compounds);

2) supply of a false target (substrate) for a toxicant (for example, the use of methemoglobin formers to create large quantities of Fe in acute cyanide poisoning);

3) compensation for the quantity and quality of the biosubstrate disturbed by the toxicant.

Physiological mechanism implies the ability of the antidote to normalize functional state body. These drugs do not enter into a chemical interaction with the poison and do not displace it from its connection with enzymes. The main types of physiological action of antidotes are:

1) stimulation of the opposite (balancing) function (for example, the use of cholinomimetics in case of poisoning with anticholinergics and vice versa);

2) “prosthetics” of a lost function (for example, in case of poisoning carbon monoxide carrying out oxygen barotherapy to restore oxygen delivery to tissues due to a sharp increase in oxygen dissolved in plasma.

Metabolism modifiers or

1) prevent the process of xenobiotic toxification - the transformation in the body of an indifferent xenobiotic into a highly toxic compound (“lethal synthesis”); or vice versa –

2) sharply accelerate the biodetoxification of the substance. Thus, in order to block the toxification process, ethanol is used in acute methanol poisoning. An example of an antidote that can accelerate detoxification processes is sodium thiosulfate for cyanide poisoning.

Antidotes (antidotes) are means used to treat poisoning in order to neutralize the poison and eliminate the effects it causes. pathological disorders. The use of antidotes in the treatment of poisoning does not exclude a number of general measures aimed at combating intoxication and carried out in accordance with general principles treatment of poisoning (cessation of contact with poison, removal of it, use of resuscitation means, etc.).

Some antidotes are used before the poison is absorbed, others after its resorption. The first includes antidotes that bind or neutralize poison in the stomach, skin and mucous membranes, the second includes substances that neutralize poison in the blood and biochemical systems of the body, as well as counteracting toxic effects due to physiological antagonism (Table 1).

Neutralization of unabsorbed poison can be carried out by adsorption or chemical interaction with subsequent removal from the body. Most effective joint use appropriate antidotes, in particular the use of an oral mixture consisting of activated carbon, tannin and magnesium oxide (MAC). Application of antidotes this kind it is advisable to combine with all measures aimed at removing unabsorbed poison ( drinking plenty of fluids, gastric lavage, emetics). In this case, it is advisable to use chemical antidotes for gastric lavage.

Resorptive antidotes are designed to neutralize absorbed poison. Neutralization of poison in the blood can be achieved by using chemical antidotes. Thus, unithiol (see) neutralizes arsenic and other thiol poisons. Calcium disodium salt of ethylenediaminetetraacetic acid (see Complexons) forms non-toxic compounds with ions of alkaline earth and heavy metals. Methylene blue (see) in large doses converts hemoglobin into methemoglobin, which binds hydrocyanic acid. The use of chemical antidotes is effective only in the initial period of intoxication, when the poison has not yet had time to interact with the biochemically important systems of the body. In this regard, their use has some limitations. In addition, the number of chemical antidotes is relatively small.

For these reasons greatest distribution have antidotes, the action of which is directed not at the toxic agent itself, but at the toxic effect caused by it. The antidote effect of such substances is based on the competitive relationship between the antidote and the poison in action on the biochemical systems of the body, as a result of which the antidote displaces the poison from these systems and thereby restores their normal activity. Thus, some oximes (pyridinaldoxime-methodide, etc.), reactivating cholinesterase blocked by organophosphorus poisons, restore the normal course of impulse transmission in the nervous system. The action of such antidotes is strictly selective and therefore very effective. However, the competitive relationship between poison and antidote in the action on the biochemical systems of the body characterizes only one of possible options mechanism of action of antidotes. Much more often we're talking about about the functional antagonism between poison and antidote. In this case, the antidote acts on the body in the opposite direction compared to the poison or indirectly counteracts the toxic effect, affecting systems not directly affected by the poison. In this sense, many symptomatic remedies should also be considered antidotes.

See also: Antidotes, Agents, Poisoning, Poisonous Substances, Food poisoning, Poisonous animals, Poisonous plants, Agricultural pesticides, Industrial poisons.

Direct action - there is a direct chemical or physical-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 non-specific fixation ( sorption) 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 possible with skin, mucous membranes, from 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), zinc oxide, ion exchange resins.

1 gram of active carbon binds several hundred milligrams of strychnine.

Chemical antidotes - as a result of the reaction between the poison and the antidote, a non-toxic or low-toxic compound is formed (due to strong covalent ionic or donor-acceptor bonds). They can act anywhere - before the poison penetrates the blood, during the circulation of the poison in the blood and after fixation in the tissues.

Examples of chemical antidotes:

a) to neutralize acids that have entered the body, salts and oxides are used, giving aqueous solutions alkaline reaction - K 2 CO3, NaHCO 3, MgO ;

b) in case of poisoning with soluble silver salts (for example, AgNO3 ) are used NaCl , which forms insoluble with silver salts AgCl ;

c) in case of poisoning with poisons containing arsenic, use MgO , ferrous sulfate, which chemically bind it;

d) in case of poisoning potassium permanganate KMnO4 , which is a strong oxidizing agent, use a reducing agent - hydrogen peroxide H2O2 ;

e) in case of poisoning with alkalis, weak organic acids (citric, acetic) are used;

f) in case of poisoning with hydrofluoric acid salts (fluorides), use calcium sulfate CaSO4 , the reaction produces a slightly soluble CaF2 ;

g) in case of poisoning with cyanides (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. 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. The mechanism of their action is presented in the diagram.

The resulting poison-antidote complex is removed from the body without causing harm to it.

Another class of antidotes direct action - 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 salts are ethylenediamine-

tetraacetic acid (EDTA), primarily sodium ethylenediaminetetraacetate.

Lesson topic: Medical supplies 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 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 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. Facilities prehospital treatment OLB.

Antidotes, mechanisms of antidote action

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

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 specific action 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 a small number of 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 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 a large surface area, 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.

Division of antidotes into specified groups conditionally, since many of them can be drugs mixed type, 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 great breadth therapeutic action; it can be administered parenterally, through the mouth. The drug is stable when stored as in crystalline state, and in the form of solutions. The creation of this antidote was made possible thanks to the discovery of the mechanism toxic effect 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 important 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 means of eliminating 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 internal exposure body with 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 from the body of many toxic metals, alkaline and rare earth elements, as well as radioactive isotopes.

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 prophylactic, 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- highly efficient remedy not only in case of 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, ethanol 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 a few lethal doses 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 nervous system, spastic state of smooth muscles, 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 katropine sulfate increases sharply, so it can be administered into 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 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, if there is more than low concentrations Carbon monoxide, compared to oxygen in the blood, causes a gradual accumulation of carboxyhemoglobin 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 acute poisoning these substances and sleeping pills. 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 various poisonings chemicals cannot be limited to the use of only specific antidotes, although in many cases they play a decisive role.

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

Treatment of acute poisoning, 1982