Organophosphorus compounds and their determination in foodstuffs. FOS structure. Properties of organophosphorus compounds. The mechanism of action of organophosphorus compounds

Many FOS, due to their special chemical affinity for cholinesterase, inhibit, i.e., block, its molecules through interaction with the esterase center. As can be seen from the diagram below, the organophosphorus poison molecule reacts with the hydroxyl group of the enzyme, and its anionic center does not take part in the reaction:

However, at the beginning of the 1950s, in Tammelin's laboratory in Sweden, such OPs were synthesized that also react with the anionic center of the enzyme. At the same time, chemists proceeded from the assumption that if the poison is similar in structure to the natural substrate of cholinesterase (acetylcholine), then it will have a stronger inhibitory effect on this enzyme. Indeed, compounds that contain a choline residue in their composition, such as methylfluorophosphorylcholine, turned out to be such powerful anticholinesterase substances. It is quite natural that when it interacts with cholinesterase, the positively charged nitrogen atom will react with the anionic center of the enzyme. This provides additional contact of the poison with the active surface of cholinesterase and makes the connection between them stronger:

One can also imagine simultaneous inhibition by one molecule of methylfluorophosphorylcholine of two molecules of the enzyme: one at the anionic, the second at the esterase center. Be that as it may, Tammelin's poisons turned out to be ten times more toxic than even such a potent FOS as sarin. The resulting phosphorylated cholinesterase, in contrast to the acetylated one, is a sufficiently strong compound and does not undergo spontaneous hydrolysis. It turned out that the process of cholinesterase inhibition is a two-stage process. Initially, at the first stage, a reversible, i.e., unstable, blocking of the enzyme occurs, and only at the second stage does the enzyme block irreversibly. Both of these steps are the result of a complex, not yet fully understood molecular rearrangement in the FOS-cholinesterase complex. Running a little ahead, we note the significance of this phenomenon for the practice of using some antidotes, the effect of which is to break the chemical bond between the poison and the enzyme. Thus, under the influence of anticholineste - various substances, the destruction of acetylcholine molecules is inhibited and it continues to have a continuous effect on cholinergic receptors. It follows that FOS poisoning is nothing more than a generalized overexcitation of cholinergic receptors caused by intoxication with endogenous, i.e., having an internal origin, acetylcholine. That is why the main symptoms of FOS poisoning can be interpreted as a manifestation of excessive, inappropriate for the body activity of a number of structures and organs, which is provided by acetylcholine mediation (first of all, this is the function of nerve cells, striated and smooth muscles, and various glands).

Currently, there is evidence of a direct excitatory effect of some FOS on cholinergic receptors. Thus, it is not excluded that FOS have a toxic effect, bypassing the cholinesterase mechanism:

In the last 10–15 years, toxicologists have increasingly paid attention to this feature of the mechanism of the effect of OPs on biostructures. In particular, their non-anticholinesterase action is manifested in the direct excitation of H-cholinergic receptors, on which, as experimental data show, the nicotine-like effects of FOS in turn depend. At the same time, their muscarino-like action is now considered with good reason to be the result of cholinesterase inhibition.

As for the comparative severity of muscarinic and nicotinic effects in various anticholinesterase substances, then, according to the study of V. B. Prozorovsky, * 3 groups can be considered:

* (Prozorovsky VB Questions of the mechanism of action and age-related toxicology of anticholineterase drugs. Abstract doc. dis. L.. 1969)

• 1) causing predominant excitation of M-cholinergic receptors (ezerin, nibufin, chlorophos);
• 2) causing excitation of both M- and H-cholinergic receptors (phosphacol, armin, diisopropylfluorophosphate);
• 3) causing a predominant effect on H-cholinergic receptors (prozerin, thiophos, mercaptophos).

From the foregoing, it follows, at least theoretically, that in case of poisoning with anticholinesterase poisons, including FOS, antidotes could be:

• 1) substances that enter into direct chemical interaction with poisons;
• 2) substances that inhibit the synthesis and release of acetylcholine into the synaptic cleft;
• 3) substances that replace the enzyme damaged by poisons (i.e., cholinesterase preparations);
• 4) substances that prevent the contact of the poison with the enzyme and thereby protect it from toxic effects;
• 5) substances that prevent the contact of acetylcholine with the cholinergic receptor;
• 6) substances that restore the activity of the enzyme by displacing the poison from its surface (i.e., reactivating the structure of cholinesterase).

Numerous toxicological experiments have shown that all these substances have some degree of specific effect on the toxic process, but the last 2 groups of antidotes are of the greatest practical importance. Let us consider in more detail the mechanisms of their action.

Organophosphorus compounds have been used as insecticides (chlorophos, karbofos, fosdrin, leptophos, etc.), drugs (phosphacol, armin, etc.), the most toxic representatives of the group have been adopted by the armies of a number of countries as chemical warfare agents (sarin , soman, tabun, Vx). The defeat of FOS people is possible in case of accidents at their production facilities, when used as agents or sabotage agents.

For the first time, FOS were synthesized by Tenar in 1846. In our country, the founder of the chemistry of FOS was A.E. Arbuzov, who in 1905 proposed a new method for their synthesis. Attention was paid to the toxic properties of these compounds only in 1932, when Lange and Krüger first described the symptoms of poisoning with dimethyl and diethyl fluorophosphate, synthesized in the process of searching for new insecticides. The indisputable practical significance of such agents was the reason for large-scale research aimed at a comprehensive study of a new class of biologically active substances. So, in a short period of time, only in Germany, in the Schrader laboratory, in order to find new means of combating harmful insects, more than 2000 FOS were synthesized and studied, many of which were highly toxic to mammals. This was the reason for the creation on their basis of new models of chemical weapons. By the beginning of World War II, German chemists had synthesized such highly toxic poisonous substances as tabun, sarin, and somewhat later, soman. At the same time, the prospects for finding even more toxic compounds for humans were determined, which was implemented in practice by Tammelin (1955), who synthesized methylfluorophosphorylcholine, which was the prototype of a new group of OPs, designated as V-gases (Vx). In the 70s - 80s of the 20th century, a technology was developed for the use of FOV in the so-called binary ammunition. At the same time, two relatively slightly toxic chemical compounds are stored, transported and placed in ammunition separately. The components are mixed only after the shot and form a highly toxic agent on the way to the target, during a chemical reaction. Extremely high toxicity and peculiarities of physicochemical properties, which make it possible to quickly create extensive foci of chemical contamination, until recently made POVs (sarin, soman, V-gases) the most dangerous of all known agents. In accordance with international agreements, stocks of OPs in most countries of the world are subject to destruction.

Currently, research in the field of creating new biologically active substances based on FOS continues. Now, as in the early 30s of the 20th century, this is mainly the search for insecticides, of which hundreds of names are known today.

Physicochemical characteristics. Toxicity

FOS - derivatives of acids of pentavalent phosphorus. All toxic compounds of phosphoric (1), alkylphosphonic (2) and dialkylphosphinic (3) acids have the structure:

Phosphorus is double bonded to an oxygen or sulfur atom; two bonds - with alkyl-, alkoxy-aryl-, mono- or dialkylamino groups, etc. (R 1 , R 2); the fifth (X) is saturated with a group that splits off relatively easily from the phosphorus atom (F - , CN - , -OR, -SR, etc.). Due to the valence released at the same time, FOS interacts with the active centers of a number of enzymes.

The structural formulas of some FOS are shown in Figure 46.

Figure 46. Structure of some organophosphorus compounds

The biological activity of FOS, including toxicity, depends on their structure (Table 43).

Table 43

Toxicity (LD 50) of some FOS for white mice

All FOS are highly reactive. Of particular importance are the reactions of phosphorylation, hydrolysis and oxidation, since it is these reactions that determine the resistance of toxicants in the environment, are related to the metabolism and mechanism of the toxic action of poisons in the body, and some principles of degassing, detection, antidote prevention and therapy of intoxications are based on them.

FOS easily donate electrons, actively react with electrophilic groups of other compounds and, due to this, phosphorylate many substances (amino acids, polyphenols, hydroxylamine, hydroxamic acids, etc.).

As an example, we give the reaction of sarin phosphorylation of hydroxylamine:

All FOS, when interacting with water, undergo hydrolysis with the formation of non-toxic products. The rate of hydrolysis of FOS dissolved in water is different (for example, sarin hydrolyzes faster than soman, and soman faster than V-gases).

In general form, the hydrolysis reaction can be represented as follows:

The reaction of FOS hydrolysis with anhydride bond cleavage also occurs in the body, both spontaneously and with the participation of enzymes.

As a result of the oxidation reaction, FOS are also destroyed, however, in some cases (during the oxidation of phosphothionates to phosphates), some substances even increase their activity. This is illustrated by the example

The toxicity of paraoxon to mammals and humans is higher than that of parathion.

The most important properties of organophosphorus poisonous substances are presented in tables 44-46.

Table 44

Main properties of sarin

Table 45

Basic properties of soman

Phosphorus (Phosphorus), P - does not occur in nature in its pure form, of the phosphorus compounds, calcium phosphate - Ca 3 (PO 4) 2, the main component of apatites and phosphorites, is of the greatest importance.

Phosphorus is a part of the animal body - calcium phosphate - the basis of bone tissue, phosphorus in the form of various compounds is found in the blood and lymph. Phosphorus is essential for the life of animals and plants.

The most important is white and red phosphorus.

White phosphorus- soft, with the smell of garlic, unstable, flammable, very poisonous

red phosphorus- solid powder of dark crimson color. Non-toxic, less reactive, non-flammable.

Physico-chemical properties of phosphorus compounds

Inorganic compounds of phosphorus.

Zinc phosphoride Zn 3 P 2 - grayish-black powder, with the smell of garlic, insoluble in water, alcohol, good in all acids

Contains 14% phosphorus, 70-80% zinc. Used as a zoocide

Phosphates- salts of phosphoric acid. Calcium phosphate is of importance - a highly soluble salt - applied fertilizer - superphosphate.

Organic phosphorus compounds

A large number of organophosphorus compounds of complex composition with various technical names. They are simply called FOS. They are widely used in medicine, veterinary medicine, agriculture and industry.

The chemical structure of FOS s is expressed by the following chemical formula:

R 1 and R 2 are different or identical alkyls, alkoxyls, alkylamines. X is the residue of an inorganic or organic acid. It is this part that determines the physiological activity of the entire compound (fluorine, halogens, CN, and other groups).

Organic compounds can be classified according to the nature of their insecticidal properties. One of them has a contact action (metafos, karbofos), others have a systemic effect.

These compounds are adsorbed by plant sap and remain active against pests.

Organophosphorus compounds(FOS) are high-molecular esters of phosphorus acids (phosphoric, pyrophosphoric, phosphorous, phosphonic, phosphinic, thio- and dithiophosphoric, thiophosphorous) and their sulfur and nitrogenous derivatives.

In crop and livestock production, more than 25 FOS are used, which are divided into:

1. preparations of contact action, causing the rapid death of insects and ticks at the time of contact with them,

2. systemic preparations that are absorbed through the leaves and root system and circulate for a long time together with plant sap, which become toxic to sucking and gnawing insects for up to 2 months without a harmful effect on the plants themselves.

To drugs contact actions include: chlorophos, DDVF, metaphos, diphos, etafos, cyodrin, karbofos, diazinon, dursban, trichlormetafos, etc.

To drugs systemic actions include: gardona, selekron, tokution, fozalon, butifos; to drugs contact system actions: antio, phosphapid, phthalophos and heterophos.

Pathogenesis. Organophosphorus compounds are highly lipidotropic substances. They are rapidly absorbed through the mucous membranes of the digestive organs, respiratory organs, through the skin, accumulate mainly in the liver, brain, cardiac and skeletal muscles, kidneys, internal adipose tissue, excreted in milk, urine, feces.

The biochemical mechanism of the toxic action of FOS on the animal organism is based on the selective blockade of the enzyme of the nervous tissue - acetylcholinesterase, as a result of which the mediator acetylcholine accumulates in the cholinergic synapses, which, being what leads to depolarization of the membranes of nerve cells, a drop in the resting potential and a sharp increase in the process of excitation of the central nervous system.

Organophosphorus pesticides in toxicological terms are nerve poisons, in the action of which there are:

muscarinic,

nicotine-like

curariform phenomena.

Muscarinic phenomena include: miosis, bronchospasm, salivation, increased sweating, increased intestinal motility, diarrhea.

Nicotine-like- tremor of skeletal muscles, cramps of the limbs, increased blood pressure, excitation and paralysis of the central nervous system.

Curarepodupdatese- weakening of the tone of the skeletal muscles, especially the neck muscles, weakening of the tone and paralysis of the muscles of the chest.

Cattle, sheep and goats are more sensitive to the toxic effects of FOS than pigs, chickens, ducks and horses. Young animals are more sensitive than adults.

SimPthen we. Poisoning of animals with FOS can occur:

lightning fast

chronically.

Mol n ion-bearing poisoning occurred 15-20 minutes after treatment, especially in animals that licked the treated skin areas on themselves or other animals. They were manifested at first by a sharp motor excitation, by the fall of animals; often there was a characteristic pose of a "prayer", hypersalivation, hyperkinesis and paralysis of the tongue, miosis, and shortness of breath developed. There were convulsions of the limbs and paralysis, frequent defecation and urination. Animals die after 1-1.5 hours in a coma with symptoms of asphyxia and paralysis of the muscles of the limbs and chest.

ABOUT With three severe poisoning in animals, anxiety, shyness, exacerbation of the reaction to sound and light irritations are noted, which is replaced by the extinction of visual and auditory reflexes and pain sensitivity of the skin; there is a diffuse tremor of the skeletal muscles, coordination of movement is disturbed, unsteadiness is noted, animals often fall. Convulsions of the extremities of a clonic and tonic nature are expressed.

Middle severity in animals, short-term salivation, tremor of skeletal muscles, periodic attacks of convulsions, sometimes impaired coordination of movement, decreased tone of skeletal muscles, bronchospasm, frequent defecation and urination are observed. After 1-2 days, these phenomena disappear, and the animals recover clinically after 5-6 days.

Easy degree of poisoning in animals, periodic slight salivation, coughing, bouts of difficulty breathing, lowering the tone of skeletal muscles, and increased intestinal motility are observed. These phenomena disappear completely within a day.

Chronic Intoxication in animals decreases the activity of food intake, there are general oppression, low mobility, weakening of muscle tone, body weight decreases, progressive emaciation is noted. In addition, the animals have constriction of the pupils, frequent urination, liquefaction of feces. Chere; 6-7 months in sheep, paresis of the muscles of the limbs and asymmetry of the tone of the cervical muscles develop, which leads to a curvature of the neck in sheep and a bowing of the head in moles. Often, skeletal muscle tremors and attacks of clonic-tonic convulsions are noted. The death of animals occurs with significant emaciation and a decrease in body temperature.

PaTOlohanatomchesToie changes. In animals with OP poisoning, hemodynamic disorders of vital organs, congestion, perivascular edema and diapedetic hemorrhages in the liver, kidneys, lungs, heart muscle, thyroid and pancreas, dystrophic and necrotic changes in the ganglion cells of the brain are pronounced.

Diagnostics FOS poisoning is carried out on the basis of:

a) a characteristic complex of neuroparalytic clinical symptoms (miosis, lacrimation, salivation, bronchospasm phenomena, impaired coordination, extinction of reflexes, tremor and convulsions of skeletal muscles, diarrhea, paresis and paralysis of the limbs, asphyxia);

b) the results of post-mortem examination of dead animals;

c) chemical-analytical detection of OP residues in the contents of the gastrointestinal tract, in adipose tissue, brain, liver and kidneys, as well as in feed and water, taking into account anamnestic data on the use of OP in farms and animal disease conditions.

Treatment animals in case of OPC poisoning is based on the complex use of anticholinergic drugs in combination with cholinesterase reactivators. Anticholinergic drugs include atropine sulfate, tropazgna sulfate, phospholithine (an atropine-like drug).

Dipyroxime (TMB-4), toxogonine and diethixime are known as cholinesterase reactivators. The antidote effect of atropine, tropacin and dipiroxime is based on their antidepolarizing effect on various FOS.

The most widely tested on all types of animals during experimental intoxication with various FOS, atropine - an anticholinergic of peripheral action,

tropacin is a centrally acting anticholinergic and

cholinesterase reactivator - dipiroxime, by intramuscular injection in one complex aqueous solution.

In practical terms, it is possible to pre-prepare the antidote mixture of these drugs as follows. First, a 10% aqueous solution of tropacin and a 20% aqueous solution of dipiroxime are prepared, and then, as necessary, they are mixed in equal volumes. Atropine sulfate is added to the mixture of these solutions at the rate of obtaining a 1.5% solution.

The antidote mixture of these drugs is used intramuscularly, according to the calculation in table 6, in the following single doses:

In practice, a mixture is prepared:

10% tropacin solution

20% dipyroxime solution

1.5% atropine solution

i / m, once:

young stock 1-2

young growth 10

sheep, goats 4

youngster 2

pigs 5-10

youngster 3

dogs 1.5

rabbits - 1.0

Prevention poisoning of animals FOS should include the following measures:

1. Strict observance of the approved sanitary rules and safety instructions for the storage, transportation and use of pesticides in agriculture;

2. feeding green fodder and plants not earlier than 6 days after treatment with contact drugs and not earlier than 45 days after treatment with systemic drugs;

3. the content of residual amounts of FOS in feed (mg/kg) should not exceed: for antio 2, butifos 3, dursban 0.2, karbofos 2 for dairy cattle and egg-laying birds and 5 for fattening animals; metaphos in feed for dairy cattle and egg-laying birds is not allowed, and for fattening animals should not exceed 0.5; methylmercaptophos 1; methylnitrophos 1 for dairy cattle and 2 for fattening animals; phosphamide 2; phthalophos 1 for dairy cattle and 2 for fattening animals; chlorophos 1 for dairy cattle and 3 for fattening cattle.

5. Spray equipment must not be washed! reservoirs for watering animals, keeping waterfowl and breeding fish.

Veterinary and sanitary examination raw animal products.

Slaughter of animals, including birds for meat, may be permitted no earlier than 25 days after suffering poisoning with organophosphorus pesticides.

In case of forced slaughter of animals in case of poisoning with OPs, it is necessary to carry out chemical and analytical studies of the residual amounts of OPs and be guided by the safe maximum allowable levels (MRL) for the content of pesticides in food products, approved by the USSR Ministry of Health on July 28, 1983.

According to the specified list of MRLs for pesticides, the content of abata (diphos) in meat and eggs in the amount of 1 mg / kg, amidophos (ruelen) in meat and meat products 0.3, baytex 0.2, dursban 0.1, trolene 0.3 is allowed mg/kg; the presence of DDVF and chlorophos in these products is not allowed.

It should be emphasized that the residual amounts of organophosphorus pesticides in meat during cooking for 2-5.5 hours are not destroyed and have a toxic effect on laboratory animals with repeated feeding.

In this regard, meat and meat products containing residual amounts of organophosphorus pesticides in excess of permissible standards are subject to technical disposal.

Phosphorus organic compounds belong to the category of pesticides, which are designed to destroy weeds, insects and rodents.

These insecticides are widely used not only in the agricultural industry, but also in everyday life. Many varieties of FOS are highly toxic and can cause serious poisoning both when they enter the body, and when they come into contact with the mucous membranes of the nasopharynx and eyes, and even with intact skin.

FOS poisoning statistics

Acute intoxication with organophosphorus compounds actually ranks first among others, not only in severity, but also in frequency. The lethality of such poisonings is almost 20%, and the frequency is about 15% of all cases of intoxication. It is of interest that alcohol is a kind of antidote for poisoning with organophosphorus compounds. In victims who were in a state of severe alcohol intoxication at the time of poisoning with insecticides, the disease proceeds much easier (convulsions and paresis of the respiratory muscles are absent). However, hemodynamic disturbances may be more pronounced.

Possible Causes of Insecticide Poisoning

Poisoning with organophosphorus compounds can be associated with professional activities and occur as a result of non-compliance with the rules for handling toxic substances. The negligence of one or more people can result not only in serious poisoning for themselves, but also lead to mass intoxication.

In addition to organophosphorus compounds, they can be of a household nature. The causes of accidents can be different, for example:

• lack of designations on containers with poisonous liquid stored at home (a person can take poison inside by mistake, or intentionally for the purpose of intoxication);
• storage of insecticides in places accessible to children (children are very curious by nature, and even if the container with the pesticide is signed, a small child can still drink a dangerous liquid and get acute poisoning);
• non-compliance with safety regulations (neglect of protective equipment when using toxic substances in the household, such as a respirator, gloves, goggles, protective clothing).

When organophosphorus compounds enter the human body in significant doses, they can cause damage to various parts of the central nervous system, which leads to neuritis, paralysis and other serious consequences, up to death.

Classification of organophosphorus compounds according to the degree of toxicity

• the most toxic - insecticides based on thiophos, metaphos, mercaptophos, octamethyl;
• highly toxic - preparations based on methylmercaptophos, phosphamide, dichlorophosphate;
• moderately toxic - chlorophos, karbofos, methylnitrophos and insecticides based on them, as well as saiphos, cyanophos, tribufos;
• low-toxic - demufos, bromophos, temefos.

Symptoms of FOS poisoning

According to the severity of poisoning are divided into 3 stages. The clinic of organophosphorus poisoning is as follows:

With a mild degree of intoxication (stage I):

• psychomotor agitation and feeling of fear;
• labored breathing;
• dilated pupils (miosis);
• spastic pain in the abdomen;
• increased salivation and vomiting;
• severe headaches;
• high blood pressure;
• profuse sweating;
• hoarse breathing.

In moderate form (stage II):

• may persist or gradually give way to lethargy, and sometimes to a coma;
• pronounced miosis, pupils stop responding to light;
• symptoms of hyperhidrosis are maximally manifested (salivation (salivation), sweating, bronchorrhea (sputum secretion from the bronchi) is maximized);
• fibrillary twitching of the eyelids, chest muscles, legs, and sometimes all muscles;
• periodic appearance of general hypertonicity of the muscles of the body, tonic convulsions;
• sharply increases the tone of the chest;
• blood pressure reaches maximum levels (250/160);
• involuntary defecation and urination, accompanied by painful tenesmus (false urges).

Severe form of poisoning (stage III):

• the patient falls into a deep coma;
• all reflexes are weakened or completely absent;
• severe hypoxia;
• pronounced miosis;
• persistence of symptoms of hyperhidrosis;
• change of muscle hypertonicity, myofibrillation and tonic convulsions by paralytic muscle relaxation;
• breathing is strongly depressed, the depth and frequency of respiratory movements are irregular, paralysis of the respiratory center is possible;
• heart rate drops to critical levels (40-20 per minute);
• tachycardia increases (more than 120 beats per minute);
• blood pressure continues to fall;
• toxic encephalopathy develops with edema and numerous diapedetic hemorrhages, predominantly of a mixed type, caused by paralysis of the respiratory muscles and depression of the respiratory center;
• the skin becomes sharply pale, cyanosis appears (skin and mucous membranes become cyanotic).

Consequences of poisoning with phosphorus-containing insecticides

When organophosphorus compounds enter the body, first aid, provided in a timely and correct manner, is one of the fundamental factors determining the further course of the disease. The diagnosis of FOS intoxication is relatively easy to make according to the characteristic clinical picture, but whether the outcome is favorable or the victim dies depends largely on the subsequent actions of physicians.

Due to the high toxicity, organophosphorus compounds, when ingested, cause irreparable harm to almost all vital organs and systems. In this regard, even with a favorable outcome, it is not possible to completely restore the functions of some organs.

Among the complications that are usually accompanied by severe intoxication with organophosphorus substances are pneumonia, rhythm and conduction disturbances of the heart, acute intoxication psychoses, etc.

Course of the disease

During the first few days after poisoning, the patient is in a serious condition due to cardiovascular collapse. Then comes the gradual compensation and his health improves. However, after 2-3 weeks, the development of severe toxic polyneuropathy is not excluded. In some cases, a number of cranial nerves may be involved in the process.

The course of such late polyneuropathies is quite protracted, sometimes accompanied by persistent movement disorders. The restoration of the functions of the peripheral nervous system is going poorly. There may also be a recurrence of acute disorders such as cholinergic crises. This is explained by the fact that the deposited organophosphorus compound is “ejected” from various tissues into the circulatory system.

Treatment

When serious organophosphorus poisoning occurs, first aid should include aggressive cleansing of the digestive tract by gastric lavage with a tube, forced diuresis, etc., maintenance of breathing, and the use of specific antidotes. Further, a set of resuscitation measures is applied, including pharmacotherapy, aimed at maintaining and restoring damaged body functions, including measures to restore cardiac activity, treatment of homeostasis disorders and exotoxic shock.

Recovery of respiratory function

Organophosphorus compounds ingested in large quantities usually cause respiratory distress, the causes of which are excessive oropharyngeal secretion, bronchospasm and paralysis of the respiratory muscles. In this regard, the first thing that doctors try to do is to restore airway patency and provide adequate ventilation. In the presence of abundant vomit and oropharyngeal discharge, aspiration is used (liquid sampling using a vacuum). In case of acute poisoning with FOS, resuscitation measures include tracheal intubation, artificial ventilation of the lungs.

Antidote therapy

The use of antidotes (antidotes) is an essential part of emergency pharmacotherapy for acute poisoning. The drugs of this group affect the kinetics of a toxic substance in the body, ensure its absorption or elimination, reduce the effect of toxins on receptors, prevent dangerous metabolism and eliminate dangerous disorders of the vital functions of the body caused by poisoning.

An antidote for organophosphorus poisoning is taken along with other specialized drugs. Pharmacotherapy is carried out in parallel with general resuscitation and detoxification therapeutic measures.

It must be remembered that if there is no possibility of urgent resuscitation, then only an antidote of organophosphorus compounds can save the life of the victim, and the sooner it is administered, the more likely the victim will have a favorable outcome of the disease.

Classification of antidotes

Antidotes are divided into four groups:

• symptomatic (pharmacological);
• biochemical (toxicokinetic);
• chemical (toxicotropic);
• antitoxic immunopreparations.

When the first symptoms of organophosphorus poisoning appear, even at the stage of hospitalization of the victim, antidotes of the symptomatic and toxicotropic groups are used, since they have clear indications for use. Drugs with a toxicokinetic action require strict adherence to the instructions, since emergency doctors cannot always accurately determine the indications for their use. Antitoxic immunopreparations are used in a medical institution.

Specific therapy for acute organophosphorus poisoning

The complex of measures includes the use of anticholinergics (drugs such as atropine) in combination with cholinesterase reactivators. In the first hour after hospitalization of the patient, intensive atropinization is carried out. Atropine in large doses is administered intravenously until the symptoms of hyperhidrosis are relieved. There should also be signs of a mild overdose of the drug, expressed by dry skin and moderate tachycardia.

To maintain this state, atropine is administered repeatedly, but in smaller doses. Supportive atropinization creates a persistent blockade of the m-cholinoreactive systems of the damaged organism against the action of the acetylcholine preparation for the time necessary for the destruction and elimination of the toxin.

Modern ones are able to effectively activate the inhibited cholinesterase and neutralize various phosphorus-containing compounds. When carrying out specific therapy, cholinesterase activity is constantly monitored.

Phosphorus organic compounds, in the everyday life of FOS, are substances in which the phosphorus atom is directly connected to the carbon atom. Phosphates are most widely used in agriculture, the second area of ​​application is household preparations, veterinary medicine. And far from the last role is played by military organophosphorus substances, which in their essence are chemical weapons.

Despite the danger of phos poisoning, these compounds are still the most used in agriculture. To date, there are more than 25 trade names in this group, which include insecticides, herbicides and acaricides. That is why it is so important to know what symptoms are caused by organophosphorus poisoning.

A similar mechanism of action and clinical picture causes a common structure for all FOS. All organophosphorus compounds have an alkoxyphosphoryl part of the molecule, which looks like P=O- and P=S-H groups. R1 and R2 are oxymethyl and hydroxyethyl radicals, and X is the same acid residue that gives the variants for the existence of various FOS.

Modern types of FOS

The chemical industry does not stand still, and synthetic pyrethroids have replaced the usual insecticides and acaricides. These compounds are thought to be less toxic and much less likely to cause phos poisoning.

It is important to know that the most highly toxic FOS have disappeared from the modern “List of chemical protection products”: metaphos, thiophos, DCVF, phtalophos, heterophos, coral, methyl mercaptophos, sometimes chlorophos can be found.

In veterinary medicine, agriculture and household plots, more modern fosbecid, diazole, phosphamide, zolon, karbofos are used .... The priority for agricultural needs are FOS, which have a systemic effect:

• Dimethoate - plants are sprayed with this substance, after which their juice becomes toxic to any sucking pests.
• Diazinon - used not only for spraying, but also for incorporation into the soil. Thus, the drug is absorbed by the root system and for several weeks the seedlings become inaccessible to pests.
• Fenitrothion - is used on an industrial scale to protect fruit, cereals, citrus and industrial crops. Vegetable crops are treated with this agent only at the stage of seed cultivation.

When using FOS in home gardens, it is very important to understand that most drugs are also based on diazinon, malathion and pyrimiphosmethyl, that is, they are highly toxic to humans!

The pathogenesis of poisoning

To understand how poisonous organophosphorus compounds are, and what kind of antidote exists, it is necessary to understand the mechanism of their action. The high permeability is due to the distribution coefficient between the two media: water and oil. This coefficient allows penetration through absolutely healthy skin, any biological membranes and even the blood-brain barrier.

Most often, intoxication occurs:

1. Orally, that is, through the oral cavity.
2. Inhalation - inhalation of vapors and small particles.
3. Percutaneously - through healthy skin.

Once in the body, organophosphorus compounds block the action of cholinesterase, or AChE. As a result, a phosphorylated enzyme is formed, which is resistant to hydrolysis. It is this enzyme that interacts with acetylcholine molecules, causing its destruction. As a result of this process, ACh accumulates on the postsynaptic membrane, its depolarization occurs, and four main effects are formed in the body that cause certain symptoms.

Clinical manifestations of poisoning

Symptomatically, poisoning with various types of organophosphorus compounds is similar in its manifestations. Therefore, for first aid and treatment, as well as for predicting long-term consequences, the stages of poisoning are more important. Also, knowing the clinic, you can pick up an antidote, since some groups of FOS often cause certain symptoms

I stage- excitement. The first symptoms occur as early as 15 minutes after FOS enters the body. A person has pronounced psychomotor agitation, headache, nausea and vomiting, dizziness, abdominal pain (regardless of the way FOS enters the body). On examination, moderate miosis (narrowing of the pupil), salivation (increased salivation), sweating, increased blood pressure, and tachycardia can be detected.

II stage- hyperkinesis and convulsions. Without specialized assistance, this stage manifests itself a few hours after intoxication. At this stage, clinical symptoms are most pronounced. The patient will complain of general malaise, blurred vision, salivation, difficulty breathing, sweating is not just increased - profuse sweat is observed. Painful tenesmus (urge to urinate and defecate), spontaneous muscle convulsive twitches are also noted.

This stage quickly passes from excitement to stupor, and then to stupor. With further progression, the patient falls into a coma. Objectively, miosis is detected, pupils do not react to light, chest rigidity, skeletal muscle tone is increased, respiratory movements of the chest are limited. The patient chokes on saliva, with auscultation, moist rales are clearly audible.

The main distinguishing feature of this stage is muscle twitching, which begins with the face and successively passes to the muscles of the neck, chest, forearm, and lower leg. The pressure can rise to critical numbers - 250/160 mm Hg, and then collapse can occur abruptly.

III stage- paralysis. For this stage, paralysis of the striated muscles becomes the leading symptom. The patient is either in stupor or in various stages of coma. The pupils are pinpoint, do not react to light. There is bradycardia and hypotension, tendon reflexes are absent. In the absence of therapy, a fatal outcome is often observed.

Principles of therapy for patients with acute intoxication

If a person has developed poisoning with any organophosphorus compounds before your eyes, then you must immediately call an ambulance and provide first aid:

Further treatment, even if the patient does not develop severe clinical symptoms of poisoning, is carried out only in a hospital. A person is given a gastric lavage, an antidote is selected, and when the first symptoms appear, drug therapy is carried out.

The basic principle of the treatment of FOS poisoning is the selection of an antidote. The most commonly used are pentafen, amizil, tropacin, dipyroxime, cholinesterase reactivators. In parallel with antidote therapy, an intramuscular injection of atropine is prescribed. Depending on the severity, several injections of atropine from 2 to 6 ml are prescribed until the first symptoms of atropine overdose appear. In especially severe cases, the amount of atropine is adjusted to 30 ml.

After introducing the antidote, the doctors continue to monitor the patient. If there is difficulty in breathing, the patient is connected to an artificial respiration apparatus, heart medications are prescribed. With convulsions, anticonvulsant therapy with hexenal, sodium barbital is mandatory. Be sure to prescribe antibiotic therapy for the prevention of various diseases, in particular - pneumonia.

Carrying out the initial therapy and selecting an antidote, the doctor must find out which organophosphorus drug caused this clinic. Some substances, avenin and methylacetophos, do not inhibit ChE, therefore, antidote therapy is not required. In this case, only symptomatic treatment is prescribed.

The antidote, at its core, is a cholinesterase reactivator. And the earlier antidote therapy began, the more pronounced the effect will be. That is why it is so important to know the stages of FOS poisoning. Each stage has its own antidote treatment regimen: the volume of drug administration, frequency.

It must be clearly understood that the antidote is effective only until a stable cholinesterase block has occurred, that is, the first six hours after the first entry of FOS into the body. Later than this time, the introduced antidote will not only not have a beneficial effect, but will also become harmful to the body - it has a toxic effect on the heart, liver, and relapses of symptoms of FOS poisoning occur.

It is very important to know that FOS poisoning can be not only acute, but also chronic. Most often, this situation occurs in production, where work with organophosphorus compounds is constant. In this case, more blurred clinical symptoms occur, and such patients are constantly monitored by an occupational pathologist who monitors the slightest changes in the human body. Accordingly, the treatment of chronic situations is slightly different, here the prevention of poisoning plays a greater role than its treatment.

Unfortunately, very often chronic poisoning with these compounds is asymptomatic. After the first exposure, if it went unnoticed, the activity of acetylcholinesterase decreases by almost 100%, but no symptoms may occur.

Phosphorus organic compounds are, of course, toxic substances, even their most modern counterparts. But in some cases, FOS are used as medicines. For example, at low concentrations, they also inhibit ChE activity, which is used to treat malignant tumors, glaucoma.

Of interest are modern studies in the field of genetics on the subject of the mutagenic effects of FOS. Scientists believe that this knowledge opens up great prospects for studying the mechanisms of hereditary factors of various pathologies and the possibility of their treatment.

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