ABSTRACT

on the topic of:

__________________________________________________________

Completed by: student of group 23

A.A. Firman

Checked:

Novosibirsk, 2010

1. The concept of an antidote

2. Delayed-acting toxic substances

3. Antidote therapy for damage caused by slow-acting substances

Antidote concept

Antidote or antidote (from ancient Greek ἀντίδοτον, lit. - given against) is a medicine that stops or weakens the effect of poison on the body.

Antidotes (antidotes)- substances capable of reducing the toxicity of a poison by physical or chemical action on it or by competing with it when acting on enzymes and receptors.

The choice of antidote is determined by the type and nature of the action of the substances that caused the poisoning; the effectiveness of use depends on how accurately the substance that caused the poisoning is identified, as well as on how quickly assistance is provided.

Depending on the mechanism of action, several groups of antidotes are distinguished:

· Sorbents are antidotes whose action is based on physical processes (activated carbon, petroleum jelly, polyphepane).

· Antidotes that neutralize poison by chemical interaction with it (potassium permanganate, sodium hypochloride), which leads to the formation of less toxic substances.

Antidotes are designed to influence the kinetics of a toxic substance entering the body, its absorption or elimination, reduce the effect of poison on receptors, prevent dangerous metabolism, and eliminate threatening disorders of the functions of organs and systems caused by poisoning. In clinical practice, antidotes and other drugs used for poisoning are used in parallel with general resuscitation and detoxification methods of treatment. And in cases where resuscitation measures cannot be carried out, the victim’s life can only be saved by administering an antidote.

Currently, antidotes have been developed only for a limited group of toxicants. In accordance with the type of antagonism to the toxicant, they can be classified into several groups (Table 1).

Table 1. Antidotes used in clinical practice

There are no true antidotes, that is, substances that would completely neutralize the effect of poison in the body.

Antidotes are substances that can neutralize or stop the action of poison in the human body. The effectiveness of antidotes depends on how accurately the poison/toxin entering the body was determined and how quickly medical care was provided to the victim.

Types of antidotes

There are several types of substances in question - they are all used for different types of poisoning, but there are also those that belong to the category of universal ones.

Universal antidotes:

Most often, the following antidotes are used for acute poisoning:

1. Unithiol . It belongs to the universal type of antidotes (antidotes) and does not have high toxicity. Used for poisoning with salts of heavy metals (lead, etc.), in case of overdose of cardiac glycosides, and poisoning with chlorinated hydrocarbons.

   Unithiol is administered intramuscularly every 6-8 hours on the first day after poisoning or overdose, on the second day the antidote is administered every 12 hours, in subsequent days - 1 (maximum two) times a day.

2. EDTA (thetacin calcium) . Used only for poisoning with salts of heavy metals (lead and others). The antidote is capable of forming complexes with metals, which are characterized by easy solubility and low molecularity. It is this ability that allows for the rapid and most complete removal of heavy metal salt compounds from the body through the urinary system.

   EDTA is administered simultaneously with glucose intravenously. The average daily dose for an adult is 50 mg/kg.

3. Oximes (dipyroxime and/or alloxime) . These antidotes are classified as cholinesterase reactivators. The substance is used for poisoning with anticholinesterase poisons, most effectively when used in the first 24 hours.
4. Nalorphine . Used for poisoning with drugs from the morphine group. When using nalorphine, drug withdrawal syndrome is subsequently observed - the patient is worried about,.

   The antidote in question is administered intramuscularly or intravenously every 30 minutes. The total dose of the administered drug should not exceed 0.05 g.

5. Lipoic acid . It is most often used as an antidote for poisoning with toadstool toxins. The effect of using lipoic acid for mushroom poisoning is only possible if the antidote is administered in the first few hours after poisoning.

   This antidote is administered only for symptoms of severe liver damage at a dose of 0.3 grams per day for a maximum of 14 days.

6. . The drug is an antidote for poisoning with cardiac glycosides, nicotine, dichloroethane, potassium and ergot.

   It is administered during the first day after poisoning in an amount of 0.7 grams.

7. Methylene blue . Used for poisoning with hydrogen sulfide, cyanides, sulfonamides, nitrates, naphthalene.

   It is administered intravenously in combination with glucose. If a 1% antidote solution is used, the dosage will be 50-100 ml, in the case of a 25% solution - 50 ml.

8. Calcium gluconate . This substance is well known to everyone and is often perceived as the simplest and most harmless drug. But in fact, it is calcium gluconate that is most often used as an antidote for stinging insects. If this antidote is inadvertently injected past a vein, necrosis of the subcutaneous fat layer may develop.

   Calcium gluconate is administered in an amount of 5-10 ml intravenously, if we are talking about a 10% solution of the drug. It is recommended to repeat the procedure after the first injection after 8-12 hours.

9. Ethanol . Antidote for poisoning with methyl alcohol and ethylene glycol. As a side effect when used, there is a deterioration in myocardial activity (its contractility decreases).

   Apply 100 ml of 30% ethyl alcohol solution orally every 2-4 hours. If methanol is diagnosed in the blood, then an ethyl alcohol solution is administered intravenously in combination with glucose or sodium chloride.

10. Potassium chloride . Most effective as an antidote for poisoning with cardiac glycosides. As a side effect, irritation of the gastric mucosa and hyperkalemia are noted.

    This antidote is administered intravenously in combination with glucose; 50 ml of a 10% potassium chloride solution can be taken orally.

11. Sodium thiosulfate . An antidote that is used for poisoning with lead, arsenic, hydrocyanic acid, mercury, etc. Side effects when using sodium thiosulfate include nausea, skin rashes of various types and thrombocytopenia.

    A 30% solution of the presented antidote, 30-50 ml, is administered intravenously, and 20 minutes after the initial administration, the procedure is repeated, but at half the indicated dose.

Antidotes in folk medicine

Traditional medicine involves the use of medicinal plants for food or chemical poisoning. The following agents are actively used as antidotes:

In addition, traditional medicine actively uses baking soda and table salt for poisoning.

Note:In no case should you trust remedies from the category of traditional medicine, because even the most effective medicinal plants in most cases cannot have the desired effect. Only after consultation with a doctor is it permissible to use some folk remedies.

Any use of antidotes must be agreed with doctors - independent use can lead to a deterioration in the health of the victim. In addition, an incorrectly administered dose of antidote or an incorrect course of treatment can aggravate the situation, leading to death. We should not forget that some antidotes can provoke the development of side effects - they also have a negative effect on the patient’s health.

Tsygankova Yana Aleksandrovna, medical observer, therapist of the highest qualification category

Actions of antidotes (antidotes)

The use of an antidote allows you to prevent the effects of poison on the body, normalize the basic functions of the body, or slow down the functional or structural disorders that develop during poisoning.

Antidotes are of direct and indirect action.

Direct antidote

Direct action - direct chemical or physico-chemical interaction between the poison and the antidote occurs.

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.

• 1 gram of active carbon binds several hundred mg 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: to neutralize acids that have entered the body, salts and oxides are used that give an alkaline reaction in aqueous solutions - K2CO3, NaHCO3, MgO.
• - in case of poisoning with soluble silver salts (for example AgNO3), NaCl is used, which forms insoluble AgCl with silver salts.
• - in case of poisoning with poisons containing arsenic, MgO and ferrous sulfate are used, which chemically bind it
• - in case of poisoning with potassium permanganate KMnO4, which is a strong oxidizing agent, use a reducing agent - hydrogen peroxide H2O2
• - in case of alkali poisoning, use weak organic acids (citric, acetic)
• - poisoning with hydrofluoric acid salts (fluorides) use calcium sulfate CaSO4, the reaction produces slightly soluble CaF2
• - 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 direct-acting antidotes is antidotes - complexons (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 ethylenediaminetetraacetic acid (EDTA), primarily sodium ethylenediaminetetraacetate.

HIGHER PROFESSIONAL EDUCATION

"SAMARA STATE MEDICAL UNIVERSITY OF THE MINISTRY OF HEALTH AND SOCIAL DEVELOPMENT OF THE RF"

Department of Mobilization Training of Health and Disaster Medicine

Abstract on the topic: “The mechanism of action of antidotes.”
Samara 2012

I. Characteristics of antidotes …………………………. 3

II.Mechanisms of action of antidotes……………..….....5

1) The mechanism of poison binding…………………..…….. 6

2) Mechanism of poison displacement…………………………..8

3) The mechanism of compensation of biologically active substances………………………………………………………..…. 9

4) Replacement mechanism for biologically active substances………………………………………………………..…10

List of references………………....11

Characteristics of antidotes

Antidotes (antidotes) are medications used in the treatment of poisoning, the mechanism of action of which is based on the neutralization of the poison or the prevention and elimination of the toxic effect caused by it.

Certain substances or mixtures are used as antidotes, depending on the nature of the poison (toxin):

• 
  ethanol can be used for poisoning methyl alcohol
• 
  atropine - used for poisoning with M-cholinomimetics (muscarine and acetylcholinesterase inhibitors(organophosphorus poisons).
• 
  glucose is an auxiliary antidote for many types of poisoning, administered intravenously or orally. Capable of binding hydrocyanic acid .
• 
  Naloxone - used for opioid poisoning and overdose

• 
  Unithiol is a low-molecular SH-group donor, a universal antidote. It has a broad therapeutic effect and is low-toxic. Used as an antidote for acute poisoning with lewisite, salts heavy metals(copper, lead), in case of overdose of cardiac glycosides, poisoning with chlorinated hydrocarbons.
• 
  EDTA-tetacin-calcium, Cuprenil - refers to complexones ( chelating agents). Forms easily soluble low molecular weight complexes with metals, which are quickly excreted from the body through the kidneys. Used for acute poisoning heavy metals(lead, copper).
• 
  Oximes (alloxime, dipyroxime) are cholinesterase reactivators. Used for poisoning with anticholinesterase poisons, such as FOV. Most effective in the first 24 hours.
• 
  Atropine sulfate is an acetylcholine antagonist. It is used for acute poisoning with FOV, when acetylcholine accumulates in excess. In case of an overdose of pilocarpine, proserin, glycosides, clonidine, beta blockers; as well as in case of poisoning with poisons that cause bradycardia and bronchorrhea.
• 
  Ethyl alcohol is an antidote for poisoning methyl alcohol, ethylene glycol.
• 
  Vitamin B6 - antidote for poisoning anti-tuberculosis drugs (isoniazid, ftivazid); hydrazine
• 
  Acetylcysteine ​​is an antidote for dichloroethane poisoning. Accelerates the dechlorination of dichloroethane, neutralizes its toxic metabolites. It is also used for paracetamol poisoning.
• 
  Nalorphine is an antidote for poisoning with morphine, omnopon, benzdiazepines .
• 
  Cytochrome-C - effective against carbon monoxide poisoning.
• 
  Lipoic acid- used for poisoning toadstool as an antidote to amanitin.
• 
  Protamine sulfate- heparin antagonist.
• 
  Ascorbic acid- antidote for poisoning potassium permanganate. Is used for detoxification nonspecific therapy for all types of poisoning.
• 
  Sodium thiosulfate- antidote for poisoning with salts of heavy metals and cyanides.
• 
  Anti-snake serum- used for snake bites.
• 
  B 12 - antidote for cyanide poisoning and sodium nitroprusside overdose.

The action of antidotes may include:

1) in binding poison (through chemical and physico-chemical reactions);

2) in displacing poison from its compounds with the substrate;

3) in the replacement of biologically active substances destroyed under the influence of poison;

4) in functional antagonism, counteracting the toxic effect of poison.

Venom binding mechanism

Antidote therapy is widely used in a complex of therapeutic measures for occupational poisoning. Thus, to prevent the absorption of poison and its removal from the gastrointestinal tract, antidotes of physical and chemical action are used, for example, activated carbon, which adsorbs some poisons on its surface (nicotine, thallium, etc.). Other antidotes have a neutralizing effect by entering into a chemical reaction with the poison, through neutralization, precipitation, oxidation, reduction or binding of the poison. Thus, the neutralization method is used for poisoning with acids (for example, a solution of magnesium oxide - burnt magnesia is administered) and alkalis (a weak solution of acetic acid is prescribed).

To precipitate some metals (in case of poisoning with mercury, sublimate, arsenic), protein water, egg white, milk are used, converting salt solutions into insoluble albuminates, or a special antidote against metals (Antidotum metallorum), which includes stabilized hydrogen sulfide, which forms practically insoluble sulfides metals

An example of an antidote that acts by oxidation is potassium permanganate, which is active in phenol poisoning.

The principle of chemical binding of poison underlies the antidote effect of glucose and sodium thiosulfate in case of cyanide poisoning (hydrocyanic acid is converted into cyanohydrins or thiocyanides, respectively).

In case of poisoning with heavy metals, complexing substances are widely used to bind the already absorbed poison, for example, unithiol, thetacin-calcium, pentacine, tetoxation, which form stable non-toxic complex compounds with ions of many metals that are excreted in the urine.

For therapeutic purposes, tetacin and pentacin are used for occupational lead intoxication. Complex therapy (tetacin, tetoxacin) also helps eliminate certain radioactive elements and radioactive isotopes of heavy metals, such as yttrium and cerium, from the body.

The administration of complexones is also recommended for diagnostic purposes, for example, in cases where there is a suspicion of lead intoxication, but the concentration of lead in the blood and urine is not increased. A sharp increase in the excretion of lead in the urine after an intravenous injection of complexone indicates the presence of poison in the body.

The antidote effect of dithiols in case of poisoning with certain organic and inorganic compounds of heavy metals and other substances (mustard gas and its nitrogenous analogues, iodoacetate, etc.) belonging to the group of so-called thiol poisons is based on the principle of complexation. Of the currently studied dithiols, unithiol and succimer have found the greatest practical application. These products are effective antidotes for arsenic, mercury, cadmium, nickel, antimony, and chromium. As a result of the interaction of dithiols with salts of heavy metals, strong water-soluble cyclic complexes are formed, which are easily excreted by the kidneys.

Mecaptide serves as an antidote for arsenic hydrogen poisoning. Recently, the complexing agent α-penicillamine has been shown to have a high antidote effect in case of poisoning with compounds of lead, mercury, arsenic and some heavy metals. Tetacincalcium is included in ointments and pastes used to protect the skin of workers who have contact with chromium, nickel, and cobalt.

In order to reduce the absorption of lead, manganese and some other metals from the gastrointestinal tract, which enter the intestines with ingested dust, as well as as a result of excretion in the bile, the use of pectin is effective.

For the prevention and treatment of carbon disulfide poisoning, glutamic acid is recommended, which reacts with the poison and enhances its excretion in the urine. As an antidote treatment, the use of agents that inhibit the conversion of poison into highly toxic metabolites is considered.

Venom displacement mechanism

An example of an antidote, the effect of which is to displace poison from its connection with a biological substrate, can be oxygen in case of carbon monoxide poisoning. When the oxygen concentration in the blood increases, carbon monoxide is displaced. For poisoning with nitrites, nitrobenzene, aniline. resort to influencing the biological processes involved in the restoration of methemoglobin to hemoglobin. The process of demethemoglobinization is accelerated by methylene blue, cystamine, nicotinic acid, and lipamide. Effective antidotes for poisoning with organophosphate pesticides are a group of agents that can reactivate cholinesterase blocked by the poison (for example, 2-PAM, toxagonin, dipyroxime bromide).

The role of antidotes can be played by some vitamins and microelements that interact with the catalytic center of enzymes inhibited by the poison and restore their activity.

Replacement mechanism for biologically active substances

An antidote can be a remedy that does not displace the poison from its connection with the substrate, but by interacting with some other biological substrate makes the latter capable of binding the poison, shielding other vital biological systems. Thus, in case of cyanide poisoning, methemoglobin-forming substances are used. In this case, methemoglobin, binding with cyanogen, forms cyanmethemoglobin and thereby protects iron-containing tissue enzymes from inactivation by the poison.

Functional antagonism

Along with antidotes, functional antagonists of poisons are often used in the treatment of acute poisoning, i.e. substances that affect the same body functions as poison, but in exactly the opposite way. Thus, in case of poisoning with analeptics and other substances that stimulate the central nervous system, anesthetics are used as antagonists. In case of poisoning with poisons that cause inhibition of cholinesterase (many organophosphorus compounds, etc.), anticholinergic drugs, which are functional acetylcholine antagonists, for example atropine, tropacin, peptafen, are widely used.

For some drugs there are specific antagonists. For example, nalorphine is a specific antagonist of morphine and other narcotic analgesics, and calcium chloride is an antagonist of magnesium sulfate.

List of used literature

1. 
   Kutsenko S.A. - Military toxicology, radiobiology and medical protection "Foliant" 2004 266 pages.
2. 
   Nechaev E.A. - Instructions for emergency care for acute diseases and injuries 82 pages.
3. 
   Kiryushin V.A., Motalova T.V. - Toxicology of chemically hazardous substances and measures in the centers of chemical damage "RGMU" 2000 165 pages
4. 
   Electronic source

Antidotes (antidotes) are means used to treat poisoning in order to neutralize the poison and eliminate the pathological disorders caused by it. 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 the general principles of treating poisoning (cessation of contact with the 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. The most effective is the combined use of appropriate antidotes, in particular the use of an oral mixture consisting of activated carbon, tannin and magnesium oxide (MA). It is advisable to combine the use of antidotes of this kind 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, the most common are antidotes whose action 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 the possible options for the mechanism of action of antidotes. Much more often we are talking about 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 of chemical agents, Poisoning, Toxic substances, Food poisoning, Poisonous animals, Poisonous plants, Agricultural pesticides, Industrial poisons.