ANTIDOTES (antidota; synonym antidotes) — pharmaceuticals for treatment poisoning, the animals called by toxic agents, industrial poisons, poisons and insects, noxious plants and medicinal substances.
Specificity of action of P. decides by mechanisms of their interaction on poisons. As P. use medicinal substances with different mechanisms of anti-toxic action. E.g., as P. apply the substances neutralizing poisons by physical. - chemical (adsorption) or chemical (a complex formation, oxidation, etc.) interactions with them or the connections forming in an organism connecting poisons. Besides, as P. pharmaceuticals, being functional (pharmacological) antagonists of poisons on action on biochemical, substrates of an organism can be used (receptors, enzymes, etc.). As P. at some types of poisonings (e.g., at stings of venomous snakes and insects) apply also immunol. means (antitoxic serums).
Kliniko-pharmakol. the main P.' characteristic is provided in the table.
Many biologically active compounds can indirectly interact with poisons; it forms a basis for rational correction of the functional disturbances arising at hron, intoxications and acute poisonings with toxic agents and also at toxic reactions to pharmaceuticals. So, methods of medicinal therapy of functional disturbances at intoxications are based on the principle of indirect interaction of medicinal substances by cardiac glycosides, salicylates, barbiturates, fenotiazina, tranquilizers, antidepressants and other substances. However as such interaction is not specific in character, the methods of therapy of poisonings based on it consider as corrective or symptomatic. The pharmaceuticals applied at the same time do not include in group P.
Do not carry to P. and some pathogenetic the pharmaceuticals operating at poisonings though they can level and even to prevent development patol, manifestations of effect of poison on an organism. So, stings of some snakes and insects are followed by intoxication with development of the disseminated intravascular blood coagulation (so-called. IDCS). E.g., poison of a gyurza causes a sharp hypofibrinogenemia, provokes emergence of fibrinogen B in blood and formation of defective fibrin. At the same time there is a falling of activity of a L-L factor. Heparin can prevent development of the IDCS, blocking endogenous pro-coagulants. However in this case P. is not heparin, but the specific immune serum neutralizing poison. Do not carry the pharmaceuticals which are also widely applied at therapy of poisonings exciting evakuatorny functions of an organism to P. (emetic, laxative, diuretic).
Items classify, using various criteria of their assessment. P.'s classification by the principles of their action and the main orientation of anti-toxic effect is included below.
Classification of antidotes
1. The antidotes operating on physical. - to the chemical principle (universal antidotes) — active coal (see).
2. The antidotes operating by the chemical principle:
a) antidotes of arsenic and metals — Unithiolum (see), Dicaptolum (see), Tetacinum-calcium (see), Pentacinum (see), Natrium thiosulfuricum (see), tannin (see), B-Penicillaminum, Deferoxaminum (see. Complexons );
b) antidotes of some alkaloids — a tannin, potassium permanganate (see);
c) antidotes of heparin — protamin sulfate (see);
e) an antidote of metgemoglobinobrazuyushchy poisons — methylene blue.
3. Competitive antagonists of poisons: antidotes of FOS (reaktivator of cholinesterase) — dipiroksy (see), Isonitrosinum, pralidoksy, obidoksy.
4. Functional (pharmacological) antagonists:
5. Immunological antidotes (specific anti-toxic serums):
a) an antidote of poison of a karakurt — protivokarakurtny serum;
b) antidotes of poison of a scorpion — antivenene serum an anti-cobra + an antigyurza, protivokarakurtny serum;
c) an antidote of poisons of a viper, a gyurza, an efa — specific antivenene serum (antigyurza) — see. Snake poison .
The drugs relating to different groups P. differ from each other in nek-ry features of anti-toxic action. So, the adsorbing means (e.g., active coal) interacting with poisons on physical. - to the chemical principle, are characterized by rather low selectivity of anti-toxic effect in this connection they received the name of universal antidotes. It must be kept in mind, however, that the adsorbing activity of active coal concerning separate substances nevertheless is not identical. E.g., Phenaminum, Primachinum, colchicine, Colchaminum, dipheninum, iodine, acetilsalicylic to - that and some other substances are adsorbed by active coal more than quinacrine, Meprotanum, aminazine, quinine, quinidine, Chingaminum, glyutetimid and methyl salicylate.
The items interacting with poisons by the chemical principle are more selective antidotes, than the adsorbing means.
Practically among this group P. antidotes of arsenic and metals are the most important (Unithiolum, Tetacinum-calcium, etc.). These antidotes have property to form inactive complexes (chelates) with arsenic and cations of some metals owing to what such antidotes prevent binding of poisons (arsenic, metals) with active groups (ligands) of proteins and enzymes in an organism and can even release cations of metals from communication with ligands.
Stability of the chelates formed by the specified antidotes varies for various metals depending on character of group of a ligand. E.g., lead and mercury have big affinity to ligands of sulfur and nitrogen, than to a ligand of oxygen, and calcium, on the contrary, has bigger affinity to oxygen ligands. Selectivity of anti-toxic action of chelating antidotes is explained by it. As an antidote of metals use also Natrium thiosulfuricum which interacts with them with formation of nontoxic sulfites.
A tannin forms insoluble compounds with salts of heavy metals and alkaloids. However with morphine, cocaine, atropine, nicotine and physostigmine a tannin forms unstable complexes which need to be deleted from a stomach by washing. Besides, a tannin can be soaked up in went. - kish. a path and to cause severe damages of a liver that should be considered at practical application of this antidote.
Potassium permanganate inactivates alkaloids of opium, aconitine, strychnine, nicotine and streptocides, oxidizing these substances. However at poisonings with cocaine, atropine and barbiturates of potassium permanganate is inefficient since these poisons are not oxidized of
the Antidote of heparin the sulfate having the expressed main properties and therefore forming connections with heparin which reacts as strong to - that is protamin.
A basis of antidotal therapy at poisonings with cyanides is formation of a methemoglobin (Hb-Fe3+) as a result of use of metgemoglobinobrazuyushchy substances — sodium of nitrite or high doses methylene blue. The methemoglobin competes with cytochrome oxydase (Tsit-Fe3+) for ions of cyanides. At the same time the methemoglobin passes in tsianmetgemoglobin (Hb-FeCN) and is recovered by cytochrome oxydase:
Apply Natrium thiosulfuricum which under influence thiosulphate-sulfidtransferazy reacts with cyanides with formation of thiocyanate (SCN-) — concerning the low-toxic which is quickly excreted by kidneys to a further detoxication. This reaction is reversible:
Antidote of metgemoglobinobrazuyushchy poisons (nitrites, aniline and its derivatives, mesoxalyl urea) is methylene blue which in small doses recovers a methemoglobin in hemoglobin. Items from group of competitive antagonists of poisons
are among reaktivator of cholinesterase which are specific antidotes at the poisonings caused by organophosphorous connections (FOS). It is known that FOS inhibit acetylcholinesterase, contacting it radio and phosphorus bonds. Mechanism of anti-toxic action of reaktivator of cholinesterase (dipiroksim, etc.) is that they recover activity of acetylcholinesterase, splitting radio and phosphorus bonds in the complexes formed by FOS with this enzyme.
From the point of view of clinical toxicology important that treatment of acute intoxications the poisons operating on certain types of receptors (adrenergic, cholinergic, etc.), is possible on the basis of interaction of these poisons at the level of receptors with P., being antagonists of poisons on action on the corresponding receptors. Such P. carry to group of so-called functional (pharmacological) antagonists of poisons. Items of this group do not join in direct physical. - chemical or chemical interaction with poisons, and is specifically korrigirut by the disturbances of functions of the corresponding receptors arising under the influence of poisons. Mean the substances operating on the same type of receptors by functional antagonists. At the same time the substance stimulating a receptor and causing a certain effect is an agonist (A), and the substance operating on the same receptor and inhibiting effect of an agonist — his antagonist (B).
Linkng of the antagonist with a receptor can be reversible and irreversible. If it is reversible, then relationship of the antagonist with an agonist has character of competitive antagonism and effect of their interaction considerably is defined by a dose of an agonist. At irreversible linkng of a receptor with the antagonist the agonist does not cause pharmakol. effects since cannot enter interaction with a receptor.
Schematically this relationship can be represented as follows (And — an agonist, B — the antagonist).
Substance A + a receptor —> a complex a receptor — substance A —> the answer.
Substance B + a receptor —> a complex a receptor — substance B —> there is no answer.
Substance A + a complex a receptor — substance B —> the answer depends on a dose of substance A if communication in a complex a receptor — substance B is reversible.
Use as antidotes of m cholinolytics is based on the principle of functional antagonism (atropine, etc.) at poisonings of m cholinomimetics, and - adrenolytic drugs (phentolamine, etc.) — at poisonings and-adrenomimetikami etc.
Functional antagonists of narcotic analgetics are the Nalorfinum, Naloxonum and levorphanol structurally close to morphine of substance interacting with opiate receptors. Among these drugs Naloxonum is almost «pure» antagonist of opiates. Nalorfinum and levorphanol concern to so-called partial antagonists of opiates since combine properties of antagonists and agonists in this connection they cause a number of the effects inherent to morphine and other agonists (analgetic effect, respiratory depression, etc.).
At any P.' use it is important to consider that their efficiency at therapy of poisonings depends on the accuracy of identification of the poison which caused poisoning, the choice of drug adequate to it from number P., timeliness of use of this drug and accuracy of respect for the principles of its dosage and ways of introduction.
Bibliography: Ganshara P. S. and Novikov A. A. The manual on clinical toxicology, M., 1979; Dushnikov E. A., Dagayev V. N. and Firsov H. H. Fundamentals of resuscitation at acute poisonings, page 333, M., 1977; Acute management at acute poisonings, under the editorship of S. N. Golikov, page 76, M., 1977; Poisonings at children's age, under the editorship of I. V. Markova and A. M. Abezgauz, page 43, L., 1977; The Guide to pharmacology, under the editorship of N. V. Lazarev, t. 2, page 436, L., 1961; Ariëns E. J. Introduction to general toxicology, N. Y., 1976; Dreisbach R. H. Handbook of poisoning, Los Altos, 1969; Ludewig R. u. Lohs K. Akute Vergiftungen, Jena, 1975; Moeschlin S. Klinik und Therapie den Vergiftungen, Stuttgart, 1964.
C. I. Zolotukhin, A. Ya. Ivleva; author of the table V. K. Muratov.