Intensive Care of Acute Poisoning - A. V. Hovenko 2010

Methods of Detoxification Therapy
Pharmacological (Antidotal) Detoxification

In certain types of poisoning, specific (antidote) therapy using particular medications capable of reducing the toxicity of poisons entering the body is of vital importance.

According to the definition by experts from the IPCS (International Programme on Chemical Safety) of the World Health Organization (1996), an antidote is a medicinal product capable of abolishing or weakening the specific action of a poison by immobilizing it, reducing its penetration to effector receptors by lowering its concentration (e.g., adsorbents), or acting as a receptor-level antagonist (e.g., pharmacological antagonists).

Antidotes are used exclusively in the toxicogenic phase of Acute Poisoning. The greatest therapeutic effect is observed when they are administered immediately or within the first hours after the poison enters the body. Antidotes exhibit selective action and are therefore administered only in the presence of specific clinical indications. There is no universal antidote. In certain cases, combined Treatment with several antidotes possessing different mechanisms of antitoxic action while mitigating the Toxic Effect of the same poison is employed (e.g., the administration of atropine, dipyroxime, and activated charcoal in organophosphate poisoning; or sodium nitrate and sodium thiosulfate in cyanide poisoning). Antidotes have no independent role in the treatment of poisonings and are effective only when combined with other Methods.

Antidotes include medicinal products with diverse mechanisms of antitoxic action. According to the Classification proposed by E. O. Luzhnikov, there are 4 main groups of antidotes:

1. Chemical (toxicotropic) antidotes — enter into physicochemical bonds with the poison in the gastrointestinal tract or in the body's humoral environment:

- nonspecific — enterosorbents, activated charcoal, white clay, KMgО₄, NaHCО₃;

- specific — unithiol, mecaptide (salts of heavy metals), protamine (heparin).

2. Biochemical (toxicokinetic) antidotes — alter the METABOLISM of poisons or the direction of biochemical reactions in which they participate (ChE reactivators for organophosphates, Lipoic Acid for amanitins, methylene blue for methemoglobin, ethanol for methanol and Ethylene glycol, naloxone for opiates, Cytochromes for CO, nitrates and sodium thiosulfate for cyanides, acetylcysteine for chlorinated Hydrocarbons).

3. Pharmacological (symptomatic) antidotes — exert an opposite pharmacological effect on the same functional systems of the body (atropine - proserine, ACh, Glucagon - Insulin, proserine - pachycarpine, potassium chloride - cardiac Glycosides).

4. Immunological antidotes (antitoxic immunopreparations) — bind poisons via an Antigen-Antibody Reaction (antitoxic sera against insect and snake venoms, antidigoxin serum, antidigoxin for cardiac glycosides).

NB! When using antitoxic immunopreparations, it is essential to consider the potential development of allergic reactions, particularly in individuals prone to allergies or diathesis.

Based on The Mechanism of their therapeutic effect, existing antidotes can be divided into the following main groups:

1. Physicochemical — their action is based on physicochemical processes (absorption, dissolution) in the digestive tract. These include adsorbents, which can be polyvalent. The most common antidote of this type is activated charcoal, which is capable of adsorbing poison entering The Stomach onto its surface. However, its activity is limited by the fact that it can only adsorb poison prior to its resorption.

2. Chemical — their action is based on a specific chemical interaction with the poison, resulting in the inactivation of the latter. Through binding, displacement, competitive reactions, or other mechanisms, the antidote converts the poison into a non-toxic substance that is excreted from the body in urine or feces.

3. Physiological or functional — their action aims to eliminate the toxic effect of the poison. Unlike the previous group, such antidotes do not react directly with the poison or alter its physicochemical state; instead, they interact with the biological substrate negatively affected by the poison. The action of physiological antidotes is based on THE PRINCIPLE OF functional antagonism.

4. Modificational — their action is based on modifying the metabolic processes of the xenobiotic.

The division of antidotes into these groups is conventional, as many of them may act as mixed-type agents whose action is more complex than that of any single group alone. An antidote may consist of a mixture of several medicinal agents that, while exhibiting therapeutic properties in various directions through the action of individual ingredients, can Complement one another or enhance the effect via summation or potentiation of the antidote action. An important factor ensuring high antidote activity is the timing of its administration following poisoning. The earlier the antidote is used, the more effective its positive impact will be.

The Criteria for the urgency of administering certain antidotes and their dosages are presented in Tables 4.2 – 4.4.

Any antidote is also a chemical substance, just like the toxicant against which it is used. As a rule, an antidote does not exhibit complete antagonism toward the poison. Therefore, its untimely administration, incorrect dosage, or improper regimen can adversely affect the patient's condition. Attempts to adjust recommended methods of antidote use based on a bedside Assessment of the patient are permissible only for highly qualified specialists with significant experience in utilizing the specific antidote. The most frequent error associated with The Use of antidotes stems from attempts to enhance their effectiveness by increasing the administered dose. Such an approach is viable only with certain physiological antagonists, yet even here, strict limitations are imposed by the patient's drug tolerance.

Class="center">Table 4.2 Criteria for the urgency of antidote administration (within 30 minutes of poisoning)

[from the WHO Expert Group, 1993]

Table 4.3 Criteria for the urgency of antidote administration (within 2 hours of poisoning)

Table 4.4 Criteria for the urgency of antidote administration (within 6 hours of poisoning)

Antidote therapy is highly specific and therefore should only be administered following clinical and laboratory confirmation of acute poisoning. Inappropriate administration of high doses of an antidote may also exert toxic effects on the patient's body.

Most specific antidotes have a rapid onset of action, and their administration must be initiated at the pre-hospital stage. This group of antidotes includes cholinesterase reactivators (alloxime, dietixime, dipiroxime, isonitrosine) used in organophosphate insecticide poisoning, naloxone (nalorphine) for opioid overdoses, physostigmine (aminostigmine, galantamine) for central antimuscarinic poisoning, methylene blue for methemoglobin-inducing agents, ethanol for methanol and ethylene glycol poisoning, and flumazenil (anexate) for benzodiazepine tranquilizer overdoses.

In certain types of poisoning, specific therapeutic effects are achieved using medications not formally classified as antidotes. For instance, vitamin B₆ (5% pyridoxine hydrochloride solution) is used for antituberculosis Drug poisoning (isoniazid), Vitamin B1 (6% thiamine bromide solution) for pachycarpine poisoning, and vitamin K (1% vicasol solution) for overdosage of indirect anticoagulants (phenylene, zoocoumarin).

A list of certain toxic substances and the antidotes used for their inactivation is provided in Appendix 8.