No 2 (2020)

The purpose of this review is to substantiate approaches for improving first aid in acute poisoning. Early administration of medical agents to the victims is advisable, but in injectable dosage form is problematic. An alternative is a nasal spray – dosage form that is suitable for systemic administration of pharmaceutical substances with small molecular weight (up to 1000 Da) and moderate hydrophilicity (log P_{octanol/water} ≥ 0), and a single dose of which can be contained in volume of up to 0, 3 ml. These criteria are met by the number of pharmaceutical substances used for the treatment of acute poisoning with substances that can form foci of mass destruction. This defines the perspective of nasal sprays as a medical device that allows to speed up, simplify and make it safer to use drugs when providing first aid in the centers of mass chemical destruction.

Fifty patients with acute severe ethanol poisoning (depression of consciousness at the time of admission was up to the level of coma) were examined. Based on the purpose of the study, patients were divided into two groups. In the first group, basic etiopathogenetic therapy was supplemented by the intravenous administration of a drug based on reduced glutathione: inosine glycyl-cysteinyl-glutamate disodium (IGCGD). In the second group, only basic therapy was performed. All patients underwent in the intensive care long-term continuous EEG monitoring, which was started at the end of basic resuscitation and stopped when the patient was clearly awake. Based on the nature of spontaneous EEG and reactivity, patients were divided into subgroups: patients with theta coma pattern and patients with delta coma pattern.

It was found that the introduction of IGCGD in the treatment of severe ethanol poisoning in the group of patients with a reactive delta pattern significantly increased the rate of formation of awakening in the EEG: in the subgroup with basic therapy, the formation time of the awakening pattern was about 3 hours, and in the subgroup of patients to whom the drug was administered 1,5 hours. In the group of patients with depression of EEG to the level of theta coma, IGCGD had no effect on the time of formation of the EEG pattern of awakening. The inclusion of inosine IGCGD in the treatment of severe alcohol intoxication was not accompanied by more frequent formation of epileptiform activity in the EEG.

The purpose of the review is to analyze the possibilities of using of pectin enterosorbents for the prevention of acute poisoning. Low-esterified pectins exhibit high sorbing activity against multicharged cations, are highly adhesive to the mucous membranes of the digestive tract and are able to reduce non-specifically the permeability of the enterohematic barrier. The expected duration of the preventive effect of pectin enterosorbents is 4-5 hours after their administration. In combination with good tolerability and ease of use, this indicates the prospects of low-esterified pectins as means of drug prevention of acute poisoning in case of increased risk of oral or inhalation intake of heavy metals, nuclear fission materials and nuclear fission products.

Research of the last decade, which revealed the relationship of various socially significant diseases (Alzheimer’s disease, parkinsonism, multiple sclerosis, etc.) with the impact of heavy metals on the human body, stimulates modern science to create drugs that can quickly and safely remove these toxic substances from the body. The article presents a review of studies on the effectiveness of heavy metal adsorption by modern enterosorbents officially registered in the Russian Federation as drugs. The prospects of using non-starch polysaccharides, which are part of modern biologically active additives, in order to create new medicinal substances for the elimination of heavy metals that pose a threat to public health are indicated.

The purpose of this work was to study the mechanisms of toxic action of unsymmetrical dimethylhydrazine (UDMH). The evaluation of genotoxic and cytotoxic effects; the study of contribution of oxidative action of UDMH to nuclear DNA in chronic administration to white rats for 7; 14; and 21 days at a dose of 10 and 20 mg/kg as well as pathomorphological studies have been performed.

The unsymmetrical dimethylhydrazine used for the experiments contained 97;26% of 1;1-dimethylhydrazine and 0;07% of N-nitrosodimethylamine.

The genotoxic and cytotoxic effects of UDMH were determined using alkaline gel electrophoresis (DNA comet assay) on leukocytes; hepatocytes; and cortical cells. It has been shown that a three-week administration of UDMH at doses of 10 and 20 mg/kg did not cause significant genotoxic and cytotoxic effect on nuclear DNA in the studied cells.

The pathomorphological study of the toxic effect of UDMH revealed moderate changes in the conducting pathways (rarefaction of the neuropil) in the brain. Full blood and single foci of necrosis of hepatocytes have been found in the liver. A slight increase in the frequency of occurrence of single foci of hepatocyte necrosis with the increase in the duration of UDMH administration has been noted.

After determining the oxidative effect of UDMH on the nuclear DNA of leukocytes; hepatocytes; and brain cells using formamidopyrimidine glycosylase DNA comet assay; an increase in the content of reactive oxygen species in hepatocytes has been found after administration of UDMH at a dose of 20 mg/kg for 14 and 21 days.

The results obtained indicate the absence of direct genotoxic effects of UDMH on the nuclear DNA of leukocytes; hepatocytes; and brain cells of white rats. The oxidative damage to DNA in hepatocytes is apparently associated with a high level of oxidative metabolism of UDMH in the liver after administration at a dose of 20 mg/kg; which is confirmed by pathomorphological studies.