METHOD FOR IN-DEPTH ASSESSMENT OF GASTRO- AND ENTEROTOXIC SIDE EFFECT OF DRUGS OF DIFFERENT PHARMACOLOGICAL GROUPS
DOI:
https://doi.org/10.11603/1811-2471.2022.v.i3.13296Keywords:
side effect, gastrotoxic, enterotoxic, method of evaluationAbstract
SUMMARY. Against the background of the expansion of the pharmaceutical market in the world, the growth of drug prescriptions and extremely wide uncontrolled use in self-medication, special attention should be paid to the negative effects of drugs of different pharmacological groups on the digestive system. Given that the most common side effects of drugs are damage to the digestive system, in particular, the gastrointestinal tract, the urgency of the question of assessing their condition under the action of drugs is unconditional. Monitoring the side effects of drugs of different pharmacotherapeutic groups on the gastrointestinal tract, a detailed study of the gastric and intestinal mucosa with long-term use of drugs against chronic rheumatic diseases, oncopathology, comorbid conditions, concomitant diseases of the digestive system are the priorities of both pharmacologists-experimenters and clinicians. The need for detailed assessment of the damaged mucous membranes of the stomach and intestines requires the development of new drugs, studying their mechanisms of actions and features of pharmacodynamics, pharmacokinetics, tropism, etc., studying the interaction of different pharmacological and/or pharmacotherapeutic groups of drugs against various diseases, including comorbid conditions, even those that are not directly related to the pathology of the stomach and intestines. The need to study the side effects, in particular, gastro- and enterotoxic effects of drugs, is undeniable, which requires the use of appropriate methods to assess the condition of the mucous membranes of the stomach and intestines.
The aim – to propose a method of an in-depth assessment of the mucous membranes of the stomach and intestines in the study of gastrotoxic and enterotoxic effects of drugs that are not used for the treatment of pathology of the stomach and intestines, and are used in various pathological conditions, including comorbid.
Material and Methods. Sexually mature nonlinear white rats of both sexes were used in the study. A macroscopic examination of gastric and intestinal mucous membranes was carried out. The presence, number, and size of all destructure were determined, and methods to estimate the frequency and intensity of their lesions both in models of various pathological conditions (including comorbid) and when using some NSAIDs were developed. The formula for the determination of gastro- and enterotoxin activity of drugs is proposed.
Results. A detailed method of extended assessment of the condition of the mucous membranes of the stomach and intestines is required to take into account the symptoms of lesions such as edema (including crypt), redness (local and total), petechiae, hemorrhages, erosions, ulcers. It is recommended to determine such indicators as the frequency of gastro- and/or enteropathy, the intensity of each type of lesion and the overall intensity of gastropathy or the intensity of enteropathy, which best characterizes all changes in the gastric and intestinal mucosa, the degree of these changes on a scale. These indicators can provide a general description of the condition of the mucous membranes of these organs, both in terms of the pathological process and in terms of the toxic effects of drugs.
The frequency of damage to the mucous membranes of the stomach and intestines under the action of drugs and pathological conditions is proposed to determine by counting each of the types of damage relative to the total number of animals in the group. The intensity of each of the types of damage to the mucous membranes of the stomach and intestines is proposed to be based on a score, which, in fact, reflects the degree of damage. The number of points for each of these injuries should be counted in all animals in this group. The ratio of the total number of points for a particular type of damage to the total number of animals in the group should determine the intensity of each lesion (hyperemia intensity, edema intensity, etc.), ie calculate the intensity as the ratio of total points for all animals in the group. The formula for determining the gastro- and enterotoxic activity of drugs is given.
Specific examples of calculating the frequency and intensity of damage to the gastric mucosa, as well as an example of determining the gastrotoxicity of nonsteroidal anti-inflammatory drugs.
Conclusions. An in-depth method of gastro- and intestinal mucous membrane state evaluation was proposed while studying the side effects (gastro- and enterotoxin) of various pharmacological groups of drugs. Specific examples of determining the frequency and intensity of damage to the gastric mucosa against the background of pathological conditions of different genesis, as well as examples of studies of gastro-toxic effects of non-steroidal anti-inflammatory drugs with different selectivity to cyclooxygenase, are presented.
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