Analysis of the main directions of therapeutic regimens for the treatment of helminthiases of the digestive system given in the new clinical treatment protocols

The treatment of helminthiases of the digestive system is a socially significant problem that is urgent for many countries in the world, including Ukraine. Over the last 5 years, cases of enterobiosis, ascariasis and trichocephalosis have been reported most frequently in Ukraine. Therefore, it is advisable to update and implement the latest treatment protocols for the specified pathology. Aim. To analyze recommendations for the treatment of helminthiasis of the digestive system, which are given in the new clinical protocols, and identify the promising directions for saturation of the domestic pharmaceutical market with drugs that meet the needs of patients with this pathology. Materials and methods. The objects of the study were guidelines for the treatment of helminthiases of the digestive system in the open access on the website of the Ministry of Health of Ukraine, scientific publications of domestic and foreign authors and our own research. The methods of generalization, systematization of theoretical and practical material, bibliosemantic and systematic analysis were used in the work. Results. The study of recommendations for the treatment of enterobiosis, ascariasis, intestinal cestodes, strongyloidosis, nematodosis and trichocephalosis has shown that the drug of choice for the treatment of this group of diseases is albendazole, which is included in each treatment protocol. Mebendazole is recommended for use in all regimens, except for the treatment of strongyloidosis. Drugs of other pharmaceutical ingredients are recommended for administration in rare cases. The main types of the pharmacological activity and side effects of albendazole are given. Conclusions. The treatment regimens recommended for helminthiasis of the digestive system have been analyzed, and the substances, based on which the development of domestic anthelmintic drugs is rational, have been determined.

The aim of this work is to analyze recommendations for the treatment of helminthiasis of the digestive system and identify the promising directions for saturation of the domestic pharmaceutical market with drugs that meet the needs of patients with this pathology.

Materials and methods
The objects of the study were guidelines for the treatment of enterobiosis, ascaridosis, intestinal cestodes, strongyloidosis, nematodosis, trichocephalosis in the open access on the website of the Ministry of Health of Ukraine, scientific publications of domestic and foreign authors and our own research. The methods of generalization, systematization of theoretical and practical material, bibliosemantic and systematic analysis were used in the work.

Results and discussion
The guidelines studied include the description of the infectious agent, the clinical picture of the disease, diagnostic tools, treatment recommendations and references.
Thus, the treatment regimens are mostly based on the use of mebendazole, albendazole and ivermectin (Tab. 1).
As can be seen from the results (Tab. 1), each treatment regimen contains recommendations for the use of albendazole. Mebendazole is recommended for use in all regimens, except for the treatment of strongyloidosis. Drugs of the other active pharmaceutical ingredients are recommended for use less often (Fig.).
Thus, albendazole is the drug of choice in the treatment of helminthiasis of the digestive system; it indicates the feasibility of developing domestic anthelmintic agents on its basis. According to the data of the PASS analysis the probability of the anthelminthic and antiparasitic activity of albendazole is greater than 0.8 (Tab. 2).
The mechanism of action of albendazole is in disorder of the metabolism of helminths. Drugs of benzimidazole group provoke metabolic disorders by selectively binding to β-tubulin and inhibiting polymerization that causes cytoplasmic formation of microtubules. However, the mechanism of helminth resistance to benzimidazoles in general and albendazole in particular should be considered: specific changes in amino acids of the β-tubulin protein lead to a decrease in affinity for it, which significantly reduces the pharmacological effect [8].
When developing a new drug the likely side effects of using albendazole should be also taken into account, making every effort to minimize them. In particular, the side effects of albendazole are given in Tab. 3 [9,10].
In view of the results obtained, it is advisable to focus on the development of domestic medicines  for the treatment of helminths of the digestive system on the basis of the above active pharmaceutical ingredients since the effectiveness of their administration is evidence-based. The most promising substance in this case is albendazole as it is present in each of the guidelines studied. Particular attention should be paid to the absence of pirvine, ivermectin and praziquantel-based drugs at the Ukrainian pharmaceutical market. It is also advisable to study the prospects of combining multiple substances in a single dosage form to potentiate the effect. 2. It has been found that albendazole and mebendazole are the drugs of choice for the treatment of parasitic diseases of the digestive system. Medicines of other pharmaceutical ingredients are recommended for use in isolated cases.
3. The mechanism of action and probable side effects of albendazole have been described; they should be taken into account when developing drugs on its basis.
Conflict of interests: authors have no conflict of interests to declare. Table 3 Side effects of albendazole Common  Rare  Isolated cases Stomach pain, fever, nausea Black tarry stool, bleeding gums, blood in urine or feces, chest pain, chills, cough, painful or difficult urination, red spots on the skin, sore throat, ulcers or white spots on lips or mouth, swollen glands unusual bleeding or bruising, unusual fatigue or weakness, dizziness, hair loss Peeling or weakening of the skin, blurred vision, dark urine, diarrhea, general feeling of fatigue or weakness, headache, joint or muscle pain, light stool, red, irritated eyes, seizures, persistent stomach pain, vomiting, yellow eyes or skin