After reading with great interest the article entitled: "Non-vitamin K antagonist oral anticoagulants (NOACs) do not increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation: insights from multi-source medical data" authored by Zhi-Chun Gu et al. and published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Oral anticoagulants are generally accepted in patients with non-valvular atrial fibrillation to prevent thrombosis and stroke. Since anticoagulants are taken daily for many months in these patients, we cannot rule out chronic poisoning and the development of liver failure. But another complication is just as likely, that being bleeding. Thus, the determining risk factor for the health of patients with a prolonged course of oral anticoagulants is hypofunctional activity of the blood coagulation system, which remains at the same level throughout the course of treatment. At the same time, it is the activity of the blood coagulation system that is an important and very sensitive link of adaptation to various external and internal factors, including anticoagulants. The fact is that regular and prolonged oral use of anticoagulants is likely to develop and tolerance to them. That is why it is necessary to carefully study the relationship between the dose of oral anticoagulants, the duration of pharmacotherapy and the development of thrombosis (bleeding) in patients with non-valvular atrial fibrillation.

Pyolytics are drugs that dissolve thick pus when applied topically. This group of drugs was discovered in early 21st century in Russia as a result of successful repurposing of antiseptics hydrogen peroxide, sodium bicarbonate and sodium chloride from antiseptics to pyolytics. Prior to this watershed event in pharmacy, the problem of effective treatment of purulent diseases had not been solved. The fact is that before that in the treatment of various purulent diseases mainly antiseptics and disinfectants solutions were used, of which hypertonic sodium chloride solution and 3 - 6% hydrogen peroxide solutions took the leading role as "antipurulent" drugs. However, the use of the known antiseptics and disinfectants solutions provided disinfection of the treated surface, but not dissolution of thick pus masses, as the solutions had no effective pyolytic action. Pyolytic activity, i.e. activity of dissolution of thick pus masses, was fantastically increased in hydrogen peroxide solutions only after the possibility of transformation of "old" drugs into "new" drugs by means of artificial changes in physical and chemical properties of their dosage forms was discovered. The greatest (explosive) effect was achieved by developing warm alkaline hydrogen peroxide solutions enriched with oxygen gas under increased pressure. In chronological order, an overview is given of Russian inventions, which formed the basis for the physicochemical repurposing of hydrogen peroxide solutions into pyolytics as well as the basis of temperature and physicochemical pharmacology and pharmaceutics.

It is reported that the interaction of hydrogen peroxide and sodium bicarbonate solution with thick sputum, mucus, pus and blood clots leads to their rapid transformation into a fluffy oxygenated foam. This mechanism of action allows repurposing hydrogen peroxide from antiseptic to expectorant and oxygen forming antihypoxant, which can find application for recanalization of airways and increasing blood oxygenation in acute respiratory syndrome. It is reported that acute respiratory distress syndrome in COVID-19 can be caused by excessive accumulation of thick sputum, mucus and pus in the airways, which complicates intra-pulmonary oxygenation of blood, causes hypoxia and causes death, since there are no drugs for urgent recanalization of the airways today. At the same time, the first evidence emerged that alkaline hydrogen peroxide solution can claim to be an inhaled expectorant and oxygen-producing drug for urgent recanalization of the airways when they are blocked by mucus, sputum, pus, blood and other colloidal fluid containing the enzyme catalase.

Introduction. A review of the scientific literature showed that the current standards for assessing the quality of drugs does not include an assessment of the osmotic activity of drug solutions and their local irritant effect on tissues at the sites of subcutaneous, intramuscular and intravenous injections. Therefore, currently injectable solutions considered to be of high quality may not have isotonic activity and high postinjection safety.Text. A study of the concentration range of quality drug solutions ready for injection showed that the acceptable concentration value of the main ingredients is in the range of 0.01 to 76 %. Direct measurement with an osmometer of the osmotic activity of injection solutions, considered qualitative today, has shown that injection solutions can have hypotonic, isotonic and hypertonic activity and their osmotic activity can be in the range of 0 – 3900 mosmol/l water. Study of acidic activity of drug solutions showed that in accordance with pharmacopoeial requirements of drug quality modern quality drug solutions ready for injection can have acidic, neutral or alkaline activity. Solutions with hypertonic activity have been found to have a local irritant effect. Moreover, an increase in hypertonic activity of drug solutions increases their local irritant effect. It has been found that excessively high hypertonic activity of drug solutions may be the cause of the development of a local postinjection complication known as "Nicolaou syndrome", the cause of which has remained unknown for a long time. Nicolaou syndrome includes local pain syndrome, aseptic inflammation, necrosis, and abscess.Conclusion. The authors conducted a literature review, the results of which led to conclusions and assumptions. Solutions containing drugs in concentrations greater than 10 % may have the highest hypertonic activity, which can cause excessive dehydrating, local irritating and cauterizing effects. Therefore, injections of such drugs are most dangerous with the development of post-injection necroses and abscesses. That is why timely dilution of concentrated drug solutions with water by 2–10 times increases injection safety. It is proposed to include the assessment of osmotic activity and local irritant effect of drug solutions in the standard of drug quality control.

No abstract