Catad_tema Chronic cerebral ischemia - articles

Therapy of chronic cerebral vascular insufficiency

M.Yu. Martynov, I.A. Shchukin, A.A. Nikonova, I.E. Serdyuk, A.P. Glukhareva
Russian State Medical University, Department of Neurology and Neurosurgery

The increase in the population of elderly and senile people in recent decades leads to an increase in the prevalence of diseases associated with this age group, including ischemic cerebral disease. The term “ischemic cerebral disease” was proposed by N.K. Bogolepov to combine a variety of acutely and chronically developing ischemic disorders, which are based on a discrepancy between the metabolic needs of brain tissue and substances entering the brain from the blood.

Ischemic cerebrovascular accidents include acute (transient and persistent cerebrovascular accidents) and chronic forms. The development of acute cerebrovascular accidents is usually preceded by chronic, long-term changes in the brain caused by an increasing deterioration in the blood supply to the brain and changes in its metabolic needs.

Pathogenesis of ischemic brain damage
The functioning of the brain requires large amounts of energy. At the same time, nervous tissue has limited energy resources, so an indispensable condition for maintaining its functional activity is consistently high perfusion. To meet the constant need of brain tissue for energy substrates and oxygen, about 14% of the total volume of circulating blood normally flows through the brain, which makes up approximately 2% of the total human body weight. At the same time, the brain utilizes about 20% of the total oxygen consumed by the body. On average, cerebral blood flow in people 20-35 years old is 75-80 ml per 100 brain matter per minute and decreases by 2.5-3.5 ml every ten years, reaching 60-65 ml at the age of 70 years and older. The most significant changes in cerebral blood flow are observed in the frontal, temporal and parietal regions. Glucose consumption in young people is 5.5-7.0 mg per 100 g of brain matter per 1 minute and also decreases with age. The addition of vascular diseases and risk factors accelerates the involution-induced decrease in cerebral blood flow, which contributes to a more significant decrease in the production of neurotransmitters, disruption of electrogenesis processes and limitation of brain functionality.

In recent years, the main stages of the pathophysiological cascade of brain damage during acute ischemia have been established. It has been shown that the transition of reversible hemodynamic, cellular and molecular changes in the area of ​​the ischemic penumbra into persistent ones with the formation of a zone of necrosis is associated with the severity of glutamate “excitotoxicity”, with the activation of intracellular enzymes and the accumulation of intracellular Ca 2+, increased synthesis of nitric oxide, and the development of oxidative stress and local inflammatory response, damage to the BBB and microcirculatory disorders. At the same time, it has been revealed that, despite the presence of universal patterns, the process of cerebral ischemia is largely individual and the features of its course are determined by the state of collateral circulation, characteristics of brain metabolism, the status and reactivity of the endocrine and immune systems. As a result of the studies, a position on the dynamic nature and potential reversibility of ischemic damage was formulated. With chronic cerebral ischemia, there is also a decrease, although not as pronounced as in the penumbra during a stroke, in cerebral blood flow with hypoxia of brain tissue and a cascade of biochemical changes, which entails diffuse changes in the substance of the brain.

Etiology of ischemic cerebral circulatory disorders
The main etiological factors of ischemic cerebrovascular accidents are atherosclerosis, hypertension or arterial hypertension and their combination.

With age, especially in people over 70 years of age, the importance of atherosclerotic lesions of the extra- and intracranial sections of the main arteries of the neck and head increases, and not only the severity of stenosis plays a role, but also the spread of the process to other vascular areas. The role of severe arterial hypertension as the main cause is somewhat reduced. At the same time, the frequency of combination of atherosclerotic lesions of the great vessels of the neck and head with mild and moderate forms of arterial hypertension is increasing. IHD is of great importance, especially complicated by myocardial infarction, which probably reflects a decrease in compensatory capabilities to maintain adequate central (cardiac) and cerebral hemodynamics. A certain role in the development of chronic cerebrovascular insufficiency is played by disturbances in the rhythm of cardiac activity, especially of a paroxysmal nature, which can lead to a decrease in systemic blood pressure and transient episodes of cerebral ischemia. Diabetes mellitus also plays a role in the development of chronic cerebrovascular insufficiency, but its effect is small, being an additional factor that accelerates the atherosclerotic process and affects blood rheology and endothelial function. In patients with vertebrobasilar insufficiency, the condition of the cervical spine (osteochondrosis) is important. Changes in the rheological properties of blood, which are represented by increased viscosity of blood and plasma, aggregation activity of blood cells, and fibrinogen levels, also have a significant impact on the progression of cerebrovascular insufficiency. A certain role, especially in younger people, is played by hereditary predisposition, alcohol abuse, smoking, excess body weight, the development of metabolic syndrome, and insufficient physical activity.

Diagnosis of chronic cerebral vascular insufficiency
Diagnosis of chronic cerebral vascular insufficiency is carried out on the basis of anamnestic, clinical and instrumental methods. Data from additional and laboratory research methods such as computed tomography and magnetic resonance imaging, Doppler ultrasound and duplex scanning, study of the hemostatic system and 24-hour blood pressure monitoring are extremely important for making a diagnosis, selecting therapy and determining the prognosis. The use of neuroimaging research methods - computer and magnetic resonance imaging in patients with chronic cerebrovascular insufficiency allows us to study the state of external and internal liquor-conducting spaces, white and gray matter, and identify previously suffered strokes. In addition, a combined analysis of MRI (CT) results, ultrasound data, clinical features of the course of vascular diseases and risk factors allows us to predict with a certain degree of probability the possibility of developing a stroke and its probable location. The results of CT and MRI studies performed over time indicate a certain sequence of changes in the liquor-conducting spaces and in the substance of the brain as cerebral vascular insufficiency increases. The earliest changes are manifested by a slight expansion of the external (mainly in the frontal and parietotemporal regions) and internal liquor-conducting spaces and changes in the white matter in the form of “caps” near the anterior and posterior horns. These changes are nonspecific and are also detected in elderly, and especially senile, people without vascular diseases and risk factors, reflecting involutional processes. With the progression of the vascular process in the brain, changes in the liquor-conducting spaces and in the substance of the brain become more pronounced. Further expansion of the subarachnoid spaces and the ventricular system is observed. Changes in the white matter of the brain extend to the periventricular and deep regions and are represented by extensive, often merging areas of high signal intensity on T2-weighted MRI images. In approximately 50% of those examined, focal changes in the brain substance are detected, reflecting previous, clinically undiagnosed (“silent”) strokes. Zones of “silent” ischemia are predominantly localized in the deep parts of the cerebral hemispheres and usually do not exceed 10-15 mm in diameter.

The use of ultrasound scanning allows one to assess the nature and direction of blood flow through the vessels, the linear and volumetric velocity of blood flow through the extra- and intracranial parts of the vascular bed, the degree of narrowing of the arteries, the presence and characteristics of collateral blood flow, and the state of vasomotor reserves. Duplex scanning or ultrasound angiography is recommended to clarify the structure of the atherosclerotic plaque and the mechanism of stroke (arterio-arterial embolism). According to duplex scanning data, changes in the intima-media index, the extent of damage to the vascular bed, the degree and localization features of stenotic processes, and the presence of collateral circulation are determined.

Rheoencephalography allows you to obtain information about the blood supply to the cerebral vessels, the state of vascular tone and venous outflow from the cranial cavity, as well as the effect of the cervical spine on the vertebral arteries and adjust the prescription of vasoactive drugs. Rheoencephalography makes it possible to detect vertebrogenic effects on the vertebral arteries from the cervical spine. Normally, during the test, there are no significant changes in the amplitude and shapes of rheographic waves, while with a compressive effect on the vertebral arteries from the cervical vertebrae, a significant asymmetry (more than 30%) of the amplitude of the signals occurs in combination with signs of increased vascular tone. Angiographic studies can be recommended to obtain more complete information about the condition of the extra- and intracranial parts of the vascular bed, to clarify the cause of cerebral vascular insufficiency and methods of treating the patient. The most commonly performed is magnetic resonance angiography.

The study of the hemostasis system reveals an imbalance of the procoagulant and anticoagulant systems with a lack of natural anticoagulants, changes in the rheological properties of blood, which are manifested by an increase in spontaneous and induced aggregation of formed elements, viscosity of blood and plasma.

Fundus examination, ECG and ECHO-CG registration (detection of mural thrombi), determination of high and low density lipids, atherogenicity index and other biochemical blood parameters are of diagnostic value. Taking into account these parameters allows not only to improve the quality of diagnosis, but also to more rationally plan treatment measures.

Treatment of chronic cerebral vascular insufficiency
Treatment of chronic cerebrovascular insufficiency should include interventions aimed at the underlying disease against which it develops (atherosclerosis, arterial hypertension, heart disease, diabetes, etc.), correction of the main syndromes, improvement of cerebral hemodynamics, rheological properties of blood, and administration of metabolic therapy.

Blood pressure correction
One of the most significant indicators that require adequate correction is blood pressure. In older people with long-term arterial hypertension, changes in the daily rhythm of blood pressure may be observed with excessive or, on the contrary, insufficient decrease or increase at night. In these cases, it is mandatory to conduct 24-hour monitoring to correct blood pressure taking into account the data obtained. Preference should be given to long-acting antihypertensive drugs, but the selection of drugs should be made taking into account the individual characteristics of the patient and his response to the prescribed drugs. Individually based selection of antihypertensive drugs based on the results of pharmacogenetic studies is very promising. The most optimal figures for systolic blood pressure against the background of drug correction in such patients are 130-150 mmHg. A separate group of patients is represented by patients with multiple stenotic processes. The increase in blood pressure in these cases may be compensatory, aimed at maintaining adequate cerebral perfusion, and its correction in these cases should be especially careful.

Correction of rheological properties of blood
Correction of the rheological properties of blood is extremely important. The use of antiplatelet drugs is justified in case of increased aggregation activity of platelets and erythrocytes. At the same time, in these cases, smokers should stop smoking or reduce the number of cigarettes they smoke. The most commonly prescribed are acetylsalicylic acid, dipyridamole, pentoxifylline, cinnarizine, clopidogrel, ticlopidine in individually selected doses. When taking these drugs, as well as when changing the dosage or switching to taking another drug, it is necessary to re-monitor the indicators of spontaneous and induced aggregation activity of platelets and erythrocytes. It is also possible to use nicotinic acid preparations, but it is necessary to take into account the possibility of tachycardia, discomfort in the heart and behind the sternum, and difficulty in venous outflow from the cranial cavity. More difficult is the correction of increased blood and plasma viscosity. To normalize these indicators, it is recommended to optimize the drinking regime, sharply reduce or stop smoking and drinking alcohol, and normalize blood pressure. It should also be noted that the presence of concomitant dyslipidemia worsens the rheological properties of the blood and makes it difficult to normalize them, therefore, in such patients, along with the prescription of antiplatelet drugs, it is necessary to use cholesterol-lowering drugs, as well as a diet. Anticoagulants are prescribed for cardiac arrhythmias in combination with the presence of a blood clot in the left side of the heart according to echocardiography. Preference is given to indirect anticoagulants. When taking drugs of this group, monitoring of the international normalized ratio (INR) is mandatory. Optimal INR numbers are 2.5-3.0. It must be remembered that in elderly people with concomitant liver pathology, titration of the anticoagulant dose and monitoring of the INR should be carried out especially carefully. In case of severe atherosclerotic damage to the internal carotid arteries (stenosis more than 70%), along with antiplatelet agents and lipid-correcting therapy (diet, statins), the issue of reconstructive surgery on the internal carotid arteries can be discussed.

Application of metabolic agents
Along with the prescription of drugs that affect blood pressure and the rheological properties of blood, metabolic agents occupy a large place in the treatment of chronic cerebrovascular insufficiency. The use of metabolic drugs can improve metabolic processes in the brain, reduce the acute and long-term consequences of ischemic damage in the form of the development of excessive synthesis of nitric oxide, oxidative stress, increased BBB permeability, activation of microglia, microcirculation disorders, and trophic dysfunction. For these purposes, nootropic and amino acid drugs, neurotransmitters (glycine, Semax, piracetam, Actovegin, Cerebrolysin, gliatilin, etc.) are used.

A summary of the manufacturer's information on drug dosing in adults is provided. Before prescribing the drug, read the instructions carefully.

One of the combination drugs that has a metabolic effect and an effect on the vascular system of the brain is fezam. Phezam is a synergistic combination of piracetam (400 mg) and cinnarizine (25 mg). The action of Phezam is carried out due to piracetam, which enhances energy metabolism, has a neuroprotective effect, increasing the resistance of brain cells to hypoxia, facilitates the transmission of impulses in synapses, and due to cinnarizine, which has a vasodilating effect due to blocking L-type calcium channels and enhancing the antihypoxic effect piracetam. In addition, cinnarizine affects the rheological properties of blood, reducing spontaneous and induced platelet aggregation and improving the elasticity of erythrocyte membranes. Studies conducted by domestic neurologists (A.N. Boyko et al., 2002) showed that taking Phezam helps reduce the severity of subjective symptoms, improve kinesthetic tests and cognitive functions, quality of life indicators, social adaptation of patients, including the elderly with chronic cerebrovascular insufficiency. It is important to note the safety of Fezam and a small number of contraindications.

Metabolic therapy is a method of correcting metabolism for the improvement, rehabilitation and treatment of people. It is now known that any tissue of the body has the ability to regulate metabolism by autocrine, paracrine or endocrine mechanisms. Depending on the source of regulatory molecules, three options for metabolic therapy can be divided: autogenous, allogeneic and xenogeneic.

To achieve the goals of metabolic therapy, various factors and medical technologies are used. Let's look at some metabolic therapy options.

Metabolic therapy through the influence of biophysical factors on the body. When exposed to various physical factors (heat, cold, vibration, massage, ultrasound, electromagnetic vibrations, hypoxia, etc.), the homeostasis of metabolites in the body tissues is temporarily disrupted. This initiates the inclusion of nonspecific (stress-related) and specific (neurohumoral and metabolic) reactions, which serve to return the parameters of the internal space of the body to their original state. Such endogenous reactions, triggered by exogenous physical factors, often return metabolic parameters to the optimal range for a given age. They are used to treat many diseases. The physiotherapist must select the strength of the physiotherapeutic effect on the body so that optimal reactions develop that ensure treatment of the disease. For group metabolic therapy, hypobaric oxygen therapy is used. In the Republic of Belarus there are pressure chambers in which many diseases are treated by keeping patients under conditions of low atmospheric pressure (high-altitude model). In Vitebsk there is a pressure chamber with 20 seats. Good results have been obtained in treating patients with bronchial asthma, hypertension, diabetes mellitus, etc. After treatment in a pressure chamber, the nonspecific resistance of the patient's body increases. This medical technology improves the performance and resilience of people in extreme situations. It is advisable to support the treatment of patients in a pressure chamber with biologically active food additives. Of interest to xenobiology are climatic pressure chambers (including mobile ones), in which, with the help of chemicals, a modified atmosphere is created that is useful for the treatment of diseases of the lungs and other organs. This is a method of targeted introduction of xenobiotics into the body through the lungs.

Therapy with exogenous low molecular weight bioregulators and macromolecules. All medicines are divided into natural (biogenic) and foreign (xenobiotics). Natural drugs are natural products of living organisms and they are able to be included in cellular metabolism (amino acids, hexoses, fatty acids, vitamins, hormones, blood and tissue preparations, etc.). These substances are characterized by biocompatibility and are used to achieve metabolic therapy goals. Xenobiotics are normally absent from the human body or are found in trace amounts. These drugs are obtained through the process of organic synthesis or they can be extracted from other organisms (microorganisms, plants, etc.). These substances are the object of study in pharmacology. The boundary between biogenic drugs and xenobiotics is arbitrary, since their final effects are realized at the metabolic level using the same molecular mechanisms. Currently, more than 30 groups of biologically active substances of plant origin are known: α- and γ-benzopyrene derivatives, lignans, quinones, iridoids, plant indoles, polysulfates, isothiocyanates, terpenoids, carotenoids, dolechols, stilbenes, phytosterols, lectins, low-molecular peptides, etc. For example, based on the analysis of the content of low molecular weight nitrogen-containing substances in the extracts of the Sasola collina Pall herb, their following use is justified:

· to stimulate reduced protein metabolism through the additional introduction of a full set of amino acids, including 8 essential amino acids;

· to maintain metabolism in nervous tissue, muscles and kidneys due to the additional production of amino acids with branched radicals (valine, leucine, isoleucine);

· to stimulate urea formation in the liver and the formation of conjugates of metabolites and xenobiotics as components of the antitoxic function of the liver (aspartate, citrulline, ornithine, taurine);

· to maintain insulin biosynthesis and the manifestation of insulin-like effects.

Among the large number of low-molecular bioregulators of animal origin, a special place is occupied by peptide bioregulators: endogenous “cytomedins”, which control gene expression and protein synthesis, “cytamins” - nucleoprotein complexes, as well as “cytogens” - preparations from various tissues that are capable of specific action in different tissues. regulate protein metabolism.

Now about 40 percent of the drugs included in the State Pharmacopoeia of the Republic of Belarus are of plant origin. Medicines from plants make up over 30 percent of all medicines produced in the world. In recent years, the interest of scientists in medicinal plants has increased markedly. Their attention is focused on such seemingly long-known plants as valerian, dried grass, viburnum, hawthorn and many others. And the whole point is that modern equipment and new research methods make it possible to rethink the place of a particular plant among other medicinal products, and to study the biologically active substances that make up medicinal plants at a higher level. New prospects are also opening up for the development of more advanced technology for the production of already known drugs, as well as for the creation of new highly effective drugs.

The effectiveness of herbal preparations is largely explained by the fact that the biologically active compounds they contain have a complex effect on the human body, causing a certain therapeutic effect. Biologically active substances are formed during the life of plants and animals and effectively affect metabolic processes in the cells of the body, have a strong antiseptic, anti-inflammatory, antimicrobial, soothing, astringent, tonic, softening effect.

Medicinal plants have another advantage: they are a natural source of a number of vital microelements - manganese, copper, cobalt, molybdenum, zinc, iron. With homeopathic medicines and biologically active food supplements, the body receives the microelements it needs. Their deficiency leads to serious diseases.

Homeopathic medicines and dietary supplements are especially often prescribed for the following diseases:

· for diseases of the musculoskeletal system and muscular system;

· for diseases of the respiratory system;

· for diseases of the digestive tract;

· for pain;

· for diseases of the central nervous system.

An important law of homeopathy is the law that states that an increased dose of a medicinal substance suppresses the system, a moderate dose can paralyze it, and a small (homeopathic) dose has a stimulating effect.

The cause of exacerbation of a number of diseases, such as bronchial asthma, asthmatic bronchitis, may be the excessive use of antibiotics, drug therapy, chemicals in everyday life, gas pollution and air pollution from industrial enterprises, which causes real outbreaks and epidemics of allergic diseases. This is why homeopathic remedies are now acquiring particular value, since they allow the doctor to prescribe antibiotics only in the most extreme cases. When prescribing homeopathic remedies, the patient’s age and duration of the disease, developmental characteristics, constitution and heredity, characteristics of reactions to environmental factors, as well as tolerance of drugs and other influences, previous and concomitant diseases, causes of the development of the disease and its exacerbation, clinical features, are taken into account. the presence of allergies, previous treatment and other factors.

The raw materials for homeopathic medicines are: minerals (30%), animal materials (10%) and plant materials (60%), from which about a thousand homeopathic medicines are prepared. Medicines are prepared in the form of drops, powders, grains, ointments. It should be noted that some homeopathic medicines are prepared, as in herbal medicine, from plant materials. Herbal treatment is the effect on the body of plant molecular agents, which is toxic, and in this sense, undoubtedly, inferior to homeopathic treatment.

The minerals that make up homeopathic preparations are actively involved in the regulation of many physiological functions, which include, in particular, the transport of oxygen to every cell of the body, the production of discharges leading to muscle contraction, and a variety of actions that ensure the normal functioning of the central nervous system. Mineral elements are necessary for growth, vital functions, restoration and maintenance of healthy tissue and bones.

The famous American scientist F.D. Moore (1959) proposed the concept of “metabolic care”, which correctly characterizes the principles and essence of metabolic therapy. He and other scientists expressed the opinion about the need to create specialized laboratories for monitoring metabolism in surgical, pediatric, oncology and other clinics.

The greatest advances have been made in the technology of intravenous metabolic therapy (parenteral nutrition). The following drugs are commonly used for parenteral nutrition.

Squirrels. The body can be provided with proteins by intravenous administration of whole blood, red blood cells, plasma, albumin and amino acid mixtures. Only with the help of amino acid mixtures containing a full set of essential amino acids can protein metabolism in cells be adequately maintained.

Carbohydrates. For intravenous nutrition, solutions of glucose, fructose (metabolized faster than glucose), maltose (has an osmotic activity half that of glucose), sorbitol (easily converted into fructose), xylitol (included in the pentose phosphate pathway of carbohydrate metabolism) are used. , glycerol (close in caloric value to glucose, but has twice the osmotic effect).

Lipids. Fat emulsions used for intravenous nutrition must have the properties of chylomicrons (intralipid, lipofundin-S, liposin-2, venolipid, emulsan). These preparations contain vegetable oil and emulsifiers to stabilize the emulsion. It is necessary to introduce into the body essential fatty acids containing 2 or 3 double bonds (linoleic and linolenic). Considering the introduction of substrates for lipid peroxidation in the form of substances with unsaturated fatty acids, care should be taken to provide additional antioxidants (vitamins E, C, carotenes, etc.).

Essential microelements(contents are normal< 50 мкг/г ткани). При натуральном питании к ним относятся железо, йод, кобальт. При внутривенном питании следует дополнить цинком, медью, селеном, хромом, молибденом; фтор относится к полуэссенциальным элементам.

Vitamins. A balanced multivitamin preparation should include vitamins that act as cofactors for enzymes of the general catabolic pathway (B 1,2,3,5,6, lipoic acid), as well as biotin, ascorbic acid, folic acid, cyanocobalamin, and the amount of fat-soluble vitamins.

For enteral correction of metabolism, natural substances and their components can be used in the form of biologically active additives - nutrients. Nutrients complement daily food with essential components. The main forms of production of natural biologically active additives are teas, mixtures, liquid extracts, dry lyophilized extracts, granules and capsules (in the presence of irritating components).

Metabolic therapy through influencing endogenous regulators of metabolism: components of autocrine, paracrine, endocrine, neurotransmitter and other regulatory mechanisms. To illustrate this point, it is enough to recall the molecular mechanisms of interaction of morphine or endogenous peptides (endorphins) with opioid receptors in the brain or the biosynthesis of leptin in fat cells as a way to regulate appetite and the expenditure of energy resources through the hypothalamus. In the functioning of these complex molecular processes, biologically active food additives can contribute both the elements necessary for the synthesis of control (regulating) molecules and natural analogues of such molecules. For example, the presence of amino acids with branched radicals can determine the positive neurotropic effect of preparations from the herb Salsola collina Pal and other medicinal plants.

Cellular metabolic therapy involves influencing metabolism through the introduction of autogenous, allogeneic or xenogeneic cells. For example, to prevent diabetic angiopathy, the injection of beta cells from the pancreatic islets of newborn piglets or rabbits is used. It is assumed that such cells can complement the work of similar cells in the patient’s body. However, in our opinion, it is more likely that the breakdown products of these cells in the body can act as activators for the functioning or proliferation of the body’s own endocrine cells.

Metabolic therapy should be based on fundamental molecular processes and determined by the molecular mechanisms of the development of pathological processes:

· metabolic processes are interconnected and have a certain direction (vector of transformations). The strength of the xenobiotic's effect depends on the ability of its active principle to objectively influence the direction of metabolite exchange, i.e. Metabolism fragment vector.

· The general metabolic strategy is to preferentially convert hydrophilic metabolites into hydrophobic ones, which leads to permanent accumulation of lipids (cholesterol) as a person moves through the life scale. In this regard, systems for hydrophilization of metabolites (for example, two stages of neutralization of xenobiotics) and excretion of hydrophobic molecules (liver and bile excretory organs) should be supported.

· Metabolic therapy should depend on the primary mechanisms of cell damage and death (apoptosis or necrosis); on the type of underlying pathological process (hypoxia, inflammation, trauma, etc.); on the state of communications (blood and lymphatic vessels, nerves); on the characteristics of the patient’s interaction with the environment (circadian rhythms, the effect of physical factors, food composition, the state of the central nervous system analyzers, features of the homeostasis of substances, etc.).

The widespread introduction of metabolic therapy technologies requires the development and improvement of the legislative framework for the use of parapharmaceuticals, dietary supplements and genetically modified nutrition. This is a new problem for the Republic of Belarus. In the USA and the countries of the European Union, GLP and GCP rules are used to study the pharmacological activity of xenobiotics and the safety of their effects on humans.

GLP rules

Since 1976, when the rules of Good Laboratory Practice (GLP) were first proposed in the United States, technologies for preclinical testing of xenobiotics - potential drugs and other biologically active substances - have been improved in many countries. The main goal of GLP is to ensure the reliability of the results of preclinical tests of natural and synthetic xenobiotics, guaranteeing their safety for humans and animals. In 1992, Russia adopted the Rules for Preclinical Evaluation of the Safety of Pharmacological Drugs (GLP, ZV 64-126-91). Main objectives of the Rules:

· ensure high quality and reliability of preclinical testing of the safety of pharmacological agents;

· create a modern and functionally reliable administrative structure of the testing center to carry out preclinical studies in accordance with international requirements;

· develop and implement clear documentation of preclinical trials into the practice of the center (protocol, standards for research methods; data registration form and final report);

· determine the requirements for test substances and reference preparations;

· ensure testing of standard biomodels on animals and guarantee the necessary conditions for their maintenance, feeding, use in experiments and humane treatment;

· create a service for the quality assessment of tests performed, rules for their control and issuance of a conclusion based on the results of the inspection.

The safety study of xenobiotics (new original potential drugs) is carried out in full: general toxicity (acute, subacute, chronic, local irritant effect, cytotoxicity), specific toxicity (drug dependence, antigenicity, teratogenicity, mutagenicity, carcinogenicity), pharmacokinetic studies (absorption , distribution, excretion, metabolism, bioavailability), general pharmacological action and pyrogenicity of injectable xenobiotics.

All chemical compounds have varying degrees of biological activity (BA) - the ability to affect living matter.

The variety of types of biological activity is determined by:

1) a variety of biological objects and a variety of reactions occurring in them;

2) depends on: the method of entry of the substance into the body, the dose; from physical form; on modes of administration;

3) on the presence or absence of additional influences (physical factors, temperature, humidity, etc.);

4) on the method, principle of selection, observation of biological objects and analysis of the information received.

The goals of determining the types of biological activity of chemical compounds:

· compounds that have beneficial properties (treatment of diseases, expansion of physiological and intellectual capabilities) are well found;

· detection of xenobiotics harmful to the body, since the danger lies in the further manifestation of their action (mutagenicity);

· finding such biological activities that can cause irreversible, uncontrollable, dangerous, unpredictable disturbances in the biological balance of natural ecosystems;

· finding chemical compounds that can be reagents and can lead to the development of fundamentally new research methods;

· accumulation of knowledge that allows one to predict the types of AD based on the chemical structure of the substance.

The desired ratio of introduction of the number of new chemical compounds is studied according to the hourglass principle: grains of sand - chemical compounds; narrow field - a system where compounds are tested for biological activity. Those substances that have crossed the isthmus are promising. The accumulation time is determined by the ability of the isthmus to pass substances (BA area).

The entire array of foreign chemical compounds is subjected to biological testing. We are talking about the organization of a testing system - its significance, the formation of an information array of the foundation of scientific knowledge about the biological activity of foreign chemical compounds.

The final result is certification of each of the xenobiotics according to their biological properties (biological passport).

An analysis of the frequency of prescriptions of various drugs in Ukraine in recent years demonstrates a strong tendency towards the leadership of so-called metabolic drugs, that is, drugs that affect metabolic processes in the body (absorption of glucose and oxygen by tissues, lipid peroxidation, etc.). In fact, upon detailed analysis, it turns out that there is, perhaps, not a single drug that does not directly or indirectly affect cell metabolism.

Antihypertensive drugs, vasoactive nootropics, venotonics, antiplatelet agents optimize blood circulation in organs and tissues, prevent sludge of red blood cells in the capillary bed, eliminate venous discirculation and thus contribute to the activation of metabolic processes, improving the absorption of oxygen from the blood perfusing the organ. In addition, many drugs have additional non-hemodynamic (pleiotropic) properties, which also affect the state of metabolism, tissue trophism and plastic processes in them. A classic example is ACE inhibitors and sartans, which exhibit cardio-, nephro-, and cerebroprotective effects even in normotensive individuals.

The breadth of the spectrum and diversity of metabolic influences do not allow the creation of a more or less consistent classification of metabolic agents, therefore most of them are considered in accordance with their predominant effect on a particular organ - hepatoprotectors, cardioprotectors, nootropics, or according to the predominant mechanism of action - antioxidants, antihypoxants, anabolics . There are also drugs with complex action, which include a number of biologically active substances that affect various parts of cellular metabolism. Such drugs include deproteinized blood dialysates (solcoseryl, actovegin), derivatives of embryonic tissue and brain tissue. The multicomponent nature of these drugs makes it difficult to specify the mechanism of action and directs the doctor exclusively to the clinical effects of their use.

The dilemma of metabolic therapy is that, on the one hand, there is practically no evidence base for improving the prognosis when using these drugs, and on the other, the clinical effect on the symptoms of a number of diseases caused by chronic hypoxia and ischemia is clearly recorded by doctors. Therefore, despite criticism in scientific articles of our doctors’ excessive enthusiasm for metabolic therapy, doctors continue to widely prescribe it. What can we expect from metabolic therapy?

Conversations with doctors allowed us to identify the following expected effects of metabolic drugs (doctors' answers):

• improvement of ischemia tolerance without hemodynamic reactions (elimination or reduction of ischemic symptoms);
• improvement of indicators of the functional state of the heart (increase in ejection fraction, elimination of ischemic changes on the ECG, decrease in the number of extrasystoles);
• improvement of the patient’s general condition and quality of life;
• elimination of vegetative imbalance;
• reduction of manifestations of asthenia;
• reducing the severity of anxiety and depressive disorders;
• improvement of liver function (normalization of enzyme parameters, bilirubin, elimination of bitterness in the mouth, feeling of heaviness in the right hypochondrium);
• increasing the effectiveness of basic pathogenetic therapy (mainly antihypertensive drugs).
• Obtaining an evidence base for metabolic agents is significantly complicated by the fact that it is almost impossible to identify the specific pathology for which they are indicated. In fact, these are all conditions (conditions, not just nosological forms) associated with metabolic disorders and hypoxia:
• arterial hypertension;
• atherosclerosis and its clinical manifestations in the form of ischemic syndromes (coronary heart disease (CHD), chronic cerebral ischemia, circulatory disorders in the lower extremities);
• chronic heart failure;
• dysfunction of the thyroid gland (including subclinical forms of hypothyroidism);
• anemia (due to chronic diseases, iron deficiency);
• latent iron deficiency;
• chronic renal failure;
• liver diseases (hepatitis, fatty hepatosis, cirrhosis);
• dyshormonal disorders in women during menopause;
• diabetes mellitus (DM) and metabolic syndrome;
• natural aging.

In clinical trials of metabolic drugs, it is almost impossible to establish efficacy endpoints, since the expected effects of such therapy cannot always be objective. This is an improvement in the general condition according to the patient, a decrease in anxiety, autonomic disorders, asthenia, and an increase in exercise tolerance. Metabolic therapy is a therapy that primarily affects symptoms, but it is the relief of symptoms of the disease that the patient primarily expects from the doctor. The importance of symptomatic therapy, along with etiotropic and pathogenetic therapy, is noted in a number of clinical guidelines. For example, partial inhibitors of fatty acid oxidation are included in European recommendations for the treatment of stable angina as agents that affect clinical symptoms and the severity of ischemia.

Let us analyze in more detail typical situations in which doctors use metabolic therapy.

Natural aging and age-related changes that contribute to chronic ischemia of tissues and organs

One cannot but agree that metabolic therapy is most often prescribed to patients in older age groups. And it is precisely in elderly and senile age that such symptomatic treatment, prescribed in addition to the basic therapy of the underlying disease, has significant clinical effects. This is due to the fact that age-related changes in the body themselves create conditions for chronic hypoxia and ischemia of tissues and organs.

Aging is a naturally occurring destructive process that leads to a limitation of the body’s adaptive capabilities, an increased likelihood of death, a reduction in life expectancy and the development of age-dependent pathologies. A common problem for elderly patients is polymorbidity - several diseases observed simultaneously, often pathogenetically related to each other (hypertension and coronary heart and brain disease). The basis for polymorbidity is created by age-related changes in the aging body, which can aggravate each other and manifest themselves over time as a clinically significant pathology. The most typical pathological process accompanying aging is chronic hypoxia and its consequence - ischemia of organs and tissues of the body. Well-known gerontologists (I.V. Davydovsky, D.F. Chebotarev, V.V. Frolkis, O.V. Korkushko, A.V. Tokar) describe a number of age-related changes in the vascular bed, rheological properties of blood, which underlie the development age-dependent pathology.

As the body ages, the vital capacity of the lungs decreases against the background of age-related pneumosclerosis and emphysema; atherosclerosis of large vessels develops and the regulation of their tone is disrupted; depletion of the microcirculatory bed, desolation of some capillaries, and their obliteration are observed; the elasticity of red blood cells decreases, a sludge phenomenon is observed in the capillary bed; the activity of enzyme systems decreases, including enzymes of the mitochondrial respiratory chain, as well as antioxidant enzymes (superoxide dismutase, catalase), glutathione. All of the above creates conditions for the development of microcirculation disorders, chronic hypoxia and ischemia, which contributes to the development of new and progression of existing chronic diseases in an elderly person.

Chronic oxygen starvation of tissues leads to the activation of energetically unfavorable anaerobic glycolysis with the accumulation of lactic acid and the development of metabolic acidosis. Activation of lipid peroxidation and oxidative damage to cell membranes with dysfunction of ion channels are observed. In organs exposed to hypoxia, the content of connective tissue increases, which also leads to a decrease in their functional activity.

IHD, cerebrovascular diseases and obliterating vascular diseases of the lower extremities

The most common and socially significant diseases caused by hypoxia, ischemia and microcirculation disorders are ischemic heart disease, cerebrovascular diseases and obliterating diseases of the vessels of the lower extremities. These factors also play an important role in the pathogenesis of diabetes. It is not surprising that, along with basic therapy, doctors are trying to use metabolic agents for these diseases, the mechanisms of action of which are aimed at increasing the resistance of target organs to hypoxia and ischemia.

One of the most common cardiovascular diseases in the Ukrainian population is ischemic heart disease, which in this regard is practically not inferior to arterial hypertension (V.N. Kovalenko, 2005, 2010). Chronic forms of IHD significantly worsen the quality of life of patients, not only limiting their physical and social activity, but also creating a constant threat of fatal complications that require long-term, active and, as a consequence, expensive treatment. It is for IHD that metabolic drugs are most often prescribed in Ukraine today. Positive features of metabolic agents are the almost complete absence of undesirable hemodynamic effects, good tolerance by patients of all age groups, focus on the deep metabolic mechanisms of ischemia development and cardiomyocytoprotective effect (C. Lu, 1998; H. Szwed, 1999; V.K. Serkova et al., 2003; V.A. Vizir et al., 2006).

No less important is the problem of cerebrovascular diseases. In Ukraine, up to 110 thousand strokes are registered annually, and chronic cerebral circulatory insufficiency is noted by neurologists almost everywhere in elderly and senile patients with hypertension. In general, more than 2 million people with various cerebrovascular diseases are registered in Ukraine.

A frequent companion to coronary artery disease (in 42% of cases) and chronic cerebral ischemia (in 36% of cases) is obliterating atherosclerosis of the lower extremities (OALC), which manifests itself as a symptom of intermittent claudication. OANC affects up to 11% of the male population in developed countries. Among patients under 70 years of age, men predominate (the ratio of sick men to women is 3:2); among patients over 70 years of age, no gender differences are observed (ratio 1:1).

Due to the common pathogenesis of these diseases, their combinations are very often observed in elderly patients (P. Poredos, B. Jug, 2007; R. Sukhija, et al., 1998). In 42% of patients with coronary artery disease, obliterating diseases of the vessels of the lower extremities are diagnosed. 36% of patients with manifestations of dyscirculatory encephalopathy also have OANC. In 24% of patients with atherosclerosis, coronary artery disease, chronic cerebral ischemia and obliterating vascular diseases of the lower extremities can be detected simultaneously.

Among patients with OANK stage II according to Fontaine, 15-20% are patients with diabetes, and in the group of stages III and IV according to Fontaine, the proportion of patients with diabetes increases to 40-50%. The presence of obliterating atherosclerosis of the lower extremities is a serious risk factor for death from cardiovascular diseases: 70% of patients with OANK die from ischemic heart disease, 5% due to ischemic stroke. More than 50% of patients with OANK are susceptible to renal vascular stenosis, which can lead to the development of resistant hypertension and renal failure.

A modern doctor has wide pharmacological and non-pharmacological possibilities to influence ischemia both to improve the prognosis and to correct symptoms.

Increased arterial blood flow to the ischemic organ due to vasodilation:

• antihypertensive drugs for hypertension;
• prostaglandins in OANK;
• nitrates and sydnonimines for ischemic heart disease;
• vasoactive nootropics (vinpocetine, nicergoline) for chronic cerebral ischemia.

Increasing the lumen of the vessel and preventing vascular remodeling:

• statins, fibrates;
• antihypertensive drugs (ACE inhibitors, ARBs, calcium antagonists);
• surgical revascularization.

Normalization of the rheological properties of blood, elimination of the sludge phenomenon and suppression of thrombus formation in the microcirculatory bed:

• antiplatelet agents (acetylsalicylic acid, clopidogrel, etc.);
• anticoagulants (heparins and oral anticoagulants).

Stimulation of venous outflow:

• venotonics (rutins, escins, diosmin) for chronic cerebral ischemia, varicose veins of the lower extremities;
• therapeutic exercises for vascular diseases of the lower extremities (simultaneous stimulation of blood inflow and outflow).

Reducing the oxygen demand of an ischemic organ:

• limitation of physical activity for ischemic heart disease and OANK;
• beta blockers for ischemic heart disease;
• other antihypertensive drugs (reducing afterload on the myocardium);
• nitrates for ischemic heart disease (reducing preload on the myocardium).

Metabolic therapy:

• antihypoxants (improving ischemia tolerance, eliminating metabolic acidosis);
• antioxidants (reducing the effects of oxidative stress against the background of ischemia);
• energy substrates (providing energy to ischemic tissues).

Physiological meaning of metabolic therapy for diseases associated with hypoxia and ischemia

With chronic hypoxia (in an aging person against the background of widespread atherosclerosis), all organs and systems suffer, which significantly worsens the patient’s quality of life. The condition can be improved by increasing the oxygen content in the inspired air (oxygen cushions) or increasing the volumetric blood flow in the organ (more blood per unit of time - more oxygen delivery). The increase in volumetric blood flow is limited by morphological changes in the vessels (severe coronary atherosclerosis), which can expand in response to medication only to a certain limit. In this case, it is necessary to adapt to the lack of oxygen, maintaining viability under hypoxic conditions. Reducing the oxygen demand of an organ can be achieved by reducing its functional activity. Thus, beta-blockers reduce myocardial oxygen demand by reducing the frequency and strength of heart contractions. But this path also has certain limitations - it is impossible to reduce activity so much that it leads to functional failure of the organ. Therefore, there is a constant search for substances that can increase the efficiency of using incoming oxygen in ischemic tissues, figuratively speaking, “train” the organ to be content with little, while maintaining high functional activity. In conditions when vasodilators have already exhausted their potential (uncontrolled vasodilation is fraught with disturbances in the autoregulation of blood flow in vital organs), and a further decrease in the functional activity of organs can lead to their functional failure (bradycardia in heart failure is accompanied by a decrease in cardiac output), significant assistance in maintaining The viability of ischemic organs can be achieved precisely by metabolic means that increase the efficiency of oxygen use, switching cell metabolism to more economical pathways, protecting tissues from the effects of oxidative stress.

Various metabolic agents and their combinations provide broad opportunities to influence metabolic processes in cells and tissues:

• increasing tissue sensitivity to insulin;
• stimulation of glucose uptake by tissues, not mediated by insulin receptors;
• increasing the supply of oxygen to the cell;
• catalyzing the Krebs cycle by introducing energy substrates and coenzymes;
• reducing cellular calcium load and preventing associated excitotoxicity;
• binding of free radicals, antioxidant effect;
• elimination of lactic acidosis as a consequence of excessive activity of anaerobic glycolysis under ischemic conditions;
• inhibition of apoptosis processes.

All these mechanisms are implemented in all tissues where metabolic processes occur, so there is no metabolic therapy specific to a particular organ. Correction of metabolism always affects the body as a whole. Therefore, the use of metabolic agents is accompanied by an improvement in the general condition of patients even in the absence of objective changes in the functional activity of organs and vascular tone.

Asthenic syndrome and nonspecific complaints

Along with ischemic conditions, asthenic syndrome is a frequent reason for prescribing metabolic therapy. Asthenia and associated general, nonspecific complaints occur in the majority of patients who seek help from internal medicine specialists, most often in the elderly.

Asthenia is characterized by a state of neuropsychic and physical weakness, which is manifested by increased

fatigue, weakening or loss of ability for prolonged physical or mental stress. It is important to distinguish asthenia from fatigue. Fatigue is a physiological, adequate reaction of the body to stress, as a result of which a reversible decrease in activity develops, which occurs after normal rest and does not require special treatment. Fatigue develops gradually as a result of depletion of energy reserves, while asthenia is a consequence of impaired regulation of energy use and, unlike fatigue, does not disappear after rest.

Asthenic syndrome is characterized by a variety of clinical manifestations. In addition to the characteristic general weakness and increased fatigue, asthenia can manifest itself as headaches, dizziness, sleep disorders, decreased memory, attention, impaired appetite, muscle pain, sexual dysfunction, mood lability and disturbances in the volitional sphere: apathy, depression or, conversely, increased irritability, excitability, inadequate response to the environment.

An asthenic state can be of a functional or organic nature, and most often, both organic and accompanying functional disorders make a certain contribution to the deterioration of the patient’s condition. Functional asthenia is associated with neuroses, depression, hypochondria, and psychosomatic disorders.

Asthenia of organic nature observed in various somatic diseases. Causes of astheniametabolicorigin there may be hyperglycemia, hyperinsulinemia and insulin resistance in diabetes or metabolic syndrome; chronic renal failure; hypercalcemia with hyperparathyroidism and myeloma metastases to the bones; hyponatremia due to diuretic abuse; electrolyte disturbances in anorexia nervosa. Asthenia of endocrine origin observed in thyroid dysfunction and Addison's disease; asthenia due to hemodynamic disturbances- for congestive heart failure, arterial hypotension, including overdose of antihypertensive drugs. Asthenia of hematological origin characteristic of iron deficiency anemia and latent iron deficiency, as well as chronic leukemia and myeloma. Asthenic syndrome is always observed in the clinical picture of other oncological diseases. Asthenia of infectious origin develops in patients with viral hepatitis, AIDS, infectious mononucleosis and enterovirus infection. In addition, it occurs iatrogenic asthenia, which can be a side effect of treatment with beta-blockers (mostly non-selective) and other antihypertensive drugs (with an excessive decrease in blood pressure), as well as with the abuse of sleeping pills, tranquilizers and anxiolytics. We observed an asthenic state in elderly patients who had been taking a fixed combination of atenolol and chlorthalidone for a long time.

In elderly people, an asthenic condition may accompany chronic cerebral ischemia. In ICD-10 Section F 06.6 “Organic emotionally labile (asthenic) disorder” is presented, which is characterized by cerebrasthenic syndrome in the form of physical and mental weakness; pronounced and constant emotional incontinence or lability, fatigue, exhaustion; excessive painful sensitivity to external stimuli, intolerance to noise, bright light and autonomic disorders.

In old age and senility, asthenia may be accompanied by cognitive dysfunction. The condition under the heading GO6.7 “Mild cognitive impairment” is characterized by a decrease in cognitive productivity: mild disorders of memory, attention, learning difficulties and decreased performance; subjective feeling of mental fatigue when solving mental problems, trying to learn new things (even with objectively successful activities), cerebrasthenic symptoms, situational mood swings.

Asthenia significantly reduces the quality of life of patients and always requires treatment, regardless of its etiology. In the treatment of asthenia, both drugs that affect the central nervous system (antidepressants, anxiolytics, nootropics) and metabolic agents that have a direct effect on metabolic processes in tissues are used.

A typical representative of the group of metabolic agents, which has a complex effect on various parts of metabolism and energy, is Solcoseryl.

Mechanisms of action and clinical effects of Solcoseryl

Solcoseryl (Meda Pharmaceuticals Switzerland GmbH) is a deproteinized hemodialysate obtained by ultrafiltration from the blood of calves.

The original production technology makes it possible to preserve in the preparation a large number of biologically active components: substrates of plastic and energy metabolism (alanine, proline, glutamate, leucine, ornithine), neurotransmitters and their precursors (choline, glutamate, aspartate, adenosine, taurine, glycine), purine and pyrimidine bases (adenosine and uridine), enzyme complexes, as well as macro- and microelements (Mg, Na, Ca, P, K, Si, Cu, Se.

Thanks to the multiple mechanisms of action of the components of Solcoseryl, the energy and antioxidant potential of cells and tissues increases under conditions of chronic ischemia.

The main metabolic effects of Solcoseryl:

• insulin-like effect- increased uptake of glucose by cells, not mediated by insulin receptors;
• activation of oxidative phosphorylation enzymes(pyruvate and succinate dehydrogenases, cytochrome C oxidase);
• acceleration of the breakdown of anaerobic glycolysis products(lactate, P-hydroxybutyrate) and elimination of metabolic acidosis;
• stimulation of aerobic glycolysis in vascular endothelial cells, which promotes the release of prostacyclin and nitric oxide (potentiation of vasodilatory reactions);
• support of the endogenous antioxidant system.

The basis of the clinical effects of Solcoseryl in diseases associated with chronic ischemia is the improvement of transport, glucose utilization and oxygen absorption by cells and tissues. Solcoseryl oligosaccharides activate the transport of glucose into the cell, bypassing insulin receptors. In experimental studies conducted on liver homogenate and liver cell mitochondria, adding 0.2 ml of Solcoseryl to the culture increased oxygen consumption by cells by 200% already at the thirtieth minute after administration (Jaeger et al., 1965).

The antioxidant effect is due to the presence of magnesium and microelements included in the prosthetic group of the superoxide dismutase enzyme. Solcoseryl reduces the activity of free radical oxidation by 24-38%.

Serofendic acid, which is part of Solcoseryl, has an antiplatelet and antioxidant effect. Hexosylceramide stimulates angiogenesis and collagen synthesis, which explains the reparative properties of Solcoseryl (Schreier et al., 1993). Thanks to its experimentally and clinically proven ability to accelerate reparative and regenerative processes in damaged tissues (Y. Yamasaki, 1990; H. Herrschaft, 1997; M. Eckhardt, A. Yaghootfam et al., 2005), solcoseryl was widely used in the treatment of ulcers of the lower extremities - diseases, stomach and duodenal ulcers.

The effectiveness of solcoseryl was demonstrated by German researchers in patients with OANK with Fontaine stages III-IV. The drug was administered intravenously initially at 20 ml/day for 10 days, and then for another 10 days at 5 ml/day. It was possible to transfer the patient from stage III to stage II according to Fontaine in 75% of cases, and from stage IV to stage III according to Fontaine in 30% of cases. Clinical improvement was accompanied by a 3-fold decrease in lactate levels in the femoral vein and a 2-fold increase in O2 saturation in the femoral artery. At the same time, patients noted a decrease in the severity of pain and an improvement in all types of sensitivity (Horsch S., et al 1994). Administration of solcoseryl 20 ml/day intravenously for 3 weeks to patients with Fontaine stage IIb contributed to an increase in pain-free walking distance by 41 m, while in the control group the distance increased by 13 m. A threefold increase in the distance of pain-free walking allowed patients to be transferred to stage 11a (S Horsch et al, 1994).

Japanese researchers studied in detail the effect of Solcoseryl on the condition of patients with chronic cerebral ischemia. Thus, Solcoseryl at a dose of 2 ml/day for 24 days had a positive effect on motor functions in patients with cerebral atherosclerosis and chronic cerebral ischemia (K. Ito et al., 1974). The authors noted an improvement in motor functions in 80% of patients receiving Solcoseryl, compared to 60% with standard therapy. In a study by K. Ohara et al. (1987) when Solcoseryl was prescribed for 8 weeks, behavioral disorders and anxiety decreased in 70% of patients, and cognitive function improved in 40%. The use of Solcoseryl 2 ml/day for 25 days in two courses per year made it possible to reduce the severity of asthenic syndrome in elderly patients with chronic cerebral ischemia (B. Vidmar et al., 1978).

In recent years, Russian scientists have become actively interested in Solcoseryl (E.I. Chukanova, A.N. Bogolepova, 2007; G.R. Tabeeva, Yu.E. Azimova, 2010), who in clinical studies demonstrated a significant decrease in the severity of various symptoms in older patients age groups with chronic cerebral ischemia.

Thus, metabolic drugs of complex action in therapeutic and, especially, geriatric practice can significantly reduce the severity of asthenia and nonspecific symptoms, improve the quality of life of patients, maintain their functional activity, which is extremely important for maintaining compliance and creates the prerequisites for a more complete implementation of the effects of etiotropic drugs. and pathogenetic therapy.

There are many ways to deliver healing components into the body of a living being: through the oral cavity - tablets and mixtures, into the rectum - suppositories and enemas (for better absorption), through the pulmonary system - aerosols, etc.

However, the most effective way is an intravascular solution or dropper.

IV– a plastic device consisting of a reservoir with a useful solution, a needle and a valve that regulates the dose.

When the drug is administered by drip, absorption reaches 100% and the treatment effect appears immediately, because thanks to its complex composition, several drugs are administered simultaneously: vitamins, glucose, saline solutions and other beneficial substances.

Composition of droppers

Depending on the disease, the solution may include:

• glucose;
• glucose-salt mixture;
• magnesia;
• sodium bicarbonate;
• preparations acesol, disol;
• narcotic analgesics (naloxone);
• thiamine, nicotinamide, riboflavin, cocarboxylase;
• various groups of vitamins, etc.

Also recently, ozone therapy has become actively used. Using an ozonator, ozone is produced from oxygen. Before introducing the drug into the body, the gas is first diluted with the patient’s blood or sodium chloride

The therapeutic effect is the high oxidation of ozone, due to which the enzyme systems of blood cells are activated, thereby improving metabolism and restoring energy. The gas also affects monocytes and lymphocytes - immune cells. Because of this, pathogens and bacteria are eliminated.

The main therapeutic effects are:

• anti-inflammatory,
• analgesic,
• immunostimulating,
• detoxification,
• bactericidal.

Actively used in the treatment of:

• chronic gastritis;
• ulcers;
• atherosclerosis;
• diabetes mellitus;
• nervousness;
• urethritis;
• prostatitis, etc.

However, in addition to the positive qualities, this treatment does not exclude negative consequences.

Since ozone belongs to the gas class of increased danger, then when interacting with cells, aggressive oxygen particles are produced that destroy cells, which leads to many diseases, including cancer.

Therefore, you should not get carried away with ozone therapy and use it only when necessary.

Therapeutic effect of droppers

This therapy is used in a number of cases:

• heart attack;
• stroke;
• dehydration– impaired functioning of the kidneys, liver, intoxication, burns, diarrhea, poisoning, etc.
• body maintenance after operation;
• exacerbation of bronchial asthma;
• preventive purposes(curing binge drinking, saturating the body with vitamins and microelements).

Indications for use

Let's look at the example of sodium chloride and glucose.

Sodium chloride is used for:

• large loss of fluid;
• deficiency of certain substances (burn, diarrhea, vomiting, etc.).

Glucose is used for:

• intestinal infectious diseases;
• lowering blood sugar levels;
• a sharp drop in blood pressure;
• pulmonary edema;
• liver treatment (hepatitis, dystrophy, atrophy);
• poisoning (drugs, acids, arsenic, carbon oxides).

Droppers to improve the body's condition: drugs

With glucose content

Packaged in sealed plastic bags or bottles, 5% glucose solution is used:

• bleeding and increased bleeding;
• a sharp decrease in blood sugar;
• diarrhea, vomiting;
• infectious diseases;
• dehydration and exhaustion.

Cautions:

1. Due to the risk of hyperglycemia, For patients who have suffered a stroke, the solution is highly not recommended, or should be administered with great caution;
2. Patients with heart failure, water intoxication, swelling of the kidneys and fluid in the lungs, it is necessary to carry out a large number of infusions under the supervision of a specialist;
3. After traumatic brain injury infusions are carried out on the first day, carefully monitoring plasma glucose levels;
4. Infants, low weight children or premature infants, in order to avoid hypoglycemia, treatment with the solution should also be carried out under the supervision of a physician.

Dosage

Taken into account from these circumstances:

• age;
• general health;
• clinical picture.

Application

1. The most important– use of sterile, sealed equipment to prevent air from entering.
2. Not recommended for use plastic bags that can be filled with air, which leads to air embolism - blockage of blood vessels with air bubbles.
3. Additional medications can be added to the solution at any time during the infusion. In this case, the prepared solution is used immediately, since it cannot be stored.

To restore water-salt balance

Sodium chloride or saline solution is used, since chlorine with potassium and sodium maintains water balance, an acid-base environment, which is necessary for full life.

A lack of these components can lead to:

• blood thickening,
• muscle spasms and convulsions,
• disruption of the cardiovascular system.

1. For dysfunction blood circulation, since it is fraught with the development of cerebral or pulmonary edema;
2. Renal, left ventricular and chronic heart failure;
3. Elevated level sodium
   It is also prohibited to administer the solution subcutaneously to avoid tissue death (necrosis).
   With frequent use, acidosis, overhydration and hypokalemia may develop.

Dosage and Application

1. For severe dehydration The average dosage is 1 liter per day;
2. Children with dehydration and a concomitant decrease in blood pressure, the solution is administered in a ratio of 20-30 ml per kg of weight;
3. During gastric lavage use a 2-5% solution;
4. For constipation, give a 5% enema 75 ml solution;
5. For pulmonary, gastric, intestinal bleeding, a 10% solution is prescribed;
6. When treating the respiratory tract They recommend rinsing, rubbing and bathing with a 1-2% solution.
7. Also for colds use inhalations with saline solution in combination with bronchodilators, for example, Berodual. To do this, mix 4 ml of berodual and 1.5 ml of sodium chloride 0.9%.

Vitamin droppers

Cautions and contraindications

Despite the general hype, many doctors question this type of treatment, since it has not been scientifically proven how intravenous vitamins affect the body of a healthy person who does not need a course of treatment.

Application

For overall strengthening of the body and after suffering from colds and viral diseases, thiamine, riboflavin, and nicotinamide are often added to glucose.

Droppers for blood thinning

Blood thickening can occur due to an unhealthy lifestyle, the development of various diseases, pathologies of the liver and endocrine system, as well as patients susceptible to intoxication.

For liquefaction, glucose-saline solutions are used, alternating a 5%-10% glucose solution and a physiological salt solution. There are a number of pharmacological agents - dextrose, lactasol, disol, trisol.

These drugs are grouped according to:

Pharmacological action - replenishes fluid levels in the body, normalizes metabolic processes, and also serves to get rid of toxins and fill with energy.

In addition to positive properties, they also have negative ones:

• violation of the ionic composition of the blood;
• thrombophlebitis;
• swelling;
• heart failure;
• pressure change;
• swelling, chills.

To improve cerebral circulation

Dysfunction of the circulatory system in the brain leads to vegetative-vascular dystonia, stroke, and atherosclerosis.

To prevent the development of diseases, medications can be used:

1. Cavinton– a herbal preparation to improve blood circulation and cleanse blood vessels. It is used to relieve spasms and dilate blood vessels, as well as to remove excess glucose, reduce blood pressure and speed up metabolism. Used together with saline solution.
2. Xanthinolnicotinate– Designed to improve blood circulation and accelerate metabolism throughout the entire circulatory system. Also, thanks to its vasodilating properties, the drug perfectly cleans the arteries.
   The main side effects are dizziness, fever, and redness of the skin.
   Contraindicated for gastrointestinal ulcers, heart attack, bleeding, severe heart failure.
3. Eufillin– against bronchial spasms, treatment of asthma and chronic pulmonary disease. Used as a diuretic. Serves to reduce intracranial pressure and pressure in the lungs.
4. Mexidol– a very strong antioxidant. In addition to thinning the blood, it is intended for tissue restoration after heart attack and stroke, and is used to treat vegetative-vascular dystonia and dysfunction of the cardiovascular system.
   Side effects: slight nausea, weakness, dry mouth. It is not recommended for use by people who are intolerant to vitamin B6.
5. Nootropics– used to improve the functioning of blood vessels, despite the fact that they have weak effectiveness, which has not been confirmed. This is due to the fact that nootropics are not suitable for every body.

Against respiratory arrest

If the victim is in serious condition, then narcotic analgesics are given to support breathing, for example, naloxone and naltrexone, which by their action block the pain shock and cleanse the body of toxins.

To protect the liver

Almost all cleansing operations involve the liver. Therefore, when overloaded, it needs to get rid of toxins, alcohol, poisons and other harmful substances.

To do this, experts prescribe droppers with saline solution, antiemetic drugs, as well as with the addition of some drugs, including Essentiale, after mixing with the patient’s blood.

However, it has a number of contraindications:

• It is forbidden to use the medicine if there is intolerance to any substance;
• Children under 12 years of age are prohibited from taking the drug.

Side effects

This drug is highly effective and there are practically no side effects.

However, the tolerance of each organism is different, and as a result there may be:

• intestinal disorder;
• stomach discomfort;
• urticaria, skin lesions (if intolerance to any component is observed).

To restore acid-base balance

When acidic foods accumulate in the body, an acid-base balance may develop, which leads to various disorders.

To avoid this, droppers are prescribed using 4% sodium bicarbonate in its pure form, which neutralizes acids by its action, after which they break down into salt and water.

During the procedure, the person's pH is checked regularly.

Contraindications

• allergy;
• chronic alkalization;
• reduced levels of calcium and chlorine.

Side effects

• nausea, vomiting;
• fatigue, general malaise;
• anxiety;
• headache.

To cleanse the body of alcohol in the blood

If the permissible limit of alcohol in the body is exceeded, a hangover may occur the next morning, but more advanced cases lead to intoxication or even death.

To improve well-being, doctors prescribe droppers using:

1. Anticonvulsants, improving blood circulation (diltiazem, verapamil, nifedipine);
2. Saline or glucose solution (up to 1500 ml);
3. Antidepressants and sleeping pills;
4. Antihistamines, as well as with the use of magnesium, potassium and calcium.

You should never self-medicate. Therapy should be carried out strictly under the supervision of a specialist. However, following this information, in an emergency situation, you can save more than one person’s life

Metabolic therapy is a therapy that involves following specialized diets, taking nutritional supplements and enzymes, and using other methods of detoxifying the body to build immunity against disease. This therapy is viewed with some skepticism because there is no data to support its effectiveness in fighting disease. Metabolic therapy is considered an alternative form of treatment for cancer patients. The most common types of metabolic therapy are the Gerson therapy, the Kelly treatment, the Issels treatment and the Gonzalez treatment.

Proponents of metabolic therapy believe that toxins - additives and preservatives - found in food and the environment contribute to chemical imbalances in the body that can cause diseases such as cancer. Metabolic therapy is believed to remove these toxins from the body and strengthen its natural immunity. Some proponents of this therapy even claim that it can help cure various serious diseases.

Metabolic therapy methods are varied. Most involve the use natural - raw or minimally processed - foods and vitamins. High enemas, which are designed to cleanse the entire large intestine and are sometimes combined with exercises to help the person relax, may use juices and coffee.

Part of Kelki's treatment method includes supplements, detoxification, and chiropractic adjustments. Gonzalez's treatment centers use digestive organ extracts and animal enzymes. Issels' whole-body wellness involves following a limited diet that excludes caffeine and tobacco, and encourages the surgical removal of all teeth that have been filled, as well as the use of psychological therapy to reduce stress.

Gerson's therapy involves following a strict diet, using coffee enemas and taking supplements.

It has not yet been determined whether the metabolism of certain cells in cancer patients differs from the metabolism of those cells in people without cancer. However, there is general agreement in the medical community that optimal nutrition plays a vital role in the success of traditional cancer treatments. However, there is no data to support the various claims made by metabolic therapy advocates.

Part of the reason for skepticism and reluctance to accept this therapy as a viable treatment option may be the fact that it has some undesirable effects. Cases of complications associated with metabolic therapy have been reported. Injecting live cells obtained from animals into humans has caused several deaths. There are also known complications associated with liver cell injections. Laetrile, a drug often used in metabolic therapy, has been found to cause nausea, dizziness and even cyanide poisoning. Relying only on metabolic therapy and abandoning traditional methods of treatment can lead to serious health problems, which subsequently cannot always be eliminated.