Divaza: a drug to restore brain activity

The medication belongs to the category of antioxidant, anxiolytic drugs, promotes the regeneration of brain structures after ischemic attacks.

Divaza contains specific, specially purified antibodies to the S-100 protein and the endothelial enzyme No-synthase. The medication is intended for the complex treatment of dysfunctions of the central nervous system and associated pathologies. The combined drug is available in the form of tablets for sublingual use - they must be dissolved in the mouth.

Composition and dosage form

The tablets are white, uncoated, flat-cylindrical in shape and have a transverse score on one side. On one side of the pills there is a MATERIA MEDICA logo, on the other side there is an engraving DIVAZA. Each tablet contains active ingredients:

affinity purified antibodies to protein: 0.006 g;
antibodies to No synthase: 0.006 g.

The combination of active compounds is delivered to the body using lactose. The base of the tablets consists of it. In addition, for uniform absorption and distribution of substances in the blood, the drug contains magnesium stearate and microcrystalline cellulose.

The tablets are packaged in cell blisters of 20 pieces. The secondary cardboard packaging of the drug contains 100 tablets - 5 blisters.

Insulin and alcohol

Such an experiment usually leads to a hypoglycemic coma, and in some cases causes death. Insulin regulates blood glucose levels in diabetes. Once in the blood, ethanol begins to actively affect the liver and kidneys, which provokes hypoglycemia. The combination of alcohol and insulin worsens a person’s well-being, and it is impossible to help a person in a state of alcohol intoxication. This condition ends in death.

How does Divaza work?

Antibodies in the composition of the drug penetrate the bloodstream into the brain, affect synaptic connections, inhibit lipid peroxidation, have neuroprotective, antihypoxic and antioxidant effects, increase tissue resistance to oxygen deficiency, and regulate metabolic processes. The effect of taking the medicine is expressed in improving the overall integrative activity of the brain:

mental performance increases;
the consequences of ischemic disorders are reduced;
the impact of psychotraumatic factors is reduced, mood improves;
memory and concentration become better, the ability to assimilate new information increases;
the brain becomes more resistant to the effects of toxins;
cerebral blood flow increases, somatovegetative connections are strengthened, thereby eliminating various adverse effects: convulsions, tremors, dizziness, numbness of the limbs and others.

It has been established that the use of Divaza has a beneficial effect on recovery processes after an ischemic stroke, improves cognitive functions, and reduces anxiety and restlessness. The medication does not affect the speed of psychomotor reactions, does not cause increased drowsiness, and does not have sedative properties. During the period of using Divaza, physical and mental activity is fully preserved. Therapy with the drug, even after long courses, does not provoke addiction or subsequent withdrawal symptoms.

In most countries of the world, cerebrovascular diseases (CVD), traditionally divided into acute and chronic, occur most often in the structure of general morbidity, primary disability and mortality of the population. Among acute forms of CVD, strokes pose the greatest danger. According to World Health Organization forecasts, by 2030, about 23.3 million people will die from cardiovascular accidents, including stroke. The risk of stroke increases more than 5 times in patients who have suffered ischemic cerebrovascular accidents, and it is maximum in the first days of the disease. Therefore, prevention of CVD implies the earliest possible start and continuous continuation throughout life.

Among the main causes of ischemic cerebrovascular accidents, a number of conditions can be identified that contribute to the early development of the disease, accelerated progression of clinical symptoms and a high likelihood of serious complications. In the pathogenesis of cerebral ischemia, an important role is played by disorders of hemorheology, hemostasis and fibrinolysis [1].

Narrowing of the lumen of the main arteries of the head due to atherosclerotic plaques leads to ischemia, disruption of metabolic processes at the neuronal level and the triggering of oxidative stress. A decrease in volumetric blood flow at the initial stage leads to functional disorders in the functioning of brain cells, and with further aggravation of hypoperfusion - to structural damage (organic neurological defect).

With arterial hypertension, as with atherosclerosis, pathological changes in the form of structural focal and circular muscular-elastic thickenings develop in the extracranial and small cerebral arteries. The loss of muscular and elastic elements of the walls of the main arteries of the head and loss of vascular tone contribute to the occurrence of pathological tortuosity and kinks, leading to cerebral circulatory disorders.

Under the influence of damaging factors (atherosclerosis, arterial hypertension), the functioning of the endothelium is disrupted, i.e., endothelial dysfunction (ED) is formed, which is considered the core of pathological changes in CVD. Laboratory display of ED is altered levels of markers in the blood (endothelin-1, nitric oxide - NO, vascular endothelial growth factor, homocysteine, etc.) before the onset of symptoms of CVD [2]. A large amount of data has been obtained on the leading role of ED in the initiation of atherosclerotic lesions, the development of pathological changes in vascular tone, and vascular structure. ED triggers the processes of inflammation, thrombus formation, and fibrinolysis [3]. All of the above factors determine the advisability of correcting pathological changes at the level of cerebral ED in CVD. However, there are relatively few drugs with a proven endothelial protective effect, and their use in cerebrovascular pathology is limited by side effects.

Treatment and prevention of cerebrovascular disorders and their consequences are aimed at preventing the progression of the main pathological processes of cerebral ischemia, with the leading place given to achieving and maintaining normal blood pressure.

Non-drug methods for preventing CVD include: smoking cessation/reducing the number of cigarettes smoked, alcohol abuse, regular physical activity, balanced nutrition, reduction of excess body weight, regular mental stress/cognitive training.

Medicinal methods for preventing CVD include: normalizing blood pressure, lipid profile, and controlling blood sugar levels. A prerequisite is the prescription of antiplatelet agents.

In some cases, surgical methods for the prevention of CVD are used - carotid endarterectomy, stenting.

The effectiveness of preventing cerebrovascular insufficiency increases significantly when all possible means are used. The combination of several methods for preventing cerebrovascular disorders can significantly reduce the risk of developing a recurrent stroke and other cardiovascular diseases.

Neuroprotection is of great importance in the treatment and prevention of CVD. The concept of “neuroprotection” includes natural or therapeutic stimulation of physiological and biochemical mechanisms that contribute to the functional stability of the brain [4].

Neuroprotection is defined as the continuous adaptation of neurons to new functional conditions, as a way to prevent damage to brain tissue caused by ischemia. Modern neuroprotection operates at the level of a molecular cascade that causes neuronal dysfunction and death. Neuroprotection for cerebrovascular accidents is aimed at increasing the period of the “therapeutic window”1᠎ and stopping the cascade of pathological reactions. Primary neuroprotection (interruption of rapid reactions of the glutamate-calcium cascade, free radical processes) makes it possible to increase the period of the “therapeutic window” for activating reperfusion; secondary neuroprotection is aimed at interrupting the long-term consequences of ischemia: excessive NO synthesis and oxidative stress; activation of microglia and associated imbalance of cytokines, immune shifts, local inflammation, disruption of microcirculation and the blood-brain barrier, trophic dysfunction and apoptosis [5].

A large number of neuroprotective drugs are used to treat patients with CVD, but only a small part of them have been studied in placebo-controlled randomized trials, and none have received evidence as a means of treating and preventing CVD. The effectiveness of other drugs remains controversial.

In recent years, the biological activity of the S100b protein at the molecular level has been considered from the perspective of its direct participation in the regulation of the development and apoptosis of nerve and glial cells. Interest in studying the mechanisms of action of proteins of the S100 group, in particular the neurospecific protein S100b, is due to its participation in the processes of integrative activity of the brain with the development of diseases of the nervous system. The S100 protein was discovered in 1965 as a fraction of glial proteins in the brain that are produced primarily by astrocytes. The S100 protein is a combination of two closely related family proteins: S100A1 (S100α) and S100b (S100β) [6]. Due to the ability to regulate the activity of a number of proteins, S100A1 and S100b are involved in the transduction of signals that control the activity of energy metabolism enzymes in brain cells, calcium homeostasis, cell cycle, cytoskeletal functions, transcription, proliferation and differentiation of cells, their motility, secretory processes, structural organization biomembranes [6]. However, the most unusual characteristic of some members of the S100 family is their ability to be secreted extracellularly. S100 proteins in the extracellular sector exhibit the properties of cytokines and interact with receptors for non-enzymatic glycosylation products (RAGE receptors), which are expressed in the nervous system by neurons, microglia, astrocytes, and vascular wall cells [7, 8].

Recent studies show that changes in the level of serum S100b protein can be diagnostically valuable in assessing the impact of a number of factors on the brain (stroke, intoxication, trauma). A number of studies have been devoted to studying the level of S100b in the blood and cerebrospinal fluid (CSF) in patients with post-traumatic brain injury [9]. In the acute stage of the disease, there is an increase in the level of S100b in the blood and CSF, which correlates with the severity of brain damage (according to CT, MRI) and can be a predictor of an unfavorable outcome [10].

For the purpose of differential diagnosis of stroke, E. Liswati et al. [11] examined the levels of biochemical markers: S100b protein, neuron-specific enolase (NSE), myelin basic protein (MBP), cardiac fatty acid binding protein (H-FABP). The study included 44 patients who had suffered a stroke, of which 25 patients had ischemic stroke (IS), 19 had hemorrhagic stroke (according to MRI). During the first 72 hours after the onset of stroke, the levels of S100b, NSE, MBP and H-FABP in the blood plasma were determined. As the concentration of markers (S100b protein and MBP) increased, the sensitivity and specificity of the method increased to 77.8 and 84.6%, respectively. The authors concluded that blood samples obtained within the first 24 hours of stroke should be used in the differential diagnosis of IS and hemorrhagic stroke.

It can be concluded that the S100b protein plays an important role in the implementation of the basic functions of the neural systems of the brain, such as the generation and conduction of nerve impulses, regulation of synaptic and metabolic processes, proliferation and differentiation of neurons and glia [12].

In patients with CVD, the use of the domestic combination drug Divaza (OOO NPF Materia Medica Holding) seems promising due to its unique composition and mechanism of action, as well as a strong evidence base. Divaza is created on the basis of release-active antibodies to the brain-specific protein S100 (RA AT S100) and to endothelial NO synthase (RA AT eNOS). The range of pharmacological effects of divase is due to its modifying effect on the functional activity of protein S100 and eNOS, i.e., key components involved in the implementation of the most important processes in the central nervous system2᠎. The mechanism of action of the RA AT eNOS is the regulation of the NO synthase → NO-guanylate cyclase → cGMP cascade. The drug has been proven to increase eNOS activity as well as cGMP production, ultimately causing vasodilation. The endothelial protective effect of RA AT eNOS was shown in a model of NO deficiency (with the administration of the NO synthase blocker L-NAME) [13].

The mechanisms for implementing the effects of the brain-specific protein S100 are achieved in several ways. The fact that S100 is Ca2+-binding explains the mechanism of action of the PA AT S100 within the framework of transmembrane ion transport [14]. Influence of R.A. AT S100 is due to a more stable binding of the S100 protein to Ca2+ ions, which triggers the Na+ current into the cell and Ca2+ outward. In this case, a change in the transmembrane potential generates an action potential, as a result of which the nerve impulse propagates to neighboring neurons. This is the modulating effect of RA AT S100 on the synaptic transmission of various receptors (GABA, serotonin, s1, NMDA).

The combined use of RA AT S100 and RA AT eNOS as part of divase is characterized by nootropic, vasoactive, antioxidant, angioprotective and antihypoxic effects. The corrective effect of the drug on the processes of neuronal plasticity and cerebral hemodynamics is manifested in the stimulation of reparative processes in the central nervous system, restoration of learning and memory processes, and increase in mental performance3᠎.

Studies conducted in recent years have shown the high effectiveness of divaza in reducing the main symptoms of cerebrovascular disorders. So, P.R. Kamchatnov et al. [15] conducted a non-comparative observational program and assessed the effectiveness and safety of Divase, prescribed for the correction of emotional disorders in patients with chronic cerebrovascular diseases (CVD). Positive dynamics in the severity of anxiety, asthenia and emotional lability were noted after 4 weeks of therapy with Divaza ( p

<0.05), subsequently, until the end of the course of therapy, manifestations of anxiety continued to decrease (
p
<0.01). Significant differences in the results of the MMSE test were obtained by the 2nd month of therapy. No deterioration of the condition or adverse events were recorded while taking Divaza; sedative and muscle relaxant effects, addiction or addiction to the drug, and negative dynamics of laboratory parameters were not noted.

In the publication by O.V. Vorobyova et al. [16] summarized the results of the experience of clinical use of divaza in medical centers of Moscow and the Moscow region, St. Petersburg, Kazan, Novosibirsk, Smolensk. After 3 months of treatment with Divasa, MMSE testing showed an improvement in cognitive functions (in particular, memory). A significant decrease in the severity of anxiety disorders was noted. It was concluded that treatment with Divaza for 12 weeks leads to significant effects in the correction of cognitive, asthenoneurotic and psychovegetative disorders.

E.I. Chukanova et al. [17] conducted a comparative clinical and laboratory study of the use of divaza in patients with moderate cognitive impairment due to chronic CVD. The patients were treated as outpatients and received sublingual divaza, 2 tablets 3 times a day, against the background of basic therapy for 12 weeks. In the first weeks of divaza therapy, anxiety disorders regressed, mood normalization was noted, and insomnia regressed. A significant decrease in the levels of von Willebrand factor and fibrinogen in the blood was obtained, which suggests a therapeutic effect of divase on the pathogenetic mechanisms of CCVD. The authors concluded that Divaza can be prescribed not only as symptomatic, but also pathogenetic therapy for chronic cerebrovascular pathology.

M.N. Dadasheva et al. [18] described a clinical case of divase administration in a 57-year-old patient with a transient ischemic attack (TIA) in the vertebrobasilar system. Despite the rapid restoration of blood flow in TIA, short-term ischemia of brain tissue was observed, which had a damaging effect on antioxidant systems. Against the background of basic therapy, the drug Divaza was prescribed. During the treatment, positive dynamics were noted. This episode was repeated once, and its intensity and duration were minimal. The described clinical case allows us to conclude that in patients with CVD, the administration of divas helps improve blood supply to the affected area of the brain without causing the steal phenomenon.

In the study by O.A. Mudrovoy et al. [19] assessed the effectiveness of divaza in the correction of cognitive and emotional disorders in patients in the early recovery period I.I. The patients were randomized into two groups. Patients in the main group received basic therapy and Divaza (2 tablets 3 times a day for 12 weeks), in the control group - only basic therapy. Divaza was prescribed from the 21st day from the start of I.I. After 3 weeks of treatment with Divaza, an improvement in memory (subjective) and a significant decrease in anxiety were noted. Positive dynamics on the MMSE scale in patients of the main group indicates that the restoration of cognitive functions in them occurred significantly faster and better than in patients treated only with basic drugs.

When is Diwaza shown?

The medicine is prescribed to adult patients: 18 years of age and older. The main areas of its application:

age-related cognitive and cerebrovascular disorders;
asthenoneurotic processes;
consequences of ischemic strokes;
severe stress, nervous exhaustion.

Divaza is used as independent therapy and as part of complex treatment. If necessary, you can combine the drug with other medications.

Alcohol and birth control

Separately, it should be said about the effect of alcohol on hormonal contraceptives. Here, too, it is difficult to talk about the desired specifics, since different drugs have different types of action and reaction to alcoholic drinks.

For example, the combination of Regulon and small doses of alcohol is practically harmless. But drinking alcohol with Visanne greatly increases the risk of developing possible side effects. Taking alcohol with contraceptives such as Lindinet 20 or Belara simply reduces the effectiveness of the drugs, increasing the risk of pregnancy.

The best way to resolve the issue of compatibility of birth control pills and alcohol is to carefully study the instructions from the manufacturer, or even better, consult with a gynecologist.

How to take the drug

Divaz tablets must be dissolved in the mouth. It is not advisable to swallow them, since the active substances die under the influence of gastric juice. Antibodies penetrate the bloodstream through the mucous membranes, reaching the brain in 15–20 minutes. You should also not split or crush pills before taking them.

The tablet must be placed under the tongue and wait until it completely melts;
if necessary, you can repeat the dose immediately or take 1-2 tablets up to 3-4 times a day, maintaining equal time intervals;
You can take the drug on an empty stomach or after a meal; the presence of food in the stomach does not affect the rate of absorption of the tablets;
immediately after taking the medicine, it is not advisable to consume hot food, water and drinks, use mouth rinses or chewing gum;
in case of severe brain damage, you can increase the frequency of taking the drug to 5-6 times a day.

You should check your treatment regimen with your doctor. The duration of a continuous course of therapy with Divaza can reach six months or longer, depending on how severe the symptoms of the disease are.

About the effect of alcohol on hormonal levels

Before answering the question about the compatibility of alcohol and hormonal pills, you need to answer another question: how does alcohol generally affect the human hormonal system?

There is no simple answer to a question like this. In general, the functioning of the internal secretion organs is disrupted, but this happens unevenly. For example, the secretion of cortisol (the so-called stress hormone) increases significantly, which can result in anxiety and irritability. But the production of sex hormones (testosterone in men and estrogen in women) decreases.

Much depends on the initial state of a person’s health, the amount of alcohol consumed and the duration of alcohol consumption over time, but one thing can be said for sure - the functioning of hormonal organs is disrupted, and sometimes in quite a serious way.

Contraindications and side effects

Divaza is prohibited for use in children and adolescents due to insufficient information about the effect of the drug. Other contraindications:

individual intolerance to lactose and other components;
malabsorption syndrome.

Pregnancy is not included in the list of contraindications. Divaza is also allowed to be used for diabetes and other chronic diseases.

The drug is well tolerated and practically does not cause any pathological reactions in the body. With repeated overdose, in rare cases, nausea, loss of appetite or dry mouth may occur.

Dangerously unpredictable combination

Since there are a huge number of options for combining alcohol and numerous types of hormonal drugs, as well as taking into account the specific diagnosis, established dosages and other factors, it is possible to predict the effect of alcohol on the functioning of the secretion glands only on an individual basis, and even then with a high probability of error. In some cases, the effect of hormonal drugs will be enhanced, and in others it will be completely neutralized. It is possible that hormonal imbalances will be so minor that they will not have any significant effect on the course of therapy, but this is more true for single use of small doses of alcohol.

In general, real medical practice speaks of the following consequences of the combination of simultaneous intake of alcohol and hormonal drugs:

Androgenic drugs: the level of estrogen increases, which causes excess hair in different parts of the body, excess weight gain, deterioration in well-being and persistent headaches.
Preparations of hormones of the pituitary gland and hypothalamus: the synthesis of one’s own hormones decreases, as a result of which the prescribed hormone replacement therapy is completely or partially ineffective.
Glucagon. This hormone is taken to increase blood sugar levels. Alcohol suppresses its effect, as a result of which the intended goals of the treatment are unattainable.
Insulin. Used to normalize blood sugar levels. The action of insulin is also suppressed by alcohol, and the consequences depend on the intensity of this process and can range from a slight deterioration in well-being to the development of a coma.
Thyroid hormone preparations: alcohol has a depressant effect, which in case of hyperthyroidism can cause the development of hypothyroidism, and in case of hypothyroidism it can simply neutralize the therapy being carried out.
Corticosteroids. Alcohol enhances the toxic effect of drugs, and also significantly increases the risk of gastric ulcer bleeding and increasing blood pressure to critical levels.

Content:

What is mephedrone
What happens if you mix alcohol with mephedrone 2.1. Mephedrone and alcohol: consequences 2.2. Combining mephedrone with alcohol: signs of overdose
Principles of addiction treatment 3.1. Rehabilitation therapy

Can mephedrone be taken with alcohol? How dangerous is such a “cocktail”? Mephedrone belongs to the group of synthetic cathinones - artificially synthesized analogues of the natural alkaloid of the Catha plant (cat), which are often called “salts”. The drug is extremely dangerous, and irreversible consequences can occur after the first use, especially if we are talking about a teenager or a person with chronic concomitant diseases. But the risk of complications increases many times over if you take mephedrone after drinking alcohol. The combination of these psychostimulants leads to severe systemic intoxication, psychotic and neurological disorders.

To drink or not to drink

Since in most cases alcohol reduces or completely neutralizes the effect of hormonal drugs, doctors recommend completely abstaining from drinking alcohol until the end of the course of treatment. It is possible that in some cases, with small and single doses of alcohol consumed, no noticeable negative consequences will occur, but still the risk is too great, because the stake in indulging in a “small weakness,” in this case, will be one’s own health. And, as you know, it cannot be assessed or measured either with money or with a full glass!

Starshinova Irina Evgenievna Psychiatrist-narcologist