Minor tranquilizers drugs. Tranquilizers. New generation drugs

The term itself comes from the Latin “tranquillo”. This word translates as “to calm,” which is why tranquilizers are hidden as anti-anxiety drugs. They have anticonvulsant, hypnotic and sedative effects. You will learn more about the types and uses of such medications below.

What is a tranquilizer

In the modern world, every day there are more and more reasons for worry and stress. To solve such problems, medications are increasingly being used. Today, tranquilizers or anxiolytics are a panacea for serious and not so serious psychoses, phobias and neuroses. These are psychotropic drugs that are highly effective against anxiety conditions of varying degrees.

The peculiarity of these medications is that they become addictive very quickly, especially with long-term use. For this reason, treatment is carried out in short courses. In addition, indications for taking anxiolytics are serious neuroses, i.e. If you have minor anxiety, it is not recommended to immediately grab such pills.

Tranquilizers - list of drugs

In modern medicine, tranquilizers often mean anxiolytics that eliminate anxiety and fears of sleep. For this reason, this concept replaces the term “tranquilizers.” You can study the list of anxiolytics by group in the table:

Tranquilizers without a doctor's prescription

Most anxiolytics can only be prescribed by a doctor, which is why such drugs are sold according to his prescription. Although there is a group of products, the purchase of which does not require a prescription from a specialist. They can be easily ordered from an online pharmacy or bought straight away in a regular one. You can purchase tranquilizers without a doctor's prescription:

• Medazepam, or Rudotel;
• Zoloft;
• Hydroxyzine, or Atarax;
• Tofisopam;
• Phenazepam;
• Stresam, or Etifoxine;
• Paxil.

New generation tranquilizers - list of drugs

A special place in the classification of anti-anxiety drugs is occupied by new generation tranquilizers. They are not addictive, but at the same time they do not exhibit their medicinal properties so strongly. In addition, such drugs often have side effects on the autonomic nervous system. This manifests itself in the form of nausea, vomiting, diarrhea and dry mouth. This group is recommended only because of the lack of addiction to its drugs. The list of new generation tranquilizers includes:

• Buspirone;
• Adaptol;
• Atarax;
• Afobazole;
• Etifoxine;
• Strezam;
• Amizil;
• Mexidol;
• Oxylidine;
• Phenibut.

Daytime tranquilizers

A separate clinical subgroup consists of daytime tranquilizers. In composition and effects they are close to benzodiazepine drugs. Daytime tranquilizers have only an anti-anxiety effect. Their sedative, muscle relaxant and hypnotic effects are minimally expressed. For this reason, such medications do not lead to lethargy and drowsiness, which is why they are prescribed to those whose work requires increased attention.

In general, such drugs help you lead a normal life during the day. They can be combined into the following list:

• Grandaxin;
• Gidazepam;
• Medazepam;
• Trimetozin;
• Trioxazine;
• Prazepam.

Classification of tranquilizers

Due to the fact that the list of anxiolytics is constantly updated with new drugs, their classification does not have a clearly defined form. Doctors still distinguish several main groups. The most common group in the classification of tranquilizers are benzodiazepine drugs. They can be divided into the following groups:

1. With a pronounced anxiolytic effect - Diazepam, Alprazolam, Phenazepam and Lorazepam. The last 2 drugs are the most powerful.
2. With moderate effects - Bromazepam, Oxazepam, Gidazepam, Clobazam.
3. With a predominantly hypnotic effect - Triazolam, Flunitrazepam, Midazolam, Nitrazepam, Estazolam.
4. With a pronounced anticonvulsant effect - Diazepam, Clonazepam.

The next group includes daytime tranquilizers. They are chemically similar to benzodiazepines, but may not be as potent. But by taking them, a person can adhere to his usual rhythm of life, because daytime tranquilizers do not lead to lethargy. These drugs include Gidazepam, Grandaxin, Medazelam and Oxazepam.

The last group includes new generation tranquilizers. Their advantage is that they are not addictive. Adaptol, Atarax and Afobazol are prominent representatives of this group of tranquilizers. They can be taken without fear of developing an addiction. Only the effect of these drugs is weak, and is often accompanied by side effects - nausea, vomiting and diarrhea.

Effect of tranquilizers

Anti-anxiety drugs have their own classification, which divides them according to their chemical composition, compatibility with other drugs and the severity of their properties. Only 5 of the latter stand out:

• anxiolytic, or anti-anxiety;
• sedative, i.e. sedative;
• sleeping pills, i.e. facilitating the onset of sleep;
• muscle relaxant, or relaxant;
• anticonvulsant, or suppressing epileptic activity.

Each drug combines these properties in different proportions. In general, the mechanism of action of tranquilizers on the body is as follows - the substances in the tablets have an effect on nerve endings called benzodiazepine receptors. As a result, a person “forgets” the state that caused him anxiety or fear. Anxiolytics do not affect more serious pathologies, such as hallucinations and delusions. In such cases, antipsychotic drugs are used. They are otherwise called “major tranquilizers.”

Tranquilizers in medicine

The use of anxiolytics is indicated for psychopathic pathologies and neuroses, which are accompanied by a whole group of symptoms. Among them are:

• panic;
• fear;
• anxiety and tension;
• emotional instability;
• irritability;
• anxiety;
• sleep disorders.

What is treated with tranquilizers besides anxiety? They are prescribed for psychosomatic disorders. These include diseases that arise as a result of the influence of physiological and psychological factors. This applies to anxiolytics, i.e. a minor tranquilizer. Neuroleptics are already used for serious mental disorders, such as schizophrenia, manic-depressive syndrome and hallucinations.

Side effects of tranquilizers

Unlike antipsychotics and antidepressants, these medications do not affect the heart and other organs. Side effects of anxiolytics most often affect the autonomic nervous system. This manifests itself in low blood pressure, urinary incontinence, constipation and decreased libido. The most dangerous consequences can occur when taking tranquilizers and alcohol at the same time. Hallucinations, dizziness and even suicide attempts are side effects of combining alcohol with an anxiolytic drug.

To the main list of side effects, you can add several other symptoms that may accompany taking tranquilizers. These are the signs:

• decreased visual acuity;
• drowsiness;
• decreased concentration;
• fatigue;
• lack of coordination;
• dizziness;
• muscle weakness;
• tremor;
• ataxia.

Price of tranquilizers

The cost of a particular medicine depends on the manufacturer, the number of pieces in the package and the degree of impact. For example, the price of the drug Grandaxin is 358 rubles for 20 tablets (50 mg). For the same medicine, but in the amount of 60 pieces, you will have to pay 800-900 rubles. The price of the drug Adaptol is similar. It costs about 750-800 rubles. Only this price is indicated for a package of 20 tablets. Paxil is also an expensive drug. The price of this drug is 700 rubles. for 30 tablets (20 mg). You can buy Zoloft at the pharmacy. The price of this over-the-counter medicine is also high - 1200 rubles. for 28 pcs.

The new generation anxiolytic drug Afobazol can be considered more affordable. Its cost is 384 rubles. for 60 tablets (10 mg). Here is the price of tranquilizers from other groups:

• Atarax – 271 rub. for 25 tablets (25 mg);
• Stresam – 339 rub. for 24 capsules (50 mg);
• Mebicar – 270 rub. for 20 capsules (300 mg).

Video: What are anxiolytics

Currently, a large number of so-called neuropsychotropic drugs are widely used - drugs that in one way or another affect the state of the patient’s emotional sphere by balancing the processes of excitation and inhibition in the central nervous system. These primarily include sedatives that enhance and concentrate the process of inhibition in the cerebral cortex, neuroleptics ("major" tranquilizers) - sedatives that weaken the process of excitation in the brain, and tranquilizers ("small") that have a calming effect. Certain neuropsychotropic drugs have different mechanisms of action and pharmacological activity in the patient's body, as well as a predominant effect on various emotional disorders (fear, anxiety, melancholy, increased nervous excitability, anger, etc.). Depending on the nature, severity and duration of emotional disorders, the choice of medication is made in each specific case. Tranquilizers and, especially, neuroleptics also have an analgesic effect and potentiate the effect of hypnotics, analgesics and muscle relaxants.

a) Sedatives

Sodium bromide (Natrii bromidum) and potassium bromide (Kalii bromidum) are more often used orally in mixtures and tablets - in doses of 0.1 to 1.0 g. Sodium bromide, in addition, can be administered intravenously at 5 - 10 ml 5 - 20% solution. Bromides are slowly eliminated from the body; due to accumulation, side effects (“bromism”) may occur: runny nose, cough, skin rash, memory loss, etc.

Bromcamphara is prescribed orally at a dose of 0.15 - 0.5 g 2 - 3 times a day.

Valerian is used in the form of infusion and alcohol tincture. Infusion of valerian (Infusum radicis Valerianae) is prepared at the rate of 6 - 10 g of root per 180 - 200 ml of distilled water and administered orally, 1 tablespoon 2 - 4 times a day. Often, valerian infusion is included in a mixture with sodium bromide. Valerian tincture (Tinctura Valerianae) is taken orally in a dose of 20 - 30 drops 2 - 4 times a day.

Motherwort herb is also used in the form of infusion and alcohol tincture. An infusion of motherwort herb (Infusum herbae Leonuri) is prepared in a ratio of 10-15 g of herb and 180-200 ml of water, prescribed 1 tablespoon 3-4 times a day. Motherwort tincture (Tinctura Leonuri) is administered orally, 30-50 drops 3-4 times a day.

b) Neuroleptics

These include phenothiazine derivatives and drugs of other pharmacological groups.

Phenothiazine derivatives:

Aminazine (Aminasi-num) - chlorpromazine - is taken orally in tablets of 0.025 - 0.1 g, and the course of treatment begins with lower dosages (0.025 - 0.075 g per day), then increases to 0.3 - 0.6 g, and by the end of the course it decreases again to the original level. The drug can be administered intramuscularly as a 0.25 - 0.5% solution (2 - 5 ml), and intravenously - as a 2.5% solution (1-2 ml of the drug is diluted in 10 - 20 ml of a 5% glucose solution and administered slowly) . With long-term use of aminazine or other phenothiazine derivatives, side effects may develop in the form of neuroleptic parkinsonian syndrome, the clinical picture of which resembles the syndrome of vascular or post-infectious parkinsonism described in Chapter II. The occurrence of such complications requires immediate discontinuation of the drug and the appointment of antiparkinsonian drugs, described below. Included in List B.

Levomepromazine (Levomepromazinum) - tizercin - is prescribed orally in tablets of 0.025 - 0.1 g 3 - 4 times a day or intramuscularly in the form of a 2.5% solution (1-2 ml). Belongs to list B.

Triftazinum - stelazine - can be used orally and intramuscularly. It is prescribed orally with a dose of 0.001-0.005 g per dose (after meals), with a gradual increase to 0.01-0.03 g, 2 - 4 times a day. The drug is administered intramuscularly in a dose of 0.001 - 0.002 g, up to 4 - 6 times a day. A peculiarity of the action of trifazine is its ability to cause in patients an increase in interest in the environment and physical activity, to facilitate their involvement in productive work. Belongs to list B.

Thioridazine (Thioridazinum) - sonapax, melleril - has, along with a sedative, a beneficial effect on pathologically altered mood - a thymoleptic effect. Oral administration is carried out in doses of 0.005 - 0.01-0.025 g 2 - 3 times a day. Belongs to list B.

All phenothiazine derivatives, with the exception of thioridazine, are contraindicated in diseases of the liver and kidneys in the decompensation phase, diseases of the hematopoietic organs, rheumatic carditis, thromboembolic disease, in severe cases of bronchiectasis, and glaucoma.

Other antipsychotics:

Haloperidol (Haloperidolum) is a sedative and antiemetic. It is prescribed orally, administered intramuscularly and intravenously. Oral dose: 0.005 - 0.01 g per day (3 - 5 doses). 0.4-1 ml of a 0.5% solution of the drug is administered parenterally 2 - 3 times a day. Belongs to list B.

Trifluperidol (Trifluperidolum) - trisedil - is similar in action to haloperidol, but also has anticonvulsant activity. It is prescribed orally and also intramuscularly. The initial dose of oral administration is 0.00025-0.0005 g per day (2-3 doses), subsequently it increases to 0.001-0.002 g per day over 4 to 6 days. For intramuscular injection, 0.00125 - 0.0025 g of the drug (0.25 - 0.5 ml of 0.1% solution) is administered. Belongs to list B.

Haloperidol and trifluperidol with long-term use can cause extrapyramidal disorders (parkinsonism), which requires the prescription of antiparkinsonian drugs. Both drugs are contraindicated in case of organic lesions of the central nervous system, decompensated diseases of the kidneys and cardiovascular system.

Indole derivatives in the form of rauwolfia alkaloids have a calming and hypotensive effect. They are used in all cases where the use of antipsychotics is indicated, especially in patients with arterial hypertension and impaired renal function.

Reserpine (Reserpinum) - rausedil, serpasil - taken orally after meals in tablets of 0.00025 - 0.0005 g 3 - 4 times a day; the course of treatment is 1-6 months. Side effects may occur in the form of gastrointestinal disorders (nausea, vomiting, diarrhea), bradycardia, dizziness. Contraindications: severe organic cardiovascular diseases, bradycardia, peptic ulcer of the stomach and duodenum. Belongs to list A.

Raunatinum has a weaker sedative and hypotensive effect than reserpine. Taken orally after meals in tablets of 0.002 g, starting with 1 tablet at night, and then 3 - 6 tablets per day. Belongs to list B.

c) Tranquilizers

Tranquilizers have a somewhat less pronounced sedative effect compared to neuroleptics, but they are better tolerated by patients and are less likely to cause side effects. Many tranquilizers have the properties of central muscle relaxants, reducing pathologically increased skeletal muscle tone.

Meprotanum - andaxin, meprobamate - is a sedative that causes relaxation of striated muscles. Taken orally in tablets of 0.2 - 0.4 g 2 - 3 times a day. Belongs to list B.

Isoprotanum (Isoprotanum) - scutamil - is also a central muscle relaxant and at the same time a tranquilizer, potentiates the effect of hypnotics and analgesics. Prescribed orally after meals, 0.2 g (1 tablet) 2 to 4 times a day. Possible side effects: drowsiness, dyspeptic symptoms. Contraindication: epilepsy. One of the forms of release of this drug is Scutamul-C, which contains 0.15 g of isoprotan and 0.1 g of the painkiller paracetamol in 1 tablet. Prescribed 1 tablet 3 times a day after meals if necessary to reduce skeletal muscle tone or reduce pain. Isoprotan and scutamyl-C are included in list B.

Chlordiazepoxide (Chlordiazepoxidum) - elenium, librium - also has a calming and muscle relaxant effect, and has an anticonvulsant effect. It is prescribed orally in the form of tablets of 0.005 - 0.01 g 2 - 4 times a day. Occasionally, side effects such as drowsiness, dizziness, and general weakness are possible.

Contraindications: acute liver and kidney diseases. Belongs to list B.

Diazepam (Seduxen) is pharmacologically more active than chlordiazepoxide and helps improve sleep. Taken orally in tablets of 0.005 - 0.01 g (1-2 tablets) 2 - 3 times a day, 2 ml of a 0.5% solution of the drug diluted with 20 ml of a 40% glucose solution is slowly injected intravenously. Belongs to list B.

Nitrazepam (Nitrazepamum) - eunoctine, radedorm - has a pronounced sedative and especially hypnotic effect. Relaxes skeletal muscles. It is taken orally in tablets of 0.005 - 0.01 g, usually 30 minutes before bedtime. Belongs to list B.

Oxylidinum is a sedative and antihypertensive drug. It is used in gradually increasing dosages orally, subcutaneously or intramuscularly. Oral administration begins with 1 tablet (0.02 g) 3-4 times a day, and then the single dose is increased to 2-4 tablets per dose. For parenteral administration, the initial dose is 0.02 g (1 ml of a 2% solution), and then increases to 0.05 - 0.1 g (1-2 ml of a 5% solution). Long-term use of the drug is possible for 1/7 to 4 months. Belongs to list B.

Trioxazin is prescribed orally at 0.3 - 0.6 g (1 - 2 tablets) 2 - 3 times a day, with a gradual increase in the single and daily dose. Side effects may occur in the form of general weakness, nausea, drowsiness, dry mouth and pharynx. Belongs to list B.

Phenibut (Phenibut) - fenigama - a new drug that has a pronounced tranquilizing effect. Being a derivative of gamma-aminobutyric acid, which is involved in metabolic processes in the central nervous system, phenibut has no contraindications and does not cause side effects. Taken orally at 0.25 - 0.5 g (1-2 tablets) 2 - 4 times a day.

Tacitin (Tacitinum) has a tranquilizing and muscle relaxant effect. Taken orally in tablets of 0.01-0.02 g (1 - 2 tablets) 2 - 3 times a day. Side effects: general weakness, dry mouth. Contraindications: severe damage to the liver and kidneys.

Magnesium sulfate (Magnesium sulfuricum) has a sedative, hypnotic, anticonvulsant, choleretic and hypotensive effect. When treating neurological patients, the drug is administered parenterally (intramuscularly or intravenously): 5 - 20 ml of 20% or 25% solution; intravenous medication should be administered slowly.

Demidenko T. D., Goldblat Yu. V.

"Sedatives, neuroleptics and tranquilizers" and others

Tranquilizers are a class of drugs that originally included drugs intended primarily to treat symptoms of anxiety and sleep disorders. The absence of both an antipsychotic effect and the ability to cause extrapyramidal disorders in the range of psychopharmacological activity served as the basis for their isolation from other psychotropic drugs. According to their chemical structure, tranquilizers are predominantly represented by derivatives of benzodiazepine, glycerol, and trihydroxybenzoic acid; azapirone derivatives and a number of other chemical compounds.

Mechanism of action of benzodiazepine derivatives

The mechanism of action of benzodiazepine derivatives became known in 1977, when benzodiazepine receptors, which are directly related to GABA, one of the main inhibitors of neurotransmitter systems, were discovered and localized in the central nervous system. When GABA combines with its receptors, the channels of chloride ions open and they enter the neuron, which forms its resistance to excitation. GABA is active predominantly in the following parts of the brain: stellate interneurons in the cerebral cortex, striatal afferent pathways globus pallidus and substantia nigra, Purkinje cells of the cerebellum. Benzodiazepine tranquilizers have a GABAergic effect, i.e. stimulate the production of this neurotransmitter and facilitate GABAergic transmission at the pre- and postsynaptic levels.

Clinical effects of benzodiazepine derivatives

The clinical effects of benzodiazepine derivatives include 6 main ones: tranquilizing or anxiolytic, sedative, central muscle relaxant, anticonvulsant or anticonvulsant, hypnotic or hypnotic, vegetostabilizing and 2 optional ones: thymoanaleptic, antiphobic. The degree of severity of various effects in the spectrum of psychotropic activity of various benzodiazepine derivatives is not the same, which forms the individual profile of a particular drug.

The use of benzodiazepine derivatives is advisable for symptoms of maladjustment caused by anxiety. The use of these drugs is not recommended in cases where the severity of anxiety is low and does not go beyond the normal response to a stressful situation. In therapy for situational and acutely developed anxiety, preference is given to low-potency drugs with a long half-life, which reduces the risk of drug dependence and withdrawal symptoms, in particular diazepam (no more than 30 mg/day). The duration of the course is determined by the time of exposure to the stress factor that contributed to the development of anxiety. When treating anxiety as part of somatic diseases, these same drugs are used.

The most pronounced effect of benzodiazepine derivatives in the treatment of panic attacks is observed provided that they are not accompanied by persistent reactions of avoidance of the situation on the part of patients. The rapid onset of the anxiolytic effect allows you to completely stop a panic attack or prevent it if you take the drug immediately before a situationally significant event. Given the high frequency of relapses, most patients are prescribed combination therapy or the use of several drugs with sequential changes during the course. Despite the relatively greater safety of long-acting drugs, their therapeutic dose can be so high that it will cause excessive sedation. If there are symptoms of depression in the structure of panic disorder, antidepressants are used in combination therapy, with preference given to selective serotonin and norepinephrine reuptake inhibitors.

In the treatment of generalized anxiety disorder, which, according to various data, has a higher degree of comorbidity with major depressive disorder than with other anxiety disorders, the target symptoms are clinical anxiety phenomena specific to this nosology, such as muscle tension, hyperactivity of the autonomic nervous system and increased level of wakefulness. In most cases with this pathology, benzodiazepine derivatives are used in conjunction with SSRIs and dual-acting antidepressants (selective serotonin and norepinephrine reuptake inhibitors). Moreover, both with monotherapy with benzodiazepine derivatives and with combined use, the effectiveness and safety are higher for prolonged drugs with a long half-life. On the contrary, when using powerful drugs with a short T1/2 (for example, alprazolam), the risk of drug dependence and relapse of anxiety between doses is increased. It is advisable to use 15-30 mg/day of diazepam or another drug in an equivalent dose. As a rule, long-term therapy (6 months or more) is effective and safe in most patients, although the dose of the drug must be reduced, monitoring the possible appearance of anxiety symptoms.

Benzodiazepine derivatives in the treatment of simple phobias are not considered drugs of choice in all cases, except for anticipatory anxiety, when it is possible to use diazepam (10-30 mg/day) as a counteract to phobic stimuli. The basis of treatment for this pathology should probably be behaviorally oriented psychotherapy.

In the treatment of obsessive-compulsive disorders, benzodiazepine derivatives are less effective than SSRIs and selective serotonin and norepinephrine reuptake inhibitors in combination with psychotherapy.

Somatoform disorders that occur in the form of isolated dysfunction of certain organs are subject to treatment with benzodiazepine derivatives only when taking into account the direct effect of these drugs on various vegetative and algic components of the pathological condition. Moreover, the effectiveness of benzodiazepine derivatives is significantly higher for leading vegetative symptoms than for isolated algic symptoms.

Despite the widespread clinical use of benzodiazepine derivatives for depressive conditions, their own antidepressant activity is low even in cases where anxiety is clearly represented in the clinical picture (anxiety-depressive disorders). In such patients, benzodiazepine derivatives should be used only as concomitant therapy to enhance the activity of antidepressants. In other words, treatment for anxiety depression begins with the use of antidepressants and, for the period necessary for the development of their therapeutic effect, a course of tranquilizers lasting 1-4 weeks is additionally prescribed. A special place in the treatment of depressive disorders is occupied by dyssomnias resistant to antidepressant therapy. In such cases, longer-term administration of benzodiazepine derivatives (diazepam, phenazepam in average therapeutic doses) is indicated.

In cases of hyperthymia and mild mania, the administration of benzodiazepine derivatives helps to reduce the insomnia disorders, irritability, anger, and feelings of bodily discomfort associated with manic affect.

In the treatment of schizophrenia, tranquilizers are used in a complex psychotropic effect as adjuvant agents intended to relieve psychotic anxiety and to reduce the manifestations of neuroleptic akathisia.

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Pharmacokinetics of benzodiazepine derivatives

Most benzodiazepines are completely absorbed when taken orally, with peak plasma concentrations of these compounds occurring within a few hours. The metabolic transformation of benzodiazepine derivatives occurs in the liver under the influence of cytochromes P450 (CYP) ZA4, ZA7 and CYP 2C19. Most of the drugs in this group (alprazolam, diazepam, medazepam, chlordiazepoxide) form active metabolites, which significantly increases their half-life. Compounds that do not form active metabolites (oxazepam, lorazepam) immediately bind to glucuronic acid and are quickly eliminated from the body, which explains their significantly better tolerability and lower risk of drug interactions. Based on the duration of their half-life, benzodiazepine derivatives are divided into long-acting drugs (T1/2 more than 20 hours): chlordiazepoxide, diazepam and medazepam; fast acting (T1/2 less than 5 hours); average duration of action (T1/2 from 5 to 20 hours); lorazepam, bromazepam, oxazepam, etc.

Characteristics of benzodiazepine derivative tranquilizers

Side effects of tranquilizers

At the early stage of therapy, the most significant effect is considered to be a sedative effect, which disappears on its own within a few weeks as the anxiolytic effect develops. Also, when using standard doses of drugs, due to individual sensitivity, confusion, ataxia, agitation, exaltation, transient hypotension, dizziness and gastrointestinal disorders may occur.

Mental disinhibition is the most serious side effect of benzodiazepine derivatives, characterized by hostility, dysphoria, and loss of control over one's own actions. The leading role of alcohol in their development has been proven when used together with benzodiazepine derivatives. The incidence of these disorders is less than 1%.

Cognitive dysfunction is observed in patients taking minimal therapeutic doses of benzodiazepine derivatives for a long time. The quality of visual-spatial activities decreases and attention deteriorates. As a rule, patients themselves do not feel this.

Classification of tranquilizers

The main groups of tranquilizers, divided depending on their mechanism of action, are shown in the table.

Classification of tranquilizers by mechanism of action (Voronina Seredenin S.V., 2002)

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Non-benzodiazepine anxiolytics

Despite the fact that benzodiazepine derivatives occupy the leading position in terms of the degree of study and breadth of application, other anxiolytics are also used in medical practice.

Afobazole (INN:azole) is a domestic pharmacological drug from the group of anxiolytics, the world's first selective anti-anxiety drug of the non-bendiazepine series. Afobazole is free from the side effects of benzodiazepine derivatives: hypnosedative effects, muscle relaxant effects, memory disorders, etc.

Afobazole has an anxiolytic effect with an activating component, not accompanied by hypnosedative effects (the sedative effect of afobazole is detected in doses 40-50 times higher than the ED50 for anxiolytic action). The drug does not have muscle relaxant properties or a negative effect on memory and attention; Drug dependence does not form and withdrawal syndrome does not develop. Reducing or eliminating anxiety (preoccupation, apprehension, apprehension, irritability), tension (fearfulness, tearfulness, restlessness, inability to relax, insomnia, fear), and therefore somatic (muscular, sensory, cardiovascular, respiratory, gastrointestinal) symptoms), autonomic (dry mouth, sweating, dizziness) and cognitive (difficulty concentrating, weakened memory) disorders are observed after 5-7 days of treatment with afobazole. The maximum effect occurs by the end of 4 weeks of treatment and persists in the post-therapeutic period for an average of 1-2 weeks.

The drug is indicated for use in the treatment of neurotic disorders. It is especially advisable to prescribe afobazole to persons with predominantly asthenic personality traits in the form of anxious suspiciousness, uncertainty, increased vulnerability and emotional lability, and a tendency to emotional stress reactions.

Afobazole is non-toxic (LD50 in rats is 1.1 g with ED50 - 0.001 g). The half-life of afobazole when taken orally is 0.82 hours, the average maximum concentration (Cmax) is 0.130±0.073 mcg/ml, the average drug retention time in the body (MRT) is 1.60±0.86 hours. Afobazole is intensively distributed throughout well-vascularized organs. Use internally after meals. The optimal single doses of the drug are 10 mg, daily doses are 30 mg, divided into 3 doses during the day. The duration of the course of use of the drug is 2-4 weeks. If necessary, the dose of the drug can be increased to 60 mg/day.

Benzoclidine inhibits the activity of cortical neurons and the reticular formation of the brain stem, reduces the excitability of the vasomotor center, and improves cerebral circulation. This drug is used to treat anxiety disorders, including anxiety-depressive conditions (especially mild ones and associated with cerebrovascular insufficiency). In addition, benzoclidine is prescribed to elderly patients with atherosclerosis with cerebral disorders, arterial hypertension, and paroxysmal tachycardia.

Hydroxyzine is a blocker of central M-cholinergic receptors and H1 receptors. Pronounced sedative and moderate anxiolytic effects are associated with inhibition of the activity of some subcortical structures of the central nervous system. Hydroxyzine is characterized by a fairly rapid development of anxiolytic action (during the first week of treatment) and the absence of an amnestic effect. Unlike benzodiazepines, with long-term use, hydroxyzine does not cause addiction or dependence, and no withdrawal or rebound syndromes have been observed.

Benactizine is a diphenylmethane derivative, the anxiolytic effect of the drug is due to the reversible blockade of central M-cholinergic receptors. Due to its pronounced effect on central cholinergic structures, benactizine is classified as a central anticholinergic. The effect on the central nervous system is clinically manifested by a calming effect, inhibition of the convulsive and toxic effect of anticholinesterase and cholinomimetic substances, increased action of barbiturates and other hypnotics, analgesics, etc. Currently, due to the presence of effective tranquilizers, as well as due to unwanted side effects associated with atropine-like effects (dry mouth, tachycardia, mydriasis, etc.), benactizine is practically not used as an anxiolytic.

Representatives of the third generation anxiolytics are buspirone, oxymethylethylpyridine succinate (Mexidol), etc. The anxiolytic effect of Mexidol is associated with its modulating effect on membranes, including the GABA receptor complex, and is manifested by an improvement in synaptic transmission.

Buspirone is a partial serotonin receptor agonist and has high affinity for serotonin 5-HT1a receptors. The mechanism of action is not fully understood. Buspirone is known to reduce the synthesis and release of serotonin and the activity of serotonergic neurons, including in the dorsal raphe nucleus. In addition, it selectively blocks (antagonizes) pre- and postsynaptic D2 dopamine receptors (moderate affinity) and increases the firing rate of midbrain dopamine neurons. Some evidence suggests that buspirone has effects on other neurotransmitter systems. Effective in the treatment of mixed anxiety-depressive conditions, panic disorders, etc. The anxiolytic effect develops gradually, manifests itself after 7-14 days and reaches a maximum after 4 weeks. Unlike benzodiazepines, buspirone does not have a sedative effect, a negative effect on psychomotor functions, does not cause tolerance, drug dependence and withdrawal symptoms, and does not potentiate the effect of alcohol.

In addition to drugs belonging to the group of anxiolytics, drugs from other pharmacological groups have an anti-anxiety effect to varying degrees: some TNF-adrenergic blockers (propranolol, oxprenolol, acebutolol, timolol, etc.), α-adrenergic agonists (clonidine). Thus, propranolol is effective in the treatment of anxiety states associated with hyperreactivity of the sympathetic nervous system and accompanied by severe somatic and autonomic symptoms; clonidine has the ability to reduce somatovegetative manifestations in the withdrawal syndrome of opium addiction.

Currently, an intensive search continues for new drugs that have an anxiolytic effect and, at the same time, are safer and more effective than existing drugs. Screening of benzodiazepine derivatives is aimed at identifying the most selectively acting drugs with the most pronounced anxiolytic effect with a minimum of side effects. The search is also carried out among substances that affect serotonergic transmission, antagonists of excitatory amino acids (glutamate, aspartate), etc.

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When prescribing benzodiazepine derivatives, special attention is paid to the personality and behavioral profile of the patient, which helps to avoid cases of abuse of these drugs.

Characteristics of people taking benzodiazeline tranquilizers for treatment and using these drugs for non-medical purposes

Withdrawal syndrome

All benzodiazepine derivatives can cause withdrawal symptoms to one degree or another. This pathological condition, as a rule, occurs in the form of various disorders of the digestive tract, hyperhidrosis, tremor, convulsions, tachycardia, drowsiness, dizziness, cephalgia, hyperacusis, irritability.

In some cases, when therapy is abruptly discontinued, severe symptoms such as severe and prolonged depression, acutely developing psychotic states, hallucinations, and opisthotonus are noted. choreoathetosis, myoclonus. delirious states with catatonic episodes, etc.

Withdrawal syndrome rarely develops if the course of therapy with benzodiazepine derivatives does not exceed 3-4 weeks. Withdrawal phenomena also include the so-called interdose symptoms, or breakthrough symptoms - the resumption of symptoms between doses of benzodiazepine derivatives (adapted from data from the American Psychiatric Association, 1990). When discontinuing treatment with benzodiazepine derivatives, it is important to follow the following basic recommendations.

• Develop a clear scheme for the therapeutic use of the drug in order to avoid its abuse.
• It is correct to take into account the ratio of benefits and possible negative aspects of treatment.
• Gradually reduce the dose and carefully monitor for possible withdrawal symptoms.
• Resolve the issue of alternative treatment (psychotherapy, behavioral therapy or medication).
• It is necessary to maintain a spirit of cooperation in the relationship with the patient to strengthen compliance.

The general recommendation for reducing the daily dose of benzodiazepine derivatives to avoid the occurrence of withdrawal syndrome is the possibility of a fairly rapid reduction by 50% of what the patient takes; however, subsequent reductions should be made more slowly (by 10-20% of the new dosage every 4-5 days).

In psychiatric practice, a fairly extensive group of pharmacological drugs is used. Psychiatry uses tranquilizers more often than other medical fields. But they are used not only to treat psychopathic diseases.

So what are tranquilizers, the principle of action of anxiolytics, and where are they used?

This type of medication, together with antipsychotics, belongs to the class of psychotropic drugs with depressant effects.

Historical reference

The development of the first drugs in this group began in the 1950s. At the same time, scientific psychopharmacology was born. The mechanism of action of tranquilizers was just beginning to be studied. The history of use began with the introduction into medical practice of Meprotan (Meprobamate) in 1958 and Elenium (Chlordiazepoxide) in 1959. In 1960, Diazepam, also known as Sibazon or Relium, was released onto the pharmacological market.

Currently, the group of tranquilizers includes more than 100 drugs. Today they are being actively improved.

Tranquilizers (anxiolytics) are used to reduce the level of aggression, restlessness, anxiety, and emotional distress. They are quite often prescribed for the treatment of neuroses, as a premedication before surgery. Benzodiazepines are the largest group of tranquilizers, which are effectively used to relieve muscle cramps and in the treatment of epilepsy.

The mechanisms of action of tranquilizers are still not clear enough. But this does not prevent their widespread use. In addition, they are fairly well classified.

Tranquilizers: classification

The mechanism of action is the first condition according to which tranquilizers are divided into three groups:

1. Benzodiazepines (benzodiazepine receptor agonists). These tranquilizers, in turn, are classified according to their mechanism of action and duration of effect:

• short-term (less than 6 hours);
• average duration of action (from 6 to 24 hours);
• long-term exposure (24 to 48 hours).

Features of biotransformation (with and without formation of FAM).

According to the severity of the sedative-hypnotic effect (maximum or minimum).

According to the rate of absorption in the gastrointestinal tract (fast, slow, intermediate absorption).

2. Serotonin receptor agonists.

3. Substances of different types of action.

The description of the mechanism of action of tranquilizers in the medical literature usually boils down to the fact that they are psychopharmacological agents designed to reduce emotional tension, fear, and anxiety. However, that's not all. Tranquilizers are designed not only to calm. The mechanism of action of tranquilizers is associated with their ability to weaken the processes of strong excitation of the hypothalamus, thalamus, and limbic system. They enhance the processes of internal inhibitory synapses. They are often used to treat diseases not related to psychiatry.

For example, the muscle relaxant effect is important not only in the treatment of neurological diseases, but also in anesthesiology. Some substances can cause relaxation of smooth muscles, which allows them to be used to treat various diseases that are accompanied by spasms, for example, ulcerative manifestations of the gastrointestinal tract.

Benzodiazepines

This is the most common and extensive group of classical anxiolytics. These tranquilizers have hypnotic, sedative, anxiolytic, muscle relaxant, amnestic and anticonvulsant effects. Benzodiazepine tranquilizers, the mechanism of action of which is associated with their effect on the limbic system and, to some extent, on the stem sections of the reticular pharmacy and the hypothalamus, are characterized by increased GABAergic inhibition in the central nervous system. These drugs have a stimulating effect on the benzodiazepine receptor of the chloride channel of the GABAergic complex, which leads to conformational changes in the receptors and an increase in the number of chloride channels. By the way, barbiturates, unlike benzodiazepines, increase the duration of opening.

The current of chlorine ions inside the cells increases, and the affinity of GABA for receptors increases. Since an excess of negative charge (chlorine) appears on the inner surface of the cell membrane, inhibition of neuronal sensitivity and its hyperpolarization begins.

If this occurs at the level of the ascending part of the reticular formation of the brain stem, a sedative effect develops, and if at the level of the limbic system, an anxiolytic (tranquilizing) effect develops. Reducing emotional stress, eliminating anxiety, fear, creating a hypnotic effect (refers to night tranquilizers). The muscle relaxant effect (muscle relaxing) develops due to the influence of benzodiazepines on polysynaptic and inhibition of their regulation.

Cons of Benzodiazepines

Even if they are used at night, a residual effect may persist during the day, which is usually manifested by lethargy, apathy, fatigue, drowsiness, increased reaction time, decreased attentiveness, disorientation, and loss of coordination.

Resistance (tolerance) develops to these drugs, so larger doses will be required over time.

Based on the previous point, they are characterized by withdrawal syndrome, which is manifested by recurrent insomnia. After a long period of use, insomnia is accompanied by irritability, attention disorder, dizziness, tremor, sweating, and dysphoria.

Benzodiazepine overdose

In case of overdose, hallucinations, muscle atonia (relaxation), impaired articulation occur, and then sleep, coma, depression of cardiovascular and respiratory functions, collapse. In case of overdose, Flumazenil is used, which is a benzodiazepine antagonist. It blocks benzodiazepine receptors and reduces or completely eliminates the severity of the effects.

Serotonin receptor agonists

Buspirone belongs to the group of serotonin receptor agonists. The mechanism of action of the tranquilizer Buspirone is associated with a decrease in the synthesis and release of serotonin, as well as a decrease in the activity of serotonergic neurons. The drug blocks post- and presynaptic dopamine D2 receptors and accelerates the excitation of dopamine neurons.

The effect of using Buspirone develops gradually. It does not have a hypnotic, muscle relaxant, sedative, or anticonvulsant effect. Practically incapable of causing drug dependence.

Substances of different types of action

The mechanism of action of the tranquilizer "Benactizine" is due to the fact that it is an M, N-anticholinergic. It has a sedative effect, which is believed to be caused by blockade of M-cholinergic receptors in the reticular part of the brain.

It has a moderate local anesthetic and antispasmodic effect. Inhibits the effects of the stimulating vagus nerve (reduces gland secretion, reduces smooth muscle tone), cough reflex. Due to its influence on the effects of the excitatory vagus nerve, "Benactizin" is often used to treat diseases that occur with spasms of smooth muscles, for example, ulcerative pathologies, cholecystitis, colitis, etc.

Sleeping pills tranquilizers

Hypnotic tranquilizers: the main mechanism of action on the body is associated with a hypnotic effect. They are quite often used to correct sleep disorders. Often tranquilizers of other groups are used as sleeping pills (Relanium, Phenazpem); antidepressants (Remeron, Amitriptyline); neuroleptics (Aminazin, Chlorprothixene, Sonapax). Some groups of antidepressants are prescribed at night (Lerivon, Remeron, Fevarin), since the drowsiness effect from them develops quite strongly.

Hypnotics are divided into:

• benzodiazepines;
• barbiturates;
• melatonin, ethanolamines;
• non-benzodiazepine hypnotics.

Imidazopyridines

Now a new generation of tranquilizers has appeared, which is divided into a new group of imidazopyridines (non-benzodiazepines). These include "Zolpidem" ("Sanval"). It is characterized by the least toxicity, lack of addiction, it does not disrupt breathing function during sleep and does not affect daytime wakefulness. Zolpidem shortens the time it takes to fall asleep and normalizes sleep phases. Has an optimal long-lasting effect. It is the standard for the treatment of insomnia.

Mechanism of action of tranquilizers: pharmacology

"Medazepam". It causes all the effects characteristic of benzodiazepines, but the sedative-hypnotic and muscle relaxant effects are weakly expressed. "Medazepam" is considered

"Xanax" ("Alprazolam"). It has virtually no hypnotic effects. Briefly relieves feelings of fear, anxiety, restlessness, and depression. Quickly absorbed. The peak concentration of the substance in the blood occurs 1-2 hours after administration. Can accumulate in the body in people with impaired kidney and liver function.

"Phenazepam". A well-known tranquilizer that was synthesized in the USSR. It exhibits all the effects characteristic of benzodiazepines. It is prescribed as a sleeping pill, as well as to relieve alcohol withdrawal (withdrawal syndrome).

"Diazepam" ("Seduxen", "Sibazon", "Relanium"). It has a pronounced anticonvulsant and muscle relaxant effect. It is often used to relieve seizures and epileptic attacks. Less commonly used as a sleeping pill.

"Oxazepam" ("Nozepam", "Tazepam"). It is similar in action to Diazepam, but it is much less active. Anticonvulsant and muscle relaxant effects are weakly expressed.

"Chlordiazepoxide" ("Librium", "Elenium", "Chlozepid"). Refers to the first, classic benzodiazepines. It has all the positive and negative effects associated with benzodiazepines.

Tranquilizers are used in the treatment of a wide range of mental disorders.

• Neurosis-like and reactive states with severe anxiety, fears or obsessions;

  Panic attacks;

  Depression of various etiologies;

  Reactive psychoses;

  Schizophrenia and schizoaffective psychoses;

  Epilepsy;

  Alcohol withdrawal;

  Sleep disorders, etc.

Side effects of tranquilizers: drowsiness, dizziness, unsteadiness of gait; muscle weakness; with long-term use, decreased libido; sometimes - menstrual irregularities, skin itching, somatovegetative disorders (hypotension, nausea, constipation); worsening of subdepressive disorders.

17. Classification of sleeping pills, effects, indications, undesirable effects.

Classification

GABA A (benzodiazepine) receptor agonists:

• Benzodiazepines: Nitrazepam, Lorazepam, Nozepam, Temazepam, Diazepam, Phenazepam, Flurosepam;

  Drugs of different chemical structures: Zolpidem, Zopiclone, Zaleplon.

Narcotic-type sleeping pills:

• Heterocyclic compounds, barbiturates: Phenobarbital, Sodium etaminal;

  Aliphatic compounds: chloral hydrate;

Selected drugs from other groups:

• H1 histamine receptor blockers: Diphenhydramine, Doxylamine;

  Anesthesia: sodium hydroxybutyrate;

  Preparations of the pineal gland hormone melatonin.

Sleeping pills are divided into three classes. First class (generation) hypnotics are represented by barbiturates, antihistamines and drugs containing bromine (brominated, for example). Barbiturates interact with barbiturate receptors located on chemo-gated chloride ion channels, and the neurotransmitter for these channels is GABA. Barbiturates interact with these receptors, which leads to an increase in the sensitivity of chemo-dependent channels to GABA and leads to an increase in the period of opening of ion channels for chloride ions - the nerve cell polarizes and loses activity. The action of barbiturates, however, is not selective, and they cause not only a sedative-hypnotic effect, but also muscle relaxation, anticonvulsant and anxiolytic effects throughout the entire dose range. Barbiturates vary widely in their duration of action. Sleep induced by barbiturates is different from natural sleep. Antihistamines block histamine H1 receptors. Histamine is one of the key neurotransmitters of wakefulness, and blockade of histamine receptors, accordingly, leads to a sedative effect. Antihistamines, as well as barbiturates, disrupt sleep architecture. Second generation hypnotics are represented by numerous benzodiazepine derivatives. If barbiturates cause an increase in the period of opening of chemo-dependent channels, then benzodiazepines increase the frequency of opening.

Indications

Sleep disorders (difficulty falling asleep, early or night awakening), including secondary sleep disorders in mental disorders.

Side effect

Side effects are observed more often with long-term use of sleeping pills. The most commonly noted residual effects or aftereffect symptoms are characterized by increased sleepiness during the day, decreased performance, concentration, and deterioration of mood. These symptoms are sometimes called behavioral toxicity of the drug, making it difficult to perform tasks that require concentration and quick reactions. Behavioral toxicity is more pronounced in hypnotics with a long T1/2. Chloral hydrate has a pronounced irritating effect on the mucous membrane of the gastrointestinal tract, has a very small breadth of therapeutic action, and also often causes allergic skin reactions.

Often, when taking sleeping pills, mainly benzodiazepine derivatives, memory impairment in the form of anterograde amnesia is noted. When prescribing hypnotics to elderly patients, the possibility of changes in sensitivity to drugs, as well as their pharmacokinetic parameters, should be taken into account; therefore, therapy is started with small doses (about half the usual amount) with a very gradual increase with careful monitoring of the patients’ condition.

Sleeping pills should be used with particular caution in patients with impaired respiratory function, chronic respiratory diseases and sleep apnea syndrome. It is believed that most sleeping pills cause depression of the respiratory center (zopiclone has the least effect).

Long-term prescription of sleeping pills can lead to the development of tolerance and drug dependence. Initial signs of addiction manifest themselves as the inability to discontinue the drug due to a rapid relapse of insomnia. In some patients, symptoms of addiction appear after 2-3 weeks of therapy. The risk of developing dependence can be reduced by using intermittent courses with changes in medications, as well as careful monitoring of the patient and constant monitoring of the dose taken.

Compared to the most common hypnotics (nitrazepam, triazolam), zopiclone and zolpidem have a more physiological effect. They do not have muscle relaxant, anticonvulsant and residual hypnotic or sedative effects, do not affect the patient's daily functioning and have a lower likelihood of dependence and tolerance development. The drugs are well tolerated. In some patients, zopiclone may cause a feeling of bitterness or dry mouth, and zolpidem may cause mild impairment of memory and psychomotor coordination.

Effects

Barbiturates have a rapid hypnotic effect even in severe cases of insomnia, but significantly disrupt the physiological structure of sleep, shortening the paradoxical phase. The main mechanism of the hypnotic, anticonvulsant and sedative effects of barbiturates is allosteric interaction with a site of the GABA receptor complex, which leads to an increase in the sensitivity of the GAB K receptor to the mediator and an increase in the duration of the activated state of chlorine channels associated with this receptor complex. The result is, for example, inhibition of the stimulating influence of the reticular formation of the brainstem on its cortex.

Benzodiazepine derivatives are most widely used as sleeping pills. Recipe for hedgehogs in the oven. Recipe for cooking hedgehogs in the oven. . Unlike barbiturates, they disrupt the normal structure of sleep to a lesser extent, are much less dangerous in relation to the formation of addiction, and do not cause pronounced side effects.

Zopiclone and zolpidem are representatives of new classes of chemical compounds. Zolpidem selectively interacts with benzodiazepine ω receptors, which facilitates GABAergic transmission. Zopiclone binds directly to the chloride ionophore regulated by GABA. An increase in the flow of chloride ions into the cell causes hyperpolarization of the membrane and, accordingly, strong inhibition of the neuron. Pax Forte can be bought online in Moscow here. . Unlike benzodiazepines, new drugs bind only to central benzodiazepine receptors and have no affinity for peripheral ones. Zopiclone, unlike benzodiazepines, does not affect the duration of the paradoxical phase of sleep, which is necessary for the restoration of mental functions, memory, and learning ability, and somewhat lengthens the slow-wave phase, which is important for physical recovery. Zolpidem increases the duration of slow-wave sleep to a lesser extent, but more often, especially with long-term use, prolongs the paradoxical phase of sleep.

Like barbiturates, meprobamate also inhibits the paradoxical phase of sleep, causing dependence to develop.

Clomethiazole and chloral hydrate have a very rapid hypnotic effect and practically do not disturb the sleep structure, but clomethiazole is classified as a drug with a pronounced ability to cause drug dependence.

Bromoureids have been rarely used in recent years. They are rapidly absorbed, but have an extremely slow metabolism, which often causes the development of accumulation and bromism (skin inflammatory diseases, conjunctivitis, ataxia, purpura, agranulocytosis, thrombocytopenia, depression or delirium).

Some antihistamines are still often used as sleeping pills: diphenhydramine, hydroxyzine, doxylamine, promethazine. They cause inhibition of the paradoxical phase of sleep, strong aftereffects (headaches, drowsiness in the morning) and have anticholinergic properties. The most important advantage of antihistamines is the absence of dependence, even with long-term use.

In general psychiatry for psychotic conditions, sedative neuroleptics or sedative antidepressants are used to correct sleep disorders, depending on the leading syndrome.