Different sleep disorders in the modern world are quite common. It has been proven that inhabitants of large cities insomnia is diagnosed in a larger percentage of the population compared to residents of villages and towns. The main method of treating sleep disorders is sleeping pills. What drugs are the strongest and is it possible to buy them without a recipe?

The girl took a tablet to facilitate sleep offensive

Classification of sleeping pills

Snowproofs call drugs causing condition, according to the characteristics approaching natural sleep and capable of accelerating the flooding process, increase sleep depth and its duration. The scientific name of the group of drugs for sleep - hypnotics. Small doses of these medicines Relaxing and soothing effect.

All hypnotifications are divided into two large groups: drugs with a narcotic and nonarcotic action.

Nonarcotic hypnotifications:

• Benzodiazepines - nitrazempam, Dormikum, flunutrazepam, Chalnie, Triazola, Wegezapam.
• Nebsenzodiazepines: Skipidem (Ivadal), Zopiclon (injured).
• Gistamine receptor blockers: donormal.
• Derivatives HAMK: Phenibut.

Drug hypnotics:

• Barbiturates (barbituric acid derivatives): Barbital, Phenobarbital, Estimal.

Benzodiazepines

This group of imaging agents consists of substances with a sleeping pills, antitle and anti-epileptic effects. When sleeping, benzodiazepines accelerate the flooding process and significantly lengthen the duration of the rest. The effect of drugs from this group affects the structure of sleep, shortening the phase of fast and periodoxal sleep, so the dream with the use of benzodiazepines - the phenomenon is infrequent.

The effectiveness of sleeping pills from a group of benzodiazepines increases due to an anxiolytic properties - removal of anxiety, tension, acute reaction to the events that take place, and therefore these funds are the drugs for the treatment of insomnia.

The list of drugs is quite extensive and includes trade names:

• Nitrazempam - "Enowlifting", "Radedorm", "Berldorm".
• Midazolam - "Dormikum", "Flormidal".
• Triazoles - "Chalning".
• Flunitrzempam - Rogpnol.

The average duration of treatment with benzodiazepines is 2 weeks. With longer use - about 3-4 weeks, develops drug addiction. The sharp cessation of the admission of these sleeping pills leads to the development of cancellation syndrome: the patient experiences anxiety, insomnia, the nightmares are tormented, the tremor of the limbs is observed.

Psychoactive preparations with sleeping pills, anxiolytic and anticonvulsant effects

The unpleasant effect of these sleeping pills is the "consequence syndrome" - after waking up, a person feels lethargy, weakness in muscles, dizziness, drowsiness, possibly disruption of coordination of movements and reduce the concentration of attention. Such symptoms are associated with slow metabolism of benzodiazepines in the body - the drugs are long absorbed into blood from the stomach, and in the liver there is an incomplete decay with an active metabolite to the blood, which support the main action of the tablets. In this regard, the property is extremely not recommended to use drugs to patients whose work requires the concentration of attention and concentration - motor transport drivers, high spirits.

Poisoning benzodiazepines occurs quite rarely due to their low-flowered.

Nevenzodiazepines

The main drugs from this group were the so-called z-preparations - zopiclon, Clap and Zaven. The soft effect of these tablets makes them more secure than derivatives of barbituric acid, and a reduced probability of the development of physical dependence and addiction in comparison with benzodiazepines provides the possibility of longer treatment.

Like any other medicinal substances, Nevenzodiazepine drugs have drawbacks - there is a chance of the development of amnesia, less often hallucinations. Long use Z-preparations may be accompanied by daylight and anxiety. Cape has a short half-life, and therefore it is safer to use in persons whose activity requires a special concentration of attention.

Snegal remedy for non-scenery

Treatment with non-heavenseypine drugs should not be discontinued if the therapy lasts more than 2 weeks, which is associated with the increased ability to develop the cancellation syndrome. The dose is reduced gradually, within a few weeks, depending on the individual characteristics of the patient.

Blockers of histamine receptors

The known property of drugs for the treatment of allergies is a hypnotic effect, which is based on the effect of a modern donormal sleeping agent. The mechanism of donormal action is based on its ability to influence individual parts of the brain responsible for the process of nervous excitation. The drug is released from the pharmacy without a recipe, so it is more affordable. Among side Effects Donormal should be isolated strong dryness in the mouth, constipation and urination delay during the reception of a sleeping remedy. The drug is not addictive, and the possibility of poisoning is very low - not a single lethal outcome for overdose was not revealed.

Barbiturates

The main part of the barbituric acid derivatives is excluded from the list of drugs for the treatment of insomnia due to the large number of side effects. In modern clinical practice Barbiturates are less and less prescribed by patients suffering from various sleep disorders. Sleep, initiated by this group of drugs, differs from normal physiological sleep - the cyclicity of the phases is disturbed and its structure changes. Drug dependence develops immediately after re-admission, and prolonged treatment provokes addiction. Sleep caused by narcotic sleeping pills, intermittent, notes the presence of nightmarish dreams. After waking up, a person is experiencing strong drowsiness, fatigue, the coordination of movements is broken.

Medicinal from Barbiturate Group

Currently, only phenobarbital and cyclobital (relatras) are allowed to use. Half of the sleeping pills of these drugs produces a relaxing effect, and the dosage exceeds a few times heavy poisoning causes several times. The cancellation syndrome is developing immediately after the cessation of drug therapy and is expressed in severe insomnia, irritability, anxiety, poor mood and oppression of working capacity.

Derivatives gamke

Gamma-amine-oil acid is the brake mediator of the central nervous system and occupies an important place in the formation of slow sleep. The main drug of this group is the means called "Phenibut". This nootropic drug that has a sleeping pill effect contributes to the normalization of falling time and restores the normal cyclicality of the sleep phases. In contrast to the drugs of benzodiazepine rows, the phenibut contributes to the extension of the phase of slow sleep, due to which the patient's health is significantly improved after waking up. The sleeping pill is small toxic, has a short list of side effects and does not cause drug addiction.

Nootropic remedy, normalizing sleep

What kind of sleeping pill is better?

Only a doctor who knows all the individual characteristics of the patient's body and takes into account the type of sleep disorders when prescribing a particular drug can be answered. Only after a detailed collection of anamnesis, the doctor may issue a list of drugs for treatment with an exact indication of how many pills should be drunk.

Preference Nina Germanovna
Associate Professor of the Department of Pharmacology of the Pharmaceutical Faculty of the First MGMU. THEM. Sechenova, Ph.D.

When taking barbiturates, a pronounced effect occurs: drowsiness, drierness, violation of coordination of movements, nystagm and other unwanted manifestations. Long therapy with these drugs causes medicinal dependence and leads to the development of addiction (decrease in the pharmacological effect). The abolition of the drug causes "cancellation syndrome", which is accompanied by insomnia, frequent awakening among the night, in patients there is a superficial dream and the nightmarish dreams are tormented. In daytime, patients are irritable and an oppressed depressed mood is observed. Barbiturates increase the activity of microsomal liver enzymes, so when repeated use, the sleeping recycled action is reduced. With overdose of barbiturates there are no specific antidotes. Currently, barbiturates have lost their importance as drugs during insomnia. Their main use is associated with an anticonvulsant effect and with induction of microsomal liver enzymes.

Benzodiazepine derivatives
Nitrazempam (Radedorm, Enownote), Flunitrzempam(Rogpnol), Triazola (Chalning), Midazolam (Dormicum), L Orazepam (Lorafen).

Benzodiazepines do not change the structure of sleep and to a lesser extent possess side effects than barbiturates. In addition to the sleeping pills, they have tranquilizing (eliminate mental stress), anxiolytic (anti-suspended), sedative (soothing), Miorolaxing (lower muscle tone), anticonvulsant and amnetic (cause short-term memory loss) actions. The mechanism of action is associated with the impact on the barbituro-benzodiazepino-gamke-ergic receptor complex and with the amplification of the brake influence of the GABA in the central nervous system. GABA is the main brake mediator CNS, performing this function in all brain departments. Benzodiazepines, like barbiturates, are not selective, and their effects are manifested through GABA, reinforcing its physiological effect. The mechanism of action of all benzodiazepines is similar to, these drugs are distinguished by the speed of the offensive and the duration of the sleeping recycling effect. Preparations with a long period of half-life nitrazempam (T½ \u003d 16-48 h.) And flunutrazepam (t 1 \u003d 24-36 hours), while Midazolam, short-acting triazoles, ½ \u003d from 1.5 hours to 3.5 and 5 hours. respectively.

Nitrazempam/ Nitrazepamum (Enowlifting, Radedorm) is used as a sleeping bag with a quickly upcoming effect. Nitrazempam acts on a limbic brain system associated with the Talamus, in which one of the sleep centers is located. Most effective with functional and emotional disorders, accompanied by insomnia. It also has an anticonvulsant action, relaxes a skeletal muscles, reduces or relieves negative emotions (feeling of fear, anxiety, voltage). When applying the nitrazempama, sleep usually occurs after 45 minutes, lasts 6-8 hours. Under the influence of the nitrazempama, the depth and duration of sleep increases. T½ \u003d 16-48 h. It is excreted mainly with urine in the form of inactive metabolites. Produced in TB. 0.005 and 0.01

Midazolam(Dormicum) has a pronounced hypoplace-drug action, accelerates the phases of falling asleep and awakening, improves sleep quality. The structure of sleep does not change. As a sleeping pills are prescribed inside in TB., PRA. Obol., 7.5 mg or 15 mg with impairment of falling asleep or early awakening. After awakening, there is a feeling of freshness and vigor.

Cyclopyrrolone derivative - Zopiclon/ ZopiClonum (injected, pylodorm) is a sleeping pills of an average duration of action, usually sleep occurs after half an hour after its reception and lasts 6-8 hours. The mechanism of its action is associated with omega1, omega2 subtypes of benzodiazepine receptors in the central nervous system formation. Zopiclon reduces the flood period and the number of night awakening. An important feature of the drug is its ability to normalize the phase structure of sleep. Zopiclon is assigned to 1 TB. Before bedtime, if necessary, the dose increases to 2 TB. Elderly patients are recommended to begin treatment with ½ TB. Produced in TB. At 0.0075, during the treatment period, alcoholic beverages are not recommended.

The derivative of imidazopyridine - Skipidem/ Zolpidem (Ivadal, Hynogen, Sanval) The derivative of imidazopyridine, unlike other sleeping pills, has a high affinity for omega1 subtype of the gamba of the receptor complex in the structures of the brain. Easy falling asleep, reduces the frequency of night awakening and lengthens sleep duration to normal (6-9 hours). The drug does not violate the structures of sleep, lengthens 3 and 4 phases deep sleep, little affecting easy Son. and REM-Fazy. Due to the selectivity of the action, there is a weak anxiolytic, anticonvulsant and minelaxing activity. An important feature of Skipidem is the lack of development of addiction in prolonged use and reducing the wake-up frequency during sleep. Available in TB. Coated with a shell, 10 mg (0.01). The duration of continuous reception of zopyl and the claripsema should not exceed 4 weeks.

Pyrazolopyrimidine derivative- Caple/ ZALEPLON (Andante), selectively binds to omega1 subtype of benzodiazepine receptors, which leads to the opening of neural ionoform channels for chlorine ions and the development of hyperpolarization and strengthening braking processes in the central nervous system, providing a pronounced sedative, minor anxolytic, anticonvulsant and central musclexistent effect. When applying the drug, the latent falling time is significantly reduced, the ratio of different phases of sleep does not change, but the duration of sleep is extended. Available in capsules of 5 mg and 10 mg. The duration of therapy should not exceed 2 weeks.

Preparation of hormone epiphiz. The hormone of the sishkovoid gland (epiphiz) is melatonin, which plays a major role in the mechanisms of circadian (near-dating) rhythms. Melatonin products depends on the time of day. Melatonin secretion increases in the dark (up to 70%), and decreases into the light (up to 30%). Melatonin increases the synthesis of gamke and serotonin in the middle brain and the hypothalamus. The normalization of the circadian biological rhythm and eliminating sleep disorder associated with movements to another time zone contributes to the synthetic analogue of this hormone - melatonin.

Melatonin (Melaxen, Melavit, Yukaline) acts on MT1 and MT2 melatonin receptors, located exclusively in brain cells. The drug normalizes circadian rhythms during desynchronosis, accelerates adaptation to the rapid change of time zones and when interpreted operation at night. Accelerates the act of falling asleep and reduces the number of night awakening, normalizes the well-being after awakening. It improves sleep quality, increases the depth and its duration. The drug does not have a "follow-up", does not cause the feeling of lethargy, breaking and fatigue after morning awakening. The most effective in the insomnia associated with the change of time belts, increased psycho-emotional status, during desynchronosis. Reception of the drug improves the mood, affects the emotional, intellectual-enemic sphere. The drug has antioxidant properties, manifests an immunostimulating effect. From side-unwanted manifestations allergic reactions, Headache, nausea, diarrhea.

The agonist of melatonin receptors- Ramelteon (Roser). New drug Treatmentacting more selectively on melatonin receptors. Stimulation MT. 1 and MT. 2 Subtypes of melatonin receptors allows you to adjust the 24-hour sleep cycle "Sleep-wake." It is used to treat primary insomnia. The half-life of Ramelteon is 3-5 hours, which significantly reduces sleep latency. The drug is well tolerated, increases the total duration of sleep without giving the next day the "effect of consequences". The recommended dose is 8 mg for half an hour before the deposit to sleep. To the side effects of reception include headache, drowsiness, dizziness, nausea and fatigue. In rare cases, allergic reactions, angioedema swelling of the tongue, pharynx and larynx causes. The cessation of drug intake does not cause a relapse of the disease.

Natural Brain Amino Acid - Glycine. Glycinographers the spread of excitation according to the structures of the brain and normalizes the processes of excitation and braking in the CNS. The synthetic analogue of this amino acid is a drug glycine - has a distinct anti-stress, anti-time effect, improves mental performance, reduces aggressiveness, irritability and weakens psycho-emotional reactions. Does not cause cancellation syndrome and increased dependence after cancellation. Take 2 TB. D / Rasis. For 20 minutes Before sleeping or immediately before bedtime.

Blocator H1-histamine receptors - Doxillamin/ DOXYLAMINE (donormil) in the chemical structure and the action of close to diphrolol and other histopufflockers, has sedative-sleeping pills, antiallergic and M-cholinolitic activity. Recommended for acute and chronic insomnia. Retains the physiological structure of sleep. No cancellation syndrome is noted. Among the possible side effects there is drowsiness, dry mouth, constipation. It is not recommended for transport drivers and persons whose occupation requires increased attentiveness and speed of reactions. Released in TB., Covered. Obol., 0,015

Clasetiazole. (Gemeinurin) in the chemical structure is close to vitamin B1, but does not possess vitamin properties. It has a sleeping pill, sedative, mioryexizing and anticonvulsant action. Increases the sensitivity of GAB-receptor to GABC. Used in disorders of sleep different character, especially shown in the states of acute excitation. Produced in capsules of 0.3 g and d / in. Lyophil. pores. 4 g Fl. with solvent.

Tenothen TB. D / PRIVAS 3 mg, contains affinity antibodies to the brain-specific protein S -100. Carries out the conjugation of synaptic and metabolic processes in the brain, modifies the functional activity of the S -100 protein. It has anxiolytic, sleeping pills and nootropic effects. It has a soothing, gamke-mimetic, neurotrophic, anti-asthenic effect and does not cause hypnogenic and minelaxing effects. Inhibits lipid peroxidation, causing an antioxidant action.

Neuter-free sleeping equipment

These drugs should not contain potent components and have a pronounced depressing effect on the central nervous system, reduce performance, attentiveness, cause addiction and addiction. All drugs have a soft soothing effect, remove the nervous tension, restore and normalize physiological sleep, improve sleep quality and contribute to a pleasant rest. Some of them protect the body from stress and facilitate the perception of nervous loads, strengthen nervous system. Many drugs contain vegetable vitamins and trace elements. After receiving such drugs, drowsiness does not occur and addiction, and in the morning hours there is a noticeable activity. Reception of drugs helps the body better rest and restores its strength faster.

Phytopreparats : Dormiplant, Passif, Valerian Forte, etc.

Dormiplant. - the combined phytopreparation contains dry extracts from the root of valerian and leaf leaves. Synergeniate sedative effect is manifested by a set of effects of active ingredients. It is used in insomnia associated with an increased nervous excitability.

Passif - The combined phytopreparation contains a thick valerian extract, liquid extracts of hop cones, chasty and tincture of hawthorn and mint. It has a soft sleeping pills. Produced in the form of a syrup in bottles of 100 ml. Shown in various sleep disorders.

Homeopathic agents: Syrup Homeopathic Passamp, EDAS 306 Granules of Snogen, Vernison, Sleep, Biolaine Inssenia, Biolaine Insomnia, TB. Nervohel and others.

Vernison - Homeopathic granules (10 g in bag) containing as active ingredients Strychnos Nux -Vomica C200, Coffee Arabica C 200, Atropa Belladonna C 200. Used in sleep disorders associated with overwork, nervous excitation, anxiety, in the abuse of caffinized beverages and a tendency to early awakening. Allergic reactions are possible, contraindicated during pregnancy and in childhood up to 18 years old.

In case of sleep disorders, Bad Morphores, Sliping, Bai Bai (Drops), Night Sleep (Capps), Triooson Plus, nerve, Nutria Kalm, Unabi Yiyuba, Mc Sleeping, Phytogypnosis, Sleep Formula, Syrup Syrup and Syrup Dr.

Bad Bai Bai (drops) has a slightening and soft soothing effect for hyperactive children. Normalizes sleep, restores sleep phases, strengthens the nervous system, relieves irritability, improves performance and improves brain functions. Reception of the drug helps the kids adapt to school loads. Take 5-10 drops for 30 minutes. Before sleep, the drops must be held in the mouth and swallow.

Phythiposnosis contains herbs extracts with sleeping pills. Helps with intermittent sleep. Active ingredients are: a dosage passiflower with soothing and sleeping effects; Green Oats - a soft sedative-soothing agent; Eshtolzia California - having a sleeping and spasmodic effect. Apply 2 TB., Souring, before bedtime. The duration of the course treatment of 20 days.

Bad Sliping contains 100 mg of California Fumurol and 100 mg of Georgin as active components. It has a soft sedative and sleeping pills, contributes to a pleasant rest.

Calm night - apply to improve the quality of sleep and removal of daytime voltage. Contains the extracts of pharmaceutical chamomile, hops, Kizyl Yamai and Valerian root. It has a soft soothing effect, causing a full-fledged refreshing sleep without severe side effects.

Reception of any prescription sleeping remedy requires a mandatory consultation of a dynologist. The decision on the immediate origin of treatment by sleeping equipment can take the patient himself. At the same time, it is necessary to carefully analyze all possible expected positive (such as eliminating breakdown, weakness, inattention) and negative (such as the occurrence of addiction, drug dependence, the irrationality of joint admission with alcohol, toxic effect when the recommended dosages is exceeded) the results of the use of sleeping pills. Only after careful weighing everyone for and against the right decision. If sleep disorder is not eliminated within 5-7 days, then the reception of this drug should be discontinued.

Reception of non-receptible drugs is safe, but most importantly - correctly select the drug, depending on the form of a breakdown of sleep and the active ingredients in it.

Zatzainlova Tamara Anatolyevna
Associate Professor of the Department of Pharmacology of the Pharmaceutical Faculty of MMA. THEM. Sechenov

Snow pillsapply to facilitate falling asleep and ensure normal sleep duration.

Modern sleeping pills must meet the following requirements: to quickly cause sleep and maintain its optimal duration, not to disturb the natural ratio of the main phases of sleep; Do not cause oppression of breathing, memory disorders, addiction, physical and mental dependence.

The classification of sleeping equipment is based on their chemical structure.

Classification of sleeping pills

1) benzodiazepine derivatives

Midazolam(Dormicum), Nitrazempam(Radedorm, Enownote), Flunitrzempam(Rogpnol), Temonds, Triazolam(Chalning), Estazolam

Preparations of this group are associated with a macromolecular receptor complex, including receptors that are sensitive to gamke, benzodiazepines, barbiturates, as well as chlorine ionophores. As a result of enhancing the action of the GABA, a more frequent opening of chlorine ionophos is occurring, the entry of chlorine ion in neurons, hyperpolarization of the latter and the development of braking processes.

In addition to the Stenic effect of benzodiazepines, they have a sedative, anxiolytic (anti-trial), anticonvulsant and central minelaxing effect. Benzodiazepines are shown in insomnia due to anxiety, stressful situation and characterized by falling asleep, frequent night and (or) early morning awakening.

2) The derivatives of imidazopyridine and pyrrolopirazine

Skipidem(Ivadal) Zopiclon(Injured, relaxon, somnol)

This is a relatively new group of sleeping pills have a number of advantages: the sleep on their background is more physiological, a quick falling is noted, a little expressed a myarlaxing effect. Such effects can be explained by more selective binding of drugs with a macroreceptor complex.

3) Pyridine derivatives

Doxillamin (Donormil)

According to the chemical structure, close to the block plactors of H1-histamine receptors, penetrates well through the hemato-encephalic barrier. The impetuous effect is due to the blockade of central H1 histamine receptors. Antallergic properties are not strong. The drug is produced in the form of ordinary or effervescent tablets.

4) Barbituric acid derivatives

Phenobarbital(Luminal) Cyclobarbital

Compared with the sleeping pills, other barbiturate groups change the structure of sleep (reduce the duration of the fast-wave phase), cause the abolition syndrome, induce microsomal liver enzymes, are more dangerous in terms of the development of drug dependence and the risk of poisoning. Currently, sleeping pill preparations from this group are rarely used. Phenobarbital is currently attributed to anticonvulsant and includes, mainly to the combined sedative preparations (Valokordin, Corvalol, Voserdin).

Cyclobarbital is part of the combined sleeping package by relators.

Table. Comparative characteristics of sleeping pills

The pharmacokinetic indicator T1 / 2 (semi-elimination period) largely determines the rate of occurrence and duration of sleep. Midazolas and Triazolas, Zopiclon and Skipidem - short-acting preparations (T1 / 2 - up to 6 hours). They should be recommended by patients who have a breakdown process. Temkespam, Estazolam, Doxylamine - Medium Duration Preparations (T1 / 2 - up to 18 hours). They should be recommended for patients who have a sleeping process, and sleep is not long. Nitrazempam and flunutrazepam - drugs long action (T1 / 2 - Over 30 hours). They should be recommended by patients whose sleep is not long.

The provisional should warn the patient about the need to establish the cause of insomnia and that these drugs should not be taken for a long time, as they can cause a number of negative side effects. The effect of hypnotic agents can be reinforced with antihistamine preparations and other means of depressing CNS. The day after receiving sleeping pills, avoid control of the car and classes requiring increased attention and speed of reaction. During treatment, alcohol is unacceptable.

Title preparations include drugs from barbiturate groups, benzodiazepines and means that are not included in these two groups (benzothiazines).

Classification of sleeping pills

Benzodiazepine derivatives

• Brotisola
• Lorazepam
• Midazolam
• Nitrazempam
• Triazola
• Flunitrzempam
• Flurazhepam
• Estazolam

Barbiturates

• Amobarbital
• Phenobarbital

Preparations of various chemical groups

• Bromisov
• Globeatimide
• Doxillamin
• Skipidem
• Zopiclon
• Clasetiazole.
• Metaqual

From the 60s Xx in. The place of barbiturates began to occupy the drugs of a group of benzodiazepines. They were less toxic than barbiturates. Relatively recently appeared even more secure sleeping pills that are not related to the group of benzo-thiazines: Zopiclon and Skipide.

According to the effects, sleeping pills can be classified as follows. Barbiturates are possessed by the most pronounced hypnotic action, as well as their combined funds. A very significant impact effect is provided by zopiclon, oilzepam, methacvulon, nitrazepams, triazoles, flunutrazepams, phlurazapes; Less pronounced - Sklipidem, Midazolam, ClaseMazole; Even weaker - bromisov.

Depending on the time of the impact effect, drugs are distinguished quick action (Sleep offensive 15-30 minutes after receiving a sleeping pin) and sleeping pills relative to slow action (sleep offensive after 60 minutes). The first group belongs to amobarbital, bromisoval, glatemide, doxylamine, zopiclon, lorazepam, methaqual, midazolam, nitrazempam, flunutrazepam, phlurazepam; To the second - phenobarbital.

The duration of the sleeping recycled effect distinguishes sleeping pills, causing a short and long sleep. Most nap (4-5 h) cause Midazolas and Triazola. Usually these drugs do not have post -ssic action. A longer sleep (5-6 h) cause bromisal and laureplates, as well as a globeymide and zopiclon. The sleep of medium duration (6-8 h) cause amobarbital, oilzepam, methacvulon, nitrazempam, phenobarbital and flurazepam.

The longest sleep (7-9 h) occurs after receiving flohunzepama.

Severity and frequency side phenomena Sleeping preparations are encouraged to try to correct the night sleep disorders by sedatives (such as the herbs of the mother-in-law, rhizomes with the roots of Valerian medicinal, peppermint leaves), as well as various non-drug methods (in particular, compliance with the mode and creating conditions for sleep) and some tranquilizers with sedative effect. However, with true insomnia (), the use of sleeping pills is more efficient and therefore widespread.

Currently, some of the previously used sleeping pills (globeymide, cleotiazole, methaqual), as well as individual benzodiazepine derivatives (brotisola) are not registered.

Mechanism of action and pharmacological effects of sleeping pills

According to modern ideas, a dream is a process in which the activity of hypnogenic (synchronizing) structures of the brain is increased, and the awakening effect of the reticular formation, causing an increase The tone of the cortex of the heavy brain hemispheres and the desynchronization of the electroencephalogram (EEG) is reduced.

Barbiturates act mainly at the level of stem structures, benzodiazepine derivatives - at the level of the limbic system and its connections with other structures that provide a cyclic change of sleep and wakefulness.

The hypnotic effect of benzodiazepine derivatives is associated with their interaction with appropriate benzodiazepine receptors and the activation of the GAB-Ergic system, making the functional activity of hypnogenic structures becomes relatively predominant. In addition, a decrease in intracellular energy exchange as a result of a decrease in the activity of mitochondria plays a reducing of intracellular energy exchange.

A decrease in the activity of intracellular metabolism lies and at the heart of the antihypoxic effect of barbiturates. However, they simultaneously reduce the excitability of the respiratory center, reducing its sensitivity to the physiological stimulus (CO2), which, with an increase in the dose of the drug, leads to oppression of cardio-respiratory activities. In addition, barbiturates enhance the activity of microsomal liver enzymes involved in metabolism and inactivation of other drugs (LS) used simultaneously, which helps to reduce the efficiency of the latter.

As established in the 60s, sleeping pills usually deform sleep formula, suppressing fast sleep phase. Wrong sleep is significantly different from natural sleep. A significant lack of sleep under the influence of sleeping pills is a sense of fatigue and breakdown, noted after awakening, which negatively affects the general state.

Along with the hypnotic effect, all drugs of this group in small doses have a sedative effect, normalize the light shapes of vegetative dysfunction. For this purpose, phenobarbital in a dose of 10-30 mg 3 times / day is used more often (usually as part of the combined means).

Benzodiazepine derivatives, primarily Lorazepam, except for sleeping pills, have a significant tranquilizing, anti-referee, anxiolytic effect, and they are often used for this purpose. Anti-Epileptic effect is characteristic of claropide, phenobarbital and benzodiazepine derivatives (nitrazempama, flunetrazepaum, chklomeazol). A significant mioroquisive effect is characteristic of benzodiazepine derivatives (nitrazempama, floh-domes), as well as Skipidem. Metaqualone, antispasmodic - phenobarbital (at a dose of 10-50 mg 3 times a day) has an analgesic properties. Antihistamine is characteristic of doxylamin. Barbiturates have antioxidant properties. Antiwheat action has Lorazepam.

Pharmacokinetics of scenery drugs

Preparations that have a sleeping pills, taken inside, fall into blood mainly from thin gut. The speed of this process depends on the properties of the drug, on the state of the intestinal mucosa, its motility, the features of the contents and pH of the medium. As a result, the sleeping pills inhibit the activity of the cells of the activating system of the reticular formation and stimulate the products of endogenous chemical compoundscontributing to the emergence and maintenance of sleep.

In the patient's body, most drugs, including sleeping pills, are subjected to biotransformation, in which the role of the relevant enzymes, in particular, microsomal liver enzymes. In the process of metabolism by conjugation and oxidation, there is a transformation of LS molecules. At the same time, relatively fine molecules are formed from larger molecules, often hydrophilic, isolated from the body mainly through the kidneys. The metabolism processes of the sleeping pills are largely dependent on many circumstances, in particular on the age of the patient, the functions of the liver, the food and the other LS introduced simultaneously. Preparations and their metabolites are derived by kidneys, to a lesser extent through the digestive tract, and in a nursing mother and with milk, which can affect the child's condition.

The duration of the impact drugs is determined by the half-life, in turn, depending on many conditions. It matters to determine the dose and time of reception of the drug, as well as the tendency to its cumulation.

Location of sleeping pills in the treatment of diseases

The main indication for the use of sleeping pills is sleep disorders with a hoping, intra-dubiary disorders and early awakening.

With transient and short-term sleep disorders, it is recommended that the reception of short-range benzadiazepines, zopilone or clarinem, as well as tranquilizers with sedative effects, is recommended. For chronic disorders Sleep the choice of the drug depends on the severity and durability of these violations, their nature and the possibility of their correction. With persistent, severe sleep disorders, preparations are used with a strong sleeping reaction in high doses, sometimes approaching the maximum permissible: flunutrazepam, claripsem, zopiclon, as well as barbiturates in combination with sedative tranquilizers, anxiolytic action in medium therapeutic doses. With moderately pronounced sleep disorders, the same drugs are used in smaller doses or lorazepams, nitrazepams in average therapeutic doses. With light impairment of sleep, it is often enough to use bromisoval, sedatives, tranquilizers with sedative and anxiolytic effect.

Difficulties when falling asleep are usually associated with psycho-emotional tension, a feeling of anxiety and the rigidity of an affective reaction. Therefore, for their relief, in most cases, it is enough to receive tranquilizers with a sedative action for 1-2 hours to sleep. With more pronounced, falling asleeps are recommended 30-40 minutes before the waste is taken to take benzodiazepine sleeping pills: nitrazempam, oilzepam, flunutrazepam.

In case of intricate disorders (superficial sleep, frequent awakening, leading, as a rule, to insufficient quality of sleep, drowsiness, sense of dissatisfaction with sleep) It is advisable to use for a long time acting drugs (Nitrazempama, Lorazepama, Flunitrzempama). The choice of the drug within this list is determined by the severity of sleep disorders; Start with more softeful LS.

With early awakening, drugs with a long action are also shown. A good effect is provided by candles, as due to slower suction, the drug begins to act in 3-5 hours. Apply short-acting preparations when awakening at night. For reception after awakening, you can choose a dose of the drug providing therapeutic effect (Often it is half the therapeutic dose when taking overnight).

In case of sleep disorders, the patients with pain syndrome are effective, as well as other sleeping pills in combination with non-nucleic analgesics in medium therapeutic doses.

Patients of senile age should not be prescribed barbiturates. First of all, you need to eliminate everything possible reasons Sleep disorders (such as pain, cough, the need for leg warming). Benzodiazepine derivatives are prescribed in minimal doses. If necessary, the dose increases, combining with other drugs to enhance the sleeping recycling effect (for example, with sedatives or analgesics, according to indications). The elderly traction to sleeping preparations, due to the usual decrease in natural sleep with age, is particularly significant. In this case, the side effects caused by the use of sleeping pores, they are usually more pronounced and include, in particular, dizziness, reduction of memory and orientation disorder, which is often mistakenly regarded as manifestations of sedense dementia. Thus, the use of sleeping pills is appropriate only by valid readings. In the process of their application, you should use minimal doses of drugs, taking them by short courses (within 3 weeks).

There are various opinions on rational medical treatment dissismy. It is carried out both episodically and courses, which, however, should not be acquired by a protracted character. When conducting courses of treatment, the drugs should be canceled with a gradual decrease in the dose of a sleeping pill preparation (the prevention of cancellation syndrome). This is especially essential when using sleeping pills from a group of barbiturates.

The question of the duration of the use of sleeping pills is complicated. Usually the course of treatment does not exceed 3 weeks. With simultaneous adequate pathogenetic and etiotropic therapy, as well as measures to develop a conditional reflex on sleep offensive (for example, the extinguishing to sleep at one time, a warm bath, reading before bedtime), you can achieve sleep normalization with a gradual cancellation of sleeping pores. In the future, they can be used episodically in special situations, with psycho-emotional overvoltage.

In addition to direct indications for receiving sleeping pills, their application is advisable both in other cases:

• With nausea and vomiting caused by chemotherapy, it is possible to use Lorazepam. The drug is prescribed after 6 hours and 12 hours after receiving chemotherapy, at a dose of up to 4 mg per day.
• When applying nitrazempam (with small seizures in children), cleotiazole.
• In neurosis as anxiolytic agents are expedient to Lorazepam, nitrazepam, estazolum.
• To relieve excitation and anxiety in elderly patients, benzodiazepine derivatives are used in minimal doses.
• To relieve the abstinal syndrome in patients, it is advisable to use benzodiazepine preparations.
• For premedication and in short surgery, they are sometimes used by both drugs such as Lorazepams, Midazolas, nitrazepams, flunutrazepam.
• Barbiturates are sometimes used as antihypoxants and to reduce intracranial pressure during the brain.

Portability and side effects of sleeping pills

When using hypnotic drugs, post -ssunical disorders are often observed (a sense of breakdown, drowsiness in the morning, dissatisfaction with sleep), especially characteristic of barbiturates, less often - other sleeping pills with a long action. In case of post-communal disorders, it is recommended to reduce the dose of the sleeping pill preparation or replace with it with a relatively short effect: zopiklon, a campidem, a laureplate, mydazolam, nitrazepam. In the event of post -ssunical adverse events, it is advisable to adopt caffeine (at a dose of 100 mg), mesocarb (at a dose of 5 mg), a spiny rhizome eleuterococcus and root or other tonic and psychostimulating drugs; Sometimes it is enough to limit the cup of strong coffee during breakfast.

The substantial disadvantages of sleeping preparations belongs to the change in the change in the structure of sleep. Normally sleep includes two alternating phases: orthodox sleep and paradoxical, or Rem-sleep (Rapid Eye Movement). For full sleep, both phases are significant, while recognized by a significant role of the REM sleep in personal adaptation.

Most sleeping pills suppress Rem sleep. A particularly significant suppression of rem-sleep is noted when taking barbiturates. Zopiclon affects the formula of sleep less than other sleeping pills.

The lack of many sleeping pills is a relatively fast (sometimes after 2 weeks) of the development of tolerance towards them, causing the need to increase the dose or replacement of the drug. Tolerance to the Lorazepam and Flunitrzempama develops relatively slowly. The development of tolerance often coincides with the occurrence of dependence, which is particularly often manifested to barbiturates with euphorizing effect. The sharp cancellation of the drug in such cases leads to the development of an abstineent syndrome, which is manifested by a feeling of anxiety, fear, psychomotor excitation, sometimes the occurrence of hallucinations, profuse sweat, gastrointestinal disorders, finemplitudinal tremor, decrease arterial pressureIt is possible to vomiting and convulsions. An abstitent syndrome occurs after 1-10 days after a sharp cessation of treatment and can last a few weeks. In the development of abstinence, it is necessary to resume the reception of the sleeping pill preparation in the same dose with its gradual cancellation while improving the state. Sometimes we need disinfecting therapy. To prevent the development of the abstinence syndrome, the dose of imaging drugs of the average duration of action should be reduced gradually: by 5-10% every 5th day. Preparations with prolonged action can be canceled faster. When applying short-acting drugs, when the probability of developing the abolition syndrome is the most high, it is necessary to reduce the dose especially slowly. When canceling barbiturates, it is recommended to reduce the dose daily to the amount equivalent to 3 mg of phenobarbital.

From other side effects, cholinolitic disorders should be noted when taking doxillamin: dryness in the oral cavity, aggravation of glaucoma, urination delay in adenoma prostatic gland. When using many barbiturates in large doses there is some hypotensive effect.

The oppression of respiration with a reduction in the minute resistance volume by 10-15%, practically significant for patients with COPD, is sometimes provoked by the reception of barbiturates, in particular phenobarbital or nitrazempama. Reducing diuresis is possible when using barbiturates, causing an increase in the secretion of vasopressin and reducing the blood supply to the kidneys.

When receiving flurazhepam, sometimes there is an edema of the age. Metal flavor is observed when taking zoplic.

Dyspeptic disorders (nausea, rarely vomiting, diarrhea) are possible when taking a campidem, zopyl, triazolam, flurazhepam, chklomeazole.

With long-term treatment with barbiturates, a toxic effect on parenchymal organs is possible, sometimes accompanied by the development of hepatitis and deficiency folic acid. Big doses of barbiturates can cause thrombocytopenia (for example, phenobarbital at a dose of more than 0.45 g per day). Under the oversized doses or cumulation of barbiturates, Skipidem and Flunitréspama there is an emergence of nystagma, discoordination of movements and ataxia.

When receiving some drugs (Midazolas, Skipidem), sometimes after awakening, the confusion of consciousness, elements of hymometry appear for some time.

Paradoxical reactions (insomnia, excitation) are possible as an individual reaction to separate drugs, in particular floh-bezes. Flunitrzempam has a local radiating effect and with intraartiaric administration is able to cause necrosis; for intravenous administration Classes There is a danger of phlebitis.

With long-term reception of large doses of sleeping pills with slow metabolism (many barbiturates), the drug and the development of chronic intoxication is possible. Chronic intoxication is manifested by lethargy, apathy, drowsiness or increased excitability Day, reduction of memory and perception of information, headache, dizziness, tremor of the limbs, in severe cases of dysarthria. Possible hallucinations, cramps, psychomotor arousal, liver, kidney and heart impairment. It should be noted that in patients of senile age, these phenomena may arise after the first testers of barbiturates. Then the abolition of the drug is necessary (with a dependence on the drug, the dose should be reduced gradually) and the purpose of disintellation, symptomatic therapy. The forecast is usually favorable.

The phenomena of bromoism during bromine intolerance can be observed when taking bromisoval.

Barbiturates, Skipidem and Flunitrazepams sometimes cause skin reactions.

In newborns whose mother took barbiturates, an increase in the frequency of neoplasms is registered; In addition, the reception of these drugs during pregnancy leads to the oppression of the respiration of the fetus. Since sleeping pills penetrate into milk nursing mothers, they can cause unwanted changes in the child's state.

Contraindications for sleeping pills

Sad preparations are contraindicated with increased sensitivity to them and their components (or to any drug of the same chemical group).

Sleeping preparations with a duration of more than 6 hours, causing post-communal disorders, should not be prescribed to patients whose activity requires a rapid and adequate reaction (for example, transport drivers, dispatchers).

In myasthenia, all hypnotic agents are contraindicated, especially with a mioral action: barbiturates and such derivatives of benzodiazepine, such as Lorazepam, Midazolas, nitrazepam.

Absolute contraindication for the use of barbiturates is porphyria.

Heavy liver diseases, kidneys also serve as a contraindication for the use of many sleeping pills, in particular barbiturates and Skipidem. At the same time, it is necessary to remember about the special danger of the use of drugs with a long action when renal failure (They are removed unchanged by the kidneys) and short - with liver failure (metabolized mainly in the liver).

With respiratory violations, the use of nitrazempama, barbiturates and Skipidem is particularly dangerous. With caution, you can apply zopiklon.

Due to the danger of a reduction in the diurea during heart failure, it is undesirable to assign barbiturates, as well as mydazolam (as it has some depressor action on the cardiovascular system). In the arterial hypotension, it is undesirable to use barbiturates in large doses (possess a hypotensive effect). In addition, in order to avoid the danger of toxic effects on the blood of barbiturates is contraindicated in infection and hyperthermia. Barbiturates should not be prescribed and elderly patients, since when using these drugs in small doses in the elderly, the development of psychotic disorders, anxiety, initiation and disturbances of consciousness is possible. The use of barbiturates is contraindicated in the hyperactivity syndrome in children.

With a tendency to the urination delay, the prostate adenoma and glaucoma do not recommend the use of drugs with cholinitic effect, in particular doxylamine.

Comately weakened patients, with organic lesions of the brain and severe depression, the appointment of Midazolam is contraindicated.

In case of a tendency to addiction or the dependence of the patient from alcohol, it should not be prescribed by sleeping pills, especially barbiturates, benzodiazepines, methacvulon and other sleeping pills to which the addiction is more often developed.

In order to avoid the teratogenic effect during pregnancy, the use of benzodiazepine derivatives, barbiturates, doxylamine, culpidem and zopilone, to a lesser extent of other sleeping pills, is contraindicated. Reception of sleeping pills, especially barbiturates, in the late period of pregnancy can lead to the oppression of the breath of the fetus. In addition, the use of all sleeping pills during lactation is not shown.

Cautions

Sad preparations, especially with a prolonged action, should not be taken by transport drivers and patients whose work is associated with urgent adoption of responsible decisions.

Interaction of sleeping pills with other medicines

Barbiturates induce liver enzymes, which leads to accelerated metabolism of some drugs used simultaneously, in particular, anticoagulants, tricyclic antidepressants, sulfonamides, hypoglycemic drugs, glucocorticoids and contraceptives for intake. As a result, the usual therapeutic dose of these drugs often becomes insufficient. If at the same time the dose of the drug is raised, then the abolition of barbiturates may be accompanied by clinical signs overdose of the associated LS.

All sleeping pills enhance the effect of psychotropic drugs with a sedative effect, analgesics, as well as alcohol. The simultaneous use of sleeping pills and alcohol is not recommended due to the danger of development are sometimes difficult to predict, individual reactions. Flunitrazes are incompatible with monoaminoxidase inhibitors.

Snowframes - LV, which cause a person from a person close to natural sleep. Apply with insomnia to facilitate falling asleep and ensure normal sleep duration.

Sleep is heterogeneous in its structure. There are two main components of sleep, differing in the nature of wave oscillations of the electrical activity of the brain cells on the electroencephalogram: a slow-wall sleep and a fast-level sleep.

The slow-wall sleep (slow, orthodox, synchronized, non-REM-SLEEP) has a duration of up to 75-80% of the total sleep time and four sequentially developing phases, from dorms (first phase) to the Δ-sleep phase (fourth phase) characterized by occurrence On the electroencephalogram of slow high-amplitude δ-waves.

Fast-roll sleep (fast, paradoxical, desynchronized) is repeated every 80-90 minutes, accompanied by intervision and fast eye movements (Rapid Eye Movement Sleep, Rem-Sleep). The duration of the quick-wave sleep is 20-25% of the total sleep time.

Sleep phase ratios and their rhythmic shift are regulated by serotonin (the main factor induced), melatonin (factor,

synchronization of sleep phases), as well as gamke, enkephalins and endorphins, peptide δ-sleep, acetylcholine, dopamine, adrenaline, histamine.

Alternations of the phases of a slow-factory and faster sleep are characteristic of a normal sleep, while a person feels vigorous and slept. Natural sleep disorders can be associated with falling asleep, sleep depth (surface sleep, alarming dreams, frequent awakening), sleep duration (lacking, long-term final awakening), sleep structures (change in the ratio of slow and fast sleep).

The main effect of sleeping pills is aimed at facilitating the flow of falling asleep and / or lengthening the duration of sleep. Depending on this, uniform means of different duration of action are used. In small doses, sleeping pills provide a sedative (soothing) effect.

The sleeping remedies act inhibitory on the synaptic transmission to the CNS, and some of them relatively selectively depress the individual structures and functions of the brain (sleeping pills with a non-nucleic type of action), while others have a total depressing effect on the CNS, i.e. Activate indiscriminate (means of narcotic type of action).

In accordance with such differences in action, as well as on the basis of differences in the chemical structure, the following main groups of sleeping pills are distinguished.

Sleeping agents with a non-nucleic type of action.

Benzodiazepine receptor agonists.

Benzodiazepine derivatives: Nitrazempam (Radedorm *, Enowlighted *), flunutrazepam (Rogpnol *), t p and a z o - Lam (Chalning *), Midazolam (Dormikum *).

Preparations of another chemical structure (nebanzodiazepines): s o n and to l about n (injured *, picodorm *), s o l p and d e m (Ivadal *, Sanval *), Zavev.

Blocators N 1 -Repceptors: doxylamine (donormil *).

Melatonian receptor agonists: R A M E L T E N *.

Non-drug type of actions.

Derivatives of barbituric acid (barbiturates): f e n o - b a r b and t a l (luminal *).

Aliphatic compounds: X l o r a l g and d r and t.

Sleep, which occurs when applying sleeping pills, is somewhat different from natural (physiological) sleep. First

the queue is concerned about changing the duration of the faster sleep: the latent period increases in the development of this phase and its total duration decreases. With the abolition of the imaging agents, the latent period of the rapid sleep phase is temporarily shortening, and the faster-wave sleep for some time is extended. At the same time, there is an abundance of dreams with the nature of nightmares, which leads to frequent awakening. These phenomena associated with the cessation of the use of a sleeping pill preparation are called the "return" phenomenon.

The sleeping pills into the unequal extent violate the ratio between the rapid and slow phases of sleep (the structural structure violates). To a greater extent, this is characteristic of derivatives of barbituric acid and to a lesser extent for benzodiazepines. Little change the structure of Sleep Skipide and Zopiclon and practically does not affect chloralhydrate.

The following basic requirements are imposed on sleeping pills: they must quickly cause sleep and maintain its optimal duration, not to disturb the natural relationship between sleep phases (not to disturb the structure of sleep), do not cause oppression of respiration, memory violations, addiction, physical and mental dependence. Currently there are no sleeping pills that fully satisfy all these requirements.

11.1. Sleeping agents with non-tarcotic type of action

11.1.1. Agonists benzodiazepine receptors

Benzodiazepine derivatives

Benzodiazepine derivatives have anxiolytic activity (eliminate the feeling of anxiety, anxiety, tension [see "Anxolytic means (tranquilizers)"] and have a sleeping pill, and in small doses soothing (sedative) action. Elimination of mental tension contributes to the reassurance and development of sleep. Except that benzodiazepines reduce the tone of skeletal muscles (the effect is associated with the suppression of polysinactic reflexes at the level spinal cord) And there is anticonvulsant activity, the effects of substances depressing CNS, including alcohol and drugs for anesthesia, and have an amnetic effect (cause anterograd amnesia).

Anxolytic and sleeping pills of benzodiazepines are due to their inhibitory effect on the limbic system and the activating reticular formation of the brain stem. The mechanism of these effects is associated with the stimulation of benzodiazepine (ω) receptors, the agonists of which they are. 3 subtypes ω-receptors (ω 1, ω 2, ω 3) are isolated (ω 1, ω 2, ω 3) is believed that the benzodiazepine's sleeping recycled effect is due to the preferential binding to ω 1 -receptors.

Benzodiazepine receptors form a complex with GABA and -receptors directly forming chlorine channel. GAMK A -receptor - glycoprotein, consisting of 5 subunits (2a, 2β and γ), directly forming a chlorine channel. GABA binds to the A- and β-subunits of the receptor and causes the opening of the chlorine channel (Fig. 11-1). Stimulation of benzodiazepine receptors located on the γ-subunit of the GABA A -receptor is accompanied by an increase in the sensitivity of the GABC and -receptor to the GABC and an increase in the effectiveness of this mediator. At the same time, the activity of GABA does not increase, which causes a lack of drug action from benzodiazepines.

Fig. 11-1. The mechanism of action of benzodiazepines. Explanations in the text

With increasing sensitivity of the GABA A -receptor to GABA under the influence of benzodiazepines, the frequency of the opening channels is increasing, as a result of a larger number of negatively charged

chlorine ions enters the neuron inside, which leads to hyperpolarization of the neural membrane and the development of braking processes.

Benzodiazepines are used in insomnia associated with anxiety, stressful situation, a sharp change of time zones and characterized by falling asleep, frequent night and / or early morning awakening. They are also used in anesthesiology for premedication to surgical operations.

Benzodiazepines are distinguished by duration of action on:

Durable drugs: flunutrazepam;

Medium duration drugs: nitrazempam;

Preparations of short action: Triazoles, Midazolam.

Preparations of long-term action and drugs of average duration cause a dream, which lasts 6-8 hours. The duration of the action of some drugs (flurazheps, diazepams) is associated with the formation of active metabolites. When using benzodiazepines, in particular the existing drugs, there are phenomena of the inception during the day, which are realized in the form of drowsiness, lethargy, slowing the reactions. Therefore, benzodiazepines should not be prescribed to patients whose professional activity requires the speed of reaction and increased attention. For repeat applications The cumulation of the substance occurs.

Feature phenomena is less characteristic of short-acting drugs. However, with a sharp abolition of briefly acting drugs, the phenomenon "return" occurs. To reduce this effect, benzodiazepine should be canceled gradually. With reuse of benzodiazepines, addiction is developing, while it is necessary to increase the dose of the drug to obtain the same sleeping recycling effect. It is possible to develop drug dependence (both mental and physical). In the case of the development of physical dependence, the abolition syndrome flows less as well as depending on barbiturates.

In terms of the severity of the sleeping pill effect, benzodiazepines are inferior to barbiturates, but they have a number of benefits: to a lesser extent, the structure of sleep is violated, they have greater larger therapeutic effects (less risk of acute poisoning), cause fewer side effects, less pronounced induction of microsomal liver enzymes. It is slower than developing tolerance and drug addiction.

Nitrazepam is most widely used in insomnia. Produced in the form of tablets. Assign for the night for 30-40 minutes to sleep. Action after administration orally occurs after 30-60 minutes and lasts 6-8 h (T 1/2 - 24-36 h). In addition, nitrazempams are used for premedication to surgical operations and in connection with its anticonvulsant action in some forms of convulsive seizures (especially in children).

For nitrazempama due to its significant duration of action, the phenomena of thesis is characterized: weakness, drowsiness, violation of the concentration of attention, slowing down mental and movement reactions. Potenties the effect of alcohol and other means of depressing CNS. Causes decrease in blood pressure, breathing is possible. There are paradoxical reactions (especially on the background of alcohol intake) - increased aggressiveness, acute states of excitement with fear, falling asleep disorders and sleep. Nitrazempam has the ability to cumulation, with long-term use, addictive is developing.

Contraindications: Hypersensitivity to benzodiazepines, Miastations, Clothing Glaucoma, Drug Dependence, Acute Poisoning with Means, Depressing CNS (including alcohol), pregnancy and lactation.

Flunitrzempam - long-term drug. The sleeping recycling effect develops after 20-45 minutes and lasts 6-8 hours (the depth of sleep increases). Metabolized in the liver, excreted by the kidneys (T 1/2 - 24-36 h). Side effects are the same as Nitrazepama.

Contraindications: lesions of liver and kidneys, myasthenia, pregnancy, breastfeeding. Do not recommend sharing with Mao inhibitors.

Triazoles - a short-acting preparation (T 1/2 is 1-5 h), with re-use, cumulates slightly, the after action is expressed to a lesser extent than in long-acting benzodiazepines.

Midazolam - a short action preparation (T 1/2 is 1-5 h). As a sleeping pills are prescribed inside to relieve falling asleep. The drug does not cumulate when repeated administration, the phenomena of the follow-up is expressed slightly. Midazolas are mainly used in anesthesiology for premedication before surgical operations (injected inside and intramuscularly) and administration into anesthesia (administered intravenously). With intravenous administration of mydazolam, breathing is possible up to its stop (especially with quick administration).

Antagonist benzodiazepines - Fluumazenil. According to the chemical structure, it is imidazobenzodiazepine, competitively blocks benzodiazepine receptors and eliminates the effects of benzodiazepines, including a sleeping pills and sedative effect (for example, when removing from anesthesia). Restores breath and consciousness in the overdose of benzodiazepines. Enter intravenously.

Preparations of another chemical structure

In recent years, drugs have emerged, in a chemical structure differing from benzodiazepines, but their sleeping recycling effect is also associated with the stimulation of benzodiazepine receptors. When stimulating benzodiazepine receptors, the sensitivity of GABA and -receptors to the GAMK increases, the frequency of the chlorine channels increases, the chlorine ions flow into the nervous cell increases and hyperpolarization of the membrane occurs. This leads to the development of brake processes that manifest themselves in the form of a sleeping bag and sedative (in smaller doses) effects. Preparations of this group include clasp, zopiclon and Skipide. A distinctive feature of these drugs is to a lesser extent than benzodiazepines violate the structural structure.

Covebrose is a pyrazolopyrimidine derivative, interacts with the binding places of benzodiazepines GABA A -receptors. Used for the treatment of transient insomnia for 7-10 days. The action is connected with the influence of the latent period of sleep. It is 2 hours, which is enough to provide 8-hour sleep.

Zopiclon is a cyclopyrrolone derivative, a mean duration of an average duration of action. The effect develops in 20-30 minutes and lasts 6-8 hours. Stimulates the GABA-Ergic

the mechanisms of synaptic transmission in the brain due to the excitation ω 1 - and ω 2 -Benzodiazepine receptors. Does not affect the total duration of the "fast" sleep.

Side effects: a feeling of bitter and metallic taste in the mouth, nausea, irritability, depressed mood, allergic reactions, dizziness and violation of coordination of movements are possible. The phenomenon "return" is expressed in a slight degree. With long-term use, addiction and drug dependence occurs, and therefore the course of use of the zopyl should not exceed 4 weeks.

Contraindications: Hypersensitivity, decompensated respiratory failure, age up to 15 years. Do not recommend applications during pregnancy and breastfeeding.

It is a derivative of imidazopyridine, an average duration of action. Agonist ω 1 -Benzodiazepine receptors. Little affects the structure of sleep. Skipidem does not have a pronounced anxiolytic, anticipable and mioryexing action. Among the side effects are headaches, drowsiness during the daytime, nightmarish dreams, hallucinations, ataxia. The phenomenon "return" is expressed in a slight degree. With prolonged use of the drug, addiction and drug addiction are developing, and therefore the course of use of Skipidem should not exceed 4 weeks.

Antagonist Skipidem, Zavelone and Zopilon - Fluumazenil.

11.1.2. Blocators H 1 -receptors

Blocators H 1 -receptors penetrating into the central nervous system have hypnotic properties. Thus, the antiallergic drug DiPhenhydramine (Dimedrol *), blocking H 1 -receptors, has a pronounced hypnotic effect. From this group of drugs, doxylamine is used as only a sleeping pills. The positive qualities of this drug include the lack of influence on the structure of sleep, low toxicity.

11.1.3. Melatonic receptor agonists

Melatonin is essential in the regulation of the sleep-vigorization cycle. Ramelteon - Agonist MT 1 - and MT 2 -melatonic recipe

mowered in the brain. As a result, in patients with chronic insomnia, the latent period of sleep is shortened. Ramelteon does not cause the "return" syndrome. Side effects, drowsiness, reduction of testosterone concentration and increasing prolactin content.

11.2. Narcotic Drug Types

These tools have an indiscriminate depressing effect on the CNS. In small doses, they cause a sedative effect, with an increase in dose, a hypnotic action is shown, and in large doses may cause anesthesia. Non-type of actions of actions are mainly represented by barbituric acid derivatives.

11.2.1. Barbituric acid derivatives (barbiturates)

Barbiturates have sedative, sleeping pills and anticonvulsant properties. In large doses, they cause a state of anesthesia, so some short-acting barbiturates (sodium title) are used for non-evaging anesthesia. In smaller doses, barbiturates have a pronounced hypnotic action, contribute to falling asleep and increase the total duration of sleep. The sedative effect (without sleeping pills) barbiturates have in smaller doses.

The inhibitory effect of barbiturates is due to their interaction with specific areas of binding (barbituatural receptors), located at the GABC and -receptor chlorine channel. The binding plots of the barbiturates of this complex differ from the places of binding benzodiazepines. When binding barbiturates with this receptor complex, there is an increase in the sensitivity of GABA A -receptor to the GABA. At the same time, the opening time of chlorine channels increases - as a result, the chlorine ions arrive through the neuron membrane to the cell, the hyperpolarization of the membrane develops and the brake effect of the GABA occurs. It is believed that the action of barbiturates is not limited to their potentiary impact on GABC and -receptors. These substances are able to directly stimulate GABC and -receptors. A pronounced gamke-mimetic effect is more characteristic of drugs for anesthesia (for example, sodium thiopental). Besides

togo barbiturates show antagonism against glutamate and, possibly, other exciting mediators.

Barbiturates are largely changing the structure of sleep - reduce the duration of the rapid (paradoxical) sleep. The sharp cancellation of drugs leads to the elongation of the rapid sleep phase, but the dream of the nightmares (the phenomenon "return") is carried away at the same time.

Barbiturates have a small therapeutic latitude of the action, so when they are used, the danger of the development of toxic effects is high (the oppression of the respiratory center is possible). For barbiturates, the inversion is characterized, which is manifested by drowsiness during the day, lethargy, violation of attention, mental and motor reactions. These phenomena can be observed even after a single reception of the drug. With repeated applications, barbiturates are cumulative, and the phenomena of the aftereffects increase. Prolonged use of barbiturates can lead to a violation of higher nervous activity.

Barbiturates (especially phenobarbital) induce microsomal liver enzymes, as a result of which the metabolism of many LVs accelerate. The speed of metabolism of the barbizers themselves increases, with which the development of tolerance is associated with their long-term use (may occur 2 weeks after the start of reception). The long-term use of barbiturates may also lead to the development of drug dependence (with the use of sufficiently high doses, the drug addiction can develop for 1-3 months). With the use of barbiturates, both mental and physical drug addiction occurs, while the abolition of the drug is accompanied by such severe disorders such as anxiety, fear, vomiting, convulsions, impairment, orthostatic hypotension, in severe cases a fatal exodus is possible.

Due to the adverse effects of barbiturates, there are currently limited applications. Bribeuric acid derivatives, widely used in the past as hypnotic drugs, are currently mainly excluded from the State Register of the LAN. Sometimes a long-term effect of phenobarbital is used as a sleeping remedy.

F E N O B A R B and T A L is a long-acting barbiturate, which has a sleeping pills, sedative and anti-epileptic effect. Basically, phenobarbital is used for epilepsy (see chapter

"Antiepileptic tools"). As a hypnotic agent, phenobarbital has limited use. In small quantities, phenobarbital is part of combined drug Valokordin * and has a sedative effect. Phenobarbital is removed from the body slowly (capable of cumulation). Duration of action - 8 h.

Side effects: hypotension, allergic reactions (skin rash). Like all barbiturates, causes a breakdown structure. When applying phenobarbital, it is possible to observe a pronounced after: general oppression, a sense of breakdown, drowsiness, motor disorders. The phenobarbital causes the pronounced induction of the microsomal liver enzymes and therefore accelerates the Metabolism of the LAN, including the metabolism of the most phenobarbital. With repeated applications, it causes the development of tolerance and drug addiction.

Etopal-sodium - barbiturate medium duration of action. Before the appearance of benzodiazepines, the drug was widely used as a sleeping bag.

Etopal-sodium is valid 6-8 h, T 1/2 is 30-40 hours. The afternoon in comparison with phenobarbital is expressed slightly.

With overdose of barbiturates (drugs with low latitude of therapeutic action), there are phenomena of acute poisoning associated with the total oppression of the central nervous system. In severe cases, a comatose state is developing, reflex activity is suppressed, consciousness turns off. In connection with the oppression of centers oblong brain (respiratory and vascular) decreases the volume of breathing and blood pressure, in addition, barbedates have a depressing effect on ganglia and direct myotropic influence on the vessels. Death comes from the stop of breathing.

In the treatment of acute poisoning, the main actions are aimed at accelerating the removal of the drug from the body and maintaining anec-

cotton breathing and blood circulation. To prevent the suction of the substance from the RAS, the stomach washing is made, salt laxatives, adsorbing agents, are made. For the removal of the premium preparation, a forced diurez (1-2 l 0.9% sodium sodium solution and a potent diuretic furosemide or mannitol, which leads to a rapid increase in diuresis), also useful for alkaline solutions (renal filtrate pH is shifted to the alkaline side and This prevents the reabsorption of barbiturates). At high concentrations of barbituatures in the blood, hemisorption is used, hemodialysis.

To stimulate breathing at lightweight forms of poisoning, anagetti is prescribed (BEMEGRID, see Chapter "Analetics"), in severe cases, they are contraindicated, as they can only worsen the patient's condition, in such cases they spend artificial respiration. In the hypotension, the development of the collapse is injected with blood substitutes, vasoconstrictors (norepinephrine *).

11.2.2. Aliphatic compounds

Chloralhydrate belongs to a sleeping pills of a narcotic type of action. The mechanism of action is associated with formation in the process of trichloroethanol metabolism, which causes a sleeping recycling effect. Little affects the structure of sleep. Since chlororalhydrate has a pronounced irritant effect, it is used mainly in drugs with mucus. As a sleeping pills are prescribed rarely. Currently used mainly in gerontology. Sometimes prescribed to relieve psychomotor excitation.

As a hypnotic agent, it is also used to be a fragment of thiamine (vitamin B 1), but does not possess vitamin properties, but has a sedative, sleeping pills, a mineral and anticonvulsant action. The mechanism of the action of cleotiazole is associated with its ability to increase the sensitivity of GAB-receptor to GABA, which may be due to its interaction with binding places of barbiturates. The drug is produced in capsules and in the form of a powder for the preparation of an infusion solution. As a sleeping pills are used inward before bedtime with all types of sleep disorders, state of excitation and anxiety (especially in