Sleeping pills that do not disrupt sleep phases. Pharmacology of sleeping pills. imidazopyridine derivative

Sleeping pills These are substances that promote the onset of sleep, normalize its depth, phase, duration, and prevent night awakenings.

The following groups are distinguished:

1) derivatives of barbituric acid (phenobarbital, etc.);

2) benzodiazepine drugs (nitrazepam, etc.);

3) pyridine drugs (ivadal);

4) drugs of the pyrrolone series (imovan);

5) ethanolamine derivatives (donormil).

Requirements for sleeping pills:

1. Must act quickly, induce deep and long (6-8 hours) sleep.

2. Induce sleep that is as similar as possible to normal physiological sleep (do not disrupt the structure).

3. Must have a sufficient breadth of therapeutic action, must not cause side effects, accumulation, addiction, mental and physical dependence.

Classification of sleeping pills based on their principle of action and chemical structure

Hypnotics – benzadiazepine receptor agonists

1 Benzodiazepine derivatives

Nitrazepam

Lorazepam

Diazepam

Phenazepam

Temazepam

Flurazepam

2. Drugs of different chemical structures

Zolpidem

Zopiclone

1. Heterocyclic compounds

Barbituric acid derivatives (barbiturates)

Etaminal - sodium

2. Aliphatic compounds

Chloral hydrate

Hypnotics – benzadiazepine receptor agonists

Benzodiazepines are a large group of substances whose drugs are used as hypnotics, anxiolytics, antiepileptics, and muscle relaxants.

These compounds stimulate benzodiazepine receptors in the membranes of CNS neurons, which are allosterically associated with GABAA receptors. When benzodiazepine receptors are stimulated, the sensitivity of GABAA receptors to GABA (inhibitory neurotransmitter) increases.

When GABAA receptors are excited, C1 channels open; C1~ ions enter nerve cells, this leads to hyperpolarization of the cell membrane. The action of benzodiazepines increases the frequency of opening of C1 channels. Thus, benzodiazepines enhance inhibition processes in the central nervous system.

Benzodiazepines(BD) stimulate benzodiazepine receptors and thus increase the sensitivity of GABA receptors to GABA. Under the action of GABA, Cl- channels open and hyperpolarization of the neuron membrane develops. Pharmacological effects of benzodiazepines: 1) anxiolytic (elimination of feelings of anxiety, fear, tension); 2) sedative; 3) sleeping pills; 4) muscle relaxant; 5) anticonvulsant; 6) amnestic (in high doses, benzodiazepines cause anterograde amnesia for about 6 hours, which can be used for premedication before surgery).

For insomnia, benzodiazepines promote the onset of sleep and increase its duration. However, the structure of sleep changes somewhat: the duration of REM sleep phases decreases (rapid eye movement sleep, paradoxical sleep: periods of 20-25 minutes, which are repeated several times during sleep, accompanied by dreams and rapid movements eyeballs- Rapid Eye Movements).

The effectiveness of benzodiazepines as hypnotics is undoubtedly facilitated by their anxiolytic properties: anxiety, tension, and excessive reaction to environmental stimuli are reduced.

Nitrazepam(radedorm, eunoctin) is prescribed orally 30-40 minutes before bedtime. The drug reduces excessive reactions to extraneous stimuli, promotes the onset of sleep and ensures sleep for 6-8 hours.

With the systematic use of nitrazepam, its side effects may appear: lethargy, drowsiness, decreased attention, slow reactions; possible diplopia, nystagmus, itching, rash. Other benzodiazepines used for sleep disorders include flunitrazepam (Rohypnol), diazepam (Seduxen), midazolam (Dormikum), estazolam, flurazepam, temazepam, triazolam.

With the systematic use of benzodiazepines, mental and physical drug dependence develops. A pronounced withdrawal syndrome is characteristic: anxiety, insomnia, nightmares, confusion, tremor. Due to their muscle-relaxing effects, benzodiazepines are contraindicated in myasthenia gravis.

Benzodiazepines are generally low toxic, but in large doses they can cause central nervous system depression with respiratory impairment. In these cases, a specific benzodiazepine receptor antagonist, flumazenil, is administered intravenously.

Non-benzodiazepine benzodiazepine receptor stimulants

Zolpidem (ivadal) and zopiclone (imovan) have little effect on sleep structure, do not have a pronounced muscle relaxant and anticonvulsant effect, do not cause withdrawal syndrome and are therefore better tolerated by patients. Narcotic-type sleeping pills

This group includes barbituric acid derivatives - pentobarbital, cyclobarbital, phenobarbital, and chloral hydrate. In large doses, these substances can have a narcotic effect.

Barbiturates- highly effective sleeping pills; promote the onset of sleep, prevent frequent awakenings, and increase the total duration of sleep. The mechanism of their hypnotic effect is associated with the potentiation of the inhibitory effect of GABA. Barbiturates increase the sensitivity of GABAA receptors and thus activate C1 channels and cause hyperpolarization of the neuronal membrane. In addition, barbiturates have a direct inhibitory effect on the permeability of the neuronal membrane.

Barbiturates significantly disrupt sleep structure: they shorten periods of rapid (paradoxical) sleep (REM phase).

Chronic use of barbiturates can lead to disorders of higher nervous activity.

An abrupt cessation of systematic use of barbiturates manifests itself in the form of withdrawal syndrome (recoil syndrome), in which the duration of REM sleep increases excessively, which is accompanied by nightmares.

With the systematic use of barbiturates, physical drug dependence develops.

Pentobarbital(ethaminal sodium, Nembutal) taken orally 30 minutes before bedtime; duration of action is 6-8 hours. After waking up, drowsiness is possible.

Cyclobarbital has a shorter effect - about 4 hours. The aftereffect is less pronounced. It is mainly used for sleep disorders.

Phenobarbital(luminal) acts more slowly and lasts for about 8 hours; has a pronounced aftereffect (drowsiness). Currently, it is rarely used as a sleeping pill. The drug is used to treat epilepsy.

Acute barbiturate poisoning is manifested by coma and respiratory depression. There are no specific barbiturate antagonists. Analeptics for severe poisoning with barbiturates do not restore breathing, but increase the brain's need for oxygen - oxygen deficiency worsens.

The main measures for barbiturate poisoning are methods of accelerated removal of barbiturates from the body. The best method is hemosorption. In case of poisoning with dialysable substances, hemodialysis is used, in case of poisoning with drugs that are excreted by the kidneys at least partially unchanged, forced diuresis is used.

Hypnotics with a narcotic type of action also include the aliphatic compound chloral hydrate. It does not disturb the structure of sleep, but is rarely used as a sleeping pill, as it has irritating properties. Sometimes chloral hydrate is used in medicinal enemas to stop psychomotor agitation. Narcotic analgesics

Pain is an unpleasant subjective sensation that, depending on its location and strength, has a different emotional coloring, signaling damage or a threat to the existence of the body and mobilizing its defense systems aimed at consciously avoiding the action of a harmful factor and forming nonspecific reactions that ensure this avoidance.

Analgesics(from the Greek an - denial, logus - pain) - this is a group of drugs that selectively suppress pain sensitivity without turning off consciousness and other types of sensitivity (tactile, barometric, etc.)

Narcotic analgesics are drugs that suppress pain and, with repeated administration, cause physical and mental dependence, i.e. drug addiction Classification of narcotic analgesics. 1. Agonists:

Promedol;

Fentanyl;

Sufentanil

2. Agonists – antagonists (partial agonists):

Pentazocine;

Nalbuphine

butorfano

buprenorphine

3. Antagonists:

Naloxone.

Mechanism of action of narcotic analgesics

It is caused by the interaction of NA with opiate receptors, located mainly in presynaptic membranes and playing an inhibitory role. The degree of affinity of NA for the opiate receptor is proportional to the analgesic activity.

Under the influence of NA, interneuronal transmission of pain impulses is disrupted at different levels of the central nervous system. This is achieved as follows:

NAs mimic the physiological effects of endopioids;

The release of pain “mediators” into the synaptic cleft and their interaction with postsynaptically located nociceptors are disrupted. As a result, the conduction of the pain impulse and its perception in the central nervous system is disrupted. Eventually analgesia occurs.

Indications for the use of narcotic analgesics 1. To eliminate pain in cancer patients.

2. In the postoperative period to eliminate pain and prevent shock.

3. In case of myocardial infarction (in a pre-infarction state) and in case of traumatic shock.

4. For a reflex cough, if the patient has a chest injury.

5. For pain relief during childbirth.

6. For colic - renal - promedol (since it does not affect the tone urinary tract), for biliary colic - lixir. Codeine can be used as an antitussive if you have a dry, debilitating cough due to whooping cough, severe bronchitis or pneumonia.

Contraindications to the prescription of narcotic analgesics: 1.respiratory disorders, respiratory depression.

2.Increased intracranial pressure, because morphine increases intracranial pressure, can trigger epilepsy.

3. Prescribing drugs to children under 2 years of age is contraindicated. This is due to the fact that children have a physiological function respiratory center is formed by 3-5 years, and it is possible to get paralysis of the respiratory center and death when using drugs, since its effect on the respiratory center is practically absent.

Clinic for acute poisoning by narcotic analgesics

Euphoria;

Anxiety;

Dry mouth;

Feeling hot;

Dizziness, headache;

Drowsiness;

Urge to urinate;

Coma;

Miosis followed by mydriasis;

Rare (up to five respiratory movements per minute), shallow breathing;

Blood pressure is reduced.

Providing assistance in case of poisoning with narcotic analgesics

Elimination of respiratory disorders using a ventilator with tracheal intubation;

Administration of antidotes (nalorphine, naloxone);

Gastric lavage.

Morphine

Pharmacodynamics.

1. Effects on the central nervous system:

Analgesia;

Sedative (hypnotic) effect;

Respiratory depression;

Decreased body temperature;

Antiemetic (emetic) effect;

Antitussive effect;

Euphoria (dysphoria);

Reduced aggressiveness;

Anxiolytic effect;

Increased intracranial pressure;

Decreased sexual desire;

Habituation;

Suppression of the hunger center;

Hypermanifestations of knee and elbow reflexes.

2. Effects on the gastrointestinal tract:

Increased tone of the sphincters (Oddi, bile ducts, bladder);

Increased tone of hollow organs;

Inhibition of bile secretion;

Decreased pancreatic secretion;

Decreased appetite.

3. Effects on other organs and systems:

Tachycardia turning into bradycardia;

Hyperglycemia.

Pharmacokinetics of morphine.

Regardless of the route of entry into the body, NAs are well absorbed into the blood and quickly penetrate into the brain, through the placenta, and into breast milk. Bioavailability at oral administration– 60%, with intramuscular and subcutaneous administration – 100%. The half-life is 3-5 hours. Smash after intramuscular and subcutaneous administration after 20 minutes. During the biotransformation process, 35% of the drug interacts reversibly with serum albumin. In phase I of biotransformation, NA undergoes dimethylation and diacetylation. In phase II, paired compounds with glucuronic acid are formed. Excretion – 75% in urine, 10% in bile.

Indications for use of morphine

1. Prevention of painful shock when:

Acute pancreatitis;

Peritonitis;

Burns, severe mechanical injuries.

2. For premedication, in the preoperative period.

3. For pain relief in the postoperative period (if non-narcotic analgesics are ineffective).

4. Pain relief in cancer patients.

5. Attacks of renal and hepatic colic.

6. For pain relief during labor.

7. For neuroleptanalgesia and tranquiloanalgesia (a type of general anesthesia with preservation of consciousness).

Contraindications

1. Children under three years of age and elderly people (due to respiratory depression);

2. traumatic brain injury (due to respiratory depression and increased intracranial pressure);

3. with an “acute” abdomen.

Side effects morphine

1. Nausea, vomiting;

2. bradycardia;

3. dizziness.

Promedol

Pharmachologic effect:

An agonist of opioid receptors (mainly mu receptors), it has an analgesic (weaker and shorter than morphine), antishock, antispasmodic, uterotonic and mild hypnotic effect.

Activates the endogenous antinociceptive system and thus disrupts the interneuronal transmission of pain impulses at various levels of the central nervous system, and also changes the emotional coloring of pain.

To a lesser extent than morphine, it depresses the respiratory center, and also stimulates the n.vagus centers and the vomiting center.

Has an antispasmodic effect on smooth muscles internal organs(in terms of spasmogenic effect it is inferior to morphine), promotes dilatation of the cervix during childbirth, increases tone and enhances myometrial contractions.

With parenteral administration, the analgesic effect develops after 10-20 minutes, reaches a maximum after 40 minutes and lasts 2-4 hours or more (with epidural anesthesia - more than 8 hours)

CHAPTER 7 HYPOPICS

CHAPTER 7 HYPOPICS

Sleeping pills promote sleep and provide the necessary duration of sleep.

Drugs of different pharmacological groups are used as sleeping pills. Traditional hypnotics (barbiturates, some aliphatic compounds), which have been used for a long time, are classified as narcotic substances due to the nature of their effect on the central nervous system and the lack of selective action. In small doses they have a sedative 1 (calming) effect, in medium doses they have a hypnotic effect, and in large doses they have a narcotic effect. To anesthetize them

1 From lat. sedatio- calmness.

not used due to the small narcotic width and long-term action - the depth of anesthesia cannot be controlled (see Fig. 6.1).

Currently, among drugs that have a hypnotic effect, anxiolytics (tranquilizers) of the benzodiazepine series, related to psychotropic substances(see chapter 11.4).

Hypnotics have an inhibitory effect on interneuronal (synaptic) transmission in various structures of the central nervous system (for example, in the cerebral cortex, afferent pathways, limbic system). Each group of hypnotics is characterized by a specific localization of action.

Drugs with hypnotic activity are classified based on their principle of action and chemical structure.

I. Hypnotics - benzodiazepine receptor agonists

1. Benzodiazepine derivatives Nitrazepam Lorazepam Nozepam Temazepam Diazepam Phenazepam Flurazepam

2. Drugs of different chemical structures (“non-benzodiazepine” compounds) Zolpidem Zopiclone

II. Narcotic-type sleeping pills

1. Heterocyclic compounds Barbituric acid derivatives (barbiturates) Etaminal sodium

2. Aliphatic compounds Chloral hydrate

It is also used to normalize sleep individual drugs other groups with hypnotic properties: histamine H receptor blockers(diphenhydramine; see Chapter 25), anesthetic drug effective when taken orally(sodium hydroxybutyrate; see Chapter 5; 5.2). For sleep disturbance associated with long-distance air travel, it is recommended pineal hormone preparations- melatonin (see chapter 20.2).

Despite the large amount of research conducted, the mechanism of action of hypnotic drugs can only be speculated. The main difficulties are related to the fact that the mechanisms of development of physiological sleep are unknown. According to modern concepts, sleep is an active process in which the function of hypnogenic 1 (synchronizing) brain structures is increased, and the activating ascending reticular formation 2 (causing EEG desynchronization) is decreased. Obviously, under the influence of hypnotics, the interaction of these two systems changes in favor of the hypnogenic one. Indeed, many of the hypnotics, such as barbiturates, have an inhibitory effect on the activating reticular formation of the brainstem, which should favor the development of sleep. However, this is only one of the possible, but not the only mechanism of action of hypnotics. Thus, benzodiazepine anxiolytics (see Chapter 11; 11.4), which promote the development of sleep, unlike barbiturates, act primarily on the limbic system and its connections with other parts of the brain, providing a cyclic change between wakefulness and sleep.

1 From Greek hypnos- dream. Hypnogenic zones include a number of structures of the thalamus, hypothalamus and caudal sections of the reticular formation.

2 Rostral part of the reticular formation.

Substances that form in brain tissue and have hypnotic activity (for example, δ-sleep peptide) attract much attention. Naturally, the isolation of endogenous compounds with hypnogenic properties is of great interest not only for understanding the mechanism of sleep development, but also for creating medicines new type.

It should be borne in mind that the sleep induced by most sleeping pills differs in its course from natural sleep. As is known, under normal conditions during sleep, the so-called “slow” sleep 1 (orthodox, forebrain, synchronized; non-REM-sleep) and “fast” sleep (paradoxical, forebrain, desynchronized; sleep accompanied by rapid eye movements) alternate several times. apples; REM-sleep 2). Last

1 In turn, in “slow” sleep there are 4 phases: Phase I - on the EEG: α-, β- and θ-rhythms; Phase II - on EEG: θ-rhythm, spindles, K-complexes; Phase III - on EEG: θ- and δ-rhythms, spindles; IV phase - on EEG: δ-rhythm; Phases III and IV - δ-sleep.

2 R.E.M.(R apide yem ovement)-sleep (English) - sleep accompanied by rapid movements of the eyeballs.

accounts for 20-25% of the total sleep duration. Long-term disturbances during each of these phases adversely affect the state of the body (behavioral, mental disorders). It turned out that most sleeping pills (barbiturates, etc.) significantly change the structure of sleep. First of all, this concerns REM sleep (the latent period for the appearance of phase I of REM sleep increases, and its total duration decreases). The withdrawal of sleeping pills may be accompanied by the so-called “rebound” phenomenon, the severity of which depends on the dose of the drugs and the period of their use. At the same time, the duration of REM sleep exceeds normal values ​​for a certain time, its latent period is shortened, an abundance of dreams, nightmares, and frequent awakenings are noted. Due to this Special attention attract hypnotics that have no or minimal effect on the ratio of sleep phases and promote the development of sleep close to natural.

There was no effect of sodium hydroxybutyrate and chloral hydrate on REM sleep, or this effect was insignificant, but both drugs have a number of disadvantages. Zolpidem and zopiclone have little effect on sleep structure. Drugs from the benzodiazepine group (nitrazepam, diazepam, etc.) shorten the REM sleep phase to a lesser extent than barbiturates.

7.1. AGONISTS OF BENZODIAZEPINE RECEPTORS

Many anxiolytics related to benzodiazepine derivatives have pronounced hypnotic activity (nitrazepam, diazepam, phenazepam, etc.). Their main effect is to eliminate mental stress. The resulting calm promotes the development of sleep.

Anxiolytics of the benzodiazepine series (see Chapter 11; 11.4) have anxiolytic, hypnotic, sedative, anticonvulsant, muscle-relaxing and amnestic activity. Anxiolytic and hypnotic effects are associated primarily with their inhibitory effect on the limbic system (hippocampus) and, to a lesser extent, on the activating reticular formation of the brain stem and cerebral cortex. The muscle-relaxing effect is due to the suppression of polysynaptic spinal reflexes. The mechanism of anticonvulsant (antiepileptic) action is obviously the result of activation of inhibitory processes in the brain, which limits the spread of pathological impulses.

The mechanism of sedative, hypnotic and other effects of benzodiazepines is associated with their interaction with special benzodiazepine receptors 1 . The latter are part of the macromolecular GABA A receptor complex, which includes receptors sensitive to GABA, benzodiazepines and barbiturates, as well as chlorine ionophores (Fig. 7.1) 2 . Due to allosteric interaction with specific receptors, benzodiazepines increase the affinity of GABA for GABA A receptors and enhance the inhibitory effect of GABA. There is a more frequent opening of chlorine ionophores. At the same time, the increase

1 Benzodiazepines interact indiscriminately with different subtypes of benzodiazepine receptors (abbreviated as BZ 1, BZ 2, BZ 3, or ω 1, ω 2, ω 3, respectively).

2 The macromolecular complex also includes a separate binding site for picrotoxin (an analeptic that blocks chloride channels; in large doses causes convulsions).

Rice. 7.1.The principle of GABA-mimetic action of benzodiazepines and barbiturates. A schematic diagram of the GABA A-benzodiazepine-barbiturate receptor complex with a chlorine ionophore is presented.

I - state of rest; II - increased conductivity of chloride channels under the influence of GABA. Benzodiazepines (III) and barbiturates (IV) allosterically enhance the effects of GABA. The flow of chlorine ions into the neuron increases, which enhances the inhibitory effect. GABA A-R - GABA A receptor; BD-R - benzodiazepine receptor; B-R - barbiturate receptor.

There is an influx of chlorine ions into neurons, which leads to an increase in the inhibitory postsynaptic potential.

The benzodiazepines used differ mainly in pharmacokinetics. Some of them undergo biotransformation with the formation of active, long-acting metabolites (flurazepam, diazepam, etc.). For such drugs, the total duration of action consists of the duration of the effects of both the parent substance and its metabolites.

A number of benzodiazepines do not form active metabolites or they are quickly inactivated (lorazepam, temazepam, etc.). Drugs of this type are preferable as hypnotics, since their aftereffects are less pronounced.

Based on the duration of psychosedative action, benzodiazepine derivatives can be represented by the following groups 1.

1. Medications with an average duration of action.

A (t 1/2 = 12-18 hours): lorazepam (Ativan), nozepam (oxazepam, tazepam), temazepam (Restrol).

B (t 1 / 2 ≈ 24 hours): nitrazepam (radedorm, eunoctin).

2. Long-acting drugs(t 1/2 = 30-40 hours or more): phenazepam, flurazepam (Dalman), diazepam (Sibazon, Seduxen).

All of the above benzodiazepines induce sleep lasting 6-8 hours. However, the longer the effect of the drug, the greater the likelihood of aftereffects, which manifest themselves during the day in the form of sedation, slowed motor reactions, and memory impairment. With repeated prescriptions, drugs accumulate, which is directly dependent on the duration of their action.

1 For guidance, figures are given that reflect the “half-life” of the drugs (t 1/2).

The rebound phenomenon that occurs during abrupt drug withdrawal is more typical for short-acting benzodiazepines. To avoid this complication, benzodiazepines should be discontinued gradually.

One of the drugs of this group widely used in our country is nitrazepam. The hypnotic effect of nitrazepam after its oral administration occurs within 30-60 minutes and lasts up to 8 hours. The aftereffect is little pronounced. Nitrazepam enhances and prolongs the effect of anesthesia, ethyl alcohol, and narcotic sleeping pills. On the cardiovascular system healthy people has virtually no effect.

Well absorbed from the intestines. Biotransformation of nitrazepam occurs in the liver. The drug accumulates. With repeated use, addiction develops.

Nitrazepam (and other benzodiazepine derivatives) differs from barbiturates for the better in the following ways: a) changes sleep structure to a lesser extent; b) has a greater breadth of therapeutic action, therefore there is less danger of acute poisoning; c) induction of microsomal liver enzymes is less pronounced; d) less risk of developing drug dependence (however, this must be taken into account).

Similar to nitrazepam, temazepam and flurazepam are used primarily as hypnotics. The remaining drugs are used more widely: as anxiolytics, hypnotics, for status epilepticus and for a number of other indications (see Chapter 14.4).

Currently, benzodiazepines are among the most optimal drugs for use as hypnotics. They are especially effective for sleep disorders associated with emotional stress, anxiety, and anxiety.

For the pharmacology of other drugs, see Chapter 14.4.

The antagonist of benzodiazepine agonists is flumazenil.

Behind last years hypnotics that are not related to benzodiazepines, but have an affinity for benzodiazepine receptors, have been synthesized. This group of drugs includes zolpidem and zopiclone (Table 7.1). The sites of their binding to benzodiazepine receptors differ from those of benzodiazepines. However, they also lead to the activation of GABA A receptors, more

Table 7.1.Comparative evaluation of zolpidem and zopiclone

frequent opening of chlorine ionophores and the development of hyperpolarization. The process of inhibition is enhanced, which underlies the developing hypnotic and sedative effects.

Zolpidem (ivadal) is an imidazopyridine derivative. It has a pronounced hypnotic and sedative effect. Anxiolytic, muscle-relaxing, anticonvulsant and amnestic effects are slightly expressed. Selectively interacts with the first subtype of benzodiazepine receptors (BZ 1 -, or ω 1 -subtype). Has little effect on sleep phases.

Side effects include allergic reactions, hypotension, agitation, hallucinations, ataxia, dyspepsia, and daytime drowsiness. The phenomenon of “recoil” is expressed to a small extent. With long-term use, addiction and drug dependence (mental and physical) occur, so short-term use of the drug is advisable (no more than 4 weeks).

A drug similar to zolpidem is zopiclone (Imovan). It is a derivative of cyclopyrrolone. It has hypnotic, sedative, anxiolytic, muscle-relaxing and anticonvulsant effects.

With prolonged use, addiction and drug dependence (mental and physical) occur. Side effects include a metallic bitter taste, sometimes nausea, vomiting, headache, dizziness, and allergic reactions. Possible mental and behavioral disorders, lack of coordination. The phenomenon of “recoil” is expressed to a small extent. The duration of use should be limited to 4 weeks. In this case, addiction and drug dependence may not be detected, and side effects are insignificant.

In case of overdose of zolpidem and zopiclone, flumazenil is used as an antidote.

7.2. Hypnotics with a narcotic mode of action

A significant number of such sleeping pills are barbituric acid derivatives.

Barbiturates have been shown to interact with the allosteric site of the GABA d -benzodiazepine-barbiturate receptor complex and increase the affinity of GABA for the GABA d -receptors (see Fig. 7.1). This leads to a longer opening of channels for chloride ions in neuronal membranes and an increase in their entry into the cell. At the same time, the inhibitory effect of GABA is enhanced. Thus, in the case of barbiturates, the sedative and hypnotic effects are also largely due to their GABA-mimetic action. However, there is reason to believe that barbiturates, interacting with the neuronal membrane and changing its physicochemical properties, disrupt the function of other ion channels (sodium, potassium, calcium). The significance of the antagonism of barbiturates in relation to a number of excitatory mediators (glutamate, etc.) is also discussed.

The group of barbiturates includes phenobarbital (luminal, phenobarbitone), etaminal sodium (pentobarbital sodium, Nembutal) and other drugs.

Isolate drugs long acting(phenobarbital) and average duration actions(ethaminal sodium). However, according to clinical observations, hypnotics from both groups promote the development of sleep lasting about 8 hours. The different duration of action is manifested in the severity of the aftereffect and the degree of cumulation.

Various processes are involved in the cessation of the hypnotic effect of barbiturates. One of them is enzymatic inactivation of substances by microsomal liver enzymes. Most often, oxidation occurs (hydroxylation of radicals at C5). In this regard, with liver pathology, accompanied by a decrease in the activity of its enzyme systems, the duration of action of barbiturates increases. The latter, naturally, applies to those drugs, the main amount of which undergoes biotransformation (ethaminal sodium). It should be borne in mind that barbiturates (especially phenobarbital) cause the induction of microsomal enzymes. Therefore, when reintroduction barbiturates, their metabolic rate increases. Obviously, the latter is one of the important reasons for the development of addiction to them. In addition, the induction of microsomal enzymes affects the rate of biotransformation of compounds from other chemical groups.

The duration of action of a number of barbituric acid derivatives also depends on the rate of their excretion by the kidneys. This applies to compounds that are largely excreted unchanged by the kidneys (phenobarbital). If renal function is impaired, the effect of such barbiturates is noticeably prolonged.

The duration of the hypnotic effect also depends on the redistribution of substances in the body. This refers mainly to a decrease in the content of barbiturates in brain tissue and their deposition in adipose tissue in the case of high lipophilicity of the compounds.

When using barbiturates (even once), the next day after waking up, an aftereffect may be noted - a feeling of lethargy, weakness, impaired psychomotor reactions, attention. The slower the drug is removed (inactivated), the more pronounced the aftereffect. Thus, a decrease in the content of phenobarbital in blood plasma by 50% of the administered dose (t 1/2) occurs after approximately 3.5 days, so aftereffects are observed relatively often. To a lesser extent, it is observed after the use of sodium etaminal (its t 1/2 is 30-40 hours).

Barbiturates are characterized by material cumulation upon repeated use. It is most pronounced in drugs that are slowly released from the body (for example, phenobarbital).

With long-term use of barbiturates, a deficit in the REM sleep phase develops. As noted, when drugs are abruptly discontinued, a so-called “rebound” phenomenon occurs, which can persist for several weeks.

Continuous long-term use of barbiturates leads to the development of addiction and can cause drug dependence (mental and physical). With daily use of barbiturates, addiction to them becomes apparent approximately 2 weeks after the start of use. The rate of development of drug dependence is largely determined by the dose of the drug. If the doses are large enough, drug dependence may develop within 1-3 months. Withdrawal of the drug in the presence of drug dependence is accompanied by severe mental and somatic disorders (withdrawal syndrome). Anxiety, irritability, fear, vomiting, blurred vision, convulsions, orthostatic hypotension, etc. occur. In severe cases, death may occur.

Barbiturates are usually administered orally, less often rectally. They are well absorbed from gastrointestinal tract. Partially binds to blood plasma proteins (mainly albumin). Easily penetrates tissue barriers. Excreted by the kidneys.

Barbiturates are mainly prescribed as hypnotics (30-60 minutes before bedtime). However, in Lately their use has declined sharply with the advent of benzodiazepine receptor agonists. Phenobarbital is practically not used as a sleeping pill. Barbiturates are also used as sedatives (1/3-1/5 or less of the hypnotic dose). In addition, phenobarbital is an antiepileptic drug (see Chapter 9).

When barbiturates are used in therapeutic doses, no significant damage to internal organs and their systems is usually observed. At the same time, allergic reactions (skin lesions, jaundice, fever, etc.) are possible. Most often they occur when phenobarbital is prescribed.

Acute barbiturate poisoning occurs as a result of accidental or intentional overdose. CNS depression occurs. In severe poisoning, coma develops, consciousness is absent, reflex activity is suppressed. The centers are oppressed medulla oblongata. Due to depression of the respiratory center, breathing volume decreases. Blood pressure drops (hypotension is associated not only with the central effect, but also with the inhibitory effect of substances on the heart, ganglia, as well as with a direct myotropic vasodilator effect). Kidney function is impaired.

Treatment acute poisoning is to accelerate the elimination of the drug from the body and maintain vital important functions. If the administered barbiturate is not completely absorbed from the gastrointestinal tract, gastric lavage is done, adsorbents and saline laxatives are given. To accelerate the excretion of already absorbed substances, large amounts of electrolyte solutions and osmotic diuretics or furosemide are prescribed (see Chapter 16), which cause a rapid and significant increase in diuresis (the so-called forced diuresis). The removal of barbiturates can also be facilitated by the use of alkaline solutions. At very high concentrations of barbiturates in the blood, hemosorption is carried out, as well as peritoneal dialysis and hemodialysis.

One of the main goals of treating barbiturate poisoning is to establish adequate breathing and eliminate or prevent hypoxia. In severe cases, artificial respiration is performed. Analeptics (bemegride, corazol, etc.; see Chapter 12) are prescribed only for mild forms of poisoning; in case of severe poisoning, they not only do not help restore breathing, but can even worsen the patient’s condition. The possibility of developing pneumonia should be considered. If hypotension or collapse occurs, blood, blood substitutes, and norepinephrine are administered. At renal failure(oliguria 1, anuria 2) hemodialysis is often indicated. The prognosis depends on the dose of the sleeping pill, the timeliness of the start of treatment, and the condition of the body.

The principles outlined for the treatment of acute barbiturate poisoning are also used in cases of overdose of hypnotics from other groups.

Chronic poisoning most often occurs when taking barbiturates that have pronounced accumulation (phenobarbital). This manifests itself as apathy, drowsiness, weakness, imbalance, slurred speech, and dizziness. Hallucinations, psychomotor agitation, and convulsions are possible. Blood circulation, digestion, liver and kidney functions may also suffer. In this case, one should take into account the possibility of developing drug dependence, in which it is impossible to immediately stop administering the drug, since it may

1 Decreased amount of urine excreted. From Greek oligos- small, uron- urine.

2 Stopping the secretion of urine by the kidneys. An(Greek) - negation.

withdrawal syndrome disappears. In this regard, when treating chronic poisoning, the dose of barbiturate is gradually reduced until it is completely discontinued. At the same time, symptomatic treatment and psychotherapy are carried out.

A number of hypnotic drugs are aliphatic compounds. One of them is chloral hydrate. This is the first synthetic sleeping pill used in practical medicine. Has a pronounced hypnotic effect. Promotes the development of sleep lasting up to 8 hours. It differs from barbiturates in that it practically does not disrupt the structure of sleep. In large doses it causes anesthesia. The narcotic range of chloral hydrate is small (suppression of the medulla oblongata centers occurs quickly).

Absorbed from the intestine quickly. Passes freely through tissue barriers. In the body it turns into trichloroethanol (its properties are similar to chloral hydrate). Chloral hydrate slightly stimulates the synthesis of microsomal liver enzymes. Metabolites and conjugates of chloral hydrate are excreted by the kidneys.

With repeated administration of chloral hydrate, addiction develops to it, and drug dependence (mental and physical) is possible. Cumulation practically does not occur.

The drug is used orally or rectally (in enemas) as a sleeping pill (15-30 minutes before bedtime), a sedative or an anticonvulsant.

Chloral hydrate has a number of negative properties. These include possible adverse effects on parenchymal organs: liver, kidneys, heart. These toxic effects appear mainly against the background of pathological changes in these organs, as well as in case of overdose. In addition, chloral hydrate has a pronounced irritant effect, so it is usually prescribed in combination with mucus. The most appropriate short-term use of chloral hydrate (1-3 days).

Sleeping pills are used quite widely. When prescribing these drugs, the possibility of developing addiction to them and drug dependence should be taken into account. Therefore, it is advisable to prescribe them in the minimum effective dose and for no longer than 1 month, or to interval between doses for 2-3 days. It is necessary to orient patients to the ability of drugs to cause aftereffects, which can negatively affect their professional activities. It is also important to keep in mind interactions with other drugs and ethyl alcohol. It is impossible not to take into account the change in the pharmacokinetics of hypnotics in pathology of the liver and kidneys. The drugs should be discontinued gradually so that the “recoil” syndrome does not develop (and in case of physical drug dependence, withdrawal syndrome).

Preferanskaya Nina Germanovna
Associate Professor, Department of Pharmacology, Faculty of Pharmacy, First Moscow State Medical University named after. THEM. Sechenova, Ph.D.

When taking barbiturates, a pronounced aftereffect occurs: drowsiness, weakness, impaired coordination of movements, nystagmus and other undesirable manifestations. Long-term therapy with these drugs causes drug dependence and leads to the development of addiction (decreased pharmacological effect). Stopping the drug causes a “withdrawal syndrome,” which is accompanied by insomnia, frequent awakenings in the middle of the night, patients experience shallow sleep and are tormented by nightmares. During the daytime, patients are irritable and have a depressed, depressed mood. Barbiturates increase the activity of microsomal liver enzymes, so their hypnotic effect decreases with repeated use. There are no specific antidotes for barbiturate overdose. Currently, barbiturates have lost their importance as drugs for insomnia. Their main use is associated with the anticonvulsant effect and the induction of microsomal liver enzymes.

BENZODIAZEPINE DERIVATIVES
Nitrazepam(Radedorm, Eunoktin), Flunitrazepam(Rohypnol), Triazolam(Halcyon), Midazolam(Dormikum), L orazepam(Lorafen).

Benzodiazepines do not alter sleep patterns and have fewer side effects than barbiturates. In addition to the hypnotic effect, they have tranquilizing (eliminate mental stress), anxiolytic (anti-anxiety), sedative (calming), muscle relaxant (lower muscle tone), anticonvulsant and amnestic (cause short-term memory loss) effects. The mechanism of action is associated with an effect on the barbiturine-benzodiazepine-GABAergic receptor complex and with an increase in the inhibitory effect of GABA in the central nervous system. GABA is the main inhibitory transmitter of the central nervous system, performing this function in all parts of the brain. Benzodiazepines, like barbiturates, are not selective, and exert their effects through GABA, enhancing its physiological effect. The mechanism of action of all benzodiazepines is similar; these drugs differ in the speed of onset and duration of the hypnotic effect. Drugs with a long half-life Nitrazepam (T½ = 16-48 hours) and Flunitrazepam (T½ = 24-36 hours), while Midazolam, Triazolam short acting, T½ = from 1.5 hours to 3.5 and 5 hours, respectively.

Nitrazepam/Nitrazepamum (Eunoctin, Radedorm) is used as a hypnotic with a rapid onset of effect. Nitrazepam acts on the limbic system of the brain, which is connected to the thalamus, which houses one of the sleep centers. Most effective for functional-emotional disorders accompanied by insomnia. It also has an anticonvulsant effect, relaxes skeletal muscles, reduces or relieves negative emotions (feelings of fear, anxiety, tension). When using Nitrazepam, sleep usually occurs after 45 minutes and lasts 6-8 hours. Under the influence of Nitrazepam, the depth and duration of sleep increases. T½ = 16-48 hours. Excreted mainly in urine in the form of inactive metabolites. Available in TB. 0.005 and 0.01 g each.

Midazolam(Dormikum) has a pronounced hypnotic-narcotic effect, accelerates the phases of falling asleep and waking up, and improves the quality of sleep. Does not change the structure of sleep. As a sleeping pill, it is prescribed orally in tuberculosis, cover. obol., 7.5 mg or 15 mg for problems falling asleep or early awakening. After waking up, there is a feeling of freshness and vigor.

Cyclopyrrolone derivative - Zopiclone/ Zopiclonum (Imovan, Piklodorm) is a hypnotic with a medium duration of action; sleep usually occurs half an hour after taking it and lasts 6-8 hours. The mechanism of its action is associated with omega1, omega2 subtypes of benzodiazepine receptors in the central nervous system and is realized through an increase in the GABAergic effects of the reticular formations. Zopiclone reduces the period of falling asleep and the number of night awakenings. An important feature of the drug is its ability to normalize the phase structure of sleep. Zopiclone is prescribed in 1 TB dose. before bedtime, if necessary, increase the dose to 2 TB. Elderly patients are recommended to start treatment with ½ tb. Available in TB. 0.0075 g each. During treatment with the drug, it is not recommended to take alcoholic beverages.

Imidazopyridine derivative - Zolpidem/ Zolpidem (Ivadal, Hypnogen, Sanval), an imidazopyridine derivative, unlike other hypnotics, has a high affinity for the omega1 subtype of the GABAA receptor complex in brain structures. Makes it easier to fall asleep, reduces the frequency of night awakenings and extends the duration of sleep to normal (6-9 hours). The drug does not disrupt the sleep structure, lengthens the 3rd and 4th phases of deep sleep, having little effect on light sleep and the REM phase. Due to the selectivity of action, it exhibits weak anxiolytic, anticonvulsant and muscle relaxant activity. An important feature of Zolpidem is the absence of addiction with long-term use and a decrease in the frequency of awakening during sleep. Available in film-coated tubes of 10 mg (0.01). The duration of continuous use of Zopiclone and Zolpidem should not exceed 4 weeks.

Pyrazolopyrimidine derivative- Zaleplon/Zaleplon (Andante), selectively binds to the omega1 subtype of benzodiazepine receptors, which leads to the opening of neuronal ionoform channels for chlorine ions and the development of hyperpolarization and increased inhibition processes in the central nervous system, providing a pronounced sedative, minor anxiolytic, anticonvulsant and central muscle relaxant effect. When using the drug, the latent time of falling asleep is significantly reduced, the ratio of the various 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.

Pineal gland hormone preparation. Hormone pineal gland(epiphysis) is melatonin, which plays a major role in the mechanisms of circadian (circadian) rhythms. Melatonin production depends on the time of day. Melatonin secretion increases in the dark (up to 70%) and decreases in the light (up to 30%). Melatonin increases the synthesis of GABA and serotonin in the midbrain and hypothalamus. The normalization of the circadian biological rhythm and the elimination of sleep disorders associated with moving to another time zone is facilitated by a synthetic analogue of this hormone - melatonin.

Melatonin(Melaxen, Melavit, Yukalin) acts on melatonin receptors MT1 and MT2, located exclusively in brain cells. The drug normalizes circadian rhythms in case of desynchronosis, accelerates adaptation to rapid changes in time zones and during shift work at night. Accelerates the act of falling asleep and reduces the number of night awakenings, normalizes well-being after waking up. It improves the quality of sleep, increases the depth and duration. The drug has no “after-effect”, does not cause a feeling of lethargy, weakness and fatigue after waking up in the morning. It is most effective for insomnia associated with jet lag, increased psycho-emotional status, and desynchronosis. Taking the drug improves mood, affects the emotional, intellectual and mnestic sphere. The drug has antioxidant properties and exhibits an immunostimulating effect. Side effects include allergic reactions, headache, nausea, and diarrhea.

Melatonin receptor agonist- Ramelteon(Rozerham). New medicinal product, acting more selectively on melatonin receptors. MT stimulation 1 and MT 2 subtypes of melatonin receptors allows you to regulate the 24-hour sleep-wake cycle. 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 a “consequence effect” the next day. The recommended dose is 8 mg half an hour before going to bed. Side effects include headache, drowsiness, dizziness, nausea and fatigue. In rare cases, causes allergic reactions, angioedema tongue, pharynx and larynx. Stopping the drug does not cause a relapse of the disease.

Natural brain amino acid - Glycine. Glycine limits the spread of excitation throughout the brain structures and normalizes the processes of excitation and inhibition in the central nervous system. Synthetic analogue this amino acid - the drug Glycine - has a distinct anti-stress, anti-anxiety effect, improves mental performance, reduces aggressiveness, irritability and weakens psycho-emotional reactions. Does not cause withdrawal syndrome or increased dependence after withdrawal. They accept 2 TB. d/rass. in 20 minutes before bedtime or just before bedtime.

H1-histamine receptor blocker - Doxylamine/Doxylamine (Donormil) is similar in chemical structure and action to diphenhydramine and other histamine blockers, has sedative-hypnotic, antiallergic and M-cholinolytic activity. Recommended for acute and chronic insomnia. Preserves the physiological structure of sleep. No withdrawal syndrome noted. Possible side effects include drowsiness, dry mouth, and constipation. It is not recommended for transport drivers and persons whose occupation requires increased attentiveness and speed of reactions. Available in TB, coated. vol., 0.015 g.

Clomethiazole(Heminevrin) is close in chemical structure to vitamin B1, but does not have vitamin properties. It has a hypnotic, sedative, muscle relaxant and anticonvulsant effect. Increases the sensitivity of GABA receptors to GABA. Used for sleep disorders of various types, especially indicated in states of acute agitation. Available in capsules of 0.3 g and d/in. lyophil. por. 4 g fl. with solvent.

Tenoten, TB d/rassas 3 mg, contains affinity-purified 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, hypnotic and nootropic effects. It has a calming, GABA-mimetic, neurotrophic, antiasthenic effect and does not cause hypnogenic or muscle relaxant effects. Inhibits lipid peroxidation, causing an antioxidant effect.

OTC hypnotics

These drugs should not contain potent components and have a pronounced depressant effect on the central nervous system, reduce performance, attentiveness, and cause addiction and dependence. All drugs have a mild sedative effect, relieve nervous tension, restore and normalize physiological sleep, improve sleep quality and promote pleasant rest. Some of them protect the body from stress and facilitate the perception of nervous stress, strengthening the nervous system. Many preparations contain plant vitamins and microelements. After taking such drugs, drowsiness and addiction do not occur, and noticeable activity is observed in the morning hours. Taking medications helps the body rest better and restore its strength faster.

Herbal remedies : Dormiplant, Passifit, Valeriana forte, etc.

Dormiplant - combined herbal medicine, contains dry extracts from valerian root and lemon balm leaves. Synergistic sedative effect is manifested by a combination of effects active ingredients. Used for insomnia associated with increased nervous excitability.

Passifit - a combined herbal medicine, contains a thick extract of valerian, liquid extracts of hop cones, thyme and tinctures of hawthorn and mint. Has a mild hypnotic effect. Available in the form of syrup in 100 ml bottles. Indicated for various sleep disorders.

Homeopathic remedies: homeopathic syrup Passambra, Edas 306 granules Somnogen, Vernison, Sleep, Bioline Insomnia, Bioline Insomnia, TB. Nervochel et al.

Vernison - homeopathic granules (10 g per sachet) containing Strychnos nux -vomica C200, Coffea arabica C 200, Atropa belladonna C 200 as active ingredients. Used for sleep disorders associated with fatigue, nervous excitement, anxiety, abuse of caffeinated drinks and addiction to early awakening. Allergic reactions are possible, contraindicated during pregnancy and childhood up to 18 years old.

For sleep disorders, dietary supplements Morpheus, Sleeping, Bayu Bai (drops) are used. Night sleep(caps.), Trioson plus, Nervostabil, Nutria Kalm, Unabi Yuyuba, Poppy sleeping pill, Phytohypnosis, Sleep formula, Sweet Dreams, Sophia sleepy (syrup), etc.

The dietary supplement Bayu bai (drops) has a general strengthening and mild calming effect for hyperactive children. Normalizes sleep, restores sleep phases, strengthens the nervous system, relieves irritability, increases performance and improves brain function. Taking the drug helps children adapt to school stress. Take 5-10 drops per 30 minutes. Before going to bed, the drops must be kept in the mouth and swallowed.

Phytohypnosis contains extracts of herbs that have a hypnotic effect. Helps with interrupted sleep. The active ingredients are: passionflower officinalis, which has calming and hypnotic effects; green oats - a mild sedative and sedative; Eschstolzia Californian - has a hypnotic and antispasmodic effect. Apply 2 TB, dissolving, before bedtime. The duration of the course of treatment is 20 days.

The dietary supplement Sleeping contains 100 mg of Californian fumarole and 100 mg of dahlia as active ingredients. It has a mild sedative and hypnotic effect and promotes a pleasant rest.

Good Night - used to improve the quality of sleep and relieve daytime stress. Contains extracts of chamomile, hops, dogwood and valerian root. It has a mild calming effect, causing a full, sound, refreshing sleep without severe side effects.

Taking any prescription sleeping pills requires a mandatory consultation with a somnologist. The decision to immediately begin treatment with sleeping pills can be made by the patient himself. In this case, it is necessary to carefully analyze all possible expected positive (such as eliminating weakness, weakness, inattention) and negative (such as the occurrence of addiction, drug dependence, irrationality). joint reception with alcohol, toxic effect when recommended dosages are exceeded) results of the use of sleeping pills. Only after carefully weighing all the pros and cons, make the right decision. If sleep disturbance does not resolve within 5-7 days, you should stop taking this drug.

Taking over-the-counter medications is safe, but the main thing is to choose the right drug, depending on the form of sleep disturbance and its active components.

Various sleep disorders in modern world occur quite often. It has been proven that insomnia is diagnosed in a larger percentage of the population among residents of large cities compared to residents of villages and towns. The main treatment for sleep disorders is sleeping pills. What drugs are the strongest and can you buy them without a prescription?

The girl took pills to facilitate sleep

Classification of sleeping pills

Sleeping pills are drugs that cause a condition that has characteristics similar to natural sleep and can speed up the process of falling asleep, increase the depth of sleep and its duration. The scientific name for a group of sleep medications is hypnotics. Small doses of these medications have a relaxing and calming effect.

All hypnotics are divided into two large groups: drugs with narcotic and non-narcotic effects.

Non-narcotic hypnotics:

• Benzodiazepines - Nitrazepam, Dormicum, Flunitrazepam, Halcion, Triazolam, Temazepam.
• Non-benzodiazepines: Zolpidem (Ivadal), Zopiclone (Imovan).
• Histamine receptor blockers: Donormil.
• GABA derivatives: Phenibut.

Narcotic hypnotics:

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

Benzodiazepines

This group of hypnotics includes substances that have hypnotic, anti-anxiety and antiepileptic effects. For sleep disorders, benzodiazepines speed up the process of falling asleep and significantly lengthen the duration of rest. The action of drugs from this group affects the structure of sleep, shortening the phases of rapid and paradoxical sleep, so dreams when using benzodiazepines are an infrequent phenomenon.

The effectiveness of sleeping pills from the group of benzodiazepines is increased due to their anxiolytic properties - relieving anxiety, tension, acute reactions to current events, and therefore these drugs are the drugs of choice for the treatment of insomnia.

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

• Nitrazepam - “Eunoctin”, “Radedorm”, “Berlidorm”.
• Midazolam - “Dormicum”, “Flormidal”.
• Triazolam - "Halcion".
• Flunitrazepam - "Rohypnol".

The average duration of treatment with benzodiazepines is 2 weeks. With longer use - about 3-4 weeks - drug dependence develops. Abrupt cessation of taking these sleeping pills leads to the development of withdrawal syndrome: the patient experiences a feeling of anxiety, insomnia, nightmares, and tremor of the limbs.

Psychoactive drugs with hypnotic, anxiolytic and anticonvulsant effects

The unpleasant effect of these sleeping pills is the “consequence syndrome” - after waking up, a person feels lethargy, muscle weakness, dizziness, drowsiness, possibly impaired coordination of movements and decreased concentration. Such symptoms are associated with the slow metabolism of benzodiazepines in the body - the drugs take a long time to be absorbed into the blood from the stomach, and incomplete disintegration occurs in the liver with the release of active metabolites into the blood that support the main effect of the tablets. Due to this property, it is highly recommended not to use the drugs for patients whose work requires concentration and concentration - vehicle drivers, high-altitude workers.

Poisoning with benzodiazepines occurs quite rarely due to their low toxicity.

Non-benzodiazepines

The main drugs from this group were the so-called Z-drugs - Zopiclone, Zolpidem and Zaleplon. The mild action of these tablets makes them safer than barbituric acid derivatives, and the reduced likelihood of developing physical dependence and addiction compared to benzodiazepines allows for longer-term treatment.

Like any others medicinal substances, non-benzodiazepine drugs have disadvantages - there is a possibility of developing amnesia, and less often - hallucinations. Long-term use of Z-drugs may be accompanied by daytime sleepiness and anxiety. Zaleplon has a short half-life, making it safer for use in individuals whose activities require special concentration.

Non-benzodiazepine hypnotic structure

Treatment with non-benzodiazepine drugs should not be stopped abruptly if therapy lasts more than 2 weeks, which is associated with an increased possibility of withdrawal syndrome. The dose is reduced gradually over several weeks, depending on the individual characteristics of the patient.

Histamine receptor blockers

A well-known property of drugs for the treatment of allergies is their hypnotic effect, which is what the effect of the modern sleeping pill Donormil is based on. The mechanism of action of Donormil is based on its ability to influence individual areas of the brain responsible for the process of nervous excitation. The drug is available from pharmacies without a prescription, so it is more affordable. Among the side effects of Donormil it should be noted severe dryness in the mouth, constipation and urinary retention while taking sleeping pills. The drug is not addictive, and the possibility of poisoning is very low - not a single one has been identified fatal outcome in case of overdose.

Barbiturates

The main part of barbituric acid derivatives is excluded from the list of drugs for the treatment of insomnia due to large quantity side effects. In modern clinical practice Barbiturates are increasingly prescribed to patients suffering from various disorders sleep. The sleep initiated by this group of drugs differs from normal physiological sleep - the cyclicity of phases is disrupted and its structure changes. Drug dependence develops immediately after repeated use, and long-term treatment provokes addiction. Sleep caused by narcotic sleeping pills is intermittent, and the presence of nightmares is noted. After waking up, a person experiences severe drowsiness, fatigue, and coordination of movements is impaired.

A drug from the group of barbiturates

Currently, only Phenobarbital and Cyclobarbital (Reladorm) are approved for use. Half the sleeping pill dose of these drugs produces a relaxing effect, and exceeding the dosage several times causes severe poisoning. Withdrawal syndrome develops immediately after cessation of drug therapy and is expressed in severe insomnia, irritability, anxiety, bad mood and depression of performance.

GABA derivatives

Gamma-aminobutyric acid is an inhibitory neurotransmitter of the central nervous system and plays an important role in the formation of slow-wave sleep. The main drug in this group is a drug called Phenibut. This nootropic drug, which has a hypnotic effect, helps normalize the time of falling asleep and restores the normal cyclicity of sleep phases. Unlike benzodiazepine drugs, Phenibut helps to prolong the slow-wave sleep phase, which significantly improves the patient’s well-being after waking up. Sleeping pills are low-toxic, have a short list of side effects and do not cause drug dependence.

Nootropic sleep aid

Which 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 disorder when prescribing a particular drug can answer this question. Only after a detailed history collection can the doctor issue a list of medications for treatment with an exact indication of how many tablets should be taken.

* Sedative (calming) effect on the central nervous system - manifests itself in doses 5-10 times less than sleeping pills.

* Vasodilator, hypotensive.

* Anticonvulsant (phenobarbital, chloral hydrate, etc.)

* Anesthetic effect - in doses exceeding hypnotics (barbiturates).

* Antispasmodic effect on smooth muscle organs (barbiturates).

* Potentiating effect on other drugs with similar properties (neuroleptics), etc.

* Cause “induction” of microsomal liver enzymes, which contributes to the inactivation of other drugs - this is characteristic only of barbiturates.

Indications for use: sleep disorders, neurotic conditions; as anticonvulsants; hypertonic disease (early stages); to potentiate the action of neuroleptics, analgesics, anesthetics, etc.

Side effects: addictive - this complication is due to the fact that with the systematic use of sleeping pills, their therapeutic effect weakens and this entails the need to increase the dose of the drug. The development of tolerance is associated with the ability to cause the induction of microsomal liver enzymes involved in the inactivation of these drugs. Habituation is cross-cutting. In order to prevent addiction, it is necessary to take breaks in therapy with sleeping pills and not prescribe these drugs without sufficient indications.

Addiction- development of drug addiction. Long-term uncontrolled use of sleeping pills can cause addiction to them, i.e. drug addiction. This occurs more often with short- and medium-acting drugs. The likelihood of this complication increases with increasing dosage of the drug. Withdrawal (abstinence from taking the drug) is manifested by irritability, aggressiveness, insomnia, tremors or convulsions. There may be vomiting, a drop in blood pressure, and delirium.

Treatment is carried out in special psychiatric hospitals.

Allergic reactions as skin rashes, jaundice occurs in 3-5% of patients systematically taking barbiturates (phenobarbital).

Classification of sleeping pills:

Benzodiazepine derivatives - nitrazepam (syn. eunoctin, radedorm), triazolam (somneton), flunitrazepam (rohypnol).

Derivatives of barbituric acid (barbiturates) - phenobarbital, etaminal sodium, barbital sodium, cyclobarbital.

Sleeping pills of other groups - bromizal, methaqualone, zopyrone (imovan).

Nitrazepam - nitrazepam. synonym: eunoctin, berlidorm, radedorm.

Its pharmacological properties are similar to benzodiazepine tranquilizers. In addition to the hypnotic effect, it has a tranquilizing, anxiolytic (anti-anxiety), muscle relaxant, and anticonvulsant.

The mechanism of action is due to the ability of the drug to enhance the inhibitory effect of GABA in brain synapses, due to the binding of nitrozepam to specific benzodiazepine receptors. Strengthens the effect of other hypnotics and analgesics. Under the influence of nitrozepam, the depth and duration of sleep increases (up to 6-8 hours).

Indications for use: various types of insomnia; neuroses, psychopathy; schizophrenia (in combination with other drugs); manic-depressive syndrome, grand mal seizures; for premedication.

Side effects: drowsiness, lethargy, lack of coordination of movements, headache, stupor.

Contraindications: pregnancy, liver and kidney damage, transport drivers. The simultaneous use of alcohol is unacceptable.

Dosage: as a sleeping pill - half an hour before bedtime - 0.005-0.01 g; for children - 0.00125-0.005 g per dose, depending on age.

Release form: tablets of 0.005 and 0.01.

Barbiturates

Barbituric acid itself does not have a hypnotic effect; when hydrogen atoms in the C 5 position are replaced by alkyl radicals, barbiturates with a pronounced hypnotic effect are obtained.

The mechanism of the hypnotic effect of barbiturates is due to the inhibitory effect on the activating reticular formation of the brain stem. In addition, barbiturates have a stimulating effect on GABAergic structures. GABA is known to be an inhibitory neurotransmitter of the central nervous system.

Barbiturates are well absorbed from the gastrointestinal tract. At the same time, they are absorbed faster sodium salts(ethaminal sodium). The duration of action of barbiturates is determined by the degree of binding (5-75%) with blood plasma albumin, as well as conversion in the body and release from it. They easily penetrate the blood-brain and placental barriers and can pass into the milk of nursing mothers. Their biotransformation occurs in the liver and excretion by the kidneys.

Barbiturates are divided into:

Long-acting drugs: phenobarbital, sodium barbital, duration of hypnotic effect - 7-8 hours.

Medium duration action: etaminal sodium, cyclobarbital - 4-6 hours.

When reintroduced into the body, barbiturates can accumulate. This is especially pronounced in long-acting drugs (phenobarbital) and is associated with their slow elimination from the body. Under the influence of barbiturates, a deficit in the REM sleep phase occurs. When drugs are discontinued, the phenomenon of “recoil” occurs - lethargy, fatigue, impaired psychomotor reactions, attention develops - this condition is also called aftereffect.

Phenobarbital - Phenobarbitalum

It has sedative, hypnotic, anticonvulsant and antispasmodic properties.

In addition, it is widely used for epilepsy, chorea and spastic paralysis, because stronger than other barbiturates, it reduces the excitability of the motor centers of the brain. It goes well with belladonna preparations, papaverine and other antispasmodic and hypotensive drugs.

Dosage: as a sleeping pill - prescribed orally (for adults) 0.1-0.2 g per dose. Sleep occurs within 30-60 minutes and lasts up to 8 hours. Children, depending on age, 0.005-0.0075 g per dose. As a sedative and antispasmodic - 0.01-0.05 g 2-3 times a day. As an anticonvulsant (for epilepsy) - for adults, starting with a dose of 0.05 g 2 times a day, gradually increasing the dose until the seizures stop, but not more than 0.6 g per day.

Side effects: general depression, increased drowsiness, ataxia, decreased blood pressure, skin rashes, changes in the blood.

Contraindications: severe damage to the liver and kidneys.

Higher doses: for adults orally - single dose 0.2 g, daily - 0.5 g.

Release form: powder, tablets of 0.05 and 0.1; for children - 0.005.

Included in the following drugs: BELLATAMINAL, TEPAFILLINE, CORVALOL.

Etaminal sodium - aethaminalum-natrium

It is used as a sedative and hypnotic, less often as an anesthetic.

Dosage: as a sleeping pill, 0.1-0.2 g is prescribed orally (for adults) and 0.01-0.1 g for children, depending on age. Can be administered rectally in enemas of 0.2-0.3 g. Intravenously administered in the form of a 5% sterile fresh solution of 5-10 ml.

Release form: powder, tablets 0.1.

bromized - bromizovalum

It has a calming and weak hypnotic effect (in large doses).

Dosage: as a sleeping pill - 0.6-0.75 half an hour before bedtime. Children are prescribed 0.3-0.1-0.05 g per dose for insomnia, chorea, whooping cough, depending on age.

Release form: powder, tablets 0.3.

methaqualone - metaqalone - Syn.: dormogen, motolon, dormotin.

It has hypnotic, sedative, anticonvulsant properties, enhances the effect of analgesics and neuroleptics.

When taken orally, sleep occurs within 15-30 minutes and lasts 6-8 hours.

Dosage: take the tablet 0.5 hours before bedtime.

Side effects: occasionally dyspeptic symptoms.

Release form: tablets 0.2 g.