From Big Medical Encyclopedia

HYPNAGOGUES (somnifera) — the pharmaceuticals applied for the purpose of simplification of backfilling and ensuring sufficient duration of a dream.

Villages of the village classify usually, proceeding from their chemical structure. On this sign among S. the page is distinguished barbiturates (see), i.e. derivatives barbituric to - you — barbamyl (see), barbital-sodium (see), phenobarbital (see), etaminal-sodium (see), etc.; derivatives of benzodiazepine — nitrazepam (see), etc.; derivatives of piperidine — glyutetimid (see); connections of an aliphatic series — bromisoval (see), Chlorali hydras (see), etc.

In some cases as S. villages use drugs of other groups of pharmaceuticals, to-rye along with the main properties have somnolent action, naira. sodium hydroxybutyrate (see), nek-ry antihistamines — Dimedrol (see), dipraziya (see), etc.

In some cases at the frustration of a dream caused nek-ry-mi patol. states, the drugs which are not relating to group of sleeping pill can be used. So, analgetics (see. Analgesic means) can eliminate the sleep disorders connected with pains, way of easing of these pains; antispasmodics (see) contribute to normalization of a dream at its frustration connected with pains of spastic genesis. Antidepressants (see) are effective at the sleeplessness caused by a depression.

On phase structure dream (see), S. arising under the influence of the majority the page, significantly differs from a natural dream. The most expressed changes of phase structure of a dream and first of all durations of a phase of a REM sleep cause derivatives barbituric to - you and glyutetimid. Moderate changes of this phase cause derivatives of benzodiazepine. At S.'s cancellation by the village the so-called phenomenon of return is observed, at Krom duration of a phase of a REM sleep during nek-ry time exceeds usual sizes, and also bright dreams of frightening character and frequent awakenings are noted. A little Chlorali hydras influences phase structure of a dream.

Development of a dream at S.'s use by the village is connected with change of functional interaction activating and gipnogennop systems of a brain in favor of the last due to influence of hypnagogues on synoptic transfer of excitement to c. N of page.

Oppression of synoptic transfer to c. by N of page under the influence of barbiturates it is caused as presynaptic action of these S. of page, the shown decrease in allocation of mediators (see), and strengthening of gyustsinaptichesky braking. Assume that in mechanisms of somnolent action of barbiturates their influence on synoptic transfer of excitement matters, with participation at - aminobutyric to - you are GAMK (see. Piperidic acid ). It is confirmed, in particular, by experimental data, according to the Crimea, increase in maintenance of GAMK in a brain leads to increase in duration of somnolent effect of barbiturates, and decrease in maintenance of GAMK — to shortening of duration of this effect. In small doses barbiturates stimulate GABA-ergic processes in c. N of page. There are data that barbiturates are capable to oppress the return neyronalny capture of GAMK. Nek-ry substances of this group promote release of GAMK. Besides, barbiturates lower turnover of serotonin, noradrenaline and dopamine in a brain. Unlike benzodiazepines small increase in a dose of barbiturates causes not selective oppression «synoptic transfer.

Somnolent effect of benzodiazepines as well as their anxiolytic action, explain with strengthening of GABA-ergic mechanisms pre-and postsynaptic braking in a brain due to interaction of these substances with specific benzodiazepine receptors. Under the influence of benzodiazepines also the maintenance of a number of mediators in a brain changes. So, benzodiazepines reduce a turn of noradrenaline in a brain. Their influence on turnover of dopamine it is ambiguous: in one structures they raise it, in others lower. Turnover of serotonin decreases, especially in structures of a mesencephalon, varoliyev of the bridge and a myelencephalon. However these phenomena, apparently, have secondary character and are caused by changes of GABA-ergic mechanisms under the influence of benzodiazepines.

Barbiturates depending on a dose cause essential changes of phase structure of a dream. They reduce time of approach of a dream, the number of awakenings and movements during sleep. Considerable reduction of the third and fourth stages of a dream is noted. Stage of latency of a phase of a REM sleep increases. The general duration of a REM sleep and quantity of its cycles decrease. The night peaks of concentration in plasma of somatotropic hormone raise, and AKTG decrease. Use of barbiturates during the day can suppress a phase of a REM sleep at night.

At daily reception of barbiturates sensitivity of an organism to their action gradually decreases, i.e. the phenomena of accustoming develop (see Barbiturates). So, after two-week use their influence on the general duration of a dream can decrease by 50%. At cancellation of barbiturates, after their prolonged use, there is a syndrome of return which is characterized by increase in a phase of a REM sleep, and also shortening of the second stage of a dream. These phenomena can be followed by dreadful dreams.

The different barbiturates applied as S. by page in general have similar effect on c. N of page also differ on a nek-eye to pharmacokinetic parameters, napr, on time of semi-removal from an organism. Depending on time of semi-removal distinguish drugs of long action (6 — 8 hours) from barbiturates — barbamyl, barbital-sodium, phenobarbital, etaminal-sodium and drugs of shorter action (6 hours), napr, cyclobarbital.

At persons with dysfunctions of breath, napr, at emphysema of lungs or bronchial asthma, barbiturates in somnolent doses can reduce the minute volume of breath and in this regard saturation of blood oxygen. In somnolent doses of S. of page of this group can lower the ABP, reducing cordial emission due to restriction of the venous return to heart caused by deposition of blood in a venous bed. Compensatory vascular reflexes at the same time are oppressed. In toxic doses barbiturates oppress functions of a myocardium, and also reduce peripheric resistance, suppressing a sympathetic innervation of vessels.

Barbiturates are inductors of microsomal enzymes of a liver. In this regard they accelerate own metabolism that is one of the reasons of development of accustoming to them, and also change the speed of biotransformation of many other drugs. At prolonged use of barbiturates there can be a medicinal dependence (see) with development of a heavy withdrawal.

Rather small width of therapeutic action is characteristic of barbiturates: their toxic doses exceed averages therapeutic approximately by 5 — 10 times.

The majority of tranquilizers of a benzodiazepine row, including diazepam, Phenazepamum, oxazepam, etc., have the somnolent properties expressed in a varying degree, and them it is possible to use page as S. However is more often than others for this purpose apply nitrazepam, etc., at to-rykh somnolent activity it is especially expressed.

Under the influence of benzodiazepines the period of backfilling is shortened. Nitrazegkham reduces time of the first stage of a dream. Benzodiazepines extend the second stage and reduce time of the third and fourth stages. Stage of latency of a phase of a REM sleep increases the majority of benzodiazepines. Frequency of movements of eyes in a phase of a REM sleep decreases. The general duration of a REM sleep under the influence of these drugs is reduced. Nitrazepam does not influence the night peaks of concentration in plasma of somatotropic and luteinizing hormones, and also prolactin.

The benzodiazepines applied as hypnagogues well are soaked up from digestive tract. At the same time time of absorption of different drugs is unequal (of 30 min. till several o'clock) and substantially depends on their dosage forms. Extent of linkng of benzodiazepines with proteins of a blood plasma is also various (at diazepam apprx. 99%, at nitrazepam apprx. 87%). After absorption a nek-swarm the amount of benzodiazepines or their metabolites get to a gleam of intestines at the expense of excretion with bile again. Biotransformation of benzodiazepines is carried out preferential in a liver with participation of microsomal enzymes. Unlike barbiturates benzodiazepines do not exert considerable impact on activity of these enzymes. However diazepam at repeated introduction can accelerate own metabolism. Time of semi-removal of benzodiazepines increases at cirrhosis and a viral hepatitis.

The conjugated metabolites of benzodiazepines are presented generally by glucuronides. Many not - the conjugated transmutation products possess high pharmakol. activity. Benzodiazepines get through a placental barrier and are emitted with mammary glands. In the doses applied to correction of a dream they influence functions of a respiratory organs, cardiovascular system, digestion a little.

At a combination of benzodiazepines to other substances, the oppressing c. the N of page, is observed the additive effect. Alcohol accelerates absorption of benzodiazepines from intestines and strengthens their oppressing action on c. N of page. At combined use of benzodiazepines with Valproatum of sodium there can be mental disorders.

Benzodiazepines can cause side reactions (a lack of coordination of movements, an ataxy), and also the paradoxical effects which are characterized by the phenomena of excitement. At long use of benzodiazepines development of accustoming and medicinal dependence is possible. Thus, benzodpa-zepina have a number of advantages in comparison with barbiturates. They to a lesser extent influence phase structure of a dream, have considerably the bigger width of therapeutic action, change activity of microsomal enzymes of a liver a little and in this regard interact with other pharmaceuticals less often. Besides, they cause medicinal dependence less often.

Glyutetimid on pharmakol. to properties it is similar to barbiturates, but concedes to them on activity. It is well soaked up from went. - kish. path. Apprx. 50% of drug communicates proteins of plasma. Less than 2% of the entered dose are removed with urine in not changed look. The most part of drug is metabolized in a liver. At the same time glyutetimid stimulates system of microsomal enzymes of a liver. Like barbiturates glyutetimid causes essential changes of phase structure of a dream.

Derivative an aliphatic series bromisoval has low somnolent activity. At metabolism of this drug in an organism ions of bromine are allocated. In this regard at prolonged use of bromisoval the phenomena of a bromism can develop (see Bromides). Chlorali hydras possesses the expressed somnolent action. Unlike barbiturates Chlorali hydras significantly does not influence a phase of a REM sleep. However existence of the expressed local irritative properties at this drug limits its use.

At S.'s overdose by the village cause acute poisonings. For a wedge, pictures of the acute poisonings caused by S. page are characteristic the following syndromes: development of coma, respiratory depression, disturbances of functions of cardiovascular system and kidneys, trophic frustration. Depending on degree of intoxication expressiveness of coma happens various: from a superficial coma with increase or decrease in reactions of pupils to light to a deep coma with an areflexia and lack of reactions to pain stimulation. Disturbances of breath at poisoning With", page in character can be aspiration obturatsionnymi, central or mixed. At disturbances of functions cordial with-with at a diet of system the hl is noted. obr. tachycardia, hypotension, and in hard cases collapse (see). Edematization of lungs is possible (see). Trophic frustration are shown usually in the form of violent dermatitis (see) or a necrotic dermatomyositis. At a renal failure there is preferential an oliguria (see) caused by decrease in a renal blood-groove owing to acute cardiovascular insufficiency.

Rendering acute management at acute poisonings

includes Rendering acute management at acute poisonings of S. of page: gastric lavage (see), introduction to it of the adsorbing means, an intubation of a trachea (see. Intubation ) or a tracheostomy (at coma), artificial ventilation of the lungs (see. Artificial respiration ) and the measures directed to reduction of concentration of poisons in blood. For this purpose widely use a method of the forced osmotic diuresis using a mannitol or urea (see. Poisonings, treatment ). At a renal failure carrying out a hemodialysis (see), peritoneal dialysis is reasonable (see) or hemosorptions (see). At therapy of functional disturbances of cardiovascular system use adrenomimetik, cardiac glycosides, glucocorticoids. Analeptics (Corazolum, etc.) at a serious poisoning are a little effective. It is possible to appoint them only in therapeutic doses at superficial coma. For prevention inf. complications apply antibiotics.

Bibliography: Andreyeva N. I. Somnolent drug nitrazepam, Chemical - pharm. zhurn., t. 14, No. 12, page 107, 1980; M and sh-to about in with to and y M. D. Pharmaceuticals, p.1, page 25, etc., M., 1977; Breimer D. D. Clinical pharmacokinetics of hypnotics, Clin. Pharmacokinet., v. 2, p. 93, 1977, bibliogr.; Clinical pharmacology, Basic principles in therapeutics, ed. by K. L. Melmon a. H. F. Morrelli, N. Y., 19^78; Greenblatt D. J. a. o. Benzodiazepine hypnotics, kinetic and therapeutic options, Sleep, v. 5, suppl. l, p. 518, 1982; Hypnotics, methods of development and evaluation, ed. by F. Kagan and. lake, N. Y., 1976; Johns M. W. Sleep and hypnotic drugs, Drugs, v. 9, p. 448, 1975, bibliogr.; Laurence D. R. a. 'Bennett P. N. Clinical pharmacology, Edinburgh — N. Y., 1980; The pharmacological basis of therapeutics, ed. by A. G. Gilman and. lake, N. Y., 1980; Pharmacology of sleep, ed. by R. L. Williams a. I. Karacan, N.Y., 1976; S k about 1 n i with k Ph. a. o. Interaction of barbiturates with benzodiazepine receptors in the central nervous system, Brain Res., v. 233, p. 143, 1982, bibliogr.

V. V. Churyukanov.\