Tranquilizers at delivery

From the troupe of small tranquilizers at delivery, use trioxazine, nosepam, phenazepam, sibazone (seduxen, diaeepam), etc.

Trioxazine

Has a moderate tranquilizing effect, combined with activation, a certain increase in mood without drowsiness and intellectual retardation, does not have a muscle relaxant effect. Trioxazine does not give side effects in the form of drowsiness, muscle weakness, decreased reflex excitability, vegetative disorders, etc., which is often found in other tranquilizers. In animal experiments extremely low toxicity of the drug was found 2.6 times lower than that of meprobamate.

Trioxazine is effective in conditions of fear, excitement; better than andaxin and other agents, eliminates vegetative-functional disorders, leading to a diffuse decrease in vegetative hypersensitivity. The therapeutic effect is proved by numerous clinical observations. After taking trioxazine tablets, patients with neurotic stratifications decreased tension, anxiety, fear, behavior normalized without disturbing higher mental processes and without diminishing interest in external events. Most authors who studied trioxazine did not reveal any side effects. Changes in urine, blood, liver, kidney and other systems were not observed even with prolonged use of the drug. No contraindications found. To overcome acute arousal, usually enough 300-600 mg of trioxazine inside. On average, 1200-1600 mg is administered per day to remove neurotic layers.

Sibazon

Diaepam, seduxen, Relanium, Valium - a derivative of diazepine. Diaepam was synthesized in 1961 by Stembach and in the same year pharmacologically studied by Randall and co-workers. Diaepam is a benzodiazepine derivative. The toxicity of the Cibaeon is extremely low. DL "for mice is 100-800 mg / kg with different modes of administration. Only when doses of sibazone administered to animals are equivalent to human ones (15-40 mg / kg) and their administration was repeated, violations of the liver, kidneys and blood were observed.

Metabolism and pharmacokinetics of Seduxen are not well understood. 75% of the drug is excreted in the urine. The half-life is 10 hours. With intravenous administration (0.1 mg / kg), seduxene is 96.8% bound to plasma proteins. Our data showed that the most effective dose of seduksen in labor is 20 mg. Studies on the pharmacokinetics of Relanium (diazepam) in humans with intravenous, intramuscular and oral administration of the drug are identical, i.e., an initiating dose amount of 20.3 mg (practically 20 mg) should result in a concentration of 0.4 mg / L, and the average effective concentration of diazepam in the blood is exactly 0.4 mg / l (according to Klein).

Sibazon penetrates the placental barrier. Its concentration in the blood of the mother and fetus is the same. With appropriate dosages of harmful effects on the mother and the fetus does not pellet.

The drug coats a pronounced sedative effect and belongs to the group of tranquilizers-relaxants. Its characteristic feature is the ability to suppress a sense of fear, anxiety, stress and to stop psychomotor agitation, ie, to block emotional stress.

The high efficacy of Seduxen as a psycho-sedative has been confirmed by studies of the skin-galvanic reflex.

Depending on the dose, seduksen is able to cause sedation, amnesia and, finally, a physiological-like sleep, with preserved main reflexes, but with a sharp decrease in the response to pain. According to studies, seduxen has a depressing effect on the cerebral cortex, reduces the excitability of the thalamus, hypothalamus, limbic system, reticular formation and polysynaptic structures. These data are confirmed by electrophysiological studies. The drug gives a pronounced anti-somatic effect, which is associated with its effect on the hypocampus and temporal lobe. The researchers concluded that seduksen inhibits transmission of excitation in both afferent and efferent brain systems, which suggests that this drug is capable of creating reliable neurovegetative protection in various stressful situations. Some authors also explain the stability of hemodynamics in the conditions of analgesia.

Seduxen

Seduxen does not have any effect on the contractility of the myocardium, the parameters of the electrocardiogram and central hemodynamics. However, Abel et al. Found that Seduxen slightly increases the contractility of the myocardium by improving the coronary blood flow and for a short time reduces the overall peripheral resistance. It is established that the drug significantly increases the threshold of myocardial excitability and potentiates the antiarrhythmic effect of lidocaine. The antiarrhythmic effect of Seduxen has a central genesis. Changes in pulmonary ventilation with the introduction of seduksen does not occur, the sensitivity of the respiratory center to CO ₂ does not change . Seduxenum prevents the accumulation of lactic acid, eliminating one of the main causes of brain damage during psixia, ie, it increases the resistance of the brain to hypoxia. Seduxen does not increase the tone of the vagus nerve, does not cause changes in the endocrine system, sensitivity of adrenoreceptors, has a significant antihistamine effect.

According to the research, seduxen reduces the basal tone of the uterus, having a regulating effect on the contractile activity of the uterus. This is due to the fact that one of the points of application of the action of seduksen is the limbic region responsible for unleashing and regulating the birth activity.

Seduxen very potentiates the effect of narcotic and analgesic drugs. Especially pronounced potentiating effect with the combination of seduxen and dipidolor.

Seduxen does not affect uteroplacental blood flow. There was no embryotoxic and teratogenic effect of the drug. The drug causes depression of the emotional-behavioral component of the pain reaction, but does not affect peripheral pain sensitivity. This indicates that diazepam practically does not change the threshold of pain sensitivity, but only increases tolerance to repeated and prolonged painful irritations, which is undoubtedly important for obstetric practice. In this case, irrespective of the way of diazepam administration, unambiguous behavioral reactions appear. Seduxen, especially in combination with dipidolor, stabilizes the parameters of hemodynamics during the initial anesthesia.

In 1977, two groups of researchers, almost simultaneously and independently of each other, discovered specific receptor sites for the binding of benzodiaepins in the brain of humans and animals and suggested that the endogenous ligands of these receptors exist in the body.

Tranquilizers of benzodiazepine series relieve the state of emotional stress both during the waiting period and at the time of direct nociceptive exposure. Most researchers consider diazepam a valuable drug in the anesthesia of complicated delivery.

Large tranquilizers

At present, the combination of psychopharmacological agents - the so-called "large" and "small" tranquilizers with antispasmodics and spasmoanalgesics - is becoming the most widespread among the medical methods of preparing pregnant women for childbirth and for anesthetizing them.

These compounds of substances are undoubtedly / promising, as they make it possible to selectively influence the psychosomatic state of the mother in labor, they have a pronounced sedative effect and spasmolytic effect with little toxicity. This is all the more important because, according to research, we have entered the era when stress plays a decisive role in the development of human diseases. Pelletier claims that up to 90% of all diseases can be associated with stress.

It is also significant that neurotropic drugs do not have a negative effect on the maternity, contraction of the uterus and fetus, which allows them to remain one of the most promising and widely used substances in obstetric practice.

In recent years, to prevent complications of pregnancy and childbirth, psychopharmacological agents are increasingly being used, which help to remove a number of negative emotions, feelings of fear, internal tension. Small tranquilizers (actually tranquilizers) are isolated in one of four separate groups of psychopharmacological agents.

All the variety of clinical effects of tranquilizers can be considered on the basis of their psychotropic activity, expressed in a universal effect on emotional excitability and affective saturation. According to the type of sedation, tranquilizers differ from sleeping pills and narcotics in that they maintain an adequate reaction to external stimuli and a critical assessment of what is happening. In addition to the tranquilizing effect, some substances in this group also possess adrenolytic and anticholinergic properties. Important and neurovegetropic action of tranquilizers, which is of great importance for obstetric practice.

Applying "large" tranquilizers from the phenothiazine group (aminazine, propazine, diprazine), in the process of the birth act it is not possible to obtain a pronounced analgesic effect. Therefore, for the purpose of anesthetizing labor, it is advisable to administer intramuscularly or intravenously analgesics with these substances (promedol, morphine, etc.).

In humans, aminazine reduces the activity of the reticular formation, the rostral parts of it are suppressed by this drug earlier and stronger than the caudal ones, and also blocks the trigger mechanism of stress reactions. Phenothiazines cause normalization of the psychosomatic state with pain stimulation, reduce the intensity of painful contractions.

Thus, to large tranquilizers belong substances of different chemical structure, with different mechanisms of action. This includes, in addition to the phenothiazine derivatives (aminazine, propazine, pipolfen, diprazine), butyrophenone derivatives (droperidol, haloperidol, etc.). The phenothiazine derivatives mainly have a central effect. Sedative action in this case is due to their depressing effect mainly on the brain stem (reticular formation, hypothalamus). Since it is in this region that neurons that react to catecholamines are localized, the sedative effect of phenothiazine derivatives is partly attributed to their adrenolithic properties. As a result, the flow of tonic impulses coming into the cortex along the reticular formation of the trunk weakens, the tone of the cortex decreases. The second area of the brain, to which the action of phenothiazines is directed, is the posterior hypothalamus. As in the middle brain, in terms of function, epinephrine and norepinephrine are very important here.

Aminazine (chlorpromazine)

One of the main representatives of neuroleptic substances. Pharmacological effects, which causes aminazine, are more or less characteristic of other preparations of the phenothiazine series. After the introduction of aminazine there is general calm, accompanied by a decrease in motor activity and some relaxation of skeletal muscles. Consciousness after the introduction of aminazine remains. The drug depresses various interoceptive reflexes, enhances the action of analgesics, drugs and hypnotics, and has a strong antiemetic effect.

A single single dose of aminazine in parturient women with expressed psychomotor agitation is 25-50 mg intramuscularly. During delivery, the dose of aminazine should not exceed 75 mg. In these cases, aminazine does not adversely affect the maternity, the cardiovascular system, the contractile activity of the uterus, and the condition of the fetus and newborn.

[1], [2], [3]

Propazine (promazine)

By structure, propazine differs from aminazine by the absence of a chlorine atom in the 2-position of the phenothiazine series and therefore has less toxicity. By pharmacological properties is close to the aminazine. Like the latter, it has a sedative effect, reduces motor activity, increases the duration and intensity of the action of narcotic drugs. However, by sedation, propazine is inferior to aminazine. Single single dose of propazin in parturient women - 50 mg; During the birth, doses of propazine should not exceed 100 mg intramuscularly. The drug is contraindicated to women in labor with significant concomitant diseases: liver damage (cirrhosis, severe hepatitis, etc.), kidney (nephritis, acute pyelitis, urolithiasis), decompensated heart diseases, severe arterial hypotension.

Diprazine (pipolfen, promethazine)

In its effect, the neuroleptic diprazine is also close to the aminazine, but differs from it by a weaker sympatholytic and central action with a stronger antihistamine effect. The drug has sedative, antispasmodic, antiemetic, analgesic properties, as well as the ability to inhibit interoceptive reflexes. Diprazin in a dose of 1/5 mg / kg in an animal experiment caused a very strong and persistent (up to 2 h) increase in tone and increased uterine contractions. The drug does not cause respiratory depression, does not change blood pressure. A single dose of pifolen in labor is 50 mg intramuscularly. During doses, doses exceeding 150 mg intramuscularly are not recommended.

Butyrophenone derivatives

The main preparations of the group of butyrophenones are strong antipsychotic agents, widely used in medicine, well absorbed and have a quick healing effect.

Of the derivatives of butyrophenone, two drugs - droperidol and haloperidol - are widely used . The drugs cause a calming effect typical for psychotropic medications ("large" tranquilizers) and significantly exceed in strength the neuroleptics from the phenothiazine group.

With parenteral administration, the effect of the drug develops rapidly and allows the acute psychic excitation of any nature to be quenched. The mechanism of tranquilizing action of butyrophenones has been studied little. In general, the picture of the sedative effect of butyrophenones both from the point of view of localization in the central nervous system and externally resembles the action of phenothiazines - a state of complete rest ensues, the motor activity of muscles is absent, but their tone increases due to blockade of inhibitory effects of the extrapyramidal system. Therefore, in labor giving birth, there is no decrease in the strength of attempts in the second stage of labor. In comparison with phenothiazines, these substances have a relatively weak peripheral a-adrenergic effect, and their use does not create a threat of a sharp drop in blood pressure. Moderate hypotension occurs only in individuals with a reduced volume of circulating blood.

Due to the central inhibition of vegetative reflexes and weak a-adrenergic action on the periphery, butyrofenones suppress excess vascular responses to pain, have anti-shock effect with a particularly pronounced ability to enhance the effect of narcotic drugs and analgesics in anesthesia. Drugs have a pronounced antiemetic effect, 50 times greater than that of aminazine; droperidol excitatory effect on the respiratory center.

Droperidol disrupts impulses in the thalamo-hypothalamus and reticular formation as a result of a-adrenergic blockade and accelerates the inactivation of catecholamines. Perhaps, it competitively captures GABA receptors, steadily disrupting the permeability of the receptor membranes and carrying out impulses to the central apparatus of the brain.

Drugs are low in toxicity, do not depress respiration and cardiovascular system. However, droperidol causes a moderate adrenergic blockade, which extends predominantly to a-adrenergic receptors, so this action underlies hemodynamic effects: vasodilation, decreased peripheral resistance, and moderate arterial hypotension.

After intravenous administration at a dose of 0.5 mg / kg, the maximum effect occurs after 20 minutes and lasts up to 3 hours, and after intramuscular injection, after -30-40 minutes to 8 hours. The drug is mainly destroyed in the liver, and a part (up to 10% ) in unchanged form is excreted through the kidneys.

Dosage of the drug in labor, droperidol - 5-10 mg (2-4 ml) in combination with fentanyl 0.1-0.2 (2-4 ml) intramuscularly in one syringe. The average one-time dose of droperidol is 0.1-0.15 mg / kg body weight of the parturient, fentanyl 0.001-0.003 mg / kg.

When choosing doses of droperidol, one should be guided by the condition of the parturient woman: in the presence of painful contractions, but without pronounced psychomotor agitation, the dose of droperidol can be reduced to 0.1 mg / kg of body weight. With significant psychomotor agitation and increased blood pressure to 150 / 90-160 / 90 mm Hg. Art. The dose of droperidol should be increased to 0.15 mg / kg.

It should be noted that the most characteristic complication is the development of moderate arterial hypotension due to adrenoblocking action. In obstetric practice, this property of droperidol is successfully used in women with high blood pressure. The main factor predisposing to severe hypotension under the influence of droperidol is unresolved hemorrhage. A relatively rare but very peculiar complication in the administration of droperidol is hyperkineto-hypertonic syndrome (Kulenkampf-Tarnov syndrome). The frequency of this complication, according to various authors, ranges from 0.3 to 10%.

Neurological symptoms, which unfolds during the use of neuroleptics, are associated primarily with the extra-pyramidal system. In clinical terms, the most pronounced tonic spasms of muscles of eyeballs, face, circular muscles of the mouth, soft palate, tongue and neck. With a convulsive protrusion of the tongue, swelling and cyanosis appear. Often, motor complications are accompanied by serious vegetative disorders, caused by the reactions of the interstitial brain: blanching or redness, profuse sweating, tachycardia, increased blood pressure. The pathogenesis of convulsive states after the administration of droperidol is complex and not entirely clear. It is assumed that neurological complications observed after the administration of droperidol are the result of complex violations of cholinergic and adrenergic reactions in the reticular formation of the brain stem.

Treatment of neurological complications caused by droperidol, it is recommended to begin with the introduction of atropine. In the absence of effect, it is possible to use agents that stimulate adrenergic structures. Good results are given by cyclodol or its analogs - artan, romparkin, beta-adrenoblockers (obzidan, inderal), seduxen. Rapid relief of extrapyramidal disorders is observed after intravenous administration of caffeine. In severe disorders, barbiturates (hexenal, sodium thiopental) are effective.

[4], [5], [6], [7]