Tranquilizers in childbirth

Among the minor tranquilizers used during childbirth are trioxazine, nozepam, phenazepam, sibazon (seduxen, diaerepam), etc.

Trioxazine

It has a moderate tranquilizing effect, combined with activation, some mood elevation without drowsiness and intellectual inhibition, does not have a muscle relaxant effect. Trioxazine does not produce side effects in the form of drowsiness, muscle weakness, decreased reflex excitability, vegetative disorders, etc., which is often characteristic of other tranquilizers. Animal experiments revealed extremely low toxicity of the drug, 2.6 times lower than that of meprobamate.

Trioxazine is effective in states of fear, excitement; better than andaxin and other drugs, eliminates vegetative-functional disorders, leading to a diffuse decrease in vegetative hypersensitivity. The therapeutic effect has been proven by numerous clinical observations. After taking trioxazine tablets, patients with neurotic layers experienced a decrease in tension, anxiety, and fear, behavior was normalized without disruption of higher mental processes and without a decrease in interest in external events. Most authors who studied trioxazine did not identify side effects. Changes in urine, blood, liver function, kidneys and other systems were not observed even with prolonged use of the drug. No contraindications have been identified. To overcome acute excitement, 300-600 mg of trioxazine orally is usually sufficient. On average, 1200-1600 mg orally is used 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 derivative of the benzodiazepine series. The toxicity of sibaeon is extremely low. DL" for mice is 100-800 mg / kg with various methods of administration. Only in cases where the doses of sibazon administered to animals are equivalent to human (15-40 mg / kg) and their administration was repeated, violations of the liver, kidneys and blood were observed.

The metabolism and pharmacokinetics of seduxen have not been studied sufficiently. 75% of the drug is excreted in urine. The half-life is 10 hours. When administered intravenously (0.1 mg/kg), seduxen binds to plasma proteins by 96.8%. Our data showed that the most effective dose of seduxen during 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. the initiating dose of 20.3 mg (practically 20 mg) should lead to 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. At appropriate dosages, it does not have a harmful effect on the mother and fetus.

The drug has a pronounced sedative effect and belongs to the group of tranquilizers-relaxants. Its characteristic feature is the ability to suppress the feeling of fear, anxiety, tension and stop psychomotor agitation, i.e. block emotional stress.

The high efficiency of seduxen as a psychosedative has been confirmed by studies of the galvanic skin reflex.

Depending on the dose, seduxen can cause sedation, amnesia and, finally, sleep resembling physiological sleep, with preserved main reflexes, but with a sharp decrease in the reaction to pain. According to research, 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 has a pronounced anticonvulsant effect, which is associated with its effect on the hippocampus and temporal lobe. Researchers have come to the conclusion that seduxen inhibits the transmission of excitation in both the afferent and efferent systems of the brain, which gives reason to believe that this drug is capable of creating reliable neurovegetative protection in various stressful situations. Some authors also explain the stability of hemodynamics under analgesia by this.

Seduxen

Seduxen has no effect on myocardial contractility, electrocardiogram parameters, or central hemodynamics. However, Abel et al. found that seduxen slightly increases myocardial contractility by improving coronary blood flow and temporarily reduces total peripheral resistance. It was found that the drug significantly increases the myocardial excitability threshold and potentiates the antiarrhythmic effect of lidocaine. The antiarrhythmic effect of seduxen is of central origin. There are no changes in pulmonary ventilation upon administration of seduxen, and the sensitivity of the respiratory center to CO2 does not change _. Seduxen prevents accumulation of lactic acid, eliminating one of the main causes of brain damage in pshoxia, i.e. it increases the brain's resistance to hypoxia. Seduxen does not increase vagus nerve tone, does not cause changes in the endocrine system, or adrenoreceptor sensitivity, and has a significant antihistamine effect.

According to research, seduxen reduces the basal tone of the uterus, having a regulating effect on the contractile activity of the uterus. This is explained by the fact that one of the points of application of seduxen's action is the limbic region, responsible for the unleashing and regulation of labor.

Seduxen greatly potentiates the action of narcotic and analgesic drugs. The potentiating effect is especially pronounced when combined with seduxen and dipidolor.

Seduxen does not affect the uteroplacental blood flow. No embryotoxic or teratogenic effects of the drug have been identified. The drug causes suppression of the emotional-behavioral component of the pain response, but does not affect peripheral pain sensitivity. This indicates that diazepam practically does not change the pain sensitivity threshold, but only increases tolerance to repeated and prolonged pain stimuli, which is undoubtedly important for obstetric practice. At the same time, regardless of the method of administration of diazepam, unambiguous behavioral reactions are manifested. Seduxen, especially in combination with dipidolor, stabilizes hemodynamic parameters during induction of anesthesia.

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

Benzodiazepine tranquilizers relieve emotional tension both during the waiting period and at the moment of direct nociceptive impact. Most researchers consider diazepam a valuable drug for pain relief in complicated labor.

Large tranquilizers

Currently, the most widespread drug-based method of preparing pregnant women for childbirth and for pain relief is a combination of psychopharmacological agents - the so-called "major" and "minor" tranquilizers with antispasmodics and antispasmodics.

These compounds of substances are undoubtedly/promising, as they provide the opportunity to selectively influence the psychosomatic state of the woman in labor, have a pronounced sedative effect and antispasmodic action with insignificant toxicity. This is all the more important because, according to research data, we have entered an 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 agents do not have a negative impact on the body of the mother in labor, the contractile activity of the uterus, or the condition of the fetus, which allows them to remain one of the most promising and widely used substances in obstetric practice.

In recent years, psychopharmacological agents have been increasingly used to prevent complications during pregnancy and childbirth. They help relieve a number of negative emotions, feelings of fear, and internal tension. Minor tranquilizers (tranquilizers proper) are classified as one of four independent groups of psychopharmacological agents.

The whole variety of clinical effects of tranquilizers can be considered on the basis of their psychotropic activity, expressed in the universal effect on emotional excitability and affective saturation. In terms of the type of sedative action, tranquilizers differ from sleeping pills and narcotics in that when they are used, an adequate reaction to external stimuli and a critical assessment of what is happening are preserved. In addition to the tranquilizing effect, some substances in this group also have adrenolytic and cholinolytic properties. The neurovegetotropic effect of tranquilizers is also important, which is of great importance for obstetric practice.

When using "major" tranquilizers from the phenothiazine series (aminazine, propazine, diprazine), it is not possible to obtain a pronounced analgesic effect during labor. Therefore, in order to relieve labor pain, it is advisable to administer analgesics (promedol, morphine, etc.) intramuscularly or intravenously with these substances.

In humans, aminazine reduces the activity of the reticular formation, its rostral sections are suppressed by this drug earlier and more strongly than the caudal ones, and also blocks the trigger mechanism of stress reactions. Phenothiazines cause normalization of the psychosomatic state during painful stimulation, reduce the intensity of painful contractions.

Thus, major tranquilizers include substances of different chemical structure and different mechanisms of action. In addition to phenothiazine derivatives (chlorpromazine, propazine, pipolfen, diprazine), these include butyrophenone derivatives (droperidol, haloperidol, etc.). Phenothiazine derivatives mainly have a central effect. The sedative effect is due to their depressant effect mainly on the brainstem (reticular formation, hypothalamus). Since neurons that respond to catecholamines are localized in this area, the sedative effect of phenothiazine derivatives is partly associated with their adrenolytic properties. As a result, the flow of tonic impulses coming to the cortex through the reticular formation of the brainstem weakens, and the tone of the cortex decreases. The second area of the brain that phenothiazines act on is the posterior hypothalamus. As in the midbrain, adrenaline and noradrenaline are functionally important here.

Aminazine (chlorpromazine)

One of the main representatives of neuroleptic substances. The pharmacological effects caused by aminazine are to some extent characteristic of other drugs of the phenothiazine series. After the administration of aminazine, general calming is observed, accompanied by a decrease in motor activity and some relaxation of skeletal muscles. Consciousness is preserved after the administration of aminazine. The drug inhibits various interoceptive reflexes, enhances the effect of analgesics, narcotics and sleeping pills, and has a strong antiemetic effect.

A single dose of aminazine for women in labor with severe psychomotor agitation is 25-50 mg intramuscularly. During labor, doses of aminazine should not exceed 75 mg. In these cases, aminazine does not have a negative effect on the body of the woman in labor, the cardiovascular system, contractile activity of the uterus, and the condition of the fetus and newborn.

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Propazine (promazine)

In its structure, propazine differs from aminazine by the absence of a chlorine atom in position 2 of the phenothiazine series and therefore has lower toxicity. In terms of pharmacological properties, it is close to aminazine. Like the latter, it has a sedative effect, reduces motor activity, increases the duration and intensity of the effect of narcotic drugs. However, in terms of sedative effect, propazine is inferior to aminazine. A single dose of propazine for women in labor is 50 mg; during labor, doses of propazine should not exceed 100 mg intramuscularly. The drug is contraindicated in women in labor with severe concomitant diseases: liver damage (cirrhosis, severe hepatitis, etc.), kidneys (nephritis, acute pyelitis, urolithiasis), decompensated heart disease, severe arterial hypotension.

Diprazine (pipolfen, promethazine)

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

Butyrophenone derivatives

The main drugs of the butyrophenone group are strong antipsychotic agents, widely used in medicine, are well absorbed and have a rapid therapeutic effect.

Of the butyrophenone derivatives, the two most widely used drugs are droperidol and haloperidol. The drugs produce a sedative effect typical of psychotropic drugs ("major" tranquilizers) and are significantly stronger than neuroleptics from the phenothiazine group.

When administered parenterally, the drug's action develops quickly and allows to stop acute mental excitement of any nature. The mechanism of tranquilizing action of butyrophenones has been little studied. In general, the picture of the sedative effect of butyrophenones both in terms of localization in the central nervous system and externally resembles the action of phenothiazines - a state of complete rest occurs, motor activity of muscles is absent, but their tone increases due to the blockade of inhibitory effects of the extrapyramidal system. Therefore, women in labor do not experience a decrease in the strength of pushing in the second period of labor. Compared with phenothiazines, these substances have a relatively weak peripheral a-adrenolytic effect, and their use does not create a threat of a sharp decrease in arterial pressure. Moderate hypotension occurs only in people with a reduced volume of circulating blood.

Due to the central inhibition of vegetative reflexes and weak a-adrenolytic action on the periphery, butyrophenones suppress excessive vascular reactions to pain, have an anti-shock effect with a particularly pronounced ability to enhance the effect of narcotic drugs and analgesics in pain relief. The drugs have a pronounced antiemetic effect, 50 times greater than the effect of aminazine; droperidol has a stimulating effect on the respiratory center.

Droperidol disrupts the conduction of impulses in the thalamohypothalamus and reticular formation as a result of a-adrenergic blockade and acceleration of catecholamine inactivation. It may competitively capture GABA receptors, persistently disrupting the permeability of receptor membranes and the conduction of impulses to the central apparatus of the brain.

The drugs are low-toxic, do not depress respiration and the cardiovascular system. However, droperidol causes moderate adrenergic blockade, which mainly affects a-adrenergic receptors, so this action underlies the 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 administration - after 30-40 minutes up to 8 hours. The drug is mainly destroyed in the liver, and part (up to 10%) is excreted unchanged through the kidneys.

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

When choosing doses of droperidol, one should be guided by the condition of the woman in labor: 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. In case of significant psychomotor agitation and an increase in blood pressure to 150/90-160/90 mm Hg, the dose of droperidol should be increased to 0.15 mg/kg.

It is necessary to take into account that the most typical complication is the development of moderate arterial hypotension due to the adrenergic blocking effect. In obstetric practice, we successfully use this property of droperidol in women in labor with high arterial pressure. The main factor predisposing to severe hypotension under the influence of droperidol is uncompensated blood loss. A relatively rare, but very specific complication with the introduction of droperidol is hyperkinetic-hypertonic syndrome (Kulenkampf-Tarnow syndrome). The frequency of this complication, according to various authors, fluctuates between 0.3 and 10%.

Neurological symptoms that develop during the use of neuroleptics are associated primarily with the extrapyramidal system. Clinically, the most pronounced are tonic spasms of the muscles of the eyeballs, face, orbicularis oris, soft palate, tongue and neck. When the tongue is convulsively protruded, it swells and becomes cyanotic. Motor complications are often accompanied by serious vegetative disorders caused by reactions of the diencephalon: pallor or redness, profuse sweating, tachycardia, increased arterial pressure. The pathogenesis of convulsive states after the introduction of droperidol is complex and not entirely clear. It is assumed that the neurological complications observed after the introduction of droperidol are the result of complex disorders of cholinergic and adrenergic reactions in the reticular formation of the brainstem.

Treatment of neurological complications caused by droperidol is recommended to begin with the introduction of atropine. If there is no effect, agents stimulating adrenergic structures can be used. Cyclodol or its analogues - artan, romparkin, beta-blockers (obzidan, inderal), seduxen - give good results. Rapid relief of extrapyramidal disorders is observed after intravenous administration of caffeine. Barbiturates (hexenal, sodium thiopental) are effective in severe disorders.

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