RU2197234C1 - Method of treatment of night enuresis of middle-severe and severe forms - Google Patents

Abstract

FIELD: medicine, urology, pediatrics. SUBSTANCE: invention relates to method of treatment of children suffering with enuresis. Method involves carrying out the complex therapy using glycine or taufon in the dose 60-70 mg/kg per 24 h. Administration is carried out in the dose 60-70 mg/kg per 24 h in 3-4 intakes before eating. Treatment duration is 4-7 weeks. Method provides high effect of treatment due to simultaneous effect on sympathetic and glycine- ergic receptors located in bladder sphincter. EFFECT: enhanced effectiveness of treatment. 2 ex

Description

 The invention relates to medicine, in particular to the treatment of urination disorders.

 Enuresis is an involuntary urination during a night or day sleep, which is based on the loss of a conditioned reflex to interoceptive impulses of the bladder, stretched by accumulated urine.

According to ICD-10, 2 forms of enuresis were distinguished:
1. Primary - when the baby urinates involuntarily from birth, i.e. the conditioned reflex is not worked out at all. Primary enuresis can be talked about in cases where involuntary urination, like in a newborn, continues as an unconditioned reflex throughout the duration of the disease. This form is found 3-4 times more often.

 2. Secondary, or psychogenic, enuresis - when a conditioned reflex that causes awakening has already been developed, but has been lost or sharply weakened for a number of reasons (mental trauma, severe infectious diseases, intoxications). Secondary enuresis occurs after a "dry" period.

Practitioners more often use a different (clinical) classification:
- Neurotic enuresis - the main reason for it is mental trauma. In some cases, it is accompanied by other signs of systemic neurosis (tics, stuttering). This form is characterized by a clear connection with a stressful situation. There is no focal symptomatology in the neurological status, however, vegetative-vascular disorders (hyperhidrosis of the hands and feet, lability of blood pressure and pulse, marbling of the skin) are expressed.

 - Residual-organic (neurosis-like) - it is based on residual-organic damage to the central nervous system (residual effects of intrauterine or birth damage to the brain or spinal cord, infection, trauma, intoxication). In neurological status in such patients there is focal microsymptomatics. Vegetative-vascular disorders join later in adolescence, when the level of neuroticization of the child increases. Often there are changes in the EEG of the organic type.

 The course of enuresis is individual for each patient. The severity of the disease is determined by the number of nights with cases of enuresis. In severe cases, involuntary urination is noted every night or every other night, often several times. In moderate severity, it is observed 1 time per week. The mild course of the disease is characterized by 1 urination per month.

 The fundamental question - what and when to consider the beginning of the disease - is not resolved at the present time. The age at which it is considered legitimate to diagnose enuresis ranges from 3 to 6 years.

 The solution to the issue of treatment of nocturnal enuresis is of great practical importance, because this disease is widespread, especially among boys. This pathology occurs in 12% of school-age children (Bryazgunov I. P. Ways of development of pediatrics. Collection of articles on the 70th anniversary of the Research Institute of Pediatrics RAMS. M., 1992, pp. 56-60).

 The treatment of patients with enuresis is a rather complicated task and requires a doctor to have knowledge on the anatomy of urination, clinical pharmacology and understanding of application points, the mechanisms of action of prescribed drugs. The choice of drugs available in the arsenal of doctors for the treatment of urination disorders is quite wide, however, it should be justified taking into account pathogenetic mechanisms. Only in this case can we count on the effectiveness of the therapy.

 A known method of treating nocturnal enuresis with tricyclic antidepressants (imipramine, amitriptyline). The disadvantage of this method is their insignificant anti-anuretic effect, probably associated with a weak anticholinergic as well as adrenergic effect, due to which the functional volume of the bladder can increase. It is known that they act at the level of the central nervous system, however, their central effect does not correlate with antianuretic activity. In other words, in doses prescribed to patients with enuresis, the effect of tricyclic antidepressants is not associated with an effect on the depth of sleep. Therapy is effective in 60% of patients, but after its completion in most cases a relapse of enuresis occurs (Jorgenses O.S. et al. Enuresis noctuma in children. Clin. Pharmacokinet. - 1980. - Vol.5. - P.386-393).

 A known method of treating nocturnal enuresis, including the use of driptan (Troshin V.M. et al. "Disorders of urination in children", guidelines, Nizhny Novgorod, 2000, 24 pp.). Driptan (oxybutynin hydrochloride) has a direct antispasmodic effect on the detrusor and eliminates the hypertonicity of the parasympathetic nervous system due to the peripheral M-cholinolytic effect. As a result, reflex bladder contractions are suppressed. Driptan relaxes the detrusor muscle in patients with unstable bladder function, thereby increasing its volume and reducing the incidence of involuntary urination. The disadvantage of this method is the lack of influence on the depth of sleep.

 The closest analogue in technical essence and the achieved therapeutic effect is a method of treatment with GABA derivatives (piracetam, picamilon) (Marushkin D.V. night incontinence in children. Abstract diss .... candidate of medical sciences, St. Petersburg, 1995, 20 from.).

 Chemically, Picamilon is considered as a combination of a GABA molecule and nicotinic acid. It improves blood circulation and the functional state of the brain, which is due to a decrease in vascular resistance and an improvement in brain tissue metabolism. Picamilon has antihypoxic, antioxidant and antiplatelet effects. Side effects from the central nervous system - dizziness and headache, from the gastrointestinal tract - nausea.

 Piracetam is a cyclic derivative of GABA, which increases the energy potential of neurons by stimulating adenylate cyclase activity and suppressing nucleotide phosphatase, which leads to an increase in ATP level. At the same time, redox processes are accelerated, glucose utilization increases. Piracetam also improves regional blood flow in ischemic structures and enhances RNA synthesis in neurons. Side effects from the central nervous system - irritability, sleep disorders, motor disinhibition, from the gastrointestinal tract - nausea, vomiting, diarrhea. The disadvantage of this method is the presence of side effects from the central nervous system, the short-term achievement of the clinical effect with enuresis, followed by the resumption of urinary incontinence.

 Inhibitory amino acids also include taufon and glycine, which were used for neurogenic bladder dysfunction in children (NDMP) and were not used to treat moderate and severe forms of enuresis (Artyukhina S.V., Marushkin D.V. Comparative efficacy of amino acids in children with NDMP, Abstracts of the 1st international conference "Clinical study of drugs", M., 2001, p. 15).

 NDMP is a form of disturbance in the reservoir and evacuation functions of the bladder that develops as a result of damage to the mechanisms of urination regulation at various levels: cortical, spinal, peripheral and manifests itself in daytime dysuric disorders of urination, the mechanism of occurrence of which differs from the mechanism of occurrence of enuresis.

 The reflex activity of the bladder is regulated by the cerebral cortex (paracentral lobule), as well as by subcortical structures (thalamus and hypothalamus). Control of the cortex over subcortical centers is established by 3-5 years. In this regard, most cases of urinary dysfunction occur in 6-7 years.

 As already indicated, there are two forms of enuresis - neurotic and neurosis-like. Moreover, the first of them revealed post-traumatic stress disorder in 43% of children suffering from bedwetting. Among the events causing it, death and illnesses of close relatives (41.8%), quarrels between parents and other children (18.2%), and the death of beloved pets (16.4%) are most often observed (Bryazgunov I.P. and other Psychological characteristics of children suffering from nocturnal enuresis (Ross. Ped. Zhurnal, 2000, 1, pp. 29-31).

 In psychological tests in children with enuresis, most patients deny any difficulties, overestimate their capabilities, differ in egocentrism, contacts with them are difficult. All of them are anxious, tense, irritable. Half of them have an epileptoid type of character accentuation.

 The objective of the invention is to increase the effectiveness of therapy for bedwetting in any clinical form due to the inclusion in the treatment complex according to the new scheme of mediator amino acids taufon and glycine with nootropic and psychogenic effects.

 The technical result of the proposed method is a simultaneous effect aimed at regulating the activity of the sympathetic nervous system and the regulation of glycerinergic receptors located directly in the sphincter of the bladder.

The technical result is achieved through the use of drugs of the nootropic series, which also have a psychotropic effect in the mode we developed (taufon or glycine). These drugs have an α ₁ -adrenergic blocking effect, which leads to normalization of intracranial pressure in the acute period of stress, and also affect glycineergic receptors directly in the sphincter of the bladder. Glycine and taufon protect neurons from the excessive effects of catecholamines during stress. The tranquilizing effect in this case is manifested in a decrease in irritability, aggressiveness, and conflict.

 On EEG, these drugs increase activity simultaneously in the frontal and occipital regions of the brain, normalize the α-rhythm; which leads to increased ability to concentrate and intellectual-mnestic functions. The introduction of glycine and taufon helps to weaken the paroxysmal activity and normalize the α-rhythm.

 Thus, the use of taufon and glycine with their multifunctional mechanism of action allows you to influence the psychotropic mechanisms of enuresis.

 We have conducted studies on different groups of patients with different forms of urination disorders in various dosages, depending on the severity of the disease. Children received taufon at a dose of 60 mg / kg per day in 3-4 doses orally before meals (with moderate form of enuresis) and 70 mg / kg per day in 3-4 doses orally before meals (in severe forms of enuresis); glycine - 60 mg / kg per day in 3-4 doses orally before meals (with moderate form of enuresis) and 70 mg / kg per day in 3-4 doses orally before meals (in severe forms of enuresis). The course of treatment for enuresis is 6-7 weeks.

 The diagnosis of neurotic and neurosis-like enuresis was established by questioning, EEG, REG, spontaneous urination rhythm, ultrasound, uroflowmetry, retrograde cystometry. If necessary, all patients are consulted by a neurologist, psychologist, urologist and nephrologist.

 In all patients with enuresis, the severity of the disease is established and, in accordance with this, a certain exposure regimen.

 This is achieved by the fact that in a new method for the treatment of enuresis, which includes complex therapy using nootropic drugs, glycine or taufon are used as the latter, both at a dose of 60 mg / kg per day, taken 3-4 times orally before meals (with a moderate form of enuresis) and 70 mg / kg per day in 3-4 doses orally before meals (with severe enuresis) for 6-7 weeks.

 The method is as follows.

 In a complex therapy, a patient with enuresis of a neurotic and neurosis-like form is prescribed sedatives, vitamins and FTL, glycine or taufon, both at a dose of 60 mg / kg per day, taken 3-4 times orally before meals (with a moderate form of nocturnal enuresis) and 70 mg / kg per day in 3-4 doses orally before meals (with severe form of nocturnal enuresis) for 6-7 weeks.

 Example 1. Patient Zh.G., 9 years old, complained of nocturnal enuresis once a week. The child is observed by a neurologist with signs of systemic neurosis in the form of stuttering. She suffers from enuresis for the past 8 months after suffering a mental trauma (divorce from her parents). According to the daily rhythm of spontaneous urination, their frequency is 9, and a hyperreflex bladder on the uroflowgram. On the EEG, there are no foci of paroxysmal activity.

 Clinical diagnosis: neurotic enuresis, moderate course.

 The child was prescribed taufon at a dose of 60 mg / kg per day in 4 divided doses orally before meals for 6.5 weeks. After 4 weeks - a gradual decrease in episodes of nocturnal enuresis.

 Example 2. Patient A.S., 10 years old, complained of nocturnal enuresis every night from birth. According to the daily rhythm of spontaneous urination, their frequency is 9, and a hyperreflex bladder on the uroflowgram. Ultrasound of the urinary system - thickening of the bladder wall, roughness of the inner contour and the impossibility of filling it. It was observed by a neurologist with minimal cerebral dysfunction syndrome. On EEG - paroxysmal activity.

 Clinical diagnosis: neurosis-like enuresis, severe course.

 The child was prescribed glycine at a dose of 70 mg / kg per day in 4 divided doses orally before meals for 7 weeks. After 5 weeks - a gradual decrease in episodes of nocturnal enuresis. On the EEG - a decrease in paroxysmal activity, normalization of ultrasound.

 Thus, this method is easy to use, therapeutically effective and can be implemented in wide medical practice both in inpatient and outpatient settings.

 The use of mediator amino acids in children with nootropic activity of taufon or glycine in the complex therapy of enuresis can reduce the number of relapses of the disease by 1.5-2 times compared with the known prototypes due to their pronounced anticonvulsant, vascular and sedative effects. Side effects in the treatment of taufon and glycine were not observed.

Claims (1)

 A method for the treatment of moderate and severe forms of enuresis in children, including complex therapy using mediator amino acids with nootropic activity, characterized in that taufon or glycine is used as the latter at a dose of 60-70 mg / kg per day, 3-4 times a day, orally, before meals, for 4-7 weeks, and the dose and duration increase depending on the severity of enuresis.