RU2000114C1 - Method of diseases treatment associated with dopamine metabolism insufficiency - Google Patents

Abstract

The invention relates to medicine and can be used to treat diseases caused by dopamine deficiency. The method improves the effectiveness of treatment by taking into account the dynamics of metabolic processes and dopamine. For this purpose, the drug NACOM is prescribed with the control of the functioning of the sympathetic-adrenal system of the patient's body. Dosages of the drug have been proposed for patients of different age groups and a variety of diseases of dopamine etiology, such as Shoshina-Vasiliev syndrome, cerebral palsy, multisclerosis, myopathy, as well as paralysis in various spinal fractures.

Description

The invention relates to medicine, namely to methods for treating neurological diseases.

A known method of treating diseases of the neuromuscular system, based on the use of drugs (Vasiliev V.N. Diagnosis and treatment of patients with neuromuscular pathology, collection of Medicine today, vol. XV, M .: Knowledge, 1990. S. 30-31 )

However, the effectiveness of this method is insufficient.

Closest to the proposed method, the prototype analogue is a method for treating diseases associated with dopamine metabolism deficiency, including the oral administration of the drug NACOM when choosing the dosage of the latter, depending on the discrepancy between the patient’s adrenogram and the reference adrenogram of a healthy person during a functional test

(Diagnosis and treatment of motor disorders caused by dopamine metabolism disorder. Guidelines, M .. 1987).

The disadvantage of the prototype is the instability of the results arising from the neglect of the dynamics of treatment.

SUMMARY OF THE INVENTION that in the method of treating diseases associated with dopamine metabolism deficiency, including the oral administration of the drug NAKOM when choosing the dosage of the latter, depending on the discrepancy between the patient’s adrenogram and the reference adrenogram of a healthy person during a functional test, the dosage of the drug NAKOM is prescribed in the range from 10 to 300 mg and a single dose of NACOM in the treatment of Shoshina-Vasiliev syndrome is selected in the range of 10-140 mg, in the treatment of cerebral palsy - in the range zone 2070

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100 mg for patients under 10 years of age. in the range of 30-120 mg for patients aged 10 to 20 years and in the range of 35-300 mg for patients over 20 pet, in the treatment of multiple sclerosis in the range of 10-100 mg, in the treatment of myopathy in the range of 10-160 mg. In addition, in the treatment of paralysis due to a fracture of the spine, the revealed violation of dopamine metabolism is compensated by taking the drug in the range of 20-200 mg.

In this case, and after 1.5-2.0 months of treatment, the drug is canceled for 2-3 days. after which the odrenogram with a functional test is repeated and the dosage of the NACOM drug is adjusted depending on the dynamics of the obtained adrenograms.

With this embodiment of the method of treating diseases associated with dopamine metabolism deficiency, the treatment efficiency is improved due to the prescribed dosage system of the drug and taking into account the dynamics of the process.

Example 1, Treatment of myopathy. Case histories N 608. Sick Ch .. 8 years. Received January 20, 89. Diagnosis: Duchenne myopathy. Complaints: weakness in the arms and legs, which is why it cannot sit down, rise from the floor, it is very difficult to climb stairs. Medical history: at 3 years old, mother noted that it is difficult for a child to climb stairs. I went to the doctor, flatfoot and curvature of the spine were noted, I did not receive treatment. Neurological status: since 1985 it has been registered with a neurologist with a diagnosis of progressive muscle atrophy, pseudo-hypertrophic form of Duchenne. The early history is calm, beginning to walk at 1 year. Heredity is not exhausted. Consulted in a number of institutes. The diagnosis is confirmed. He was prescribed treatment courses according to the schemes. However, drug treatment has not been used. Recently, the condition has worsened, weakness has increased.

The control (when taking the patient) adrenogram showed the presence of acute paroxysms in the morning and in the afternoon, a pronounced decrease in DOPA excretion compared with the reference adrenogram of a healthy person.

An adrenogram during a functional test with 0.1 g of L-DOPA compared with a healthy person’s adrenogram (reference adrenogram) showed an increase in DA synthesis to 206, 271, 382, and 111 ng / min, respectively (each value in the given sequences corresponds to

the period of its receipt (9-12. 12-16. 16-22, 22-9 h) during the analysis of urine), and HA-do34.7; 20.5; 17.1; 6.7 ng / min. At the same time, warming of the limbs was observed and

feeling of lightness, especially in the hands, increased strength of the hands. the patient was able to rise much easier from the floor.

Since the synthesis of DA in this case is not active enough, a dose was prescribed

0.048 g of NACOM. In accordance with the control (during treatment) adrenogram, DA excretion was 521, 708, 906, and 400 ng / min, respectively. ON - 68.4; 32.5: 71: 20.8 ng / min, A - 9.0; 14.4; 9.5;

5 6.2 ng / min. A thorough examination confirmed the optimal dosage, since it showed a significant reduction in symptoms. A scheduled examination after a month and a half showed an improvement in the clinical condition of 0, an increase in weight by 1.2 kg. increased hand strength.

The drug cancellation for two days revealed (according to the control of an addressgram during this period) a decrease in the synthesis of DA and HA to 5 values: 72, 85, 208, 45-dL of DA and 4.3; 75; 11.7 and 2.4 ng / min for dl.

An adrenogram during a repeated functional test with 0.1 g of L-DOPA revealed an increase in the synthesis of DA to a value of 327, 453, 506, 214 ng / min and HA to 45.3 when compared with the reference adrenogram. 37.T; 23.5 and 11.1 ng / min.

Based on an analysis of the results and the general condition of the patient, the dose of NACOM was

5 reduced to 0.035 g. In this case (according to the control data for the treatment of an adrenogram), the synthesis of DA was 828, 718, 1120 and 398 ng / min. HA-45.4; 14.3; 18.8; 11.9 ng / min, A - 7.6; 10.6; 9.9; 7.5 ng / min.

0 A routine examination with a repeat of the cycle of conducting and comparing adrenograms after another two months of taking the prescribed dose showed significant clinical improvements, in addition, an increase in muscle mass by 3.4 kg, the appearance of muscle strength; in hands almost up to the norm, getting up from the floor and independent free movement.

Based on this, the patient is prescribed

0 further administration of a dose of 0.035 g of NAKOM with periodic (two months) inspection.

Example 2. Treatment of patients with Shoshina-Vasiliev syndrome. Medical history

5 N: 821. Sick X., 7 years old. Received September 21, 89. Diagnosis: cerebral palsy, pyramidal insufficiency, syndrome of increasing cerebral dysfunction with pyramidal insufficiency, asthenoneurotic reactions, complete immobility. does not hold his head.

The control (when taking the patient) adrenogram revealed a sharp decrease in the excretion of DA and DOPA against the background of increased A excretion as compared to the reference data of healthy people.

Comparison of the edrenogram with the introduction of a functional sample of 0.1 g of DOPA orally compared to the reference adrenogram showed blocking the synthesis of DA, whose amounts were 707, respectively. 241. 25 and 7 ng / min, NA - 58: 42: 16 ; 4.3 ng / min, and A - 38.2: 25.4: 7.8 and 4.9 ng / min.

The patient was prescribed a dose of 90 mg of HA-COM, once a day, in the morning, after eating, drink YODOY.

The control (during treatment) adrenogram showed the following:

YES: 300 216 180 91 ng / min

AT: 32 27 11 6.7 ng / min

A: 14.2 19.8 9.9 8.3 ng / min.

These data indicate the optimal dosage, since at a dose of 100 mg, a value of 707 ng / min is a reflection of the hypersynthesis of DA for these patients, which entails secondary spasticity.

At the prescribed dose of 90 g, NAKOM was ill on the first day, sat down on her own, and by the evening hyperkinesis of her arms and then legs had disappeared. On the second day the patient made an attempt to get up, and on the third - at first with support, and then began to walk on her own. I was able to run on the fifth day of NAKOM's intake. Analysis of the control (after 1.5 months of treatment) adrenogram showed that the excretion of DA was 269, 200, 192.78. Isolation of other catecholamines: HA and A also remained virtually unchanged (compared to the previous one).

At a scheduled examination after two months, drug withdrawal for two days after 1 day caused a sharp deterioration in the patient's condition with the return of the paralysis clinic: she lay down, stopped holding her head, and increasing cerebral dysfunction.

The analysis of the control (during this period) adrenergic gram showed its principal similarity with the initial adrenogram and the DA content was only 22-35 ng / min, namely: 29, 34, 16. 11 ng / min.

This indicates the need for replacement therapy.

The repeated adrenogram after administration of the functional test is similar to the corresponding first.

A dose of 90 mg of NACOM is optimal and after another two months of re-examination and beyond.

Adrenograms indicate the need for administration of exogenous DOPA and the absence of addiction to it.

A child in neurological status and psychophysical development corresponds to the norm corresponding to age. She successfully studies in a regular school, is engaged in physical education, in particular tennis.

Example 3. The treatment of multisclerosis. Case histories of Mg 42. Patient T., 38 years old, was admitted 04.11.88. Diagnosis: multisclerosis, progressive cerebro-spinal form, pronounced tetraparesis, locomotion, general immobility, impaired function of the pelvic organs. „

The control (when taking the patient) adrenogram showed a decrease in the excretion of adrenaline (A) and norepinephrine (HA) compared with the reference adrenogram of a healthy person. General asthenation of the system, sleep disturbance. Hypothalomic syndrome.

A functional test with 0.1 g of L-DOPA revealed dopamine hypersynthesis (DA), especially in the daytime and evening. In this case, a pronounced autonomic reaction was observed, significant warming of the legs (burning sensation), hands, urination, short-term vision improvement. The increase in the synthesis of DA was 9610, 14309, 11780, and 865 ng / min in comparison with the corresponding figures of the reference adrenogram of a healthy person. A comparison of these data made it possible to determine the dose of NAKOM's single dose of 0.02-0.03 g. Moreover, the administration of 25 mg of NAKOM resulted in an increase in the synthesis of DA to 670.820, 405, 71 ng / min. and the introduction of 30 mg of NAKOM dramatically increased the synthesis of DA to 1270, 2938, 1060, and 355 ng / min, respectively (according to the control adrenograms), which was accompanied by an increase in spasticity, tremor of the limbs and trunk, involuntary urination, an increase in pupils, etc., t. e. a sharp exacerbation of symptoms.

A dose of 20 mg was not enough to increase DA synthesis, which, according to the control adrenogram, was only 208, 117, 51, 22 ng / min. Thus, a dose of 0.025 seemed optimal for this case.

Two months later, the patient was admitted for re-examination. The cancellation of NACOM for two days caused a sharp deterioration in the clinic of the disease with exacerbation of vegetative disorders. In the control (during this period) adrenogram, a significant decrease in DA synthesis was revealed, which indicated the need for continued treatment.

Adrenergism with a functional breakdown of 0.1 g of L-DOP A, performed two days after the withdrawal of NACOM, revealed a hypersynthesis of DA, characteristic of patients with multisclerosis.

Drenogram of this draenogram with the reference (healthy person) showed a slight decrease in the synthesis of DA. Thus, the synthesis of DA was only 510.670, 308, and 16 ng / min. On this basis, the dose of NAKOMe was increased to 0.028 g. In this case, the excretion of DA (according to the control data) during treatment (adrenogram) was respectively: 748, 982, 417 and 129 ng / min, HA-38.7; 18.4; 14.6; 11.4 ng / min; A - 10.0; G.2; 9.1; 5.7 ng / min.

After two months, the patient underwent a repeated similar examination. It showed the following. The patient began to walk on her own, full normalization of pelvic organ activity, vision, and physical activity was observed, although atoxicity still appeared at times. She took a maintenance dose of NACOM 28 mg during the entire treatment period. The last adrenogram corresponded to: excretion of DA - 811, 758, 365. 100 ng / min, HA - 21.4; 16.2; 9.3; 4.2 ng / min, A 4.4; 5.7; 1.9; 7.4 ng / min, which is optimal for continued treatment of the patient with the above dose of NACOM.

Example 4. Treatment of patients with cerebral palsy. Case histories No. 116. Sick L., 36 years. Received in 1989. Diagnosis: cerebral palsy, double hepiplegi, severe choreiform hyperkinesis. He does not sit on his own, does not walk. Dysarthria, paresis in all limbs, more on the right. Tendon reflexes are difficult. Delay in mental development, oligophrenia in the stage of debility.

The control (upon receiving the patient) adrenograms showed general asthenia of the sympathoadrenal system with the effects of acute paroxysm in the morning and afternoon. Hypothalamic recordability.

Comparison of the adrenogram for a functional test with 0.1 g of NACOM oral administration with the reference adrenogram of a healthy person showed an increase in dopamine synthesis, characteristic of cerebral palsy, by 30 times and norepinephrine by 16 times, adrenaline by 9 times, the Patient was prescribed a dose of 50 mg of NAKOM one once a day. After 1.5 months, a second examination of the patient was carried out. During this time, significant clinical improvement was noted: the patient began to sit independently in a chair, stand up to 6-8 minutes, sit down from a position of one hundred, raise her hands well and clench them into fists. Spasticity of arms and legs disappears at times.

The patient, to determine the next dosage, was canceled by NACOM for two days.

But the control (during this period) adrenogram revealed an improvement in the synthesis of norepinephrine, the DOPA content was close to normal. The excretion of dopamine also improved, but by the evening the picture worsens - the synthesis of dopamine and adrenaline decreases, which indicates the need for continued treatment.

Comparison of a Zdrenogram at a Functional Test with Oral Administration

0.1 g of L-DOPA with a reference adrenogram showed a slightly improved dynamics of catecholamine synthesis, but still different from normal. The prescribed dose of NACOM is left unchanged - 50 mg once a day.

After two months, the patient was re-examined. The patient began to move independently, speech appeared, although she was still somewhat diarthritic. Paresis not detected. Hyperkines practically

do not show up. Sick began to draw and write. With the help of crutches, she can go out on her own. Helps around the house.

After the abolition of NACOM for two days

the control adrenogram showed an improvement in the independent synthesis of dopamine, but still lower than normal. Comparison of the adrenogram during a functional test with 0.1 g of L-DOPA with the reference adrenogram also revealed an increase in dopamine synthesis compared with the reference adrenogram. Based on this, treatment was continued, but the dosage was spaced apart by 0.030 g of NAKOM

in the morning and 0.020 g in the evening after a meal.

Example 5. Treatment of patients with paralysis in case of spinal fracture. Case history No. 607. Patient G., 31 years old, was admitted 2.06.90. Diagnosis: compression fracture of the lower spine in 1981, after which numbness of the feet appeared, which later spread to the knee joint, difficulty urinating and defecating 1 time in three days, movement in the street.

The control (upon admission of the patient) adrenogram revealed a decrease in the synthesis of DA and HA and an increase in A against the background of a decrease in the excretion of DOPA. Acute paroxysms in the morning, afternoon and evening.

A functional test with the oral administration of 0.1 g of L-DOPA caused a warming of the feet, a feeling at first of heaviness, and then lightness in the feet, and the higher

knee joint. The feeling of numbness decreased, he tried to move his toes.

Comparison of the adrenogram after a functional test with a reference adrenogram showed the possibility of increasing the synthesis of DA, which amounted to 1385, 829. 101, 66 ng / min. At the same time, the values of NA were noted - 79.5; 46.1; 33.8; 8.4 ng / min; and A 64.4; 4.7; 21.9; 14.7 ng / min;

Based on these data, the patient was prescribed a dose of 0.030 g of NAKOM at 9 o’clock (in the morning) and 0.025 g of NAKOM at 16 o’clock (in the evening) in order to maintain DA synthesis evenly throughout the day and prevent its fall in the evening.

On the control (during treatment) adrenogram, an increase in the synthesis of DA was noted and equal to its excretion in the evening.

A: 16 10.1 9.8 3.1

ON: 35 9.9 21.5 6.2

YES: 528 170 324 110

A routine examination after two months showed marked clinical improvements: lack of numbness in the legs, regulation of urination and everyday stool, easier movement in the wheel, attempts to move on crutches.

Comparison of the adrenogram during the test with 0.1 L-DOPA with the reference gave reason to increase the dose of NAKOM administered to 0.045 g at 9 hours and 0.035 g at 1 b hours.

Obtained on the control (during treatment) adrenogram, excretion showed:

A: 50.1 22.4 11.2 3.8

ON: 16.0 13.2 1508 6.6

YES: 721 204 458 82

which is optimal in the ratio YES: ON: A.

After the next two months, upon examination of the patient, further clinical improvement was noted - the patient can move on crutches independently

goes to the street and even to the store for shopping, completely serves in cooking, the functions of the pelvic organs are normalized.

The cancellation of NACOM for two days caused a deterioration in the condition, but not as pronounced as before. However, there is still a drop in the synthesis of DA. although not as much as before. Thus, the content of DA on the control adrenogram during the withdrawal of NACOM was 238. 94. 71 and 28 ng / min, which is already closer to the reference data of healthy people. The old dose was left ..

Claims (1)

SUMMARY OF THE INVENTION A method for treating diseases associated with dopamine metabolism deficiency, comprising the oral administration of NAKOM when choosing a dosage of the latter, depending on the difference between the patient’s adrenogram and the reference adrenogram of a healthy person during a functional test, characterized in that a single dose of NAKOM in the treatment of Shoshina-Vasiliev syndrome they are selected in the range of 10-140 mg, in the treatment of cerebral palsy in the range of 20-100 mg for patients under the age of 10 years. in the range of 30-120 mg - for patients aged 10 to 20 years and in the range of 35-300 mg - for patients older than 20 years, in the treatment of multiple sclerosis - in the range of 10-100 mg, in the treatment of myopathy - in the range of 10 -160 mg, in the treatment of paralysis caused by a fracture of the spine, in the range of 20-200 mg, while in the course of treatment after 1.5-2.0 months the drug is canceled for 2-3 days. after which the adrenogram with a functional breakdown is repeated and the dosage of NAKOM is adjusted depending on the dynamics of the obtained adrenograms.