UA131595U - METHOD OF TREATMENT OF PATIENTS WITH NON-HOSPITAL PNEUMONIA OF MEDIUM SEVERE - Google Patents

Abstract

The method of treatment of patients with community-acquired pneumonia of moderate course is the appointment of antibacterial and mucolytic therapy. Additionally, an amino acid preparation containing arginine hydrochloride and levocarnitine is administered intravenously daily in pharmacopoeially acceptable doses.

Description

The useful model belongs to the field of medicine, primarily to pulmonology, and can be used for the treatment of patients with non-hospital pneumonia of moderate course.

According to the classification, community-acquired pneumonia is an acute disease that occurred outside the hospital (outside the hospital or later than 4 weeks after discharge from it, or was diagnosed in the first 48 hours from the moment of hospitalization).

A known method of treatment of patients with non-hospital pneumonia of mild viral etiology (see Method of treatment of patients with non-hospital pneumonia of mild viral etiology: pat. 46943 Ukraine. Mo 0200907704; application 22.07.2009; publ. 11.01.2010, Bull. Mo 1 ( book 1). 2 c), according to which antibacterial, antiviral, mucolytic therapy and additionally the drug thiotriazoline are used for the treatment of patients with non-hospital pneumonia of viral etiology of mild course. However, this method does not take into account the role of metabolic therapy in the treatment of patients with community-acquired pneumonia.

As the closest analog, the "Unified protocol for providing medical care to adult patients with community-acquired pneumonia" was chosen (see Unified protocol for providing medical care to adult patients with community-acquired pneumonia. Community-acquired pneumonia in adults: etiology, pathogenesis, classification, diagnosis, antibacterial therapy and prevention /

Yu. I. Feshchenko and others. // Adapted evidence-based clinical guideline. K.: National Academy of Medical Sciences, 2016. P. 49-50), according to which antibacterial and mucolytic therapy is used for the treatment of adult patients with non-hospital pneumonia of medium severity. However, the protocol does not take into account the role of pathogenetic and energetic processes in the body during the inflammatory process in the lungs.

It is known that pneumonia, as a disease in itself, and antimicrobial drugs lead to the development of oxidant stress both in the lungs and in other organs. Therefore, the development of a local acute inflammatory infectious process in the lungs of patients is accompanied by the systemic activation of free radical processes in the body with the induction of oxidative stress and the process of lipid peroxidation and, as a result, a relative functional insufficiency of its antioxidant protection.

Considering this, it is advisable to additionally prescribe a pharmacological agent with an antioxidant type of action to the patient against the background of antibacterial and mucolytic therapy. These requirements

It corresponds to an amino acid preparation that contains the amino acids of arginine hydrochloride and levocarnitine, which became the basis for its use in the complex therapy of patients with non-hospital pneumonia of a moderate course.

The basis of a useful model is the task of improving the method of treatment of patients with non-hospital pneumonia of a moderate course, in which, against the background of antibacterial and mucolytic therapy, an amino acid preparation containing arginine hydrochloride and levocarnitine is additionally prescribed daily intravenously, to overcome the functional insufficiency of the body's antioxidant protection, which leads to a reduction in the duration of symptoms of intoxication, a reduction in the duration of treatment, a decrease in the severity of systemic activation of free radical processes in the body, induction of oxidative stress, the process of lipid peroxidation, and an improvement in the state of the body's antioxidant defenses.

The task is solved by the fact that in the method of treatment of patients with non-hospital pneumonia of medium severity, which consists in the appointment of antibacterial and mucolytic therapy, according to a useful model, an amino acid preparation containing arginine hydrochloride and levocarnitine is additionally prescribed daily intravenously in pharmacopoeially acceptable doses to overcome functional deficiency of antioxidant protection of the body.

The new medicinal product (Tivorel) of domestic production is the amino acids arginine hydrochloride and levocarnitine (registration number OA/15067/01/01 dated 04/06/2016, Mo 320, valid until 04/06/2021).

Arginine (α-amino-8-guanidinovaleric acid) is an amino acid that belongs to the class of conditionally essential amino acids and is an active and versatile cellular regulator of numerous vital functions of the body, showing important protective effects in the critical state of the body. It has an antihypoxic, membrane-stabilizing, cytoprotective, antioxidant, antiradical, detoxifying effect, manifests itself as an active regulator of intermediate metabolism and energy supply processes, plays a certain role in maintaining hormonal balance in the body. It is known that arginine increases the content of insulin, glucagon, somatotropic hormone and prolactin in the blood, participates in the synthesis of proline, polyamine, agmatine, is included in the processes of fibrinogenolysis, spermatogenesis, and exerts a membrane depolarizing effect.

Levocarnitine is a natural substance involved in energy metabolism, as well as the metabolism of ketone bodies. Only the I-isomer of carnitine is biologically active. It is necessary for transporting long-chain fatty acids into mitochondria for their further beta-oxidation and energy production. Fatty acids are used as an energy substrate by all tissues except the brain. In skeletal muscles and myocardium, fatty acids are the main substrate for obtaining energy.

In the literature available to us, there is no data on the use of an amino acid preparation containing arginine hydrochloride and levocarnitine in the treatment of patients with non-hospital pneumonia of a moderate course.

The method is carried out as follows.

Patients with community-acquired pneumonia of moderate severity are prescribed ceftriaxone 1.0 g twice a day intravenously for 7 days, azithromycin 500 mg once a day for

From day one, abrol 75 mg, 1 tablet once a day for 7 days, and additionally daily intravenous amino acid preparation, which contains arginine hydrochloride and levocarnitine, at a dose of 100 mg per day until overcoming the functional deficiency of the body's antioxidant protection.

All patients underwent venous blood tests to determine free radical activity and the level of important antioxidant enzymes (malondialdehyde (MDA), active products of thiobarbituric acid (TBK-AP), dinitrophenylhydrazone (A 370) and (A 430) (DNPH), ceruloplasmin (CP ), superoxide dismutase (SOD), catalase, factor of the antioxidant system (FAS)).

We give specific examples of the application of the method.

Example 1 (according to the analogous method).

Patient E., 21 years old, medical history No. 2632, admitted to the pulmonology department

of the National Military Medical Clinical Center "Main Military Clinical Hospital" due to non-hospital pneumonia of the lower lobe of the right lung of medium severity. From the accompanying pathology - acute bilateral sinusitis. Before the start of treatment, the patient underwent a biochemical and clinical examination of a venous blood sample, a general clinical analysis of capillary blood, and a microbiological examination of sputum.

The patient was prescribed combined therapy: ceftriaxone 1.0 g twice a day intravenously for 10 days, azithromycin 0.5 g once a day for 5 days, as well as ambroxol hydrochloride 75 mg per day for 7 days.

Initial data of a biochemical blood test:

MDA - 4.33; SOD - 2.18; Catalase - 2628; FAS - 1323; DNFH (AZ7O0) - 4.3; DNFH (L430) - 2.3; CPU - 543.

After 10 days of antimicrobial and mucolytic therapy, the biochemical indicators were at the following level:

MDA - 2.62; SOD - 6.00; Catalase - 1400; FAS - 3211; DNFH (AZ70O) - 4.7; DNFGA 430) - 2.6; CPU - 290.

Thus, as a result of the treatment, the following was achieved: improvement of the indicators of the pro-oxidant/antioxidant system; resorption of pneumonic infiltration; symptoms of intoxication lasted 7 days; antibiotic therapy lasted 10 days; adverse events - diarrhea, there was no need for treatment correction.

Example 2 (according to the claimed method).

Patient S., 20 years old, medical history No. 4556, admitted to the pulmonology department

of the National Military Medical Clinical Center "Main Military Clinical Hospital" for non-hospital pneumonia of the lower lobe of the left lung of medium severity. Without accompanying pathology. Before the start of treatment, the patient underwent a biochemical study of a venous blood sample, a general clinical analysis of capillary blood, and a microbiological study of sputum.

The patient was prescribed combined therapy: ceftriaxone 1.0 g twice a day intravenously for 7 days, azithromycin 0.5 g once a day for 3 days, ambroxol hydrochloride 75 mg per day for 7 days, and additionally daily intravenous amino acid drug, which contains arginine hydrochloride and levocarnitine, at a dose of 100 mg per day for 10 days. Initial data of a biochemical blood test:

MDA - 7.95; SOD - 3.60; Catalase - 2380; FAS - 1165; DNFH (AZ7O0) - 3.0; DNFH (L430) - 0.6; CPU - 293.

After 10 days of combined therapy, the biochemical indicators were at the following level:

MDA - 2.62; SOD - 4.60; Catalase - 2110; FAS - 3704; DNFH (AZ70O) - 1.6; DNFH (L430) - 0.6; CPU

Thus, as a result of the treatment, the following was achieved: normalization of indicators of the pro-oxidant/antioxidant system (FAS, catalase, CP); complete resolution of pneumonic infiltration; symptoms of intoxication lasted 4 days; antibiotic therapy lasted 7 days; There were no 5 adverse events.

Example C (according to the claimed method).

Patient S., 20 years old, medical history No. 4556, admitted to the pulmonology department

of the National Military Medical Clinical Center "Main Military Clinical Hospital" due to non-hospital pneumonia of the lower lobe of the right lung of medium severity. From the accompanying pathology - acute catarrhal bilateral sinusitis. Before the start of treatment, the patient underwent a biochemical study of a venous blood sample, a general clinical analysis of capillary blood, and a microbiological study of sputum.

The patient was prescribed combined therapy: ceftriaxone 1.0 g twice a day intravenously for 7 days, azithromycin 0.5 g once a day for 5 days, ambroxol hydrochloride 75 mg per day for 5 days, and additionally daily intravenous amino acid preparation, which contains arginine hydrochloride and levocarnitine, at a dose of 100 mg per day for 10 days.

Initial data based on the results of a biochemical blood test:

MDA - 7.95; SOD - 3.60; Catalase - 2380; FAS - 1165; DNFH (AZ70) - 3.0; DNFH (АЯ430) - 0.82;

CPU - 293.

After 10 days of combined therapy, the biochemical indicators were at the following level:

MDA - 2.62; SOD - 4.60; Catalase - 2110; FAS - 3704; DNFH (AZ70) - 1.62; DNFH (L430) - 0.6;

CPU - 329.

Thus, as a result of the treatment, the following was achieved: normalization of indicators of the pro-oxidant/antioxidant system (MDA, DNFC(L430), FAS, catalase); complete resolution of pneumonic infiltration; symptoms of intoxication lasted for a day; antibiotic therapy lasted 7 days; adverse events - short-term diarrhea, did not require correction of treatment.

The effectiveness of treatment of patients with non-hospital pneumonia of moderate course was studied in 20 patients who were divided into 2 groups. The first group includes 10 patients (50 95), who were treated according to the claimed method. The second group includes 10 patients (5,095) who received combined therapy (ceftriaxone, azithromycin, ambroxol hydrochloride) according to an analogous method.

The age-sex composition of the patients, the prevalence of the inflammatory process in the lungs, and the severity of the course of pneumonia were comparable in both groups.

Table 1 shows data on the dynamics of biochemical indicators during the treatment of patients of the 1st (according to the claimed method) and 2nd group (according to the analogous method). As can be seen from Table 1, the treatment of patients of the 1st group has significant statistically probable advantages in comparison with the usual treatment. In the initial state before the start of treatment in both groups of patients, absolute leukocytosis was determined in the peripheral blood (respectively, (7.95-1.4) and (8.7-41.1) G/l), which confirmed the presence of an acute inflammatory process in lung tissue, diagnosed based on the results of X-ray and clinical laboratory studies.

As a result, oxidative stress was detected in both groups of patients, evidenced by the accumulation of malondialdehyde in blood erythrocytes (respectively, (4.27 0.66) and (3.40:50.44) nmol/g against (2.51240.22 ) nmol/g in donors, and active products of thiobarbituric acid (respectively (3.62:20.62) and (3.73:20.36) nmol/g versus (2.50:20.25) nmol/g in In this connection, the functional tension in the enzyme antioxidant system of the patients' body was determined, which was indicated by a decrease in the activity of the antiradical enzyme superoxide dismutase (tissue) (respectively, (3.69x0.31) and (4.08:30.45) bw units/mg protein)min) vs. (3.29:0.20) bw. units.Hmg of protein)min) in donors.

The use of an amino acid preparation, which contains arginine hydrochloride and levocarnitine, in the combined therapy of patients with non-hospital pneumonia of a moderate course contributed to a more significant decrease, to the level of donors, in the content of the final product of lipid peroxidation - malondialdehyde in the erythrocytes of patients of the 1st group (up to (3 ,08:20.26) nmol/g) and active products of thiobarbituric acid (up to (2.56:-0.29) nmol/ml) in comparison with patients of the 2nd group (respectively, MDA up to (2.79: 20.33) nmol/g versus (2.5120.22) nmol/g in donors), TBK-AP to (3.62:20.55) nmol/ml). The use of this drug in the complex treatment of patients of the 1st group significantly reduced the functional tension in the antiradical chain of antioxidant protection of the body, compared to the combined antibacterial and mucolytic treatment of patients of the 2nd group. In particular, this was manifested by the normalization of the activity of the enzyme superoxide dismutase (tissue) by 65 95 - to (6.11-0.38) um. units/mg of protein) min vs. (3.69:0.31) bw. units//mg of protein) min in the initial state and (3.2920.20) wt. units//mg of protein) min in donors). While the use of antibacterial and mucolytic treatment in patients of the 2nd group led to the normalization of the activity of this enzyme by only 26 95 (to (5.15:0.37) human units/mg of protein) min) against (4.08: 0.45) um. units/mg hemoglobin) min in the initial state, and (3.29:20.20) bw. hmg of hemoglobin) min in donors).

Table 1

Indicators of the state of the pro-oxidant-antioxidant system in patients with non-hospital pneumonia of moderate course before and after treatment, M x t

Practically, the 1st group (p-10, the 2nd group (p-10

Indicators are healthy. After After n-10 Before treatment treatment Before treatment treatment 11111213 | 4 1 5 | 6

The number of leukocytes in the blood) 4.00-9.00 7.95-1.4 5.80.5 87-31, 7.050.5

G/l 2,510,22 4,270,66 3,0850,267 3,40-20,44 2,1920,337 det 379), 4,3340,29 4,0340,21 3,5740,24 | 4955086 | 3.7220.42" opt. units/ml house 430), opt) 2755021 | 20150227 1.99-40.29 | 2.4540.29 |) 2.2340.29

TBK-AP, nmol/ml | 2.5050.25 3.6250.42 2.5650.297 3.73520.367 3.62530.55

SOD activity) 3295020 | 36901 | battles | 4085045 | 51550.377 wholesale unit/ml Hb

Activity 17935101 20455182 19404125 | 227341967 | 21183182 catalase, min. mg NO

Ceruloplasmin content, 355117 40836 329529 416541 339538 mg/l

FAS, d. units 25002360 22115323 40982503 27095400 38085428

Notes: significant differences in indicators (re 0.05), 7 - between indicators (columns 2, 3, 4 and 2, 5, 6); i - between indicators (columns 4-6).

Comparative results of the effectiveness of treatment of patients with non-hospital pneumonia of moderate course using the claimed method and a similar method are shown in Table 2.

Table 2

Effectiveness of treatment of patients with non-hospital pneumonia of medium severity

Indicators 1st group (n-10) 2nd group (n-10) P

Duration of intoxication symptoms 2.6:0.2 4.5:50.3

Duration of therapy 6,90,3 9,10,8

Normalization of the state of antioxidant protection after treatment:

TBK-AP 2.56:20.29 3625055 | 0 4098503 38082428 6,110.38 5,1520.37

Therefore, the additional use of an amino acid preparation, which contains arginine hydrochloride and levocarnitine, in the complex therapy of patients with non-hospital pneumonia of medium severity (see Table 2) allows: to shorten the duration of the intoxication syndrome by an average of 2 days; reduce the duration of treatment by an average of 3.8 days; reduce the severity of systemic activation of free radical processes in the body, the induction of oxidative stress and the process of lipid peroxidation, and improve the state of the body's antioxidant protection from 26 95 to 65 Ob.

The proposed method can be recommended for wide implementation in the clinical practice of pulmonology and therapeutic departments of medical and preventive institutions

of Ukraine.

Claims (1)

USEFUL MODEL FORMULA The method of treatment of patients with non-hospital pneumonia of medium severity, which consists in the appointment of antibacterial and mucolytic therapy, which is distinguished by the fact that an amino acid preparation containing arginine hydrochloride and levocarnitine is additionally prescribed daily intravenously, in pharmacopoeially acceptable doses to overcome the functional deficiency of the body's antioxidant protection.