Aspartic acid. Ornithine - instructions for use, doses, side effects, contraindications, price, where to buy - geotar medicinal reference book Properties and functions

13.05.2020

21.022 (Preparation for parenteral nutrition - solution of amino acids and electrolytes)
11.093 (Hypoammonaemic drug)
21.026 (Preparation for parenteral nutrition (amino acid solution) used for liver failure)
21.021 (Preparation for parenteral nutrition - amino acid solution)
21.025 (Preparation for parenteral nutrition - solution of amino acids, electrolytes, vitamins)

Hypoammonaemic remedy. Reduces elevated levels of ammonia in the body, in particular in liver diseases. The action is associated with the participation of Krebs in the ornithine cycle of urea formation (the formation of urea from ammonia). Promotes the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.

Ornithine aspartate in the body dissociates into the amino acids ornithine and aspartate, which are absorbed in the small intestine by active transport through the intestinal epithelium. It is excreted in the urine.

For oral administration - 3-6 g 3 times / day after meals. W / m - 2-6 g / day; in / in a jet 2-10 g / day; the frequency of administration is 1-2 times / day. IV drip 10-50 g / day. The duration of infusion, frequency and duration of treatment are determined individually.

During pregnancy, use is possible only under the strict supervision of a physician.

If necessary, use during lactation should decide on the termination of breastfeeding.

Seldom: skin manifestations.

In some cases: nausea, vomiting.

Acute and chronic liver disease accompanied by hyperammonemia. Hepatic encephalopathy.

For the dynamic study of the function of the pituitary gland.

As a corrective supplement for parenteral nutrition drugs in patients with protein deficiency.

Severe renal dysfunction (serum creatinine content more than 3 mg / 100 ml).

If nausea or vomiting occurs, the rate of administration should be optimized.

When using a certain dosage form of ornithine, compliance with specific indications should be observed.

Influence on the ability to drive vehicles and use mechanisms

Ornithine can cause disturbances in concentration and psychomotor speed.

INFESOL ® 100 (INFESOL ® 100) solution for inf.: Fl.

0 ml or 500 ml 10 pcs. in set with holder
... HEPA-MERZ (HEPA-MERZ) conc. d / prigot. solution for inf. 5 g / 10 ml: amp. 10 pieces.
... GEPA-MERZ (HEPA-MERZ) ◊ granules for prigot. solution for oral administration 3 g / 5 g: sachets 10 or 30 pcs.
... ORNICETIL (ORNICETIL) powder for prigot. solution for inf. 5 g: fl. 1 PC.
... AMINOPLASMAL E 15 (AMINOPLASMAL E 5) solution for information: bottles of 500 ml, 10 pcs.
... AMINOPLASMAL E 5 (AMINOPLASMAL E 5) solution for information: bottles of 500 ml, 10 pcs.
... AMINOSOL (AMINOSOL) solution for information: fl. 500 ml
... AMINOPLASMAL E 10 (AMINOPLASMAL E 10) solution for inf.: 500 ml bottles 10 pcs.
... AMINOPLASMAL HEPA (AMINOPLASMAL HEPA) solution for inf. 10%: fl. or 500 ml bottle

vmede.org

Pharmacological properties

pharmacodynamics. In vivo L-ornithine-L-aspartate exposure is mediated by amino acids, ornithine and aspartate through two key methods of ammonia detoxification: urea synthesis and glutamine synthesis.
Synthesis of urea occurs in peri-portal hepatocytes, where ornithine aspartate acts as an activator of two enzymes: ornithine carbamoyl transferase and carbamoyl phosphate synthetase, as well as a substrate for urea synthesis.
Glutamine synthesis occurs in the peri-venous hepatocytes.

Particularly under pathological conditions, aspartate and dicarboxylate, including the metabolic products of ornithine aspartate, are absorbed into cells and used there to bind ammonia in the form of glutamine.
Glutamate is an amino acid that binds ammonia in both physiological and pathological conditions. The resulting amino acid glutamine is not only a non-toxic form for the elimination of ammonia, but also activates an important urea cycle (intracellular glutamine metabolism).
Under physiological conditions, ornithine and aspartate do not limit the synthesis of urea.
Experimental studies in animals have shown that the ammonia-lowering property of L-ornithine-L-aspartate is caused by the accelerated synthesis of glutamine. Selected clinical studies have found this improvement for branched chain amino acids / aromatic amino acids.
Pharmacokinetics. L-Ornithine-L-Aspartate is rapidly absorbed and broken down into ornithine and aspartate. T ½ of ornithine and aspartate is short - 0.3-0.4 hours. A small part of aspartate is excreted in the urine unchanged.

Composition and form of release

gran. 3 g / 5 g 5 g bag, No. 30, No. 50, No. 100

Other ingredients: water for injection.

No. UA / 0039/01/01 from 23.12.2013 to 23.12.2018

Indications

treatment of patients with concomitant diseases and complications caused by impaired liver detoxification function (in particular with liver cirrhosis) with symptoms of latent or severe hepatic encephalopathy, especially impaired consciousness (precoma, coma).

Application

inside. Dissolve the contents of 1-2 packages of Hepa-Merz in a large amount of liquid (in particular a glass of water or juice) and take it during or after meals up to 3 times a day.
I / O. The dosage is often up to 4 ampoules (40 ml) per day. In case of precoma or coma, inject up to 8 ampoules (80 ml) within 24 hours, depending on the severity of the condition. Before the introduction, add the contents of the ampoule to 500 ml of the solution, but do not dissolve more than 6 ampoules in 500 ml of the infusion solution.
The highest rate of administration of L-ornithine-L-aspartate is 5 g / h (which corresponds to the contents of 1 ampoule).
The period of treatment with the drug Hepa-Merz is determined by the doctor depending on the clinical condition of the patient.

Contraindications

hypersensitivity to L-ornithine-L-aspartate or any drug component; severe renal failure (plasma creatinine level\u003e 3 mg / 100 ml).

Side effects

from the digestive tract: rarely (\u003e 1/10 000,<1/1000) — тошнота, рвота, боль в желудке, метеоризм, диарея.
From the musculoskeletal system: rarely (<1/10 000) — боль в суставах.
These adverse reactions are often short-lived and do not require discontinuation of the medication. They disappear when the dosage or rate of drug administration is reduced.
Allergic reactions are possible.

special instructions

with intravenous administration of Hepa-Merz in high doses, the level of urea in blood plasma and urine should be monitored. In case of severe liver dysfunction, in accordance with the patient's condition, it is necessary to reduce the rate of administration of the infusion solution in order to prevent nausea or vomiting. Hepa-Merz, concentrate for infusion solution, should not be injected into an artery.
Hepa-Merz granulate contains 1.13 g of fructose in each package (equivalent to 0.11 XE), which should be taken into account by patients with diabetes mellitus. Do not use in patients with congenital fructose intolerance. Long-term use can be harmful to teeth (caries development).
Use during pregnancy or lactation.

There are no data regarding the use of the Hepa-Merz drug during pregnancy. Animal studies using L-ornithine-L-aspartate to study its toxic effects on reproductive function have not been conducted. Therefore, the use of the drug during pregnancy should be avoided.
But if treatment with Hepa-Merz during pregnancy is necessary for health reasons, the doctor should carefully weigh the ratio of the possible risk to the fetus / child and the expected benefit for the pregnant / mother.
It is not known whether L-ornithine-L-aspartate passes into breast milk. You should avoid using the medication during breastfeeding.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms... Due to the disease, the ability to drive vehicles or work with other mechanisms may be impaired during treatment with L-ornithine-L-aspartate, therefore, this type of activity should be avoided during the treatment period.
Children... The experience of use in children is limited, therefore the drug should not be used in pediatric practice.

Interactions

no studies have been conducted, no data available.
Incompatibility... Since studies for incompatibility have not been conducted, the drug with IV administration should not be mixed with other medicinal drugs. Hepa-Merz can be mixed with conventional infusion solutions.

Overdose

no signs of intoxication due to an overdose of L-ornithine-L-aspartate were observed. Increased side effects are likely. In case of overdose, symptomatic treatment is offered.

Storage conditions

at a temperature not exceeding 25 ° C.

medprep.info

Clinical and pharmacological group:

Hypoammonaemic drug.

pharmachologic effect

Hypoammonaemic drug. Reduces elevated levels of ammonia in the body, particularly in liver diseases. The action of the drug is associated with its participation in the ornithine cycle of Krebs urea formation (the formation of urea from ammonia).

Promotes the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.

Pharmacokinetics

Ornithine aspartate dissociates into its constituent components - the amino acids ornithine and aspartate, which are absorbed in the small intestine by active transport through the intestinal epithelium. It is excreted in the urine through the urea cycle.

Indications for the use of the drug GEPA-MERC

acute and chronic liver diseases, accompanied by hyperammonemia;
hepatic encephalopathy (latent or severe), incl. as part of complex therapy for impaired consciousness (precoma and coma)
as a corrective supplement to parenteral nutrition drugs in patients with protein deficiency.

Dosage regimen

Sachets:

The drug is administered orally, 1 sachet of granules dissolved in 200 ml of liquid, 2-3 times a day, after meals.

Intravenously injected up to 40 ml (4 ampoules) per day, dissolving the contents of the ampoules in 500 ml of infusion solution.

In hepatic encephalopathy (depending on the severity of the condition), up to 80 ml (8 ampoules) per day are injected intravenously.

The duration of infusion, frequency and duration of treatment are determined individually. The maximum infusion rate is 5 g / h.

Side effect

From the digestive system: in some cases - nausea, vomiting.

Others: allergic reactions.

Contraindications to the use of the drug GEPA-MERC

severe renal failure (serum creatinine\u003e 3 mg / 100 ml);
lactation period (breastfeeding);
hypersensitivity to drug components.

The drug should be prescribed with caution during pregnancy.

Application of the drug GEPA-MERC during pregnancy and breastfeeding

The drug should be used with caution during pregnancy.

The drug is contraindicated for use during breastfeeding.

Application for violations of liver function

The drug is used according to indications.

Application for impaired renal function

The drug is contraindicated in severe renal failure (creatinine index 3 mg / 100 ml).

Influence on the ability to drive vehicles and use mechanisms

In hepatic encephalopathy, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: increased severity of side effects.

Treatment: gastric lavage, intake of activated carbon, symptomatic therapy is performed.

Drug interactions

The drug interaction of the drug Hepa-Merz is not described.

Terms of dispensing from pharmacies

The drug is approved for use as a means of OTC.

analogs-drugs.rf

Name:

Ornitox (Ornitox)

Pharmachologic effect:

Ornitox is a hepatoprotective drug that also has a detoxifying and hypoazotemic effect. Ornitox promotes the utilization of ammonia groups in the synthesis of urea and a decrease in the level of urea in the plasma, leads to the normalization of the pH balance of the body, and normalizes the synthesis of growth hormone and insulin. Ornitox also improves protein metabolism and has some anabolic effects. Thanks to aspartate, Ornitox stimulates inactive and damaged hepatocytes, improves regenerative processes, as well as the synthesis of glutamine in muscles and perivenous hepatocytes. The drug normalizes energy processes in the affected liver tissues.

Due to the hypoazotemic action, Ornitox prevents the development of the neurotoxic effect of ammonia in patients with insufficient liver function.

After oral administration, the active component dissociates to form ornithine and aspartate, which are well absorbed in the small intestine. Active components are metabolized in the liver. Excreted stepwise, mainly in the form of metabolites by the kidneys.

Indications for use:

Ornitox is intended for the treatment of patients suffering from various forms of liver disease, accompanied by an increase in plasma ammonia concentrations.

Including Ornitoks is used in acute and chronic forms of fatty hepatosis, hepatitis and cirrhosis of the liver with symptoms of liver failure.

The drug in the form of a solution for injection can also be used to treat patients with cirrhosis of the liver, accompanied by hepatic failure, including in a coma and precoma.

Application method:

Ornitox granules for oral solution:

The drug is intended for the preparation of a solution for oral administration. Before using Ornitox preparation, dissolve the contents of the sachet in a glass of drinking water. It is also allowed to dissolve the powder in juice or warm tea. It is advisable to take Ornitox during meals. The duration of therapy and the dose of Ornitox is determined by the doctor, taking into account the patient's condition and concomitant therapy.

Children over 8 years old and adults, as a rule, are recommended to prescribe 1 sachet of Ornitox three times a day.

In severe forms of diseases, it is allowed to increase the daily dose of ornithine aspartate to 18 g (6 sachets of Ornitox). The daily dose should be divided into 3 doses.

Ornitox injection solution:

The drug is intended for parenteral (intramuscular or intravenous) administration. Intravenously, the drug is allowed to be administered as a jet slowly or drip slowly. To prepare an intravenous infusion, the required amount of Ornitox is dissolved in 500-1000 ml of 0.9% sodium chloride solution. The resulting solution for infusion is recommended to be administered at a rate of 4-8 drops per minute. The duration of therapy and the dose of Ornitox is determined by the doctor.

The average recommended dose for patients with hepatic insufficiency, including those in coma and precoma, is 8 ampoules of Ornitox per day. Do not inject more than 1 ampoule of Ornitox per hour.

In 500 ml of isotonic sodium chloride solution, no more than 5 ampoules of Ornitox can be dissolved.

Ornitox preparation can also be dissolved in 5% or 10% glucose solution or water for injection.

The duration of therapy is determined by the doctor. If necessary, a second course of therapy with Ornitox is carried out 2-3 months after the end of the previous course.

Adverse events:

Ornithox is usually well tolerated by patients. It has been reported on isolated cases of the development of adverse effects due to ornithine aspartate, including:

From the digestive system: flatulence, vomiting, nausea, stool disorders.

Allergic reactions: urticaria, allergic rhinitis, lacrimation, redness of the skin.

Also, in some cases, the development of myalgia was noted (this effect does not require specific therapy and goes away on its own).

In addition, when taking Ornitox, it is possible to develop an increase in the level of uric acid in the plasma, but this effect was observed only with the use of high therapeutic doses of ornithine aspartate.

Contraindications:

Ornitox is not indicated for patients with known hypersensitivity to the ingredients of the powder.

Ornitox is not used to treat patients with severe renal failure.

Ornitox is not prescribed in pediatric practice for children under 8 years old.

Patients with diabetes mellitus should take Ornitox granules with caution (it should be borne in mind that 1 sachet contains 1.78 g of sucrose (0.18 bread units)).

During pregnancy:

During pregnancy, Ornitox can be prescribed only if the potential risks to the fetus are less than the expected benefit to the mother.

During lactation, it is advisable to cancel breastfeeding before starting therapy with Ornitox.

Interaction with other medicinal products:

Ornitox injection solution should not be mixed with other parenteral drugs in the same syringe or drip system (excluding parenteral solutions recommended for the preparation of Ornitox infusion solution).

Overdose:

When using overestimated doses of ornithine aspartate, it is possible to develop an increase in the concentration of urea in blood plasma and urine.

There is no specific antidote. In case of an overdose, it is recommended to flush the stomach and prescribe enterosorbents. The patient's condition should be monitored and, if necessary, symptomatic therapy should be carried out.

Release form of the drug:

Granules for preparation of Ornitox solution for oral administration, 5 g in sachets, 10 sachets are inserted in a cardboard box.

Ornitox solution for parenteral use, 10 ml in ampoules, in a cardboard box 5 ampoules, enclosed in a polymer cell package.

Storage conditions:

Ornitox, regardless of the form of release, can be used for 2 years after release, provided that it is stored in its original packaging at a temperature of 15 to 25 ° C.

Composition:

5 g of granules for preparation of Ornitox oral solution contain:

L-ornithine-L-aspartate - 3 g,

Additional ingredients including sucrose and aspartame.

1 ml of solution for parenteral administration Ornitox contains:

L-ornithine-L-aspartate - 0.5 g,

Additional ingredients.

www.provizor-online.ru

In a clinical multicenter comparative study, the efficacy and safety of L-ornithine-L-aspartate (Hepa-Merz), which belongs to the group of hepatoprotective agents affecting metabolic disorders, was studied. The study included 232 patients with acute pancreatitis. It has been established that L-ornithine-L-aspartate (Hepa-Merz) reduces the severity of neurological disorders in pancreatic necrosis. The drug has pronounced hepatoprotective properties.

According to the literature and our observations, the incidence of acute pancreatitis is steadily increasing, in frequency it ranks third after acute appendicitis and cholecystitis. Treatment of acute pancreatitis, especially its destructive forms, is still a difficult problem in surgery due to the high mortality rate - from 25 to 80%.

The liver turns out to be the first target organ, which receives the main blow of pancreatogenic toxemia in the form of a massive inflow of activated pancreatic and lysosomal enzymes, biologically active substances, toxic decomposition products of the pancreatic parenchyma during necrobiosis and activation of the kallikrein-kinin system into the blood flowing through the portal vein.

As a result of the action of damaging factors in the liver parenchyma, deep microcirculatory disorders develop, in hepatocytes, mitochondrial cell death factors are activated and apoptosis of hepatic cells is induced. Decompensation of the internal mechanisms of detoxification aggravates the course of acute pancreatitis due to the accumulation in the body of many toxic substances and metabolites that are concentrated in the blood and create a secondary hepatotropic effect.

Liver failure is one of the most serious complications of acute pancreatitis. It often determines the course of the disease and its outcome. It is known from the literature that in 20.6% of patients with edematous pancreatitis and in 78.7% of patients with a destructive process in the pancreas, various liver functions are impaired, which significantly worsens the results of treatment and is the direct cause of death in 72% of cases.

In view of this, the need for adequate prevention and treatment of liver failure in each patient with acute pancreatitis using the entire range of conservative measures is obvious. Today, one of the priority areas of complex therapy for liver failure in acute pancreatitis is the inclusion of hepatoprotectors in treatment, in particular L-ornithine-L-aspartate (Hepa-Merz).

The drug has existed in the pharmaceutical market for several years, it has proven itself well and is successfully used in therapeutic, neurological, toxicological practice for acute and chronic liver diseases. The drug stimulates the detoxification function of the liver, regulates metabolism in hepatocytes, and has a pronounced antioxidant effect.

In the period from November 2009 to March 2010, a multicenter non-randomized clinical trial was conducted to study the effectiveness of the hepatoprotector L-ornithine-L-aspartate (Hepa-Merz) in the complex treatment of patients with acute pancreatitis. The study included 232 patients (150 (64.7%) men and 82 (35.3%) women) with acute pancreatitis, confirmed by clinical, laboratory and instrumental methods. The age of the patients varied from 17 to 86 years, with an average of 46.7 (34; 58) years. In 156 (67.2%) patients, edematous pancreatitis was diagnosed, in 76 (32.8%) - destructive forms: in 21 (9.1%) - hemorrhagic pancreatic necrosis, in 13 (5.6%) - fatty, in 41 (17.7%) - mixed, 1 (0.4%) - post-traumatic.

All patients received basic complex conservative therapy (blockade of exocrine pancreatic function, infusion-detoxification, antibacterial agents).

L-ornithine-L-aspartate (Hepa-Merz) in a complex of therapeutic measures was used in 182 (78.4%) patients (main group); 50 (21.6%) patients made up the control group, in which this drug was not used. The drug was prescribed from the 1st day of the patient's inclusion in the study according to the developed scheme: 10 g (2 ampoules) intravenously with an injection rate of no more than 5 g / h per 400 ml of saline sodium chloride solution for 5 days, from the 6th day - orally (preparation in the form of granules, 1 sachet, 3 g, 3 times a day for 10 days).

The severity of the patient's condition was assessed using the SAPS II scale of the severity of the physiological condition. Depending on the total SAPS II score in both groups, 2 subgroups of patients were identified: with a total score<30 и >30.

SAPS II severity subgroup<30 баллов составили 112 (48,3%) пациентов, в том числе 97 (87%) — из основной группы: мужчин — 74 (76,3%), женщин — 23 (23,7%), средний возраст — 40,9 (33; 45) года, тяжесть состояния — 20,4±5,2 балла; из контрольной группы было 15 (13%) пациентов: мужчин — 11 (73,3%), женщин — 4 (26,7%), средний возраст — 43,3 (28,5; 53) года, тяжесть состояния — 25±6 баллов.

The subgroup with a total SAPS II score\u003e 30 consisted of 120 (51.7%) patients, including 85 (71%) from the main group: men - 56 (65.9%), women - 29 (34.1%) ), the average age was 58.2 (45; 66.7) years, the severity of the condition was 36.3 + 5.6 points; from the control group there were 35 (29%) patients: men - 17 (48.5%), women - 18 (51.4%), average age - 55.4 (51; 63.5) years, severity of the condition - 39 , 3 ± 5.9 points.

The study identified 4 basic points: 1st, 3rd, 5th and 15th days. To assess the effectiveness of treatment, the severity of the patient's condition was determined in dynamics according to the SOFA Integral Scale; investigated laboratory parameters: the concentration of bilirubin, the level of protein, urea and creatinine, cytolysis enzymes - alanine aminotransferase (ALT), aspartate aminotransferase (ACT). The degree of impairment of cognitive functions and the rate of their recovery during treatment were assessed using the number link test (NNT).

The mathematical processing of the factual material was carried out using the basic methods of biomedical statistics using the Microsoft Office Excel 2003 and BIOSTAT software package. When describing the group characteristics, the standard deviation of the mean value of the trait was calculated for its parametric distribution and the interquartile range for nonparametric distribution. The significance of differences between the 2 parameters was assessed using the Mann-Withney and x2 tests. Differences were considered statistically significant at p \u003d 0.05.

In patients of the main group with the severity of the condition according to SAPS II<30 баллов применение L-орнитин-L-аспартата (Гепа-Мерц) в комплексе лечения привело к более быстрому восстановлению нервно-психической сферы, что оценивалось в ТСЧ. При поступлении у пациентов обеих групп длительность счета была выше нормы (норма — не более 40 с) на 57,4% в основной группе и на 55,1% — в контрольной: соответственно 94 с (80; 98) и 89,5 с (58,5; 116). На фоне терапии отмечалась положительная динамика в обеих группах. На 3-й сутки длительность счета составила 74 с (68; 78) в основной группе и 82,3 с (52,5; 100,5) — в группе сравнения, что превышало норму на 45,9 и 51,2% соответственно (р=0,457, Mann-Withney). На 5-е сутки время в ТСТ составило 50 с (48; 54) в основной группе и 72,9 с (44; 92) — в контрольной, что превышало норму на 20 и 45,2% соответственно (р=0,256, Mann-Withney). Статистически достоверные изменения отмечены на 15-е сутки исследования: в основной группе — 41 с (35; 49), что превышало нормальное значение на 2,4%, а в контрольной — 61 с (41; 76) (больше нормы на 34,4%; р=0,038, Mann-Withney) — рисунок «Динамика состояния нервно-психической сферы у больных с суммарным баллом по SAPS II <30».

Dynamics of the state of the neuropsychic sphere in patients with a total score according to SAPS II<30

In patients with SAPS II severity\u003e 30 points, the study revealed a positive effect of L-ornithine-L-aspartate (Hepa-Merz) on the dynamics of biochemical parameters of blood serum; the most significant changes concerned the indicators of cytolytic syndrome (ALT, ACT) and the rate of recovery of neuropsychic functions.

Dynamic observation of the severity of the patient's condition, assessed by the SOFA scale, also showed a more rapid normalization in the main group (Figure "Dynamics of the severity of the condition in patients with a total SAPS II score\u003e 30"). The severity of the condition of patients in the main and control groups on the 1st day of the study on the SOFA scale was 4 (3; 6.7) and 4.2 (2; 7) points, respectively, on the 3rd day of the study - 2 (1; 3 , 7) and 2.9 (1; 4) points (p \u003d 0.456, Mann-Withney), on the 5th day - 1 (0; 2) and 1.4 (0; 2) points, respectively (p \u003d 0.179 , Mann-Withney), on the 15th day: in the main group, on average 0 (0; 1) points, in 13 (11%) patients - 1 point; in the control group, signs of organ dysfunction were observed in 12 (34%) patients, the average SOFA value in this group was 0.9 (0; 2) points (p \u003d 0.028, Mann-Withney).

The dynamics of the severity of the condition in patients with a total SAPS II score\u003e 30

The use of L-ornithine-L-aspartate (Hepa-Merz) in our study was accompanied by a more pronounced decrease in cytolysis indices than in the control (Figures "Dynamics of ALT content in patients with a total SAPS II score\u003e 30" and "Dynamics of ACT content in patients with a total SAPS II score\u003e 30 ").

On the 1st day, ALT and ACT levels exceeded the upper limit of the norm in all patients. The average ALT content in the main group was 137 U / L (27.5; 173.5), in the control group - 134.2 U / L (27.5; 173.5), ACT - respectively 120.5 U / L ( 22.8; 99) and 97.9 U / l (22.8; 99). On the 3rd day, the ALT content was 83 U / L (25; 153.5) and 126.6 U / L (25; 153.5) (p-0.021, Mann-Withney), respectively, ACT - 81.5 U / l (37; 127) and 104.4 U / l (37; 127) (p \u003d 0.014, Mann-Withney). On the 5th day, the average ALT content in the main and control groups was 62 U / L (22.5; 103) and 79.7 U / L (22.5; 103), respectively (p \u003d 0.079, Mann-Withney), a ACT - 58 U / L (38.8; 80.3) and 71.6 U / L (38.8; 80.3) (p \u003d 0.068, Mann-Withney). The concentration of ALT and ACT in patients who received L-ornithine-L-aspartate (Hepa-Merz) reached normal values \u200b\u200bon the 15th day. The ALT level in the main group was 38 U / L (22.5; 49), in the comparison group - 62 U / L (22.5; 49) (p \u003d 0.007, Mann-Withney), the ACT level was 31.5, respectively. U / L (25; 54) and 54.2 U / L (25; 70) (p \u003d 0.004, Mann-Withney).

The study of attention using HST in patients with a severity of the SAPS II condition\u003e 30 points also revealed the best results in the main group (Figure "Dynamics of the state of the neuropsychic sphere in patients with a total SAPS II score\u003e 30").

Dynamics of the state of the neuropsychic sphere in patients with a total SAPS II score\u003e 30

The counting rate by the 3rd day was higher than in the comparison group by 18.8%: 89 s (69.3; 105) and 109.6 s (90; 137) were spent, respectively (p \u003d 0.163, Mann -Withney); by the 5th day, the difference reached 34.7%: 59 s (52; 80) and 90.3 s (66.5; 118), respectively (p \u003d 0.054, Mann-Withney). On the 15th day in the main group, the account took an average of 49 s (41.5; 57), which was 47.1% more than in the control group: 92.6 s (60; 120); p \u003d 0.002, Mann-Withney.

The immediate results of treatment should also include a decrease in hospitalization times by an average of 18.5% in patients of the main group (p \u003d 0.049, Mann-Withney).

In the control group, there were 2 (6%) deaths from increasing multiple organ failure (p \u003d 0.15; Χ 2), in the main group there were no deaths.

Observation showed that in the vast majority of cases, L-ornithine-L-aspartate (Hepa-Merz) was well tolerated by patients. In 7 (3.8%) patients, side effects were noted, in 2 (1.1%) the drug was canceled due to the development of an allergic reaction, in 5 (2.7%) dyspeptic symptoms were noted in the form of nausea, vomiting, which were stopped with a decrease in the rate of administration of the drug.

Timely use of L-ornithine-L-aspartate (Hepa-Merz) in the complex of therapeutic measures for acute pancreatitis is pathogenetically justified and can significantly reduce the severity of endogenous intoxication. L-ornithine-L-aspartate (Hepa-Merz) is well tolerated by patients.

Literature

1. Bueverov A.O. Hepatic encephalopathy as the main manifestation of liver failure // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 8.

2. Ivanov Yu.V. Modern aspects of the onset of functional liver failure in acute pancreatitis // Mathematical morphology: electronic mathematical and biomedical journal. -1999; 3 (2): 185-195.

3. Ivashkin V.T., Nadinskaya M.Yu., Bueverov A.O. Hepatic encephalopathy and methods of its metabolic correction // RMZh Library. - 2001; 3 (1): 25-27.

4. Laptev V.V., Nesterenko Yu.A., Mikhailusov S.V. Diagnostics and treatment of destructive pancreatitis - M .: Binom, 2004 .-- 304 p.

5. Nadinskaya M.Yu., Podymova S.D. Treatment of hepatic encephalopathy with Hepa-Merz // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 12.

6. Ostapenko Yu.N., Evdokimov E.A., Boyko A.N. The experience of conducting a multicenter study in a medical institution in Moscow to study the effectiveness of the use of Hepa-Merz in endotoxicosis of various etiologies // Materials of the second scientific-practical conference, June 2004, Moscow. - S. 31-32.

7. Popov T.V., Glushko A.V., Yakovleva I.I. and others. Experience of using the drug Selenase in the complex of intensive care of patients with destructive pancreatitis // Consilium Medicum, Infections in surgery. - 2008; 6 (1): 54-56.

8. Saveliev B.C., Filimonov M.I., Gelfand B.R. et al. Acute pancreatitis as a problem of urgent surgery and intensive care // Consilium Medicum. - 2000; 2 (9): 367-373.

9. Spiridonova E.A., Ulyanova Ya.S., Sokolov Yu.V. The use of Hepa-Merz preparations in the complex therapy of fulminant viral hepatitis // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 19.

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11. Nekam K. et al. Effect of in vivo treatment with ornitin-aspartate hepamerz on the activity and expression of superoxidedismutase SOD in patients with cirrhosis of the liver // Hepatology. -1991; 11: 75-81.

Summary

The work presents the pathogenesis of the onset of liver failure. The data on the treatment of patients with liver cirrhosis of various etiology complicated by hepatic encephalopathy are presented. A large number of different tests and biochemical parameters have shown the positive role of L-ornithine-L-aspartate (Ornitox) in stabilizing the patient's condition, reducing the clinical manifestations of the disease, and normalizing biochemical parameters.

Keywords

Ammonia, liver failure, ways of correction, Ornitox, Glutargin.

Ammonia is the end product of nitrogen metabolism in the human body. It is formed during the metabolism of proteins, amino acids and other nitrogenous compounds. It is highly toxic to the body, and most of it during the ornithine cycle is converted by the liver to the less toxic compound carbamide (urea) and excreted by the kidneys.

Simultaneously, ammonia is involved in the resynthesis of amino acids and keto analogs of amino acids, and this process is called "reductive amination".

A certain balance of ammonia is constantly maintained in a healthy body, and the main sources of its formation are:

- large intestine (processing of protein and urea by the bacterial flora);

- musculature (in proportion to physical activity);

- small intestine (breakdown of the amino acid glutamine - the main source of energy for the cells of the intestinal mucosa);

- liver (breakdown of proteins).

With various diseases leading to impaired ammonia metabolism (most often this occurs with impaired liver function - hepatitis, cirrhosis), the level of this chemically active substance becomes one of the main reasons for the development of severe endotoxicosis.

The pathological symptoms arising in acute or chronic hepatic encephalopathy are based on the hypothesis that endogenous neurotoxins and amino acid imbalances resulting from hepatocyte insufficiency and / or portosystemic shunting of blood lead to edema and functional disorders of astroglia.

The leading role in this process belongs to ammonia, mercoptans, short- and medium-chain fatty acids, phenols. Their toxic effect leads to disruption of the permeability of the blood-brain barrier, disruption of the functions of ion channels and neurotransmission, and as a result, the supply of neurons with high-energy compounds decreases.

The role of an increase in the content of GABA (gamma-aminobutyric acid), an important inhibitory mediator, is also undoubted. As a result of liver damage, the level of activity of GABA-transaminase, which plays an important role in the elimination of excess GABA content, decreases, which aggravates the course of encephalopathy.

In recent years, the main reason for the development of liver failure is the glia hypothesis, which links two levels: the liver - the brain. According to this hypothesis, hepatocellular failure leads to amino acid imbalance and accumulation of ammonia, that is, ammonia endotoxicosis occurs. Hyperammonemia in liver diseases is associated with a decrease in urea and glutamine in it. Ammonium compounds (ammonia) in non-ionized form penetrate the blood-brain barrier, involving aromatic amino acids in this process, as a result of which the synthesis of false neurotransmitters and serotonin is enhanced.

Thus, hepatic encephalopathy is a neuropsychic syndrome with impaired intelligence, consciousness, neurological disorders, which develops in patients with acute or chronic hepatic failure against the background of various liver lesions. In accordance with these manifestations, several variants of this syndrome are distinguished. In addition to the signs shown in table. 1 use a variety of psychometric tests.

Regardless of the causes of liver failure, in the treatment of this disease an important role is played by a diet with limited protein, drugs that affect the main links of pathogenesis, in particular, the use of universal cytoprotectors - cytoflavin, reamberin, that is, substances that reduce toxic-hypoxic damage to neurons and restoring their energy reserves, and drugs aimed at stopping hyperammonemia.

These include lactulose, a synthetic disaccharide that reduces the concentration of ammonia in the blood by reducing its intake from the intestine; to reduce the formation of toxins, including ammonia, antibiotics such as vancomycin, ciprofloxacin, nitronidazole, and branched-chain amino acid preparations are sometimes used. Zinc can also be used as an adjunctive therapy.

In recent years, the most promising for the disposal of ammonia has been the prescription of drugs based on L-ornithine-L-aspartate. L-ornithine activates ornithinecarbamoyltransferase and carbamoylphosphate synthetase in periportal hepatocytes, the first enzyme in the urea synthesis cycle.

L-ornithine and L-aspartate are substrates for the synthesis cycle of both urea and glutamine. The glutamine synthetase reaction is activated by the action of L-ornithine-L-aspartate not only in the liver, but also in the muscles.

It is also important that aspartate is incorporated into the Krebs cycle, that is, it increases the synthesis of macroergs and reduces the formation of lactic acid, which, in turn, reduces the BBB permeability for toxic substances.

Here are its main pharmacological properties.

L-Ornithine-L-Aspartate (Ornitox) has a dual mechanism of incorporating both amino acids into the ornithine cycle.

L-ornithine:

- is included in the urea cycle as a substrate (at the stage of citrulline synthesis);

- is a stimulant of carbamoyl phosphate synthetase I (the first enzyme of the urea cycle);

- is an activator of the glutamine synthetase reaction in the liver and muscles, reduces the concentration of ammonia in the blood plasma;

- helps to normalize the acid-base balance of the body;

- promotes the production of insulin and growth hormone;

- improves protein metabolism in diseases requiring parenteral nutrition.

L-aspartate:

- is included in the urea cycle at the stage of arginine succinate synthesis;

- is a substrate for the synthesis of glutamine;

- participates in the binding of ammonia in perivenous blood, hepatocytes, brain, and other tissues;

- stimulates the synthesis of glutamine in muscles and perivenous hepatocytes;

- has a stimulating effect on inactive or affected liver cells;

- stimulates regeneration, improves energy processes in damaged liver tissue;

- participates in the tricarboxylic acid cycle;

- has the ability to penetrate cell membranes by active transport;

- inside the cell, it participates in the processes of energy metabolism in the mitochondria, thereby increasing the energy supply of the tissue;

- has an anabolic effect on muscles.

The second most important drug in the treatment of this pathology is the drug Glutargin (arginine glutamate), which has also shown its sufficient effectiveness in clinical practice. And when it was created and appeared in the clinic (more than 10 years ago), arginine glutamate was a kind of “lifesaver”.

At the same time, certain side effects of this drug are possible. These include:

- changes in the balance of intracellular potassium;

- hyperthermia, shortness of breath, the appearance of pain behind the breastbone - these episodes most often occur after a rapid intravenous injection of the drug;

- heart rhythm disturbances in the form of atrial fibrillation (restriction of administration in patients with rhythm disturbances);

- headache, dizziness, tremor, general weakness (which, against the background of encephalopathy, creates certain diagnostic difficulties).

These effects are associated with the mechanism of action of glutamic acid, which is part of arginine glutamate, which belongs to the class of excitatory amino acids, therefore, the binding of glutamate to specific receptors of neurons leads to their excitation. In some cases, this can lead to overexcitation of neurons and their death.

It should be noted that these effects of the drug do not detract from the merits of arginine glutamate, but may limit its use.

The aim of the study was to determine the efficacy and safety of complex therapy in patients with hepatic encephalopathy of various origins, ІІ-ІІІ degrees.

Materials and methods

45 patients with liver cirrhosis of various genesis, who were diagnosed with liver failure, were examined. The average age of the patients was 50.1 ± 6.8 years, among the examined men prevailed - 72.0%. The duration of the disease was 3.5 ± 1.5 years, the cause of the disease in 66.4% of cases was alcohol abuse, 15.6% had liver damage of mixed origin and 18.0% had viral etiology.

When assessing the objective status, dyspeptic syndrome was diagnosed in 100% of patients, pain - in 78%, icteric - in 67%, edematous-ascites - in 82%, cytolytic syndrome - in 82%, hypersplenism - in 74%.

The patients were divided into three equal groups.

The first (main) received Reamberin, Cyto-flavin, Lactulose, detoxification therapy and L-ornithine-L-aspartate (Ornitox) intravenously.

The second (control) group received essential phospholipids instead of L-ornithine-L-aspartate (Ornitox).

The third group (comparison group) received arginine glutamate (Glutargin) at a dose of 6 g per day by intravenous drip, the rate of administration is 60 drops per minute.

Assessment of the condition and biochemical studies were carried out on the day of admission and 10 days after the start of treatment.

The average dose of L-ornithine-L-aspartate (Ornitox) was 10 g, which were injected intravenously per 400 ml of saline. The rate of administration is 8-12 drops per minute. The duration of therapy was 10 days. In the future, patients were recommended oral administration of the drug.

Signs of hepatic encephalopathy were exhibited in all patients and are presented in table. 2.

Results and its discussion

Assessment of the general condition of patients 10 days after the start of treatment showed a positive trend in patients of all groups, but in the main group a significant improvement was detected already by the 5th day from the start of treatment. These positive changes were more pronounced by the 10th day of stay in the clinic (Tables 3, 4). Positive, but less significant changes were noted in patients in the comparison group.

Similar data were obtained when studying the levels of enzyme and bilirubin, ammonia.

The revealed positive shifts in the homeostasis of the examined patients, especially in the patients of the main group, also correlated with a decrease in the clinical manifestations of the symptoms of hepatic encephalopathy. This improvement was more pronounced in patients in the Ornitox group (Table 5).

The pronounced positive dynamics in the form of a decrease in the symptoms of hepatic encephalopathy in patients of the main group correlated with a decrease in ALT, AST, total bilirubin, and ammonia content.

Comparative analysis of clinical and biochemical parameters in patients of the main group and the comparison group showed certain advantages of using L-ornithine-L-aspartate (Ornitox) in comparison with other drugs, in particular with arginine glutamate (Glutargin). This is especially true for reducing the level of ammonia, urea, alkaline phosphatase in patients of the main group. Obviously, this is due to the fact that L-ornithine-L-aspartate participates in biochemical cycles at earlier stages of disturbed metabolic processes, as well as due to the incorporation of both amino acids into the ornithine cycle, which contributes to more efficient neutralization (utilization) of ammonia and, as a consequence - more effective improvement of the clinical picture of the disease.

Thus, the results obtained, the mechanism of action of L-ornithine-L-aspartate (Ornitox) indicate the advisability of including this drug in the treatment of patients with hepatic insufficiency, especially complicated by hepatic encephalopathy. Proceeding from the fact that the violation of ammonia metabolism occurs immediately with liver damage, it is obvious that L-ornithine-L-aspartate - (Ornitox) should be included in therapy in the early stages of the disease. The duration of treatment depends on many reasons and may continue, in our opinion, for a long time. The use of higher doses of the drug is advisable in patients with acute hepatic failure.

With long-term administration of Ornitox in sufficiently large doses, we did not observe side or undesirable effects, which indicated the safety of this drug.

And in conclusion, it should be noted that the obtained positive results of the use of this drug were obtained in patients with stage II-III of hepatic failure against the background of the use of universal cytoprotectors, which improve the function of not only hepatocytes, but also neurons.

List of references

1. Golubovskaya O.A., Shkurba A.V. The effectiveness of Ornithox in the complex treatment of fulminant hepatic failure in the clinic of infectious diseases // Suchasni Infections. - 2010. - No. 2. - S. 10-13.

2. Kondratenko P.G., Smirnov N.L. L-ornithine-L-aspartate in the treatment of patients with urgent surgical abdominal pathology // Surgery. - 2010. - No. 3. - S. 112-115.

3. Shipulin V.P., Chernyavsky V.V. Toxic hepatitis: how to improve the effectiveness of treatment // News of Medicine and Pharmacy. - 2010. - No. 348. - S. 25-29.

4. Samogalskaya O.E. The effectiveness of the use of thio-cetam in the treatment of liver failure // International neurological journal. - 2006. - No. 3 (70). - S. 48-53.

5. Babak O.Ya., Kolesnikova E.V., Kozyrev T.E. Modern possibilities of correction of hepatic encephalopathy in patients with liver cirrhosis // Suchasna gastroenterology. - 2010. - No. 4 (54). - S. 38-43.

Hepatic failure is one of the most serious complications of acute pancreatitis. It often determines the course of the disease and its outcome. It is known from the literature that in 20.6% of patients with edematous pancreatitis and in 78.7% of patients with a destructive process in the pancreas, various liver functions are impaired, which significantly worsens the results of treatment and is the direct cause of death in 72% of cases.

In the period from November 2009 to March 2010, a multicenter non-randomized clinical trial was conducted to study the effectiveness of the hepatoprotector L-ornithine-L-aspartate (Hepa-Merz) in the complex treatment of patients with acute pancreatitis. The study included 232 patients (150 (64.7%) men and 82 (35.3%) women) with acute pancreatitis, confirmed by clinical, laboratory and instrumental methods. The age of the patients varied from 17 to 86 years, with an average of 46.7 (34; 58) years. Edematous pancreatitis was diagnosed in 156 (67.2%) patients, in 76 (32.8%) - destructive forms: in 21 (9.1%) - hemorrhagic pancreatic necrosis, in 13 (5.6%) - fatty, in 41 (17.7%) - mixed, 1 (0.4%) - post-traumatic.

All patients received basic complex conservative therapy (blockade of exocrine pancreatic function, infusion-detoxification, antibacterial agents).

SAPS II severity subgroup<30 баллов составили 112 (48,3%) пациентов, в том числе 97 (87%) - из основной группы: мужчин - 74 (76,3%), женщин - 23 (23,7%), средний возраст - 40,9 (33; 45) года, тяжесть состояния - 20,4±5,2 балла; из контрольной группы было 15 (13%) пациентов: мужчин - 11 (73,3%), женщин - 4 (26,7%), средний возраст - 43,3 (28,5; 53) года, тяжесть состояния - 25±6 баллов.

The subgroup with a total SAPS II score\u003e 30 consisted of 120 (51.7%) patients, including 85 (71%) from the main group: men - 56 (65.9%), women - 29 (34.1%) ), the average age is 58.2 (45; 66.7) years, the severity of the condition is 36.3 + 5.6 points; from the control group there were 35 (29%) patients: men - 17 (48.5%), women - 18 (51.4%), average age - 55.4 (51; 63.5) years, severity of the condition - 39 , 3 ± 5.9 points.

The mathematical processing of the factual material was carried out using the basic methods of biomedical statistics using the Microsoft Office Excel 2003 and BIOSTAT software package. When describing the group characteristics, the standard deviation of the mean value of the trait was calculated for its parametric distribution and the interquartile interval for nonparametric distribution. The significance of differences between the 2 parameters was assessed using the Mann-Withney and x2 tests. Differences were considered statistically significant at p \u003d 0.05.

In patients of the main group with the severity of the condition according to SAPS II<30 баллов применение L-орнитин-L-аспартата (Гепа-Мерц) в комплексе лечения привело к более быстрому восстановлению нервно-психической сферы, что оценивалось в ТСЧ. При поступлении у пациентов обеих групп длительность счета была выше нормы (норма - не более 40 с) на 57,4% в основной группе и на 55,1% - в контрольной: соответственно 94 с (80; 98) и 89,5 с (58,5; 116). На фоне терапии отмечалась положительная динамика в обеих группах. На 3-й сутки длительность счета составила 74 с (68; 78) в основной группе и 82,3 с (52,5; 100,5) - в группе сравнения, что превышало норму на 45,9 и 51,2% соответственно (р=0,457, Mann-Withney). На 5-е сутки время в ТСТ составило 50 с (48; 54) в основной группе и 72,9 с (44; 92) - в контрольной, что превышало норму на 20 и 45,2% соответственно (р=0,256, Mann-Withney). Статистически достоверные изменения отмечены на 15-е сутки исследования: в основной группе - 41 с (35; 49), что превышало нормальное значение на 2,4%, а в контрольной — 61 с (41; 76) (больше нормы на 34,4%; р=0,038, Mann-Withney) - рисунок "Динамика состояния нервно-психической сферы у больных с суммарным баллом по SAPS II <30".

In patients with SAPS II severity\u003e 30 points, the study revealed a positive effect of L-ornithine-L-aspartate (Hepa-Merz) on the dynamics of biochemical parameters; the most significant changes concerned the indicators of cytolytic syndrome (ALT, ACT) and the rate of recovery of neuropsychic functions.

Dynamic observation of the severity of the patient's condition, assessed by the SOFA scale, also showed a faster normalization in the main group (Figure "Dynamics of the severity of the condition in patients with a total SAPS II score\u003e 30"). The severity of the condition of patients in the main and control groups on the 1st day of the study on the SOFA scale was 4 (3; 6.7) and 4.2 (2; 7) points, respectively, on the 3rd day of the study - 2 (1; 3 , 7) and 2.9 (1; 4) points (p \u003d 0.456, Mann-Withney), on the 5th day - 1 (0; 2) and 1.4 (0; 2) points, respectively (p \u003d 0.179 , Mann-Withney), on the 15th day: in the main group, on average 0 (0; 1) points, in 13 (11%) patients - 1 point; in the control group, signs of organ dysfunction were observed in 12 (34%) patients, the average SOFA value in this group was 0.9 (0; 2) points (p \u003d 0.028, Mann-Withney).

The study of attention using HST in patients with the severity of the SAPS II condition\u003e 30 points also revealed the best results in the main group (Figure "Dynamics of the state of the neuropsychic sphere in patients with a total SAPS II score\u003e 30").

The immediate results of treatment should also include a decrease in hospitalization times by an average of 18.5% in patients of the main group (p \u003d 0.049, Mann-Withney).

In the control group, there were 2 (6%) deaths from increasing multiple organ failure (p \u003d 0.15; Χ 2), in the main group there were no deaths.

Literature

2. Ivanov Yu.V. Modern aspects of the onset of functional liver failure in acute pancreatitis // Mathematical morphology: electronic mathematical and biomedical journal. -1999; 3 (2): 185-195.

3. Ivashkin V.T., Nadinskaya M.Yu., Bueverov A.O. Hepatic encephalopathy and methods of its metabolic correction // RMZh Library. - 2001; 3 (1): 25-27.

4. Laptev V.V., Nesterenko Yu.A., Mikhailusov S.V. Diagnostics and treatment of destructive pancreatitis - M .: Binom, 2004 .-- 304 p.

8. Saveliev B.C., Filimonov M.I., Gelfand B.R. et al. Acute pancreatitis as a problem of urgent surgery and intensive care // Consilium Medicum. - 2000; 2 (9): 367-373.

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The liver plays a central role in the metabolism of ammonia. In this regard, patients with chronic liver disease may experience hyperammonemia. There is evidence that many patients with chronic liver disease have elevated blood ammonia levels in the absence of clinical signs of hepatic encephalopathy. Experimental data have been obtained on the stimulating effect of hyperammonemia on hepatic stellate cells, which may contribute to the progression of portal hypertension and fibrosis in the liver. In this regard, it is of interest to use the results of determining ammonia in the blood to monitor the effectiveness of various types of treatment. L-Ornithine-L-Aspartate (LOLA) is used in the treatment of chronic liver diseases, reliably reduces the level of ammonia in the blood when taken orally. ...

The aim of our work was to evaluate the effectiveness of the oral form of LOLA in hyperammonemia in patients with chronic liver disease at the pre-cirrhotic stage.

Material and research methods

An open clinical study was carried out to evaluate the effectiveness of the LOLA drug, which included 37 patients (11 men and 26 women, mean age 42.5 ± 6.8 years) with chronic liver diseases (16 with chronic viral hepatitis "C", 21 - with fatty liver disease), initially elevated blood ammonia levels, minimal activity, fibrosis stage 1-2 (according to elastometry data), who were treated at polyclinic No. 3 in Khabarovsk. The medical history ranged from 10 to 25 years.

All patients received LOLA 3 g per os 3 times a day for 4 weeks.

The concentration of ammonia ions in venous blood was determined by the enzymatic method (BIOLABO REAGENTS, France) (norm \u003d 11-35 μmol / l) before and after the course of treatment.

Cognitive function was investigated using the number connection test (NNT) (up to 40 seconds normal) before and after the course of treatment.

The comparison group consisted of 17 apparently healthy volunteers, in whom the level of ammonia in the blood was determined and the number binding test was performed.

Statistical processing of the obtained data was carried out using the Microsoft Office 2010 (Excel) and Biostat-2000 software package. The reliability of the difference between the two mean values \u200b\u200bwas assessed by the Student's t-test; in the case of repeated measurements, a paired test was used. Differences in the results were considered statistically significant at the p<0,05. Количественные переменные представлены в работе в виде среднего значения ± стандартная ошибка среднего значения (x±mx).

Research results and their discussion

The level of ammonia in the blood of 17 apparently healthy individuals in the comparison group was 24.0 ± 2.5 μmol / l and was within the normal range. The blood ammonia level in 37 patients included in the study before treatment was increased to 56.1 ± 6.2 μmol / L. The differences in ammonia parameters between these groups are statistically significant (p1<0,01). Через 4 недели лечения LOLA уровень аммиака в крови у пациентов с гипераммониемий достоверно снизился до 34,7±4,2 мкмоль/л (p2<0,01) (рис.1).

The time to perform HSP in all 17 apparently healthy individuals in the comparison group was less than 40 seconds (35.1 ± 0.4 seconds). The time to perform HSP in all 37 patients included in the study before treatment exceeded 40 seconds (59.1 ± 0.7 seconds). Differences in the indicators of the time of HST performance between these groups are statistically significant (p1<0,001). Через 4 недели лечения время выполнения ТСЧ у пациентов с гипераммониемией достоверно уменьшилось до 39,2±0,5 сек (p2<0,001) (рис. 2).

Prolongation of the HST performance time over 40 seconds, as a rule, is detected in patients with hepatic encephalopathy.

Thus, we have established that hyperammonemia is observed in patients with chronic liver diseases at the pre-cirrhotic stage. Our results confirm the data of other authors. Due to the fact that all 37 patients with hyperammonemia examined by us initially had an increase in the time of HSP over 40 seconds, it seems to us advisable to carry out HSP in patients with chronic liver diseases in the early stages of fibrosis. In the case of its lengthening over 40 seconds, it is advisable to study the level of ammonia in the blood. If hyperammonemia is detected, it is necessary to carry out a course of treatment with the oral form of LOLA, 1.0 g 3 times a day, for 4 weeks in order to normalize the level of ammonia in the blood, improve cognitive functions. Hyperammonemia is a leading factor in the development and progression of hepatic encephalopathy, and, possibly, based on the experimental data obtained by British scientists, a significant factor in the progression of portal hypertension and liver fibrosis. In this regard, the use of hypoammonoemic drugs in chronic liver diseases receives new additional justification. Further research is needed on the clinical significance of early detection of hyperammonemia and its correction LOLA.

Time to run the Number Link Test

conclusions

Hyperammonemia occurs in patients with chronic liver diseases at the pre-cirrhotic stage and is accompanied by an increase in the duration of HSP over 40 seconds. Treatment with oral LOLA for 4 weeks lowers the level of ammonia in the blood, improves the performance of the number binding test. Early detection of hyperammonemia and its correction LOLA is of interest for further research on the possibility of preventing the development and progression of hepatic encephalopathy, portal hypertension and liver fibrosis.

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Summary

Purpose of the study. Evaluation of the efficacy of oral LOLA in hyperammonemia in patients with chronic liver disease at the pre-cirrhotic stage.

Material and methods.An open clinical study was carried out to evaluate the effectiveness of LOLA in the treatment of 37 patients with hyperammonemia in chronic liver diseases, fibrosis stage 1-2.

Results. There was a positive effect of the treatment on the level of ammonia in the blood and the time to perform the number binding test. The ammonia level decreased from 56.1 ± 6.2 μmol / L after 4 weeks of LOLA treatment to 34.7 ± 4.2 μmol / L (p<0,01), время выполнения ТСЧ — с 59,1 ± 0,7 сек до 39,2 ± 0,5 сек (p<0,001).

Conclusions. Hyperammonemia occurs in patients with chronic liver diseases at the pre-cirrhotic stage and is accompanied by an increase in the duration of the HSP over 40 seconds. Treatment with oral LOLA for 4 weeks lowers the level of ammonia in the blood, improves the performance of the number binding test. Early detection of hyperammonemia and its correction LOLA is of interest for further research on the possibility of preventing the development and progression of hepatic encephalopathy, portal hypertension and liver fibrosis.

E.A. Ageeva 1,doctor gastroenterologist of the highest qualification category, KGBUZ "City Clinical Polyclinic No. 3" of the Ministry of Health of the Khabarovsk Territory,[email protected]
S.A. Alekseenko 2,doctor of Medical Sciences, Professor, Head of the Department of Hospital Therapy, Far Eastern State Medical University, Ministry of Health of Russia,[email protected]_dv.ru

1 KGBUZ "City clinical polyclinic No. 3" ("City clinical polyclinic No.3"), Ministry of Health of the Khabarovsk Territory
2 SBEE HPE "Far Eastern State Medical University" ("Far Eastern State Medical University") of the Ministry of Health of Russia

Part of preparations

ATX:

A.05.B.A.06 Ornithine oxoglurate

Pharmacodynamics:

Ornithine acts as a catalyst for the enzymes carbamoyl phosphate synthetase and ornithine carbamoyl transferase, and is also the basis for the synthesis of urea. In addition, the drug reduces the level of ammonia in the body due totilization of ammonium groups in the synthesis urea (in the ornithine cycle of Krebs urination).

Also, the drug promotes the production of growth hormone and insulin, improves protein metabolism.

Reduces the concentration of ammonia in blood plasma, promotes normalization acid-base statethe body and the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.

Pharmacokinetics:

When taken orally, ornithine aspartate dissociates into its constituent components (and aspartate), which are absorbed in the small intestine by active transport through the intestinal epithelium.

It is excreted in the urine through the urea cycle.

Indications:

Acute and chronic liver diseases (hepatitis, liver cirrhosis, hepatic encephalopathy (latent and pronounced), including as part of complex therapy for impaired consciousness (precoma or coma), which are accompanied by hyperammonemia.

Hyperammonemia.

Dynamic study of the function of the pituitary gland.

As a corrective supplement for parenteral nutrition preparations for patients with protein deficiency.

IV.E40-E46.E46 Protein-energy malnutrition, unspecified

XI.K70-K77.K72 Hepatic impairment, not elsewhere classified

IV.E70-E90.E72.2 Metabolic disorders of the urea cycle

XI.K70-K77.K74 Fibrosis and cirrhosis of the liver

XI.K70-K77.K76.9 Liver disease, unspecified

Contraindications:

Severe renal failure (creatinine concentration more than 3 mg in 100 ml).

Hypersensitivity.

Lactation.

Children under the age of 18.

Carefully:

Pregnancy.

Pregnancy and lactation:

If necessary, use during lactation should decide on the termination of breastfeeding.

Method of administration and dosage:

Inside, intravenously, intramuscularly.

Orally: after meals, 3 g of granulate, previously dissolved in 200 ml of liquid, 2-3 times a day.

Intramuscularly: 2-6 g per day, 1-2 times per day.

Intravenous drip: dose, duration and frequency of infusions, duration of treatment are determined individually, usually 20 g per day (pre-diluted in 500 ml of infusion solution, maximum infusion rate - 5 g per hour or 40 drops per minute); it is possible to increase the dose to 40 g per day.

Intravenous jet 2-4 g 1-2 times a day.

Side effects:

Skin reactions.

Nausea.

Vomiting.

Overdose:

Symptoms: increased severity of dose-related side effects. Treatment: the drug should be discontinued, gastric lavage, activated charcoal intake, symptomatic treatment.

Interaction:

Preparation f pharmaceutically incompatible(R solutions cannot be mixed in one syringe)with vitamin K, benzathine benzylpenicillin, diazepam, meprobamate, phenobarbital, rifampicin, ethionamide.

Special instructions:

If nausea or vomiting occurs, the rate of administration should be optimized.

When using a certain dosage form of ornithine, compliance with specific indications should be observed.

The course of treatment can be repeated every 2-3 months.

When the drug is administered in high doses, the concentration of urea in blood plasma and urine should be monitored.

Influence on the ability to drive vehicles and use mechanisms

The drug can cause a slowdown in the speed of psychomotor reactions and impaired concentration.

Instructions

Pharmacological properties

Composition and form of release

Indications

Application

Contraindications

Side effects

special instructions

Interactions

Overdose

Storage conditions

Clinical and pharmacological group:

pharmachologic effect

Pharmacokinetics

Indications for the use of the drug GEPA-MERC

Dosage regimen

Side effect

Contraindications to the use of the drug GEPA-MERC

Application of the drug GEPA-MERC during pregnancy and breastfeeding

Application for violations of liver function

Application for impaired renal function

Influence on the ability to drive vehicles and use mechanisms

Overdose

Drug interactions

Terms of dispensing from pharmacies

Name:

Pharmachologic effect:

Indications for use:

Application method:

Ornitox granules for oral solution:

Ornitox injection solution:

Adverse events:

Contraindications:

During pregnancy:

Interaction with other medicinal products:

Overdose:

Release form of the drug:

Storage conditions:

Composition:

Materials and methods

Results and its discussion

Material and research methods

Research results and their discussion

Time to run the Number Link Test

conclusions

Summary

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