is a related amino acid to arginine. Combining them into one group is caused by a similar effect on the body. L ornithine, derived from the liver of a shark in 1937 by D. Akkarman, as well as arginine, stimulates the synthesis of growth hormone - somatotropin. As a non-essential amino acid, ornithine is not found in proteins, but its popularity among athletes in bodybuilding is due to the fact that it promotes rapid muscle gain.
There are two subgroups of ornithine: L and D. Group D has no value for bodybuilders. In sports nutrition, only the amino acid of group l is used. In a small amount, a colleague of arginine is found in connective tissue and in human blood plasma. Ornithine is also isolated from plant products.
Ornithine is a related amino acid to arginine
Properties and functions
Amino acid is used not only in sports nutrition, but also in medicine. Medicinal preparations with the addition of a biologically active component are characteristic in the treatment of the following diseases:
- hepatitis;
- kidney failure;
- cirrhosis of the liver;
- protein deficiency;
- an excess of urea in the blood.
Ornithine, as a hepatoprotector, is a powerful defender of the body. The use of amino acids has a positive effect on the regeneration and restoration of liver cells. At the same time, ornithine protects the body from the negative effects of toxic substances, which is significant for people with impaired liver function. Scientific studies testify to the acceleration of the movement of blood through the vessels under the influence of a non-essential amino acid.
Amino acid is used in the treatment of hepatitis
Also, the additive is used in burn therapy. Amino acid has a positive effect on tissue regeneration. The advantage of its use will be an increase in the overall tone of the skin.
Amino acid supplement promotes the synthesis of niacin (nicotinic acid) in the body.
The benefit of niacin is to speed up the metabolism, which has a positive effect on the rate of weight loss.
Niacin deficiency manifests itself in loss of appetite, muscle weakness, roughness and flaking of the skin. Taking ornithine helps to accumulate the necessary amount of nicotinic acid in the body and, in synergy with it, overcome the noted problems.
L ornithine is involved in the removal of ammonia from the body. Under the influence of amino acids, ammonia, as a breakdown product of proteins, is converted into urea and excreted from the body. Exceeding the permissible norm of ammonia in the blood is dangerous for human life, as it can cause endotoxicosis. The processing of ammonia into urea with its subsequent withdrawal blocks the development of negative processes under the influence of toxic substances. This process has a beneficial effect on reducing the overall excitability of a person.
L ornithine is involved in the removal of ammonia from the body
The detoxifying properties of the amino acid are used in the complex therapy of malignant tumors.
ABOUT Rnitine has a number of other properties:
- strengthening the immune system and, as a result, increasing the body's resistance to diseases;
- strengthening of connective tissues;
- generating energy in the process of splitting fats;
- muscle recovery;
- maintaining the acid-base balance of the body.
The amino acid related to arginine is of great importance in the treatment of diseases of the gastrointestinal tract, alcohol dependence, schizophrenia and Down syndrome. As a sedative, the amino acid is introduced into the diet of aggressive people with hyperactivity syndrome.
The amino acid related to arginine is of great importance in the treatment of diseases of the gastrointestinal tract.
You can buy L ornithine on the American website, where promotions are always held, and using our link you are guaranteed to receive an additional 5% discount. It also works. Therefore, if you have already decided which L ornithine suits you best, then you can find it at.
Importance of amino acids for athletes
A feature of sports is the increased consumption of protein foods, which leads to an overload of the body with decay products. Although ornithine is synthesized in the body by converting to arginine, its amount is not enough to achieve significant results in bodybuilding and reduce the load on the liver. Therefore, an additional intake of amino acids, as a hepatoprotector, is indicated for bodybuilders and powerlifters. This is due to the positive effect of ornithine on the overall effectiveness of training and health.
First, ornithine stimulates the production of growth hormone, which accumulates in the pituitary gland. Growth hormone contributes to the rapid burning of fat and the accumulation of muscle mass, which helps to lose weight and acquire an athletic figure. The hormone also has the properties of normalizing glucose levels.
For greater effect, ornithine is taken at bedtime, and the peak of hormone secretion occurs at 90 minutes of a night's rest.
For greater effect, ornithine is taken at bedtime, and the peak of hormone secretion occurs at 90 minutes of night's rest.
It is worth noting that the intake of amino acids stimulates the mobilization of fat not in response to sleep, but in response to a set of measures: proper nutrition, strength training, good sleep.
Insulin synthesis is the second most important property of an amino acid supplement for an athlete. Increased insulin secretion is necessary in bodybuilding when bodybuilders work on mass.
Ornithine is not replaceable when drying the body. The breakdown of fats occurs under the action of growth hormone both during the day and at night. At the same time, the athlete does not feel exhausted, since ornithine increases the energy of the body. In addition, the amino acid supplement reduces pain sensitivity.
The importance of amino acids for strengthening and restoring ligaments and tendons.
The importance of amino acids for strengthening and restoring ligaments and tendons
The amino acid that synthesizes growth hormone is found in plant foods. There is no ornithine in animal products. However, it can be synthesized from arginine, which is found in protein foods. These are nuts, pumpkin seeds, meat, fish and eggs. Therefore, obtaining l ornithine from food is insignificant and does not cover the required daily dose of a bodybuilder, which explains the need for the introduction of nutritional supplements.
Admission rules
Depending on the goals pursued, it is recommended to take ornithine 5 g three times a day. It is best to take it in the morning on an empty stomach, and follow up after a meal. Wash down the sports supplement with juice or water and in no case with milk. To increase the secretion of growth hormone, the third dose is taken immediately before bedtime.
l ornithine found in walnuts
With intramuscular consumption, the daily dose of ornithine ranges from 4 to 14 g, divided into 2 injections. Intravenously, 4 g of the active substance is administered once a day.
To increase the rate of fat burning, the intake of ornithine is supplemented with amino acids such as carnitine, arginine. In synergy with niacinamide, calcium, vitamin B6, vitamin C and potassium, the rate of growth hormone synthesis increases.
Contraindications and side effects
Ornithine is contraindicated in pregnant and lactating women.
It is unacceptable to use a dietary supplement as a sports nutrition for people suffering from schizophrenia and renal failure in excess of the maximum permissible norm of creatinine (3 mg / 100 ml).
The amino acid supplement may cause nausea, diarrhea, and vomiting.
The drug reduces the speed of motor reactions. As a sedative, ornithine leads to a general decrease in concentration.
In rare cases, jet administration of an amino acid leads to shortness of breath and pain in the sternum.
Summary
The paper presents the pathogenesis of liver failure. Data on the treatment of patients with liver cirrhosis of various etiologies complicated by hepatic encephalopathy are presented. A large number of different tests and biochemical parameters showed the positive role of L-ornithine-L-aspartate (Ornitox) in stabilizing the condition of patients, 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 is converted by the liver to the less toxic compound urea (urea) during the ornithine cycle and excreted by the kidneys.
At the same time, ammonia is involved in the resynthesis of amino acids and keto analogs of amino acids, and this process is called "reductive amination".
In a healthy body, a certain balance of ammonia is constantly maintained, and the main sources of its formation are:
- large intestine (processing of protein and urea by bacterial flora);
- musculature (in proportion to physical activity);
- small intestine (decomposition of the amino acid glutamine - the main source of energy for the cells of the intestinal mucosa);
- liver (breakdown of proteins).
In various diseases that lead to disorders of ammonia metabolism (most often this occurs in violation of liver function - hepatitis, cirrhosis), the level of this chemically active substance becomes one of the main causes of severe endotoxicosis.
The pathological symptoms that occur in acute or chronic hepatic encephalopathy are based on the hypothesis that endogenous neurotoxins and amino acid imbalance resulting from hepatocyte deficiency and/or portosystemic shunting of the 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 a violation 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 macroergic compounds is reduced.
Undoubtedly, the role in this process of increasing the content of GABA (gamma-aminobutyric acid) - an important inhibitory mediator. As a result of liver damage, the level of activity of GABA transaminase, which plays an important role in the elimination of excess GABA, decreases, which aggravates the course of encephalopathy.
In recent years, the main cause of the development of liver failure is the glia hypothesis, which links two levels: the liver - the brain. According to this hypothesis, hepatocellular insufficiency 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 a 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, and neurological disorders that develops in patients with acute or chronic liver 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 given in table. 1 use a variety of psychometric tests.
Regardless of the causes of liver failure, an important role in the treatment of this disease is played by a protein-restricted diet, 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, preparations of amino acids with a branched side chain are sometimes used. Zinc may also be used as an adjunctive therapy.
In recent years, the most promising for the utilization of ammonia is the appointment of drugs based on L-ornithine-L-aspartate. L-ornithine activates ornithine carbamoyl transferase and carbamoyl phosphate synthetase, the first enzyme of the urea synthesis cycle, in periportal hepatocytes.
L-ornithine and L-aspartate are substrates of both urea and glutamine synthesis cycles. Glutamine synthetase reaction is activated under the action of L-ornithine-L-aspartate not only in the liver, but also in the muscles.
It is also important that aspartate is integrated into the Krebs cycle, that is, it increases the synthesis of macroergs and reduces the formation of lactic acid, which, in turn, reduces the permeability of the BBB for toxic substances.
Here are its main pharmacological properties.
L-ornithine-L-aspartate (Ornitox) has a dual mechanism by 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 stimulator 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;
- contributes to the normalization of the acid-base balance of the body;
- promotes the production of insulin and somatotropic 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 taking place in mitochondria, due to which it increases the energy supply of the tissue;
- has an anabolic effect on the muscles.
The second most important drug in the treatment of this pathology is Glutargin (arginine glutamate), which has also shown to be sufficiently effective 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:
- change in the balance of intracellular potassium;
- hyperthermia, shortness of breath, the appearance of pain behind the sternum - these episodes most often occur after rapid intravenous administration 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 neuron receptors 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 advantages of arginine glutamate, but may limit its use.
The purpose of the study was to determine the effectiveness and safety of complex therapy in patients with hepatic encephalopathy of various genesis II-III degree.
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 predominated — 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, in 15.6% of cases liver damage was of mixed origin and in 18.0% of viral etiology.
When assessing the objective status, dyspeptic syndrome was diagnosed in 100% of patients, pain syndrome in 78%, icteric syndrome in 67%, edematous-ascitic syndrome in 82%, cytolytic syndrome in 82%, hypersplenism in 74%.
The patients were divided into three equal groups.
The first (main) received Reamberin, Cytoflavin, 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 intravenously, at a rate of 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 dose of L-ornithine-L-aspartate (Ornitox) averaged 10 g, which was administered per 400 ml of saline intravenously. The rate of administration is 8-12 drops per 1 minute. The duration of therapy was 10 days. In the future, patients were recommended oral administration of the drug.
Signs of hepatic encephalopathy exhibited in all examined and are presented in Table. 2.
Results and its discussion
Evaluation of the general condition of patients after 10 days from 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 in the study of the levels of fermentemia 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 symptoms of hepatic encephalopathy. This improvement was more pronounced in patients in the Ornitox group (Table 5).
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 levels.
A 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 is involved in biochemical cycles at earlier stages of disturbed metabolic processes, and also due to the incorporation of both amino acids into the ornithine cycle, which contributes to more efficient neutralization (utilization) of ammonia and, as a result, - 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. Based on the fact that a violation of ammonia metabolism occurs immediately with liver damage, it is obvious that it is advisable to include L-ornithine-L-aspartate - (Ornitox) in therapy in the early stages of the disease. The duration of treatment depends on many reasons and can last, in our opinion, for a long time. The use of higher doses of the drug is advisable in patients with acute liver failure.
With long-term use of Ornitox in sufficiently large doses, we did not observe side or undesirable effects, which indicated the safety of this drug.
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 insufficiency against the background of the use of universal cytoprotectors, which improve the function of not only hepatocytes, but also neurons.
Bibliography
1. Golubovskaya O.A., Shkurba A.V. The effectiveness of Ornitox in the complex treatment of fulminant liver failure in the clinic of infectious diseases. - 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. Khirurgiya. - 2010. - No. 3. - S. 112-115.
3. Shipulin V.P., Chernyavsky V.V. Toxic hepatitis: how to increase 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 thiocetam 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. Modern gastroenterology. - 2010. - No. 4 (54). - S. 38-43.
Included in medications
ATH: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 to
tilization of ammonium groups in the synthesis urea (in the ornithine Krebs urinary cycle).Also, the drug promotes the production of somatotropic hormone and insulin, improves protein metabolism.
Reduces the concentration of ammonia in the blood plasma, contributes to the normalization acid-base state body and the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.
Pharmacokinetics:When ornithine is ingested, 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, cirrhosis of the liver, hepatic encephalopathy (latent and severe), 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 additive to preparations for parenteral nutrition in patients with protein deficiency.
IV.E40-E46.E46 Protein-energy malnutrition, unspecified
XI.K70-K77.K72 Liver failure, not elsewhere classified
IV.E70-E90.E72.2 Urea cycle metabolic disorders
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 per 100 ml).
Hypersensitivity.
Lactation.
Children's age up to 18 years.
Carefully:Pregnancy.
Pregnancy and lactation:If necessary, use during lactation should decide on the termination of breastfeeding.
Dosage and administration: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 a day.
Intravenous drip
: dose, duration and frequency of infusions, duration of treatment are determined individually, usually 20 g per day (previously diluted in 500 ml of infusion solution, the maximum infusion rate is 5 g per hour or 40 drops per minute); it is possible to increase the dose to 40 g per day.Intravenous bolus 2-4 g 1-2 times a day.
Side effects:Skin reactions.
Nausea.
Vomit.
Overdose:Symptoms: increased severity of dose-dependent side effects. Treatment: the drug should be discontinued, gastric lavage, activated charcoal, symptomatic treatment.
Interaction:Preparation f pharmaceutically incompatible(R Solutions must not be mixed in the same 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 particular dosage form of ornithine, compliance with specific indications should be observed.
The course of treatment can be repeated every 2-3 months.
With the introduction of the drug in high doses, the concentration of urea in blood plasma and urine should be monitored.
Influence on the ability to drive vehicles and control mechanisms
The drug can cause a slowdown in the speed of psychomotor reactions and impaired concentration.
Instructions2,5-diaminopentanoic acid
Chemical properties
Ornithine - diaminovaleric acid . Structural formula of the chemical compound: NH2CH2CH2CH2CH(NH2)COOH. In peptide sequences, the substance is designated Orn. The agent is present in free form in living organisms, is a component of some.
If carbon monoxide 4 is split off from the molecule of diaminovaleric acid (the reaction occurs during the process of rotting the corpse), then putrescine - one of the main components of cadaveric poison. L-ornithine (L-ornithine) is the optical isomer of the substance. It was first synthesized from shark liver tissue in 1937. The amino acid is a colorless crystal that is readily soluble in water and alcohol, and sparingly soluble in ether. Molecular weight of a chemical compound = 132.2 grams per mole. About 50 tons of this lek are produced annually in the world. facilities.
In the composition of various drugs, the substance is most often in the form ketoglutarate or aspartate .
pharmachologic effect
Hepatoprotective , detoxification , hypoazotemic .
Pharmacodynamics and pharmacokinetics
Ornithine takes part in the synthesis processes urea (V ornithine cycle ), contributes to the utilization of ammonium groups, reduces the concentration ammonia in blood. Thanks to this drug, the acid-base balance of the body is normalized and GH is also produced.
If you use the medicine for diseases that require parenteral nutrition, it significantly improves protein metabolism.
After oral administration ornithine aspartate dissociates into aspartate And ornithine , which are quickly and completely absorbed in the small intestine using active transport reactions through epithelial tissues. The drug is excreted through the kidneys with urine, during the urea cycle.
Indications for use
The drug is prescribed:
- at hyperammonemia ;
- patients with or;
- with latent or pronounced hepatic encephalopathy ;
- as part of the complex treatment of disorders of consciousness ( precoms and ) due to hepatic encephalopathy ;
- as an additive to parenteral nutrition for patients with protein deficiency;
- for diagnostics, dynamic study of work.
Contraindications
L-ornithine contraindicated to receive:
- for this substance;
- patients with severe renal insufficiency ( creatinine more than 3 mg per 100 ml).
Side effects
Ornithine is well tolerated. Rarely may occur: allergic skin rashes, vomiting, nausea. If an allergy occurs, it is recommended to consult a doctor.
Ornithine, instructions for use (Method and dosage)
The drug is administered intravenously, orally or intramuscularly.
Intravenously, the drug is prescribed in the form of infusions. Dosing regimen, frequency and duration of infusion depend on various parameters and are determined by the attending physician on an individual basis. Usually 20 grams of a substance is dissolved in 500 ml infusion solution . The maximum rate at which the drug can be administered is 5 grams per hour. The maximum daily dosage is 40 g.
Overdose
There is no information about drug overdose.
Interaction
Ornithine is not pharmaceutically compatible with benzylpenicillin benzathine , , , And ethionamide .
The medicine must not be mixed in the same syringe with and benzathine benzylpenicillin .
Terms of sale
No prescription needed.
special instructions
If vomiting or nausea occurs during intravenous administration of the drug, it is recommended to reduce the rate of infusion.
It is necessary to strictly observe the compliance of a certain dosage form of the drug with indications for admission.
During pregnancy and lactation
Only the attending physician can prescribe medicine to pregnant women according to direct indications. It is recommended to stop breastfeeding, as the drug is excreted in milk.
Preparations containing (Analogues)
Coincidence in the ATX code of the 4th level:Structural analogues of this substance: , Ornilatex , Larnamin , Ornitsetil . Also lek. the agent is a part of: solution for infusion administration Aminoplasmal Hepa , Aminoplasmal E , .
0
In a clinical multicenter comparative study, the efficacy and safety of L-ornithine-L-aspartate (Hepa-Merz), belonging to the group of hepatoprotective agents that affect metabolic disorders, were 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 terms of frequency, it ranks third after acute appendicitis and cholecystitis. Treatment of acute pancreatitis, especially its destructive forms, is still a difficult surgical problem due to high mortality - from 25 to 80%.
The liver is the first target organ that bears the brunt of pancreatogenic toxemia in the form of a massive intake 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, deep microcirculatory disorders develop in the liver parenchyma, activation of mitochondrial factors of cell death and induction of apoptosis of hepatic cells occur in hepatocytes. Decompensation of internal detoxification mechanisms 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 severe complications of acute pancreatitis. Often it predetermines 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, there is a violation of various liver functions, which significantly worsens the results of treatment and in 72% of cases is the direct cause of death.
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 directions in the complex therapy of liver failure in acute pancreatitis is the inclusion of hepatoprotectors in the treatment, in particular L-ornithine-L-aspartate (Hepa-Merz).
The drug has been on the pharmaceutical market for several years, it has proven itself 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 study 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 patients ranged from 17 to 86 years, on average - 46.7 (34; 58) years. In 156 (67.2%) patients, the edematous form of pancreatitis was diagnosed, in 76 (32.8%) - destructive forms: in 21 (9.1%) - hemorrhagic pancreatic necrosis, in 13 (5.6%) - fatty pancreatitis, in 41 (17.7%) - mixed, 1 (0.4%) - post-traumatic.
All patients received basic complex conservative therapy (blockade of the exocrine function of the pancreas, infusion-detoxification, antibacterial agents).
L-ornithine-L-aspartate (Hepa-Merz) in the 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 inclusion of the patient in the study according to the developed scheme: 10 g (2 ampoules) intravenously at a rate of administration of not 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 a granulate, 1 sachet, 3 g, 3 times a day for 10 days).
The severity of the patients' condition was assessed using the SAPS II physiological condition severity scale. Depending on the total SAPS II score, both groups were divided into 2 subgroups of patients: with a total score<30 и >30.
Subgroup with the severity of the condition according to SAPS II<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 >30 consisted of 120 (51.7%) patients, including 85 (71%) from the main group: men - 56 (65.9%), women - 29 (34.1%) ), mean age - 58.2 (45; 66.7) years, severity of condition - 36.3+5.6 points; there were 35 (29%) patients from the control group: men - 17 (48.5%), women - 18 (51.4%), mean age - 55.4 (51; 63.5) years, severity of condition - 39 .3±5.9 points.
The study identified 4 base points: 1st, 3rd, 5th and 15th days. To assess the effectiveness of treatment, the severity of the patients' condition was determined in dynamics according to the SOFA Integral Scale; studied 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 in the number connection test (TST).
Mathematical processing of the actual material was carried out using the basic methods of biomedical statistics using the Microsoft Office Excel 2003 and BIOSTAT software package. When describing group characteristics, we calculated the standard deviation of the mean value of a trait with its parametric distribution and the interquartile interval - with a nonparametric one. The significance of differences between the 2 parameters was assessed using the Mann-Withney and x2 tests. Differences were considered statistically significant at p=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 the severity of the condition according to SAPS II> 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 were related to the parameters of the cytolytic syndrome (ALT, ACT) and the rate of recovery of neuropsychic functions.
During dynamic monitoring of the severity of the condition of patients, assessed by the SOFA scale, more rapid normalization was also noted in the main group (Figure "Dynamics of the severity of the condition in patients with a total SAPS II score> 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), respectively. .7) and 2.9 (1; 4) points (p=0.456, Mann-Withney), on the 5th day - 1 (0; 2) and 1.4 (0; 2) points, respectively (p=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 = 0.028, Mann-Withney).
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 the ALT content in patients with a total SAPS II score > 30" and "Dynamics of the ACT content in patients with a total SAPS II score >30").
On the 1st day, the levels of ALT and ACT exceeded the upper limit of normal in all patients. The average content of ALT 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 respectively 83 U/l (25; 153.5) and 126.6 U/l (25; 153.5) (p-0.021, Mann-Withney), ACT - 81.5 U /l (37; 127) and 104.4 U/l (37; 127) (p=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=0.079, Mann-Withney), a ACT - 58 U/l (38.8; 80.3) and 71.6 U/l (38.8; 80.3) (p=0.068, Mann-Withney). The concentration of ALT and ACT in patients treated with L-ornithine-L-aspartate (Hepa-Merz) reached normal values on 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=0.007, Mann-Withney), the ACT level was 31.5, respectively. U/l (25; 54) and 54.2 U/l (25; 70) (p=0.004, Mann-Withney).
The study of attention with the help of TSC in patients with the severity of the condition according to SAPS II >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 >30").
By the 3rd day, their counting rate was 18.8% higher than in the comparison group: it took 89 s (69.3; 105) and 109.6 s (90; 137), respectively (p=0.163, Mann -Withney); by day 5, the difference reached 34.7%: 59 s (52; 80) and 90.3 s (66.5; 118), respectively (p=0.054, Mann-Withney). On the 15th day in the main group, it 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=0.002, Mann-Withney.
The immediate results of treatment should also include a reduction in the duration of hospitalization by an average of 18.5% in patients of the main group (p=0.049, Mann-Withney).
In the control group, there were 2 (6%) deaths from increasing multiple organ failure (p=0.15; Χ 2), in the main group there were no deaths.
The 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 discontinued due to the development of an allergic reaction, in 5 (2.7%) dyspeptic symptoms were noted in the form of nausea, vomiting, which stopped with a decrease in the rate of drug administration.
The 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.
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