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The intensity of systemic oxidative stress and optimization of therapeutic tactics in patients with opioid addiction
Abdullaeva Vasila Karimbekovna, Tashkent Pediatric Medical Institute, chief of department of psychiatry and addiction E-mail: vasila.abdullaeva@tashpmi.uz
The intensity of systemic oxidative stress and optimization of therapeutic tactics in patients with opioid addiction
Abstract: The pathogenetic significance of systemic oxidative stress, depending on the duration of opioid narcotization and availability of comorbid damage to the liver for further optimization of therapeutic tactics is examined in the article. Inclusion of alpha-tocopherol in the complex treatment of opioid addiction contributes to sustainable and prolonged suppression of free radical oxidation in the blood, observed immediately after treatment.
Keywords: opioid addiction, systemic oxidative stress, therapeutic tactics, alpha-tocopherol.
In recent times, more and more attention is paid to the participation pathochemical reactions in the genesis of many diseases [5, 60-62]. The study of the liver in heroin addiction is extremely important, because depends on it for abstinence for neutralization and clearance of the drug is carried by the liver [6, 10-12]. In the literature, there is enough information, says the activation of free radical oxidation and the presence of endogenous intoxication with heroin addiction, shows aggravation of lipid peroxidation, increase the level of nitric oxide and peroxide hemolysis of red blood cells with increasing doses of heroin, as well as the correlation between low levels of NO and low concentrations of antioxidants plasma (vitamin E and C) at prolonged narcotization [1, 59-63]. Nevertheless, the association of the level of reactive oxygen species (ROS) and the characteristics of the course ofwithdrawal symptoms, the impact of somatic pathology, have been conducted.
The aim of the study was to investigate the pathogenetic significance of systemic oxidative stress, depending on the duration of opioid narcotization and availability of comorbid damage to the liver for further optimization of therapeutic tactics.
Material and methods. The study included 52 male patients aged from 18 to 55 years with clinically-defined the drug addiction (ICD-10 — F11.2). To analyze the importance of clinical and dynamic factors in the development of opioid addiction patients are divided into 2 groups: one group of opioids addicts in conjunction with somatic disorders and the comparison group is represented by opioids addicts without physical illness. Data on the primary somatic disorders in the primary study group: the presence of viral hepatitis B and C. The main methods of investigation were clinical-psycho-pathological. To determine the intensity of lipid peroxidation (LPO) to determine the level of malondialdehyde was conducted (MDA) in serum [4, 66-68], the activity of catalase in the blood [3, 81-83], the definition of middle molecules (SMP) [2, 10-15].
Results and discussion. During the study we found that the total level of enzyme was higher in the study group than the control group, but is within the reference range (11-66 U/L), indicating the absence of acute or chronic liver disease. A deeper analysis of the data revealed that the rate of generation of RO S in the blood, and ALT activity in the examined patients varies widely, and increases with increasing duration of narcotization, accession of liver damage in the form of toxic and infectious hepatitis, which was the basis to allocate a group ofpa-tients with duration of narcotization up to 1 year — 8.3 ± 2.1 months and addicts who use opium for more than 1 year — 20.2 ± 9.8 months.
With this approach to the interpretation of the data could reveal that patients with a duration of narcotization up to 1 year has moderately severe endotoxemia — SMP (0.063 ± 0.009*) increase 3 times and oxidative stress—MDA (1.31 ± 0.10*) increase 2.6 times due to lower activity of catalase in 1.5 times (26.9 ± 1.1*) compared with the control
(MDA 0.51 ± 0.09 nmol/mg protein, SMP 0.021 ± 0.001 AU/mg protein, catalase 40.1 ± 1.7 mmol of H2O2/mln. Erith * m), whereas patients with more than one year duration of narcotization the reduction of catalase activity was observed in 3.5 times — 11.6 ± 0.9** and the level ofMDA — 2.61 ± 0.13** and SMP — 0.109 ± 0.012** exceeded control in 5.0 and 5.5 times, respectively (Note: * — Significant in relation to the control, P < 0.05; ** — Significantly with respect to narcotization duration up to 1 year). In the blood increase in ROS generation in opioid addicts occur with increasing time of drug dependence and connection of liver damage. Differences indicators MDA, SMP, catalase and blood ALT, depending on the duration of narcotization in all cases were significant (P < 0.05).
It should be noted that our results of research on the state of the antioxidant system in patients who use opioids, according to the oppression of the enzymatic link of antioxidant protection and the need to include substances with antioxidant properties, in the treatment of these patients. Relief of oxidative stress necessary to normalize membrane-destructive processes in the body, primarily in the brain and liver, will provide adequate metabolism microsomal oxidative preparations system used in treatment — antidepressants, antipsychotics, etc., optimizes post opioid detoxified, thus shortening during the withdrawal syndrome and reduce its severity.
Based on the identified pathochemical features of the course of acute and chronic drug intoxication opiates, as well as the availability of the system operating in the blood of opioid addicts, the traditional therapeutic tactics has been optimized as follows: included pathoge-netic therapy with an effect on metabolic processes with the use of antioxidants, apply individual approaches appointment ofpsychotropic drugs in the framework of the existing treatment standards. In relief of withdrawal syndrome used psychopharmacological drugs according to the protocol of treatment of opioid, aimed at the relief of its main components: analgesics (diclofenac), tranquilizers (sibazon), as well as a means to suppress craving for drug (carbamazepine). By this scheme, in some cases, for the relief of the craving for the drug was added neuroleptic. Limited use of antipsychotic drugs in patients with comorbid pathology was associated with a paradoxical clinical effects by increasing agitation, high frequency of side effects with the development of phenomena neuroleptic syndrome, neurological complications. When included in the treatment regimen neuroleptic his choice was determined by the peculiarities of psychopathological component withdrawal syndrome. In opioid addicts with comorbid disorders during the treatment of withdrawal symptoms as pathoge-netic therapy of viral hepatitis carried out a massive infusion of crystalloid and colloid solutions, glucose solutions with the correction of electrolyte composition blood and acid-base balance. Adequate fluid therapy led to an improvement in general condition ofpatients and increased the tolerance used in the relief of withdrawal symptoms of
Section 4. Medical science
drugs. Along with the traditional as membrane-pathogenetic therapy administered alpha-tocopherol at a dose of 800 mg/day for 2 admission. Also, patients with comorbid pathology throughout the course of treatment prescribed gepatoprotektors. Doses of drugs consumed were determined taking into account biological factors: a daily dose of heroin, the duration of narcotization, the constitution and weight of the patient. To reduce the risk of complications and minimize the side effects of psychotropic drugs prescribed may lower doses in patients with comorbid pathology. At post abstinent disorders drugs ofchoice were antidepressants and neuroleptics. The study was conducted to compare the efficacy ofconventional therapy and optimize treatment with the antioxidant alpha-tocopherol. Excessive ROS during abstinence initiates the process of lipid peroxidation (LPO) in the blood of patients in both clinical groups, as evidenced by the increase in MDA level, depending on the duration of narcotization with respect to the norm. The most important role in the regulation of free-radical process belongs to the antioxidant enzyme catalase, which functions conjugate and inhibits lipid peroxidation in the step of activation of oxygen, the origin and the chain branching process.
A comparative study of two groups of drug users receiving different treatments — traditional and optimized in combination with alpha-tocopherol shows a more pronounced therapeutic effect bioreg-ularly antioxidant therapy. In the traditional method of treatment, the level ofMDA was significantly higher than before the treatment in the subgroup with the duration of narcotization over 1 year (2.94 ± 0.10**) and did not differ significantly from the index before treatment in the subgroup with the duration of narcotization to 1 year (1.24 ± 0.09**), indicating that the lack of effect of traditional therapy on the operating parameters. Moreover, in patients with liver damage, the operating system on the background of intensified conventional therapy.
When using the alpha-tocopherol in the composition optimized therapy lowering MDA levels observed in patients both subgroups, although its concentration is not reached control values. The catalase activity was restored to the control level in all patients and was not statistically different from the control group level. It is
also noteworthy that there were significant differences between the effectiveness of the optimized therapy with antioxidant relatively traditional in terms of MDA, SMP and catalase.
As in people, long-term opiate abusers and drug addicts with experience within a 1-year-optimized therapy including antioxi-dants have beneficial effects more pronounced in patients subgroup with duration of narcotization over 1 year. They noted a significant decrease from baseline in SMP (0.045 ± 0.012***) and MDA (1.33 ± 0.10***), which proves that the contribution of the liver in the system OS development with opiate addiction, as well as the fact that the recovery of the antioxidant capacity of the body leads to the relief of the OS (Note: * — Significant in relation to the traditional method of treatment, P < 0.05; ** — Significantly relative to controls (P < 0.05); *** — significantly relative to the treatment (P < 0.05)).
The study period of abstinence in patients receiving optimized treatment including an antioxidant, found that significantly reduced the duration ofwithdrawal symptoms, reduced craving for the drug, and the low intensity of the generation of ROS in the blood correlates with the effectiveness of therapy. Listing of alpha-tocopherol in the range of optimized therapy for opioid dependence contributes to sustainable and prolonged suppression of free radical oxidation in the blood, observed immediately after treatment.
Conclusion. Using optimized therapy helped achieve a significant reduction from baseline indicators of lipid peroxidation, which proves that the liver contribute to the development of the system operating in opium addiction, as well as the fact that the recovery of the antioxidant capacity of the body leads to the relief of the oxidative stress. The study period of abstinence in patients receiving optimized treatment including an antioxidant, found that significantly reduced the duration of withdrawal symptoms, reduced craving for the drug, and the low intensity of the generation of active forms of oxygen in the blood correlates with the effectiveness of therapy. Inclusion of alpha-tocopherol in the complex treatment of opioid addiction contributes to sustainable and prolonged suppression of free radical oxidation in the blood, observed immediately after treatment.
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Azizova Nigora Davlyatovna, senior staff scientist of Republican Specialized Scientific and Practical Medical Center of Pediatric, Republic of Uzbekistan
E-mail: evovision@bk.ru
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