Optimization of therapeutic tactics in patients with opioid addiction

Introduction: Treatment and rehabilitation of patients with opioid addiction is a complex medical and social problem, covering not only the restoration of normal mental status, but also the physical health of patients. In this regard, the search for effective means that can neutralize the effects of chronic drug intoxication is one of the priorities in the treatment of these patients. In recent times, more and more attention is paid to the participation pathochemical reactions in the genesis of many diseases [2]. 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 [3]. 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 at prolonged narcotization [1]. Nevertheless, the association of the level of reactive oxygen species and the characteristics of the course of withdrawal symptoms, the impact of somatic pathology, have been conducted. The object of the study was to examine the pathogenetic significance of systemic oxidative stress, depending on the duration of opioid narcotization and the effectiveness of antioxidant therapy.

Methods: The study included 52 male patients aged from 18 to 55 years with clinically-defined the drug addiction (ICD-10 — F11.2). All patients were male, average age 36.9 ± 6.7 years, experience of regular use of drugs from 1 year to 10 years. Patients were examined in the clinic of addiction in Tashkent. Two groups of patients were examined: the 1st group-26 patients who received complex treatment according to the conventional scheme; the 2nd group-26 patients who underwent conventional treatment in combination with antioxidants. To analyze the importance of clinical and dynamic factors in the development of opioid addiction we used clinical-psychopathological, biochemical and statistical methods. Also used clinical scale qualified assessments morbid attraction of Vinnikova (2001). To determine the intensity of lipid peroxidation to determine the level of malondialdehyde was conducted (MDA) in serum, the activity of catalase in the blood, the definition of medium molecular peptides (MMP). The control group consisted of 12 healthy men of the corresponding sex and age.

Results: The generation of reactive oxygen species is accompanied by damage to protein and lipid molecules. In the interaction of reactive oxygen species with these molecules are formed low molecular weight products with toxic effects. These products include medium-molecular peptides having a molecular weight of not more than 5000 Da. 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. 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 — medium molecular peptides (0.063 ± 0.009*) increase 3 times and oxidative stress — malondialdehyde (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 (malondialdehyde 0.51 ± 0.09 nmol/mg protein, medium molecular peptides 0.021 ± 0.001 AU/mg protein, catalase 40.1 ± 1.7 mmol of H2 O2 /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 of malondialdehyde — 2.61 ± 0.13** and medium molecular peptides — 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). Differences indicators, depending on the duration of narcotization in all cases were significant (Р < 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 pathogenetic therapy with an effect on metabolic processes with the use of antioxidants, apply individual approaches appointment of psychotropic drugs in the framework of the existing treatment standards. Along with the traditional as membrane-pathogenetic therapy administered ethylmethylhydroxypyridine succinate (mexidol) at a dose of 500 mg/day for 2 admission. A comparative study of two groups of drug users receiving different treatments — traditional and optimized in combination with ethylmethylhydroxypyridine succinate (mexidol) shows a more pronounced therapeutic effect bioregularly antioxidant therapy. As in people, long-term opiate abusers and drug addicts with experience within a 1-yearoptimized therapy including antioxidants have beneficial effects more pronounced in patients subgroup with duration of narcotization over 1 year. They noted a significant decrease from baseline in MMP (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 of withdrawal symptoms, reduced craving for the drug, and the low intensity of the generation of oxidative stress in the blood correlates with the effectiveness of therapy.

Discussion: Thus, the peculiarity of biochemical disorders of homeostasis in this category of patients is the development of enhanced generation of reactive oxygen species in the blood, resulting in the development of endotoxemia due to the accumulation of degradation products of macromolecules of protein and lipid nature. Probably, such an increase in the studied parameters was a consequence of the insufficiency of the protective system, including both enzymes with antiperoxide and antiradical mechanism of action, and antioxidants. Excessive formation of reactive oxygen species in abstinence initiates the process of lipid peroxidation in the blood of patients, which is confirmed by an increase in the level of MDA in plasma by 80–92% relative to the norm. Intensification of lipid peroxidation in drug addiction can lead to oxidative damage of biomolecules and cell structures. The results of the study show that in the first group of patients the dynamics of most of the studied biochemical parameters indicates the preservation of oxidative stress. The inclusion of antioxidants in the complex treatment of patients of the second group leads to the stimulation of the antioxidant system of the blood. 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.

Conclusions: 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 ethylmethylhydroxypyridine succinate (mexidol) in the complex treatment of opioid addiction contributes to sustainable and prolonged suppression of free radical oxidation in the blood, observed immediately after treatment.