New approaches of synthetic opioids poisoning treatment: the use of large Naloxone doses and prospects for the alternative antidotes creation

Abstract

Introduction. In the conditions of the spread of powerful synthetic opioids, the traditionally recommended doses of Naloxone may be insufficient; instead, a significant increase in the dose of Naloxone leads to side effects, which in turn creates a threat to life. Aim. Analysis of the results of own research and scientific information regarding the use of Naloxone in the treatment of synthetic opioids poisoning and the development of alternative antidotes. Materials and Methods. The medical data of 174 patients treated with the diagnosis: "Acute narcotic poisoning" (ICD-10:Т40.0-Т40.3) were studied. Laboratory studies were carried out by the method of immunochromatographic analysis and chromatographymass spectrometry. Statistical data processing was performed using the IBM SPSS Statistics 29.0.0.0 program, using Spearman's rank correlation analysis (r), with p ≤ 0.05. Results. Among patients who received Naloxone, the best dynamics according to the Glasgow coma scale at the 4th and 6th hours of observation were those who received 2-6 mg of Naloxone. A significant part of patients (76 cases, 43.68 %) required repeated administration of Naloxone due to the renarcotization, in such cases a direct correlation was established with the occurrence of undesirable clinical effects (r = 0.864, p = 0.05). A direct relationship between an increase in the dose of Naloxone and the development of arterial hypertension (r = 0.945, p = 0.01), convulsions (r = 0.887, p = 0.01), withdrawal and pain syndrome (r = 0.881, p = 0.01). In general, the occurrence of clinical effects was correlated with an increase in the dose of Naloxone (R2 = 0.92), however, the rank correlation analysis did not confirm the relationship between the dose of Naloxone and the development of pulmonary edema (r = 0.938, p > 0.05), cardiac arrhythmia (r= 0.598, p > 0.05), cardiac arrest (r= -0.146, p > 0.05). Conclusions. The use of high doses of Naloxone does not solve the problem of prevention of opioid overdoses and their effective treatment. The development of new models of antidotes to opioids using сovalent Naloxone nanoparticles, serotonin 5-HT1A agonists, Fentanyl-binding Cyclodextrin scaffolds, specific vaccines, etc. is considered promising. Keywords: opioids, antidotes, Naloxone, Fentanyl.