Gabriela Kehayova

Fentanyl is an extremely potent and highly lipophilic synthetic opioid, whose toxicity is marked by significant respiratory depression and central nervous system impairment. Naloxone is the primary antidote for opioid overdose; however, there is an increasing interest in intravenous lipid emulsion (ILE) as a supplementary therapeutic approach for poisoning with lipophilic agents. This study aimed to assess the antidotal effect of ILE in cases of experimental fentanyl toxicity and to compare its effectiveness with that of naloxone, both when administered alone and in combination. The research was performed on male Wistar rats. Various parameters were monitored, including heart rate, respiratory rate, nociceptive response (Hot Plate test), motor coordination (Rota-rod test), and behavioral metrics (Open Field test). Fentanyl induced significant cardiorespiratory depression and analgesia. Naloxone successfully counteracted the respiratory and nociceptive effects. ILE demonstrated positive effects on specific cardiorespiratory parameters, especially in the initial recovery phase, although its influence on analgesia was less pronounced and occurred later. The combination of naloxone and ILE appeared to promote earlier cardiorespiratory enhancement compared to naloxone used alone; nevertheless, these variations must be viewed with caution due to the brief duration of fentanyl’s effects and the absence of evidence supporting an increased maximal therapeutic benefit. These findings endorse the potential role of ILE as an adjunctive, rather than a standalone, antidotal treatment for acute fentanyl poisoning.

Fentanyl is a highly potent and lipophilic μ-opioid receptor agonist associated with severe neurorespiratory toxicity and a growing incidence of overdose. Although naloxone remains the standard antidote, its relatively short half-life and exclusively pharmacodynamic mechanism of action may limit its efficacy in intoxications involving highly lipophilic opioids. The aim of this study was to evaluate the therapeutic effects of intravenous lipid emulsion (ILE), administered alone or in combination with naloxone, in a rat model of acute fentanyl toxicity. Thirty adult male Wistar rats were randomly assigned to five groups ( n = 6 per group): vehicle control; fentanyl (0.44 mg/kg, i.p.); fentanyl + naloxone (1.0 mg/kg, i.p.); fentanyl + ILE (20%, 1.5 mL/kg, i.p.); and fentanyl + naloxone + ILE. Survival and clinical manifestations (loss of righting reflex [LORR], catatonia-like behavior, respiratory impairment, and convulsions) were assessed over 120 min. Survival was analyzed using Kaplan–Meier methodology, and nonparametric tests were applied for ordinal outcomes. No statistically significant differences in survival were observed ( p = 0.406). However, combination therapy significantly reduced the incidence of LORR compared to fentanyl alone ( p = 0.0152) and produced the most pronounced improvement in catatonia and respiratory impairment scores ( p < 0.001, Kruskal–Wallis test). In conclusion, combined naloxone and lipid emulsion therapy demonstrated superior attenuation of fentanyl-induced neurobehavioral and respiratory toxicity compared to monotherapy, suggesting complementary pharmacodynamic and pharmacokinetic mechanisms. Further adequately powered studies are warranted.

Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions.

Pharmacists are participants in the treatment and management of mental disorders as integral members of multidisciplinary healthcare teams. Their roles extend beyond dispensing medications to providing counseling, promoting adherence, managing drug interactions, assessing treatment outcomes, and supporting symptom management—all while ensuring empathy and confidentiality. They face challenges such as nonadherence, communication barriers, and public stigma. Pharmacists manage complex drug interactions, particularly those between psychiatric medications and nutritional supplements. In hospitals, clinical pharmacists optimize therapy, monitor treatment effectiveness, and train staff in mental health pharmacotherapy. This article emphasizes the need for specialized training for pharmacists to enhance their mental health care competencies. Countries such as the USA, UK, and Australia have successfully implemented such programs, while Bulgaria is integrating mental health care into pharmaceutical practice, expanding the responsibilities of pharmacists and raising public awareness. These achievements highlight the essential contribution of pharmacists to improving mental health outcomes and addressing related challenges.

N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC’s diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems—including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways—by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC’s role in gene expression and the regulation of cortisol levels. The extensive range of NAC’s neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research.

The aim of this study was to evaluate the antidiabetic therapy during hospitalization, as well as that recommended at discharge from a single university endocrinology clinic for all type 2 diabetes patients admitted over a 12-month period. Of the 464 cases, 345 (74.4%) were emergency admissions and 119 (25.6%) were planned hospitalizations for poor glycemic control. At discharge, one antidiabetic medication was prescribed in 133 patients (28.7%), two in 169 (36.3%), three in 103 (22.2%), and 48 (10.4%) received four or more glucose-lowering agents. Of all patients, 175 (37.7%) were taking sodium-glucose cotransporter 2 inhibitors (SGLT2i), 71 (15.3%) glucagon-like peptide 1 receptor agonists (GLP1-RAs), and 42 (9.1%) both organ-protective classes. Among patients with concomitant cardiovascular disease, chronic kidney disease, or both (n = 300; 64.7%), SGLT2i was prescribed in 150 (50.0%), GLP1-RA in 51 (17.0%), and both in 34 individuals (11.3%). Our results indicate that more than half of the patients at cardio-renal risk (55.7%) received at least one organ-protective medication.

Botulinum toxin, a potent neurotoxin produced by Clostridium botulinum, has widespread applications in both medical and aesthetic practices due to its ability to inhibit neuromuscular transmission. In clinical medicine, it is used to treat various conditions such as chronic migraines, spasticity, and hyperhidrosis. In aesthetic medicine, it is primarily employed for wrinkle reduction and facial rejuvenation, providing significant efficacy with minimal recovery time. Despite its established therapeutic benefits, improper administration of botulinum toxin can lead to serious adverse effects, including muscle weakness, respiratory compromise, and localised reactions. Therefore, it is essential to ensure precise dosing, skilled injection techniques, and appropriate patient selection to maximise therapeutic outcomes while minimising risks. As the use of botulinum toxin continues to expand in both medical and cosmetic settings, there is a critical need for enhanced safety protocols and stringent regulation to ensure its safe and effective application.

The misuse of fentanyl and its analogs has significantly worsened the opioid crisis, leading to a sharp increase in overdose fatalities. Fentanyl overdose primarily causes severe respiratory depression, which can result in hypoxia, cardiac arrest, and death, often exacerbated by co-intoxication. Additionally, the opioid in question can induce chest wall rigidity, further complicating treatment procedures. Despite international control efforts, the drug’s high potency and low cost have fueled its widespread trafficking, including in counterfeit pills. While naloxone is the primary antidote, its effectiveness is limited, highlighting the need for stronger, long-acting treatments. Factors such as polypharmacy, prescription misuse, and environmental exposure – as well as the potential for fentanyl’s use as a chemical weapon – pose significant public safety risks. In conclusion, addressing the current wave of the opioid crisis requires a comprehensive approach, integrating treatment solutions, prevention, and harm reduction strategies.

Fentanyl, a potent synthetic opioid, is widely used for severe pain management and anesthesia but poses significant risks due to its extreme potency and addictive potential. It acts primarily on μ-opioid receptors, with additional effects on κ- and δ-receptors, producing analgesia and adverse effects, such as respiratory depression, mediated via G-protein and β-arrestin signaling pathways. Fentanyl’s pharmacokinetics include rapid onset and a short duration, with extensive liver metabolism via CYP3A4 enzymes. Its high lipophilicity allows it to cross the blood-brain barrier quickly, contributing to its rapid central nervous system effects and associated risk of respiratory depression. Despite its therapeutic value, fentanyl’s potential to induce tolerance and dependence, coupled with escalating illicit use, underscores the need for enhanced prevention strategies, improved overdose management, and stricter regulatory measures to balance therapeutic utility with abuse prevention.

The nature and epidemiology of plant intoxications are still not well understood, with recent data being limited. The present study aims to report cases of plant poisoning in the clinical practice of the Clinical Toxicology Department at the Naval Hospital—Varna, Bulgaria, over a 20-year period (2003–2023). A documentary retrospective analysis of the hospitalized cases of poisoning with poisonous plants and their grouping into toxidromes was performed. During the study period, patients with plant poisoning admitted to our hospital unit accounted for 0.35% of a total of 12,857 hospitalized individuals. The distribution across the toxidromes based on clinical presentation revealed the highest frequency of anticholinergic, cyanogen, and ricin toxidromes. The majority of the intoxications resulted from unintentional exposure to plant toxins in adult individuals. Most cases followed a mild to severe clinical course, with patient discharge occurring between 2 and 5 days. No fatalities were recorded, thanks to the reported treatment methods. A relatively low incidence of plant-related poisonings was observed, with their predominant manifestations affecting the gastrointestinal, nervous, and cardiovascular systems. Increased reporting of epidemiological data and clinical experiences in the management of plant intoxications would substantially enhance researchers’ understanding of them and facilitate the development of a standardized treatment protocol.