16 research outputs found
Study of the Effects of Intravenous Lipid Infusion in Acute Intoxications with Some Xenobiotics // Проучване ефектите на интравенозна липидна инфузия при остри интоксикации с някои ксенобиотици
No full textWe investigate the protective role of intravenous infusion of fat emulsions as an antidote in acute intoxications with some lipophilic xenobiotics, exhibiting neurotoxic effects - drugs and organophosphorus pesticides (clinical data) and in the experiment of insecticide dimethoate.
To achieve this goal, a retrospective study of poisonings with drugs from the group of benzodiazepines, antiepileptics and pesticides, with a focus on the widely used insecticide dimethoate for a 10-year period (2010-2020) of patients who passed through - Clinic for Intensive Treatment of Acute Poisoning and Toxic Allergies — Military Medical Academy – Varna. A comparative analysis of the main parameters entered in the medical records of patients treated without and with intravenous lipid emulsion - demographic data, cause of poisoning, type of toxic agent, comorbidity, clinical, clinical and laboratory studies on admission and treatment.
To identify adverse reactions associated with the use of the emulsion as an antidote, complications in the course of therapy, the length of hospital stay and the outcome of intoxication, with emphasis on mortality, were monitored.
In an in vivo experimental model of dimethoate-induced acute intoxication in experimental rats, the protective effect of the recommended bolus dose of 1.5 mL/kg 20% intralipid emulsion was investigated by examining changes in total motor activity, research behaviour, respiratory and heart rate of animals.
The effectiveness of the lipid emulsion was evaluated by analysing clinical and laboratory parameters related to basic vital functions.Настоящият дисертационен труд изследва протективната роля на интравенозната инфузия на мастни емулсии в качеството й на антидот при остри интоксикации с някой липофилни ксенобиотици, проявяващи невротоксично действие – медикаменти и фосфорорганични пестициди (клинични данни) и при експериментален модел на остра интоксикация с органофосфатния инсектицид диметоат.
За да се постигне целта е направено ретроспективно проучване на отравянията с лекарствени средства от групата на бензодиазепини, антиепилетиците и пестициди, с насока към широко използвания инсектицид диметоат за 10 годишен период (2010- 2020 година) на пациенти преминали през КИЛООТ- ВМА- Варна. Направен е сравнителен анализ на основните параметри, вписани в медицинската документация на болните лекувани без и със интравенозна липидна емулсия – демографски данни, причина за отравянето, вид на токсичния агент, коморбидност, клинични, клинико-лабораторни изследвания при постъпването и проведеното лечение.
За установяване на нежелани лекарствени реакции, свързани с приложението на емулсията като антидот, са проследени усложненията в хода на терапията, продължителността на болничния престой и изхода от интоксикацията, с акцент върху леталитета.
В in vivo експериментален модел на индуцирана с диметоат остра интоксикация при опитни плъхове е проучен протективния ефект на препоръчаната в хуманната медицина болус доза 1.5 mL/kg 20 % интралипидна емулсия, чрез изследване промените в общата двигателна активност, изследователското поведение, дихателна и сърдечна честота на животните.
Оценена е ефективността на липидната емулсия, като са анализирани клинико-лабораторни показатели, свързани с основни жизнени функции
Intravenous Lipid Emulsions in Anticonvulsants’ Toxicity
No full textIn recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity
Botulinum toxin in modern clinical and aesthetic medicine: history, applications, risks and future perspectives
No full textBotulinum 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
Marine-Derived Natural Substances with Anticholinesterase Activity
No full textAlzheimer’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
Meroterpenoids from Terrestrial and Marine Fungi: Promising Agents for Neurodegenerative Disorders—An Updated Review
No full textBackground: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation
The role of pharmacists in managing mental health disorders: a review
Full text linkPharmacists 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
Trehalose: Neuroprotective Effects and Mechanisms—An Updated Review
No full textTrehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose’s impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose’s neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut–brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases
Historical perspectives and emerging trends in fentanyl use: Part 1 – Pharmacological profile
Full text linkFentanyl, 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
Historical perspectives and emerging trends in fentanyl use: Part 2 – overdose and misuse
Full text linkThe 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
The role of lipid emulsion in organophosphorus pesticide poisoning in clinical practice
Full text linkIntroduction: A major clinical and important for the public health issue causing many deaths is acute organophosphorus pesticide (OP) poisoning. The clinical behaviour during these cases of intoxication has improved slightly in recent years, but the same two antidotes are still used—atropine and oximes, as well as the standard resuscitation and detoxification methods. There are many experiments and clinical cases that demonstrate the benefit of lipid emulsions (LEs) in cases of intoxication with lipophilic agents, as well as with pesticides.Case Presentation: A retrospective study has been performed on 20 patients with cases of acute exogenous pesticide intoxication. An intravenous LE was administered to four of them as an add-on therapy to the main therapeutic regimen. Results: A quantitative assessment of consciousness was made—the majority of patients entered the hospital in a severe condition, the state of consciousness of 3 patients receiving LE (75%) was defined as obnubilation and one patient (25%) was in a coma. In LE-free control cases, the most common complications were exotoxic shock (37.5%), acute respiratory failure (31.25%), and arterial hypotension (31.25%). In the patient control group, the mortality was 50% (8 cases), and in those treated with LE, 1 patient died (25% of cases).Conclusion: Based on these clinical data, we believe that lipid emulsion can be useful in the treatment of intoxication with acute exogenous pesticides as an add-on to antidote therapy
