Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Humans ; Fentanyl/therapeutic use* ; Opioid-Related Disorders/drug therapy* ; Drug Overdose/prevention & control* ; Analgesics, Opioid/adverse effects* ; Vaccines/therapeutic use* ; Brain

PURPOSE: The Korean government approved selected nonprescription drugs (Over-The-Counter drug; OTC drug) to be distributed in convenience stores from 15. Nov. 2012. This study examined the changes in the incidence and the clinical outcome of acute pharmaceutical drug poisoning after the deregulation of OTC drug sales. METHODS: This study analyzed the data of Emergency Department based Injury In-depth Injury Surveillance (EDIIS), Korea Centers for Disease Control and Prevention, from 2011 to 2014. The following items were examined: age, gender, intention, alcohol association, pharmaceutical drugs resulting acute poisoning, the clinical outcomes in emergency department, and the admission rate of intensive care unit (ICU). This is a retrospective cross section observational study. RESULTS: A total of 10,162 patients were subject to pharmaceutical drug poisoning. Acute poisoning by acetaminophen and other drugs were 1,015 (10.0%) and 9,147 (90.0%) patients, respectively. After the deregulation of OTC drug sales, acute poisoning by other drugs increased from 4,385 to 4,762 patients but acute poisoning by acetaminophen decreased from 538 to 477 patients (p < 0.05). The rate of admission of acetaminophen poisoning increased from 36.1% (194/538) to 46.8% (223/477). The admission rate to the ICU by acetaminophen poisoning increased from 4.6% (25/538) to 11.3% (54/477) after the deregulation of OTC drug sales (p < 0.05). CONCLUSION: Since the deregulation of OTC drugs sales, pharmaceutical drug poisoning has increased but acetaminophen poisoning has decreased. The rate of hospitalization and ICU admission by pharmaceutical drug poisoning with or without acetaminophen has also increased.
Acetaminophen ; Centers for Disease Control and Prevention (U.S.) ; Commerce* ; Drug Overdose ; Emergencies* ; Emergency Service, Hospital* ; Hospitalization ; Humans ; Incidence ; Intensive Care Units ; Intention ; Korea ; Nonprescription Drugs ; Observational Study ; Poisoning* ; Retrospective Studies

This article made a brief analysis of clinical adverse effects of cinnabar. Except for allergic reaction, almost all the adverse events of cinnabar were caused by unreasonable application. The majority of the poisoning cases were associated with excessive and/or long-term dosage, and improper preparation methods, such as decocting, heating or fumigating. Children showed to be prone to poisoning. The poisoning caused by unreasonable use of cinnabar should be considered to be drug alert, but not advert effect. And the toxicity of cinnabar could be avoided by normalizing the preparation method, controlling the dosage and duration.
Chemical and Drug Induced Liver Injury ; etiology ; Coma ; chemically induced ; Drug Compounding ; adverse effects ; Drug Incompatibility ; Drug Overdose ; Gastrointestinal Diseases ; chemically induced ; Humans ; Hypersensitivity ; etiology ; Mercury Compounds ; adverse effects ; poisoning ; Mercury Poisoning ; prevention & control ; therapy

PURPOSE: Some advanced countries have reported annual statistics for poisoning based on data from poison control centers. This study was conducted to propose a baseline format and statistics of poisoning in Korea from a national representative database. METHODS: This study was a retrospective analysis of poisoning patients based on data from an emergency department (ED) based injury in-depth surveillance project by the Korea Centers for Disease Control and Prevention in 2016. Bite or sting injuries were not included. Variables related to poisoning were summarized using a similar format as the National Poison Data System in the United States. RESULTS: A total of 7,820 poisoning patients presented to 23 EDs. Adults ≥20 years accounted for 84% of the population, while the proportion of intentional poisoning was 59.4%. The most common poisoning substances were therapeutic drugs (45%), gas (21%), pesticides (15%), and artificial toxic substances (13%). Overall, 34.5% of patients were admitted for further treatment. The mortality was 3.2% (248 cases), and the most common causative substances were carbon monoxide, glyphosate, and paraquat, in order. CONCLUSION: This study showed the recent status of poisoning in Korea. However, a comprehensive poisoning registry based on poison control centers may be required to provide more accurate national statistics in the future.
Adult ; Bites and Stings ; Carbon Monoxide ; Centers for Disease Control and Prevention (U.S.) ; Drug Overdose ; Emergency Service, Hospital ; Humans ; Information Systems ; Korea ; Mortality ; Paraquat ; Pesticides ; Poison Control Centers ; Poisoning* ; Retrospective Studies ; United States

Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC.
Treatment Outcome ; Overdose ; Male ; Insulin/*administration & dosage ; Heart Arrest/*chemically induced/physiopathology/*prevention & control ; Drug Combinations ; Dose-Response Relationship, Drug ; Dogs ; Cardiopulmonary Resuscitation/methods ; Cardiac Output/*drug effects ; Bupivacaine/*adverse effects/analogs & derivatives ; Blood Pressure/*drug effects ; Blood Flow Velocity/drug effects ; Animals ; Anesthetics, Local