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Paracetamol overdose

Sandeep B Subramanya, Balaji Venkataraman, Mohamed Fizur Nagoor Meeran, Sameer N Goyal, Chandragouda R Patil, Shreesh Ojha
Acetaminophen (APAP), which is also known as paracetamol or N -acetyl- p -aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Current clinical therapy for APAP-induced liver toxicity is the administration of N -acetyl-cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular glutathione (GSH) stores in the liver...
November 28, 2018: International Journal of Molecular Sciences
Anselm Wong, Natalie Homer, James W Dear, Kay Weng Choy, James Doery, Andis Graudins
CONTEXT: To compare degree of liver injury and paracetamol metabolite concentrations after treatment with standard of care (20-h) vs. abbreviated (12-h) acetylcysteine regimens used in paracetamol overdose (NACSTOP trial). METHODS: Timed blood samples from a cohort of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-h acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) were assayed for paracetamol metabolites as a pilot study, using liquid chromatography/mass spectrometry...
November 19, 2018: Clinical Toxicology
Soo Liang Ooi, Ruth Green, Sok Cheon Pak
N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders...
2018: BioMed Research International
A Chauhan, T Lalor, S Watson, D Adams
No abstract text is available yet for this article.
November 9, 2018: QJM: Monthly Journal of the Association of Physicians
Carla Carnovale, Faizan Mahzar, Sara Scibelli, Marta Gentili, Elena Arzenton, Ugo Moretti, Olivia Leoni, Marco Pozzi, Gabriëlla G A M Peeters, Emilio Clementi, Massimo Medaglia, Sonia Radice
Recent epidemiological studies have reported an increase in central nervous system (CNS)-active drug abuse rates in paediatric settings, raising several public health concerns. No study to date has explored this issue worldwide. We performed an extensive analysis of drugs abuse/overdose reported for children in the last decade by using the largest pharmacovigilance database, i.e. the VigiBase, collecting adverse drug reaction reports that involved at least one suspect drug belonging to the Anatomical Therapeutic Chemical code "Nervous System" through the Standardised Medical Dictionary for Drug Regulatory Affairs Queries for Drug abuse...
October 29, 2018: European Journal of Pediatrics
Nicholas Moore, Stéphanie Duret, Adeline Grolleau, Régis Lassalle, Vanessa Barbet, Mai Duong, Nicolas Thurin, Cécile Droz-Perroteau, Sinem Ezgi Gulmez
INTRODUCTION: Acute liver injury (ALI) is a major reason for stopping drug development or removing drugs from the market. Hospitalisation for ALI is relatively rare for marketed drugs, justifying studies in large-scale databases such as the nationwide Système National des Données de Santé (SNDS), which covers 99% of the French population. METHODS: SNDS was queried over 2010-2014 for all hospital admissions for acute toxic liver injuries not associated with a possible other cause, using a case-population approach...
October 25, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Lotte Christine Groth Hoegberg, Frank Refsgaard, Steen Hauge Pedersen, Mark Personne, Shahid Ullah, Georgios Panagiotidis, Tonny Studsgaard Petersen, Anita Annas
OBJECTIVE: Extended release (ER) tablets/capsules in massive ingestion overdoses are prone to form pharmacobezoars potentially increasing the risk of late-appearing toxic effects and prolonged symptoms. Oral activated charcoal is often sufficient to prevent drug absorption, but in a recent massive ingestion of highly toxic substances, prior orogastric lavage might be considered. The disintegration characteristics of ER preparations in overdose situations is valuable to understand if the time line and course of the intoxication might be prolonged, but information on these characteristics are unavailable...
October 11, 2018: Clinical Toxicology
Katy Saide, Victoria Sherwood, Grant N Wheeler
INTRODUCTION: Failure to predict drug-induced liver injury (DILI) remains a major contributing factor to lead compound drop-out during drug development. Xenopus embryos are amenable for early stage medium throughput small molecule screens and so have the potential to be used in pre-clinical screens. To begin to assess the usefulness and limitations of Xenopus embryos for safety assessment in the early phases of drug development, paracetamol was used as a model hepatotoxin. Paracetamol overdose is associated with acute liver injury...
September 30, 2018: Toxicology Letters
Diego Castanares-Zapatero, Valérie Dinant, Ilaria Ruggiano, Harold Willem, Pierre-François Laterre, Philippe Hantson
Acute paracetamol poisoning due to a single overdose may be effectively treated by the early administration of N-acetylcysteine (NAC) as an antidote. The prognosis may be different in the case of intoxication due to multiple ingestions or when the antidote is started with delay. The aim of this work was to investigate the outcome of paracetamol poisoning according to the pattern of ingestion and determine the factors associated with the outcome. We performed a retrospective analysis over the period 2007⁻2017 of the patients who were referred to a tertiary hospital for paracetamol-related hepatotoxicity...
September 29, 2018: Toxics
Kathryn Woodhead, Bernard A Foex
A short-cut review was carried out to establish whether oral N-acetylcysteine is as effective as intravenous N-acetylcysteine in the management of paracetamol overdose. Seven studies were directly relevant to the question. The author, year and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that oral N-acetylcysteine is a safe alternative in patients for whom the intravenous route is not an option...
October 2018: Emergency Medicine Journal: EMJ
Jun Chul Park, Deok-Seo Yoon, Eunjin Byeon, Jung Soo Seo, Un-Ki Hwang, Jeonghoon Han, Jae-Seong Lee
To investigate the adverse effect of two widely used pharmaceuticals, paracetamol (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus rotundiformis (B. rotundiformis), the animals were exposed to various environmentally-relevant concentrations. Up to date, acetaminophen and oxytetracycline have been considered as toxic, if used above threshold concentration, i.e. overdosed. However, this study demonstrated these two pharmaceuticals even at low concentration (i.e., μg/L scale) elicited oxidative stress through the generation of reactive oxygen species (ROS) along with the increased glutathione S-transferase activity, despite no-observed effect in in-vivo population growth...
November 2018: Aquatic Toxicology
Yuanqiang Wang, Weiwei Lin, Nan Wu, Xibing He, Junmei Wang, Zhiwei Feng, Xiang-Qun Xie
Paracetamol is a relatively safe analgesia/antipyretic drug without the risks of addiction, dependence, tolerance, and withdrawal when used alone. However, when administrated in an opioid/paracetamol combination product, which often contains a large quantity of paracetamol, it can be potentially dangerous due to the risk of hepatotoxicity. Paracetamol is known to be metabolized into N-(4-hydroxyphenyl)-arachidonamide (AM404) via fatty acid amide hydrolase (FAAH) and into N-acetyl-p-benzoquinone imine (NAPQI) via cytochrome P450 (CYP) enzymes...
August 18, 2018: Journal of Molecular Modeling
Ehsan Kheradpezhouh, Fiona H Zhou, Greg J Barritt, Grigori Y Rychkov
Transient Receptor Potential Melastatin (TRPM) 2 is a non-selective Ca2+ permeable cation channel and a member of the Transient Receptor Potential (TRP) channel family. TRPM2 has unique gating properties; it is activated by intracellular ADP-ribose (ADPR), whereas Ca2+ plays a role of an important co-factor in channel activation, increasing TRPM2 sensitivity to ADPR. TRPM2 is highly expressed in rat and mouse hepatocytes, where it has been shown to contribute to oxidative stress-induced cell death and liver damage due to paracetamol-overdose...
September 10, 2018: Biochemical and Biophysical Research Communications
Angelo Di Giorgio, Emanuele Nicastro, Davide Dalla Rosa, Gabriella Nebbia, Aurelio Sonzogni, Lorenzo D'Antiga
BACKGROUND: in adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The paediatric classification does not considered this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features and outcome of children with ALF-CLD to those with a proper ALF. METHODS: Patients admitted between 1996-2017 because of ALF defined by PALF criteria (raised transaminases, INR ≥2...
July 19, 2018: Transplantation
Johan L Å Nilsson, Anders Blomgren, Ulf J Nilsson, Edward D Högestätt, Lars Grundemar
Paracetamol overdosing may cause liver injury including fulminant liver failure due to generation of the toxic metabolites, N-acetyl-p-benzoquinone imine (NAPQI) and p-benzoquinone (p-BQ). Herein, the chelating agent, N,N'-Bis(2-mercaptoethyl)isophthalamide (NBMI), was examined for its potential ability to entrap NAPQI and p-BQ and to prevent paracetamol-induced liver injury. Both NBMI and the conventional paracetamol antidote N-acetylcysteine (NAC) were investigated with regard to their abilities to scavenge the NAPQI and p-BQ in a Transient Receptor Potential Ankyrin 1-dependent screening assay...
June 16, 2018: Basic & Clinical Pharmacology & Toxicology
Said Benlamkaddem, Imane Iken, Nawfal Houari, Abderrahim Elbouazzaoui, Brahim Boukatta, Hicham Sbai, Sanae Achour, Nabil Kanjaa
Paracetamol is the most widely drug involved in accidental paediatric exposures and deliberate self-poisoning cases because of its availability. N-acetyl cystein is the main treatment for this poisoning. We report a case of a 24-year-old Arab female who has deliberately ingested 100 tablets of 500 mg paracetamol each (50g). Her first examination was normal. She has received oral N-acetyl cystein (NAC) 6 hours after the ingestion. Serum paracetamol level done 18 hours post ingestion was 900 mg/l. On review the next days, she did not develop any symptoms of liver failure...
2018: Pan African Medical Journal
Radharani Benvenutti, Matheus Marcon, Carlos G Reis, Laura R Nery, Camila Miguel, Ana P Herrmann, Monica R M Vianna, Angelo Piato
Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N -acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins...
2018: PeerJ
William Bernal, Roger Williams
The King's prognostic criteria for patients with acute liver failure (ALF) introduced in 1989 have been used worldwide. This distinguished for the first time cases with 'hyper-acute' course (characteristically paracetamol overdose) where there is a better chance of recovery with medical supportive care alone from those etiologies with a less acute course and paradoxically lower chances of 'spontaneous' recovery. Ongoing use showed the limited sensitivity of the criteria to constitute a significant practical limitation...
May 2018: Hepatology International
Ege Arzuk, Burak Turna, Murat Sözbilen, Hilmi Orhan
Paracetamol (PAR) overdose is associated with massive hepatic injury; it may induce kidney toxicity as well. It is essential to measure organ-specific activities of related CYPs for evaluating the overdose cases. Available HPLC-based methods require high amounts of tissue samples. In order to develop liquid chromatography mass spectrometry (LC-MS)-based methods to process small amounts of human tissues, liver and kidney samples were obtained. Individual microsomes were prepared and incubated with PAR (for quantifying bioactivation), with nifedipine (for measuring CYP3A4 activity) and with p-nitrophenol (for measuring CYP2E1 activity)...
July 2018: Environmental Toxicology and Pharmacology
Shao Hui Koh, Kian Hua Barry Tan, Sashikumar Ganapathy
INTRODUCTION: Paediatric poisoning accounts for 1% of daily emergency department presentations. The aim of this study was to review the characteristics and outcomes of paediatric patients who presented with drug overdose over a five-year period. METHODS: We performed a retrospective review of paediatric poisoning cases at KK Women's and Children's Hospital (KKH), the largest children's public hospital in Singapore, from 1 January 2009 to 31 December 2013. RESULTS: A total of 1,208 cases of poisoning were seen in KKH's Department of Children's Emergency during the study period...
May 2018: Singapore Medical Journal
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