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Paracetamol overdose

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...
July 31, 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
Lars E Schmidt, Ditlev N Rasmussen, Tonny S Petersen, Ines M Macias-Perez, Leo Pavliv, Byron Kaelin, Richard C Dart, Kim Dalhoff
CONTEXT: The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen...
May 24, 2018: Clinical Toxicology
Hiiti B Sillo, Nelson E Masota, Sunday Kisoma, Lembit Rago, Veronica Mgoyela, Eliangiringa A Kaale
BACKGROUND: Availability of correct and adequate information about medicines is an important aspect in ensuring rational use of medicines and hence facilitating safety and expected efficacy of medicines during therapy. Package inserts have proven to be a good source of information to the prescribers and patients whereby they have been useful in highlighting important information pertaining proper use and handling of the medicines. The present study was aimed at establishing the extent to which package inserts of medicines circulating on the markets of the East African Community (EAC) Partner States conform to medicines information requirements as established in the harmonized guidelines as well as national guidelines...
2018: PloS One
Christina Gade, Hanne R Christensen, Kim P Dalhoff, Jens Christian Holm, Helle Holst
Obesity can affect the pharmacokinetics of most drugs, which may result in under- or overdosing if traditional pediatric dosing strategies are used. To investigate currently applied dosage strategies in children with overweight or obesity (overweight/obesity), in a clinical treatment facility. In particular, whether dosing guidelines were available and metrics of body size applied. A retrospective cohort study of 200 patients admitted to the Danish Children's Obesity Clinic. Data were collected from 2007 to 2015...
June 2018: Pharmacology Research & Perspectives
L M O'Sullivan, N Ahmed, A J Sidebottom
No abstract text is available yet for this article.
April 27, 2018: British Dental Journal
Chantelle L Mason, Joseph Leedale, Sotiris Tasoulis, Ian Jarman, Daniel J Antoine, Steven D Webb
Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable...
June 2018: CPT: Pharmacometrics & Systems Pharmacology
F Ben Mbarka, K Ben Jeddou, E Allouche, I Boukhris, N Khalfallah, H Baccar, Z Ouahchi
Background: Vitamin K antagonists are widely used in the treatment and prevention of thromboembolic disease. However, these drugs can cause serious side effects, especially bleeding. This study aims to evaluate frequency and risk factors of both bleeding and asymptomatic overdose in North African patients undergoing Vitamin K antagonist therapy. Methods: We performed a cross-sectional study in patients undergoing Vitamin K antagonist therapy. A statistical analysis has been conducted to identify overdose and bleeding risk factors by using chi-square test (p < ...
March 2018: The Egyptian heart journal: (EHJ): official bulletin of the Egyptian Society of Cardiology
Anthony P Morrison, Heather Law, Lucy Carter, Rachel Sellers, Richard Emsley, Melissa Pyle, Paul French, David Shiers, Alison R Yung, Elizabeth K Murphy, Natasha Holden, Ann Steele, Samantha E Bowe, Jasper Palmier-Claus, Victoria Brooks, Rory Byrne, Linda Davies, Peter M Haddad
BACKGROUND: Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis. METHODS: We did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK...
May 2018: Lancet Psychiatry
Elie Harmouche, Robert S Hoffman, Mary Ann Howland
No abstract text is available yet for this article.
March 26, 2018: Clinical Toxicology
Rachel Rendell, Sarah Fairhall, Stuart Graham, Steve Rutter, Philippa Auton, Adam Smith, Rosi Perrott, Bronwen Jugg
The toxic industrial chemical (TIC1 ) phosgene remains an important chemical intermediate in many industrial processes. Inhalation of phosgene can cause an acute lung injury (ALI) which, in severe cases may result in death. There are currently no effective pharmacological therapies or evidence-based treatment guidelines for managing exposed individuals. N-acetylcysteine (NAC) is a commercially available drug licensed in the UK and elsewhere for the treatment of paracetamol (acetaminophen) overdose. It has a number of mechanisms of action which may provide therapeutic benefit for the treatment of phosgene-induced ALI...
June 15, 2018: Toxicology Letters
Anselm Wong, Benjamin Cheung, Charlotte Nejad, Michael Gantier, Andis Graudins
CASE DETAILS: A 19-year-old girl presented to the emergency department following overdose of 10 g of paracetamol on a background history of cystic fibrosis. Paracetamol concentration was below the nomogram line, but was treated with acetylcysteine seven hours post-overdose given her symptomatology. Nineteen hours following her overdose she developed hepatotoxicity, despite early initiation of acetylcysteine. She was discharged well six days post-ingestion. On presentation, delta miRNA-122-miR483 was 20 times that of control patients, however, alanine aminotransferase was normal...
March 22, 2018: Clinical Toxicology
Frédérique Rodieux, Laszlo Vutskits, Klara M Posfay-Barbe, Walid Habre, Valérie Piguet, Jules A Desmeules, Caroline F Samer
Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children's inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults...
2018: Frontiers in Pharmacology
Rowa' Al-Ramahi, Hamzeh Al-Zabadi, Ghadeer Al-Shareef
BACKGROUND: Paediatric patients are highly sensitive to drug-related problems such as dosing errors. Some dosing errors are preventable with suitable strategies. The aim of this study was to assess the prevalence of drug dosing errors in outpatient paediatric patients who attended primary health-care centres in Nablus and to identify possible associated factors. METHODS: For this cross-sectional study, we reviewed doctors' prescriptions for paediatric patients aged between 1 day and 12 years...
February 21, 2018: Lancet
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