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acetaminophen and acute hepatic failure

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https://www.readbyqxmd.com/read/29417856/gastrointestinal-safety-and-tolerability-of-oral-non-aspirin-over-the-counter-analgesics
#1
Nicholas Moore, James M Scheiman
Over-the-counter (OTC) analgesics are routinely used worldwide for self-management of various painful conditions. Despite this, there has been little in-depth review of the safety of non-aspirin analgesics at OTC doses. This paper reviews the available literature on the gastrointestinal (GI) and hepatic safety of non-aspirin OTC analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen; safety in overdose is also reviewed. Each non-aspirin OTC analgesic has a distinct adverse event (AE) profile, with GI AE rates for OTC dosing in one study ranging from 37% for diclofenac to 7...
February 8, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29388410/-high-anion-gap-metabolic-acidosis-pyroglutamic-acidosis-induced-by-chronic-acetaminophen-use
#2
J Tchougang Nono, V Mistretta, I Noirot, J L Canivet, P Damas
Acetaminophen is the most consumable analgesic in the world in the form of medical prescription or self-medication. It is one of the active ingredients most often involved in voluntary poisoning. Lethal dose of acetaminophen classically induces acute hepatic failure on hepatic necrosis. Chronic intake of sub-lethal doses (i.e. near recommended therapeutic doses) of acetaminophen in the presence of certain risk factors may be responsible for another much less recognized pathological manifestation: severe metabolic acidosis with an increased anion gap due to the accumulation of 5-oxoproline or pyroglutamic acid...
January 2018: Revue Médicale de Liège
https://www.readbyqxmd.com/read/29364842/natural-dietary-pigments-potential-mediators-against-hepatic-damage-induced-by-over-the-counter-non-steroidal-anti-inflammatory-and-analgesic-drugs
#3
REVIEW
Herson Antonio González-Ponce, Ana Rosa Rincón-Sánchez, Fernando Jaramillo-Juárez, Han Moshage
Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites...
January 24, 2018: Nutrients
https://www.readbyqxmd.com/read/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#4
Steven R McGreal, Bharat Bhushan, Chad Walesky, Mitchell R McGill, Margitta Lebofsky, Sylvie E Kandel, Robert D Winefield, Hartmut Jaeschke, Natasha E Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a post-translational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and WT controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0-24 hr...
January 9, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#5
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29199145/acetaminophen-induced-acute-liver-failure-is-more-common-and-more-severe-in-women
#6
Jessica B Rubin, Bilal Hameed, Michelle Gottfried, William M Lee, Monika Sarkar
BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n=250) or acetaminophen-induced ALF (n=912) from January 2000 through September 2016...
November 30, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29174983/comparison-of-hepatic-transcriptome-profiling-between-acute-liver-injury-and-acute-liver-failure-induced-by-acetaminophen-in-mice
#7
Chunmin Li, Yanan Ming, Wenting Hong, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao
Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in many countries. In the present study, we developed stable mouse models of acute drug-induced hepatic injury (DILI) and acute drug-induced hepatic failure (DILF) by sub-lethal and lethal APAP injection respectively. The differences in hepatic transcriptome profiling between these two models were compared by RNA sequencing, which were validated by qPCR, western-blot and ELISA. In results, serum IL-6, TNF-a and IL-10 levels are higher in DILF than in DILI...
November 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29088996/aggressive-treatment-of-life-threatening-hypophosphatemia-during-recovery-from-fulminant-hepatic-failure-a-case-report
#8
Brittany D Bissell, Jason E Davis, Alexander H Flannery, David A Adkins, Melissa L Thompson Bastin
Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/28986131/selenoprotein-msrb1-deficiency-exacerbates-acetaminophen-induced-hepatotoxicity-via-increased-oxidative-damage
#9
Ki Young Kim, Geun-Hee Kwak, Mahendra Pratap Singh, Vadim N Gladyshev, Hwa-Young Kim
Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1(-/-) mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1(+/+)) mice...
October 3, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28874859/editorial-severe-acute-liver-injury-cause-connects-to-outcome
#10
EDITORIAL
Curtis K Argo, Stephen H Caldwell
Severe acute liver injury (ALI) is a common condition with little objective study of its natural history and outcomes. In this paper by Koch et al. and the Acute Liver Failure (ALF) Study Group, the authors utilize a consensus definition of ALI requiring newly elevated bilirubin, alanine aminotransferase (ALT), and international normalized ration (INR) without evidence of hepatic encephalopathy (HE), with HE as the key differentiator of ALI from ALF. They show significantly higher rates of progression to ALF, liver transplantation, or death in non-acetaminophen etiologies of ALI...
September 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#11
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
December 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#12
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28687253/connexin-hemichannel-inhibition-reduces-acetaminophen-induced-liver-injury-in-mice
#13
Michaël Maes, Sara Crespo Yanguas, Joost Willebrords, James L Weemhoff, Tereza Cristina da Silva, Elke Decrock, Margitta Lebofsky, Isabel Veloso Alves Pereira, Luc Leybaert, Anwar Farhood, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen...
August 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28680622/a-case-of-reversible-drug-induced-liver-failure
#14
Mohammad Ansari, Sabrina Arshed, Mohammed Islam, Shuvendu Sen, Abdalla Yousif
Acute fulminant liver failure and acute renal failure are devastating complications caused by many drugs. The use of N-acetylcysteine has been well established in acetaminophen toxicity, but it remains controversial in other cases. Dialysis is a very effective method of removing certain drugs from the system. With the invention of new street drugs such as "synthetic marijuana," it may be beneficial in patients whom the substances ingested are unknown. We report a case of a 42-year-old male who developed acute fulminant hepatic failure and acute renal failure, who was cured with dialysis, N-acetylcysteine, and other supportive measures...
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28611340/role-of-n-acetylcysteine-treatment-in-non-acetaminophen-induced-acute-liver-failure-a-prospective-study
#15
Tauseef Nabi, Sumaiya Nabi, Nadeema Rafiq, Altaf Shah
BACKGROUND/AIMS: Acute liver failure (ALF) is a rare but severe medical emergency. To date, there is no established treatment for non-acetaminophen-induced acute liver failure (NAI-ALF) other than liver transplantation, and little is known about the use of N-acetylcysteine (NAC) in NAI-ALF. A randomized case control study was conducted with the aim to determine the effect of NAC on the mortality of NAI-ALF patients, as well as to evaluate the safety and efficacy of NAC use. PATIENTS AND METHODS: A total of 80 patients diagnosed with NAI-ALF were included in the study...
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28459937/cxcl16-deficiency-attenuates-acetaminophen-induced-hepatotoxicity-through-decreasing-hepatic-oxidative-stress-and-inflammation-in-mice
#16
Hong Wang, Yihui Shao, Saisai Zhang, Anqi Xie, Yanna Ye, Lihua Shi, Leigang Jin, Xuebo Pan, Zhuofeng Lin, Xiaokun Li, Shulin Yang
Chemokine C-X-C ligand 16 (CXCL16), a single-pass Type I membrane protein belonging to the CXC chemokine family, is related to the inflammatory response in liver injury. In present study, we investigated the pathophysiological role of CXCL16, a unique membrane-bound chemokine, in acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were injected with APAP, and blood and tissue samples were harvested at different time points. The serum high-mobility group box 1 and CXCL16 levels were quantified by sandwich immunoassays...
June 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28447858/risk-prediction-of-hepatotoxicity-in-paracetamol-poisoning
#17
REVIEW
Anselm Wong, Andis Graudins
CONTEXT: Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment...
September 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28444411/-acute-liver-failure
#18
A Koch, C Trautwein, F Tacke
Acute liver failure (ALF) is a rare, but life-threatening disease that is characterized by the acute onset of jaundice, coagulopathy, and hepatic encephalopathy (HE) in patients without pre-existing liver disease. Main causes in Germany are drug toxicity, acetaminophen overdose, and viral hepatitis (A, B, E). For the initial assessment of patients with ALF and the diagnostic algorithm, the early detection of HE, exclusion of liver cirrhosis, immediate diagnosis of the underlying etiology, and evaluation for the necessity of liver transplantation (LT) are critical...
May 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28440304/the-natural-history-of-severe-acute-liver-injury
#19
David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B McGuire, R T Stravitz, A M Larson, I Liou, O Fix, M L Schilsky, T McCashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben
OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2...
September 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28379590/hepatotoxicity-of-paracetamol-and-related-fatalities
#20
R Tittarelli, M Pellegrini, M G Scarpellini, E Marinelli, V Bruti, N M di Luca, F P Busardò, S Zaami
Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion...
March 2017: European Review for Medical and Pharmacological Sciences
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