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https://www.readbyqxmd.com/read/28099803/deep-learning-to-predict-the-formation-of-quinone-species-in-drug-metabolism
#1
Tyler B Hughes, S Joshua Swamidass
Many adverse drug reactions are thought to be caused by electrophilically reactive drug metabolites that conjugate to nucleophilic sites within DNA and proteins, causing cancer or toxic immune responses. Quinone species, including quinone-imines, quinone-methides, and imine-methides, are electrophilic Michael acceptors that are of- ten highly reactive, and comprise over 40% of all known reactive metabolites. Quinone metabolites are created by cytochromes P450 and peroxidases. For example, cy- tochromes P450 oxidize acetaminophen to N-acetyl-p-benzoquinone imine, which is electrophilically reactive and covalently binds to nucleophilic sites within proteins...
January 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28097507/in-vitro-phase-i-and-phase-ii-drug-metabolism-in-the-liver-of-juvenile-and-adult-g%C3%A3-ttingen-minipigs
#2
Els Van Peer, Frank Jacobs, Jan Snoeys, Jos Van Houdt, Ils Pijpers, Christophe Casteleyn, Chris Van Ginneken, Steven Van Cruchten
PURPOSE: In view of pediatric drug development, juvenile animal studies are gaining importance. However, data on drug metabolizing capacities of juvenile animals are scarce, especially in non-rodent species. Therefore, we aimed to characterize the in vitro biotransformation of four human CYP450 substrates and one UGT substrate in the livers of developing Göttingen minipigs. METHODS: Liver microsomes from late fetal, Day 1, Day 3, Day 7, Day 28, and adult male and female Göttingen minipigs were incubated with a cocktail of CYP450 substrates, including phenacetin, tolbutamide, dextromethorphan, and midazolam...
January 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28097095/limited-knowledge-of-acetaminophen-in-patients-with-liver-disease
#3
Sammy Saab, Peter G Konyn, Matthew R Viramontes, Melissa A Jimenez, Jonathan F Grotts, Wally Hamidzadah, Veronica P Dang, Negin L Esmailzadeh, Gina Choi, Francisco A Durazo, Mohamed M El-Kabany, Steven-Huy B Han, Myron J Tong
Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28096230/haemodialysis-in-acute-paracetamol-poisoning
#4
L Serjeant, J Evans, F Sampaziotis, W G Petchey
A woman aged 23 years presented late with clinical and biochemical features of a life-threatening paracetamol (acetaminophen) overdose. Despite instigating N-acetylcysteine treatment, due to evidence of mitochondrial dysfunction together with an exceedingly high paracetamol level, the decision was made to dialyse the patient acutely to remove the parent drug. This was highly effective, and with on-going supportive care, the patient made a full recovery without the need for transplantation. This case highlights the role of extracorporeal therapy as a treatment option in selected cases of paracetamol overdose, consistent with the international guidelines...
January 17, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28093998/potential-of-plant-alkaloids-as-antipyretic-drugs-of-future
#5
Imad Ahmad, Haroon Khan, Anwar Ul-Hassan Gilani, Mohammad A Kamal
Fever or Pyrexia means abnormal rise in body temperature above the usual range of normal in response to a variety of infectious, immunological and neoplastic stimuli. To normalize these febrile conditions, several synthetic agents are in clinical practice such as acetaminophen, ibuprofen, and aspirin. However, they are having many side effects which sometimes challenge their applications. The various sources are under investigation worldwide to overcome issues of unwanted effects and to better therapeutic response...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28089749/pyroglutamate-5-oxoproline-measured-with-hydrophilic-interaction-chromatography-hilic-tandem-mass-spectrometry-in-acutely-ill-patients
#6
Carel J Pretorius, Michael C Reade, Chris Warnholtz, Brett McWhinney, Meng Mei Phua, Jeffrey Lipman, Jacobus P J Ungerer
BACKGROUND: Pyroglutamic acid (PGA) is challenging to quantify in plasma and is a rare cause of metabolic acidosis that is associated with inherited disorders or acquired after exposure to drugs. METHOD: We developed a hydrophilic interaction liquid chromatography tandem mass spectrometry method with a short analysis time. We established a reference interval and then measured PGA in acutely ill patients to investigate associations with clinical, pharmaceutical and laboratory parameters...
January 12, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#7
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28086854/in-vitro-assessment-of-hepatoprotective-agents-against-damage-induced-by-acetaminophen-and-ccl4
#8
Liliana Torres González, Noemí Waksman Minsky, Linda Elsa Muñoz Espinosa, Ricardo Salazar Aranda, Jonathan Pérez Meseguer, Paula Cordero Pérez
BACKGROUND: In vitro bioassays are important in the evaluation of plants with possible hepatoprotective effects. The aims of this study were to evaluate the pretreatment of HepG2 cells with hepatoprotective agents against the damage induced by carbon tetrachloride (CCl4) and paracetamol (APAP). METHODS: Antioxidative activity was measured using an assay to measure 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The in vitro hepatotoxicity of CCl4 and APAP, and the cytotoxic and hepatoprotective properties of silymarin (SLM), silybinin (SLB), and silyphos (SLP) were evaluated by measuring cell viability; activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH); total antioxidant capacity (TAOxC); and reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde (MDA) levels)...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28080146/perceptions-vs-evidence-therapeutic-substitutes-for-antipsychotics-in-patients-with-dementia-in-long-term-care
#9
Brianne L Olivieri-Mui, John W Devlin, Aileen Ochoa, Danielle Schenck, Becky Briesacher
OBJECTIVE: To compare differences between clinician perceptions of therapeutic substitutes for antipsychotics prescribed to patients with dementia in long term care (LTC) and published evidence. METHODS: A mixed-methods approach that included a drug information search, online survey of 55 LTC clinicians and a comprehensive literature review was used. For 41 pharmacologic antipsychotic substitute candidates identified, LTC clinicians rated the likelihood they would substitute each for patients with dementia and identified non-pharmacologic antipsychotic substitutes...
January 12, 2017: Aging & Mental Health
https://www.readbyqxmd.com/read/28079560/prenatal-exposures-and-the-development-of-childhood-wheezing-illnesses
#10
Christian Rosas-Salazar, Tina V Hartert
PURPOSE OF REVIEW: To critically evaluate and summarize studies published between July 2015 and June 2016 linking prenatal exposures and the onset of childhood wheezing illnesses and to discuss future research directions in this field. RECENT FINDINGS: The aggregated evidence indicates a consistent detrimental effect of prenatal exposure to parental smoking, outdoor air pollution, and maternal stress on childhood wheezing illnesses. Less consistent evidence suggests an adverse impact of maternal obesity during pregnancy and prenatal exposure to antibiotics on these outcomes...
January 11, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28074028/assessment-of-postoperative-pain-control-with-an-elastomeric-pain-pump-following-cardiothoracic-surgery
#11
Anuvrat Chopra, Jeff Hurren, Susan Szpunar, Stephanie B Edwin
OBJECTIVE: To assess the effectiveness of local anesthesia, delivered via elastomeric pump to manage pain in patients undergoing cardiothoracic surgery. METHODS: A retrospective, comparative analysis evaluating adult cardiothoracic surgery patients (by median sternotomy) who received continuous infusion bupivacaine + traditional methods of pain control (N = 100) or traditional pain control alone (N = 100) from July 2011-October 2013. The primary efficacy end point was total postoperative opioid requirements for 96 hours following surgery...
January 10, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28072811/evaluation-of-the-ototoxicity-potential-of-once-daily-single-entity-hydrocodone-in-patients-with-chronic-pain-results-of-two-phase-3-clinical-studies
#12
Kathleen Campbell, J Walter Kutz, Angela Shoup, Warren Wen, Shau Yu Lynch, Ellie He, Steven R Ripa
BACKGROUND: Use/misuse of the opioid combination hydrocodone-acetaminophen has been associated with permanent hearing loss. Although reports have been rare, this potential effect can have significant detrimental effect on patients' overall quality of life. To date, the ototoxic effect of hydrocodone alone has not been systematically investigated. OBJECTIVE: In this report, we aimed to evaluate the potential ototoxicity of a novel, single-entity, once-daily, extended-release hydrocodone tablet (Hysingla® ER; HYD)...
January 2017: Pain Physician
https://www.readbyqxmd.com/read/28070111/a-monkey-model-of-acetaminophen-induced-hepatotoxicity-phenotypic-similarity-to-human
#13
Satoshi Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, Hitomi Shimoda, Wataru Takasaki, Kazuhiko Mori
Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28068511/inhibition-of-glycogen-synthase-kinase-3-accelerated-liver-regeneration-after-acetaminophen-induced-hepatotoxicity-in-mice
#14
Bharat Bhushan, Samikshya Poudel, Michael W Manley, Nairita Roy, Udayan Apte
Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice...
January 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28067703/anesthesia-for-ambulatory-pediatric-surgery-in-sub-saharan-africa-a-pilot-study-in-burkina-faso
#15
Yvette B Kabré, Idriss S S Traoré, Flavien A R Kaboré, Bertille Ki, Alain I Traoré, Isso Ouédraogo, Emile Bandré, Albert Wandaogo, Nazinigouba Ouédraogo
BACKGROUND: Long surgical wait times and limited hospital capacity are common obstacles to surgical care in many countries in Sub-Saharan Africa (SSA). Introducing ambulatory surgery might contribute to a solution to these problems. The purpose of this study was to evaluate the safety and feasibility of introducing ambulatory surgery into a pediatric hospital in SSA. METHODS: This is a cross-sectional descriptive study that took place over 6 months. It includes all patients assigned to undergo ambulatory surgery in the Pediatric University Hospital in Ouagadougou, Burkina Faso...
February 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28064122/correlation-between-degradation-pathway-and-toxicity-of-acetaminophen-and-its-by-products-by-using-the-electro-fenton-process-in-aqueous-media
#16
Thi Xuan Huong Le, Thi Van Nguyen, Zoulkifli Amadou Yacouba, Laetitia Zoungrana, Florent Avril, Duy Linh Nguyen, Eddy Petit, Julie Mendret, Valerie Bonniol, Mikhael Bechelany, Stella Lacour, Geoffroy Lesage, Marc Cretin
The evolution of the degradation by-products of an acetaminophen (ACE) solution was monitored by HPLC-UV/MS and IC in parallel with its ecotoxicity (Vibrio fischeri 81.9%, Microtox(®) screening tests) during electro-Fenton (EF) oxidation performed on carbon felt. The aromatic compounds 2-hydroxy-4-(N-acetyl) aminophenol, 1,4-benzoquinone, benzaldehyde and benzoic acid were identified as toxic sub-products during the first stage of the electrochemical treatment, whereas aliphatic short-chain carboxylic acids (oxalic, maleic, oxamic, formic, acetic and fumaric acids) and inorganic ions (ammonium and nitrate) were well identified as non-toxic terminal sub-products...
December 21, 2016: Chemosphere
https://www.readbyqxmd.com/read/28061320/gastric-emptying-in-critically-ill-children
#17
Enid E Martinez, Luis M Pereira, Kathleen Gura, Nicole Stenquist, Katelyn Ariagno, Samuel Nurko, Nilesh M Mehta
BACKGROUND: Delayed gastric emptying (GE) impedes enteral nutrient (EN) delivery in critically ill children. We examined the correlation between (a) bedside EN intolerance assessments, including gastric residual volume (GRV); (b) delayed GE; and (c) delayed EN advancement. MATERIALS AND METHODS: We prospectively enrolled patients ≥1 year of age, eligible for gastric EN and without contraindications to acetaminophen. Gastric emptying was determined by the acetaminophen absorption test, specifically the area under the curve at 60 minutes (AUC60)...
January 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28060446/successful-treatment-of-donor-derived-hepatitis-c-viral-infection-in-three-transplant-recipients-from-a-donor-at-increased-risk-for-bloodborne-pathogens
#18
Ashesh P Shah, Andrew Cameron, Pooja Singh, Adam M Frank, Jonathan M Fenkel
We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to 3 HCV-negative recipients - 2 renal transplants and 1 liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner...
January 6, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28059913/liposomal-bupivacaine-use-in-transversus-abdominis-plane-blocks-reduces-pain-and-postoperative-intravenous-opioid-requirement-after-colorectal-surgery
#19
Audrey L Stokes, Sanjib D Adhikary, Ashley Quintili, Frances J Puleo, Christine S Choi, Christopher S Hollenbeak, Evangelos Messaris
BACKGROUND: Enhanced recovery protocols frequently use multimodal postoperative analgesia to improve postoperative outcomes in patients undergoing colorectal surgery. OBJECTIVE: The purpose of this study was to evaluate liposomal bupivacaine use in transversus abdominis plane blocks on postoperative pain scores and opioid use after colorectal surgery. DESIGN: This was a retrospective cohort study comparing outcomes between patients receiving nonliposomal anesthetic (n = 104) and liposomal bupivacaine (n = 303) blocks...
February 2017: Diseases of the Colon and Rectum
https://www.readbyqxmd.com/read/28057946/ismp-adverse-drug-reactions-sildenafil-induced-erythema-multiforme-acute-liver-injury-due-to-febuxostat-intravenous-acetaminophen-induced-acute-hepatotoxicity-acute-transient-myopia-induced-by-zanamivir-lidocaine-induced-hoigne-syndrome
#20
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
December 2016: Hospital Pharmacy
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