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Sample records for acetaminophen

  1. How to Safely Give Acetaminophen

    ... All About Food Allergies How to Safely Give Acetaminophen KidsHealth > For Parents > How to Safely Give Acetaminophen ... without getting a doctor's OK first. What Is Acetaminophen Also Called? Acetaminophen is the generic name of ...

  2. Acetaminophen, Butalbital, and Caffeine

    The combination of acetaminophen, Butalbital, Caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 hours ... explain any part you do not understand. Take acetaminophen, Butalbital, Caffeine exactly as directed. Do not take ...

  3. Acetaminophen dosing for children

    Taking acetaminophen (Tylenol) can help children with colds and fever feel better. As with all drugs, it is important to give children the correct dose. Acetaminophen is safe when taken as directed. But taking ...

  4. Treatment of acetaminophen poisoning.

    Sellers, E M; Freedman, F.

    1981-01-01

    Acetaminophen is an analgesic that is frequently used in Canada, and the occurrence of overdoses with this drug seems to be increasing. The most serious complication of acetaminophen overdose is hepatic failure. Because of pathophysiologic effects of acetaminophen poisoning and the mechanisms of its toxic effects are now better understood, a rational approach to treatment is possible. Several precursors of glutathione, acetylcysteine in particular, are effective in preventing liver damage if ...

  5. Acetaminophen and Codeine

    The combination of acetaminophen and codeine comes as a tablet, capsule, and liquid to take by mouth. It usually is taken every 6 ... explain any part you do not understand. Take acetaminophen and codeine exactly as directed.Codeine can be ...

  6. Don't Double Up on Acetaminophen

    ... for advice. FDA has an online list of brand names of products containing acetaminophen . back to top ... t Mix For More Information Acetaminophen Information Acetaminophen Awareness Coalition’s Know Your Dose Campaign Using Acetaminophen and ...

  7. Acetaminophen and Codeine

    Acetaminophen and codeine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: dizziness lightheadedness drowsiness upset stomach vomiting constipation stomach pain rash difficulty urinating If you experience either of ...

  8. Acetaminophen for Chronic Pain

    Ennis, Zandra Nymand; Dideriksen, Dorthe; Vaegter, Henrik Bjarke;

    2016-01-01

    conducted according to PRISMA guidelines. All studies were conducted in patients with hip- or knee osteoarthritis and six out of seven studies had observation periods of less than three months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little......Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first-line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search...... evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended. This article is protected by copyright. All rights reserved....

  9. Acetaminophen and codeine overdose

    ... Comprehensive Study Guide. 7th ed. New York, NY: McGraw-Hill; 2011:chap 180. Ferri FF. Acetaminophen poisoning. ... Comprehensive Study Guide. 7th ed. New York, NY: McGraw-Hill; 2011:chap 184. Kellerman RD. Physical and ...

  10. Acetaminophen: old drug, new warnings.

    Schilling, Amy; Corey, Rebecca; Leonard, Mandy; Eghtesad, Bijan

    2010-01-01

    The US Food and Drug Administration (FDA), concerned about the incidence of acute liver failure due to acetaminophen (Tylenol) overdose, has mandated new labeling on acetaminophen packaging. It is also considering (but has not enacted) reducing the maximum daily dose from 4 g (possibly to 3,250 mg), banning acetaminophen-narcotic combination products, and changing the current maximum single dose of 1 g to prescription status, making 650 mg the highest recommended nonprescription dose. We review the epidemiology, toxicology, and management of acetaminophen overdose and steps the FDA and physicians can take to prevent it. PMID:20048026

  11. Acetaminophen toxicosis in a Dalmatian

    MacNaughton, Sarah M.

    2003-01-01

    An 11-year-old, spayed female Dalmatian was presented with suspected acetaminophen toxicosis. The dog was severely depressed. Methemoglobinemia, facial edema, and hemoglobinuria responded to treatment with intravenous fluids, N-acetylcysteine, ascorbic acid, and sodium bicarbonate. There was no clinical evidence of hepatic damage typical of acetaminophen toxicity in the dog.

  12. Paracetamol (acetaminophen) poisoning

    Buckley, Nick; Eddleston, Michael

    2007-01-01

    Paracetamol (acetaminophen) is a common means of self-poisoning in Europe and North America, often taken as an impulsive act of self-harm in young people. Mortality from paracetamol overdose is now about 0.4%, although without treatment, severe liver damage occurs in at least half of people with blood paracetamol levels above the UK standard treatment line.In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children witho...

  13. Interventions for paracetamol (acetaminophen) overdoses

    Brok, J; Buckley, N; Gluud, C

    2002-01-01

    Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation.......Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation....

  14. Know Concentration Before Giving Acetaminophen to Infants

    ... For Consumers Consumer Updates Know Concentration Before Giving Acetaminophen to Infants Share Tweet Linkedin Pin it More ... Consumer Updates RSS Feed Download PDF (221 K) Acetaminophen Safety (Podcast) On this page Overdosing Has Been ...

  15. Acetaminophen induced nephrotoxicity in an adolescent girl

    Belde; Mehmet; Demet; Alper; Salih

    2011-01-01

    Acetaminophen induced nephrotoxicity is not a frequent consequence of acetaminophen overdose. The pathophysiology has been attributed to oxidative stress. Here, we report a 16-year-old female patient who developed non-oliguric acute renal failure without hepatotoxicity following ingestion of 14 tablets of 500 mg acetaminophen and recovered spontaneously in a week. (Turk Arch Ped 2011; 46: 343-5)

  16. Multiple-dose acetaminophen pharmacokinetics.

    Sahajwalla, C G; Ayres, J W

    1991-09-01

    Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject. PMID:1800709

  17. Intravenous paracetamol (acetaminophen).

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text]. PMID:19192939

  18. Acetaminophen injection: a review of clinical information.

    Jones, Virginia M

    2011-01-01

    Acetaminophen injection is an antipyretic and analgesic agent recently marketed in the United States as Ofirmev. Five published trials directly compare acetaminophen injection to drugs available in the United States. For management of pain in adults, acetaminophen injection was at least as effective as morphine injection in renal colic, oral ibuprofen after cesarean delivery, and oral acetaminophen after coronary artery bypass surgery. In children (3 to 16 years old), single-dose acetaminophen injection was similar to meperidine intramuscular (i.m.) for pain after tonsillectomy; readiness for discharge from the recovery room was shorter with acetaminophen injection (median 15 minutes) compared with meperidine i.m. (median 25 minutes), P = .005. In children (2 to 5 years old) postoperative adenotonsillectomy or adenoidectomy, the time to rescue analgesia was superior with high-dose acetaminophen rectal suppository (median 10 hours) compared with acetaminophen injection (median 7 hours), P = .01. One published trial demonstrated acetaminophen injection is noninferior to propacetamol injection for fever related to infection in pediatric patients. Dosing adjustments are not required when switching between oral and injectable acetaminophen formulations in adult and adolescent patients. Acetaminophen injection represents another agent for multimodal pain management. PMID:21936636

  19. Decreased expression of acetaminophen-metabolizing enzymes and glutathione in asthmatic children after acetaminophen exposure

    Stephenson, Susan T.; Hadley, Graham; Brown, Lou Ann; Fitzpatrick, Anne M.

    2011-01-01

    Children with moderate-to-severe asthma have decreased expression of acetaminophen metabolizing genes and glutathione that may account for the previously-reported risk of acetaminophen in this vulnerable population.

  20. Acetaminophen: Beyond Pain and Fever-Relieving

    MiaozongWu

    2011-01-01

    Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever) and antipyretics (fever reducer). According to the U.S. Food and Drug Administration (FDA), currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage ca...

  1. Compound list: acetaminophen [Open TG-GATEs

    Full Text Available acetaminophen APAP 00001 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/acetamin...ophen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/acetamin...cedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/acetaminophen.Rat.in_vivo.Liver.Repeat.zip ftp...://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/acetaminophen.Rat.in_vivo.Kidn...ey.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/acetaminophen.Rat.in_vivo.Kidney.Repeat.zip ...

  2. 21 CFR 862.3030 - Acetaminophen test system.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Acetaminophen test system. 862.3030 Section 862....3030 Acetaminophen test system. (a) Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained...

  3. Acetaminophen in children: An old drug with new warnings

    Goldman, Ran D.

    2013-01-01

    Question I frequently suggest to parents to use acetaminophen to treat their children’s fever and pain. Recently, I had a child in my office who presented with a target-lesion skin rash a day after receiving acetaminophen. The rash resolved after 3 days and after stopping administration of acetaminophen. Does acetaminophen carry a risk of adverse events such as this?

  4. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard

    2015-01-01

    Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure ...

  5. Potentiation of cadmium nephrotoxicity by acetaminophen

    Bernard, A.M.; Russis, R. de; Ouled Amor, A.; Lauwerys, R.R.

    1988-10-01

    The possible interactions between acetaminophen and cadmium (Cd) on the kidney were investigated in female Sprague-Dawley rats. Acetaminophen was administered in the food at an average dose of 900 mg/kg and Cd in drinking water at the concentration of 200 ppm. The treatment with acetaminophen and Cd lasted 2 and 10 months, respectively. No interaction between Cd and acetaminophen was observed during the period of their concomitant administration: the increase in albuminuria caused by Cd and acetaminophen was additive, while the tubular impairment caused by acetaminophen (increased ..beta../sub 2/-microglobulinuria and decreased kidney concentrating ability) was not exacerbated by Cd. None of these treatments affected the glomerular filtration rate. Four months after the end of acetaminophen treatment, the renal changes had almost completely disappeared in the rats which had received the analgesic alone. Those continously exposed to Cd had developed slight tubular damage, as evidenced by an increased urinary excretion of ..beta../sub 2/-microglobulin and ..beta..-N-acetylglucosaminidase. By contrast, rats pretreated with acetaminophen for 2 months and exposed to Cd showed a marked increase in urinary excretion of albumin and ..beta../sub 2/-microglobulin, suggesting an interaction between both treatments. At the end of the study, only the interaction with ..beta../sub 2/-microglobulin excretion was still evident; that with the urinary excretion of ..beta..-N-acetylglucosaminidase and albumin having been masked by the chronic progessive nephrosis affecting most animals at that stage. As acetaminophen had no effect on the renal accumulation of Cd, it may be concluded that pretreatment with this analygesic at a dose causing slight tubular dysfunction renders rat kidney more sensitive to the nephrotoxic action of Cd. This observation may be of clinical relevance for population groups occupationally or environmentally exposed to Cd.

  6. The Social Side Effects of Acetaminophen

    Mischkowski, Dominik

    About 23% of all adults in the US take acetaminophen during an average week (Kaufman, Kelly, Rosenberg, Anderson, & Mitchell, 2002) because acetaminophen is an effective physical painkiller and easily accessible over the counter. The physiological side effects of acetaminophen are well documented and generally mild when acetaminophen is consumed in the appropriate dosage. In contrast, the psychological and social side effects of acetaminophen are largely unknown. Recent functional neuroimaging research suggests that the experience of physical pain is fundamentally related to the experience of empathy for the pain of other people, indicating that pharmacologically reducing responsiveness to physical pain also reduces cognitive, affective, and behavioral responsiveness to the pain of others. I tested this hypothesis across three double-blind between-subjects drug intervention studies. Two experiments showed that acetaminophen had moderate effects on empathic affect, specifically personal distress and empathic concern, and a small effect on empathic cognition, specifically perceived pain, when facing physical and social pain of others. The same two experiments and a third experiment also showed that acetaminophen can increase the willingness to inflict pain on other people, i.e., actual aggressive behavior. This effect was especially pronounced among people low in dispositional empathic concern. Together, these findings suggest that the physical pain system is more involved in the regulation of social cognition, affect, and behavior than previously assumed and that the experience of physical pain and responsiveness to the pain of others share a common neurochemical basis. Furthermore, these findings suggest that acetaminophen has unappreciated but serious social side effects, and that these side effects may depend on psychological characteristics of the drug consumer. This idea is consistent with recent theory and research on the context-dependency of neurochemical

  7. Synthesis of acetaminophen-d4

    A synthetic procedure for the analgesic acetaminophen-d4 (4'-hydroxyacetanilide - 2',3,5',6'-d4) is described. The preparation was achieved in two steps from nitrobenzene-d5 in an overall yield of 40%. (author)

  8. Acetaminophen prevents hyperalgesia in central pain cascade

    Crawley, Brianna; Saito, Osamu; Malkmus, Shelle; Fitzsimmons, Bethany; Hua, Xiao-Ying; Yaksh, Tony L.

    2008-01-01

    Acetaminophen is an analgesic and antipyretic drug believed to exert its effect through interruption of nociceptive processing. In order to determine whether this effect is due to peripheral or central activity, we studied the efficacy of systemic (oral) and intrathecal (IT) application of acetaminophen in preventing the development of hyperalgesia induced through the direct activation of pro-algogenic spinal receptors. Spinal administration of substance P (SP, 30 nmol, IT) in rats produced a...

  9. Acetaminophen hepatotoxicity: NO to the rescue

    Wallace, John L

    2004-01-01

    Severe liver injury as a result of overdose or chronic use of acetaminophen (paracetamol) remains a significant clinical problem, accounting for as much as 40% of cases of acute liver failure. The mechanisms underlying the liver injury caused by acetaminophen have become much better understood in recent years. In this issue, Fiorucci et al. report that delivery of nitric oxide (NO) in small amounts to the liver, via a novel derivative of the bile acid ursodeoxycholic acid, results in signific...

  10. Acetaminophen: beyond pain and fever-relieving

    MiaozongWu

    2011-11-01

    Full Text Available Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever and antipyretics (fever reducer. According to the U.S. Food and Drug Administration (FDA, currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage can arise. In addition to well known use pain relief and fever reduction, recent laboratory and pre-clinical studies have demonstrated that acetaminophen may also have beneficial effects on blood glucose levels, skeletal muscle function, and potential use as cardioprotective and neuroprotective agents. Extensive laboratory and pre-clinical studies have revealed that these off label applications may be derived from the ability of acetaminophen to function as an antioxidant. Herein, we will highlight these novel applications of acetaminophen, and attempt, where possible, to highlight how these findings may lead to new directions of inquiry and clinical relevance of other disorders.

  11. Parents: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

    ... the-Counter Pain Relievers and Fever Reducers Parents: Acetaminophen in pain relief medicines can cause liver damage ... More sharing options Linkedin Pin it Email Print Acetaminophen (a∙SEET∙a∙MIN∙o∙fen) is an ...

  12. Careful: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

    ... the-Counter Pain Relievers and Fever Reducers Careful: Acetaminophen in pain relief medicines can cause liver damage ... More sharing options Linkedin Pin it Email Print Acetaminophen (a∙SEET∙a∙MIN∙o∙fen) is an ...

  13. Acetaminophen Won't Help Arthritis Pain, Study Finds

    ... nlm.nih.gov/medlineplus/news/fullstory_157822.html Acetaminophen Won't Help Arthritis Pain, Study Finds Prescription ... 18, 2016 THURSDAY, March 17, 2016 (HealthDay News) -- Acetaminophen -- commonly known as Tylenol in the United States -- ...

  14. Acetaminophen

    Meda Cap® ... as a tablet, chewable tablet, capsule, suspension or solution (liquid), extended-release (long-acting) tablet, and orally ... the manufacturer to measure each dose of the solution or suspension. Do not switch dosing devices between ...

  15. Acetaminophen

    ... cough and colds that contain nasal decongestants, antihistamines, cough suppressants, and expectorants should not be used in children younger than 2 years of age. Use of these medications in young children can ... of age, combination cough and cold products should be used carefully and ...

  16. Pharmacological screening of glycine amino acid prodrug of acetaminophen

    Arun Parashar

    2015-01-01

    Objective: To develop an amino acid prodrug of acetaminophen with comparable therapeutic profile and less hepatotoxicity than acetaminophen. Materials and Methods: Acetaminophen prodrug was synthesized by esterification between the carboxyl group of amino acid glycine and hydroxyl group of acetaminophen. Analgesic, antipyretic, ulcer healing, and hepatotoxic activities were performed on Wistar rats in this study. Results: Prodrug showed a 44% inhibition in writhings as compared to 53....

  17. Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management

    Mazer, Maryann; Perrone, Jeanmarie

    2008-01-01

    Acetaminophen-induced liver necrosis has been studied extensively, but the extrahepatic manifestations of acetaminophen toxicity are currently not described well in the literature. Renal insufficiency occurs in approximately 1–2% of patients with acetaminophen overdose. The pathophysiology of renal toxicity in acetaminophen poisoning has been attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney, although other mechanisms have been elucidated, including the ro...

  18. In Vitro Antibacterial Activity of Ibuprofen and Acetaminophen

    AL-Janabi, Ali Abdul Hussein S.

    2010-01-01

    Background: Ibuprofen and acetaminophen are common chemical agents that have anti-inflammatory, antipyretic, and analgesic activity. Aims: To detect any potential antibacterial effects of ibuprofen and acetaminophen on pathogenic bacteria. Materials and methods: Ibuprofen and acetaminophen were tested for antibacterial activity against seven isolates of bacteria including gram positive bacteria (Staphylococci aureus and Bacillus subtilis) and gram negative bacteria (E. coli, Enterobacter a...

  19. Safety of rapid intravenous of infusion acetaminophen.

    Needleman, Steven M

    2013-07-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I-III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  20. [Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

    Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

    2013-06-01

    Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. PMID:23628119

  1. Acetaminophen Modulation of Hydrocodone Reward in Rats

    Nazarian, Arbi; Are, Deepthi; Tenayuca, John M.

    2011-01-01

    Abuse of prescription opioid analgesics in non-medical context has been on the rise over the past decade. The most commonly abused analgesic in this drug class consists of a combined formulation of hydrocodone and acetaminophen. The present study was aimed to determine the rewarding effects of hydrocodone, acetaminophen, and their combination using the conditioned place preference (CPP) paradigm. Using a 6-day CPP paradigm, rats were paired with hydrocodone (0.5, 1.0 or 5.0 mg/kg) or acetamin...

  2. Tramadol and acetaminophen tablets for dental pain.

    Medve, R. A.; Wang, J.; Karim, R

    2001-01-01

    The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 40...

  3. Study of an anaphylactoid reaction to acetaminophen.

    Liao, Chien-Ming; Chen, Wu-Charng; Lin, Ching-Yuang

    2002-01-01

    Generalized itching, urticaria and anaphylactic shock developed in a 9-year-old girl on two separate occasions after she ingested acetaminophen. She was admitted to our hospital for observation during oral challenge. Total eosinophil counts, total serum IgE, IgA, IgG, IgM, C3, and C4, specific IgE antibodies to six common allergens, and skin prick tests to purified acetaminophen and acetylsalicylic acid (aspirin) were unremarkable. No reaction occurred on open challenge with acetylsalicylic acid and mefenamic acid. However, urticaria and itching sensation occurred 45 min after ingesting 50 mg of purified acetaminophen. Dizziness, shivering, tachycardia and fainting also developed later. These symptoms resolved after treatment with a diphenhydramine injection and intravenous infusion of normal saline. There was a marked increase in the blood histamine level after challenge. In vitro histamine release before oral challenge was also abnormally as high as 50%. In summary, she had an immediate allergic reaction to acetaminophen but was tolerant to acetylsalicylic acid. PMID:12148965

  4. Acetaminophen-induced cellulitis-like fixed drug eruption

    Neila Fathallah

    2011-01-01

    Full Text Available Acetaminophen is a widely used analgesic drug. Its adverse reactions are rare but severe. An 89-year-old man developed an indurated edematous and erythematous plaque on his left arm 1 day after acetaminophen ingestion. Cellulitis was suspected and antibiotictherapy was started but there was no improvement of the rash; there was a spectacular extension of the lesion with occurrence of flaccid vesicles and blisters in the affected sites. The diagnosis of generalized-bullous-fixed drug eruption induced by acetaminophen was considered especially with a reported history of a previous milder reaction occurring in the same site. Acetaminophen was withdrawn and the rash improved significantly. According to the Naranjo probability scale, the eruption experienced by the patient was probably due to acetaminophen. Clinicians should be aware of the ability of acetaminophen to induce fixed drug eruption that may clinically take several aspects and may be misdiagnosed.

  5. Caffeine Accelerates Absorption and Enhances the Analgesic Effect of Acetaminophen

    Renner, Bertold; Clarke, Geoff; Grattan, Tim; Beisel, Angelika; Mueller, Christian; Werner, Ulrike; Kobal, Gerd; Brune, Kay

    2013-01-01

    The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic effects were assessed by means of an experimental pain model based on pain-related cortical pot...

  6. Acetaminophen overdose associated with double serum concentration peaks

    Papazoglu, Cristian; Jonathan R. Ang; Mandel, Michael; Basak, Prasanta; Jesmajian, Stephen

    2015-01-01

    Acetaminophen is the most commonly used analgesic–antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-y...

  7. Exacerbation of Acetaminophen Hepatotoxicity by the Anthelmentic Drug Fenbendazole

    Carol R. Gardner; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-01-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8–12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administra...

  8. Rhabdomyolysis after Intentional Acetaminophen and Carbon Monoxide Poisoning

    Iago Rodríguez–Lago; Delia D’Avola; Mercedes Iñarrairaegui; José Ignacio Herrero; Bruno Sangro; Jorge Quiroga

    2012-01-01

    Acetaminophen is one of the most frequent causes of acute liverfailure. Rhabdomyolysis is a rare adverse reaction reported withthis drug. Carbon monoxide (CO) can also lead to muscle injury butonly after severe intoxication. We present a case of rhabdomyolysisassociated to Acetaminophen over dosage and mild carbon monoxideexposure. A 38-year-old man was admitted because of acute hepaticinjury due to voluntary acetaminophen overdose. He also reporteda mild carbon monoxide exposure. He showed a...

  9. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Judge Bryan S; James Laura P; Green Jody L; Heard Kennon J; Zolot Liza; Rhyee Sean; Dart Richard C

    2011-01-01

    Abstract Background Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from ...

  10. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  11. [A Case of Acetaminophen Poisoning Associated with Tramcet Overdose].

    Urabe, Shigehiko; Terao, Yoshiaki; Tuji, Tikako; Egashira, Takashi; Goto, Shino; Fukusaki, Makoto

    2016-06-01

    Tramcet is a mixture of tramadol and acetaminophen. Acetaminophen poisoning may be caused by excessive intake of Tramcet. A 17-year-old female took excessive quantity of Tramcet before noon. She reported it herself in the emergency room. Her main complaint was nausea and dizziness. Acetaminophen may cause liver damage with dose-dependent manner. Because there was a possibility of acetaminophen poisoning, we started oral acetylcysteine. She was discharged from hospital 5 days later without side effects of acetylecysteine and liver damage. PMID:27483669

  12. Acetaminophen overdose associated with double serum concentration peaks

    Cristian Papazoglu

    2015-12-01

    Full Text Available Acetaminophen is the most commonly used analgesic–antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy.

  13. N-acetylcysteine overdose after acetaminophen poisoning.

    Mahmoudi, Ghafar Ali; Astaraki, Peyman; Mohtashami, Azita Zafar; Ahadi, Maryam

    2015-01-01

    N-acetylcysteine (NAC) is used widely and effectively in oral and intravenous forms as a specific antidote for acetaminophen poisoning. Here we report a rare case of iatrogenic NAC overdose following an error in preparation of the solution, and describe its clinical symptoms. Laboratory results and are presented and examined. A 23-year-old alert female patient weighing 65 kg presented to the emergency ward with weakness, lethargy, extreme fatigue, nausea, and dizziness. She had normal arterial blood gas and vital signs. An excessive dosage of NAC over a short period of time can lead to hemolysis, thrombocytopenia, and acute renal failure in patients with normal glucose-6-phosphate dehydrogenase, and finally to death. Considering the similarity between some of the clinical symptoms of acetaminophen overdose and NAC overdose, it is vitally important for the administration phases and checking of the patient's symptoms to be carried out attentively and cautiously. PMID:25767408

  14. Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain.

    Sunshine, A; Marrero, I; Olson, N; McCormick, N; Laska, E M

    1986-03-24

    The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p less than or equal to 0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac. PMID:3515924

  15. N-acetylcysteine overdose after acetaminophen poisoning

    Mahmoudi GA; Astaraki P; Mohtashami AZ; Ahadi M

    2015-01-01

    Ghafar Ali Mahmoudi,1 Peyman Astaraki,1 Azita Zafar Mohtashami,1 Maryam Ahadi2 1Faculty of Medicine, Department of Internal Medicine, Lorestan University of Medical Sciences, 2Legal Medicine Research Center of Lorestan, Khorramabad, Iran Abstract: N-acetylcysteine (NAC) is used widely and effectively in oral and intravenous forms as a specific antidote for acetaminophen poisoning. Here we report a rare case of iatrogenic NAC overdose following an error in preparation of the solution, and des...

  16. Understanding lactic acidosis in paracetamol (acetaminophen) poisoning

    Shah, Anoop D; Wood, David M; Dargan, Paul I

    2011-01-01

    Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver sl...

  17. N-acetylcysteine overdose after acetaminophen poisoning

    Mahmoudi GA

    2015-02-01

    Full Text Available Ghafar Ali Mahmoudi,1 Peyman Astaraki,1 Azita Zafar Mohtashami,1 Maryam Ahadi2 1Faculty of Medicine, Department of Internal Medicine, Lorestan University of Medical Sciences, 2Legal Medicine Research Center of Lorestan, Khorramabad, Iran Abstract: N-acetylcysteine (NAC is used widely and effectively in oral and intravenous forms as a specific antidote for acetaminophen poisoning. Here we report a rare case of iatrogenic NAC overdose following an error in preparation of the solution, and describe its clinical symptoms. Laboratory results and are presented and examined. A 23-year-old alert female patient weighing 65 kg presented to the emergency ward with weakness, lethargy, extreme fatigue, nausea, and dizziness. She had normal arterial blood gas and vital signs. An excessive dosage of NAC over a short period of time can lead to hemolysis, thrombocytopenia, and acute renal failure in patients with normal glucose-6-phosphate dehydrogenase, and finally to death. Considering the similarity between some of the clinical symptoms of acetaminophen overdose and NAC overdose, it is vitally important for the administration phases and checking of the patient's symptoms to be carried out attentively and cautiously. Keywords: N-acetylcysteine, overdose, acetaminophen poisoning, medication error

  18. Electronic Spectra of the Jet-Cooled Acetaminophen

    Lee, Seung Jun; Min, Ahreum; Kim, Yusic; Choi, Myong Yong; Chang, Jinyoung; Lee, Sang Hak; Kim, Seong Keun

    2010-06-01

    Resonant two-photon ionization (R2PI), laser induced fluorescence (LIF) and UV-UV double resonance spectra of the jet-cooled acetaminophen, widely used as a pain reliever and fever reducer, were obtained in the gas phase. Conformational characterizations for acetaminophen will be presented with an aid of spectroscopic techniques and DFT B3LYP calculations.

  19. Acetaminophen developmental pharmacokinetics in premature neonates and infants

    Anderson, Brian J; van Lingen, Richard A; Hansen, Tom G;

    2002-01-01

    The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens.......The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens....

  20. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Morteza Talebi Doluee

    2015-01-01

    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  1. Interventions for paracetamol (acetaminophen) overdoses. Protocol for a Cochrane Review

    Brok, J; Buckley, N; Gluud, C

    2001-01-01

    Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning.......Poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation are interventions for paracetamol poisoning....

  2. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity in CD-1 mice: I. Enhancement of acetaminophen nephrotoxicity by acetaminophen-cysteine

    Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Recent studies suggest a contributory role for glutathione (GSH)-derived conjugates of APAP in the development of nephrotoxicity. Inhibitors of either γ-glutamyl transpeptidase (γ-GT) or the probenecid-sensitive organic anion transporter ameliorate APAP-induced nephrotoxicity but not hepatotoxicity in mice and inhibition of γ-GT similarly protected rats from APAP nephrotoxicity. Protection against APAP nephrotoxicity by disruption of these GSH conjugate transport and metabolism pathways suggests that GSH conjugates are involved. APAP-induced renal injury may involve the acetaminophen-glutathione (APAP-GSH) conjugate or a metabolite derived from APAP-GSH. Acetaminophen-cysteine (APAP-CYS) is a likely candidate for involvement in APAP nephrotoxicity because it is both a product of the γ-GT pathway and a probable substrate for the organic anion transporter. The present experiments demonstrated that APAP-CYS treatment alone depleted renal but not hepatic glutathione (GSH) in a dose-responsive manner. This depletion of renal GSH may predispose the kidney to APAP nephrotoxicity by diminishing GSH-mediated detoxification mechanisms. Indeed, pretreatment of male CD-1 mice with APAP-CYS before challenge with a threshold toxic dose of APAP resulted in significant enhancement of APAP-induced nephrotoxicity. This was evidenced by histopathology and plasma blood urea nitrogen (BUN) levels at 24 h after APAP challenge. APAP alone was minimally nephrotoxic and APAP-CYS alone produced no detectable injury. By contrast, APAP-CYS pretreatment did not alter the liver injury induced by APAP challenge. These data are consistent with there being a selective, contributory role for APAP-GSH-derived metabolites in APAP-induced renal injury that may involve renal-selective GSH depletion

  3. Nalbuphine, acetaminophen, and their combination in postoperative pain.

    Forbes, J A; Kolodny, A L; Chachich, B M; Beaver, W T

    1984-06-01

    In a double-blind study with the use of subjective reports of patients as indices of analgesia, we compared the analgesic effect of oral nalbuphine and acetaminophen and determined the contribution of each to the efficacy of their combination. In this parallel 2 X 2 factorial study, 129 inpatients after surgery were randomly assigned to treatment with a single oral dose of nalbuphine hydrochloride (30 mg), acetaminophen (650 mg), the combination of nalbuphine (30 mg) and acetaminophen (650 mg), or placebo. In the factorial analysis, both the nalbuphine and acetaminophen effects were significant for virtually every measure of total and peak analgesia, whereas the interaction contrast was not significant for any measure of analgesic effect. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the results of studies of combinations of codeine and other opioids with aspirin or acetaminophen. There were few adverse effects other than sedation, which occurred twice as frequently in patients treated with nalbuphine as in those receiving acetaminophen or placebo. Our data suggest that this combination should prove at least as effective as any currently marketed narcotic-containing combination. Since nalbuphine has less dependence liability than narcotics and exhibits a ceiling on respiratory depression, its combination with acetaminophen should also be safer than comparable narcotic combinations. PMID:6734037

  4. Potential role of caveolin-1 in acetaminophen-induced hepatotoxicity

    Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1-/-) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increases in serum transaminases. This was correlated with decreased expression of Cav-1 in the liver. Acetaminophen-induced hepatotoxicity was significantly attenuated in Cav-1-/- mice, an effect that was independent of acetaminophen metabolism. Acetaminophen administration resulted in increased hepatic expression of the oxidative stress marker, lipocalin 24p3, as well as hemeoxygenase-1, but decreased glutathione and superoxide dismutase-1; no differences were noted between the genotypes suggesting that reduced toxicity in Cav-1-/- mice is not due to alterations in antioxidant defense. In wild-type mice, acetaminophen increased mRNA expression of the pro-inflammatory cytokines, interleukin-1β, and monocyte chemoattractant protein-1 (MCP-1), as well as cyclooxygenase-2, while 15-lipoxygenase (15-LOX), which generates anti-inflammatory lipoxins, decreased. Acetaminophen-induced changes in MCP-1 and 15-LOX expression were greater in Cav-1-/- mice. Although expression of tumor necrosis factor-α, a potent hepatocyte mitogen, was up-regulated in the liver of Cav-1-/- mice after acetaminophen, expression of proliferating cell nuclear antigen and survivin, markers of cellular proliferation, were delayed, which may reflect the reduced need for tissue repair. Taken together, these data demonstrate that Cav-1 plays a role in promoting inflammation and toxicity during the pathogenesis of acetaminophen-induced injury.

  5. Acetaminophen-induced acute liver injury in HCV transgenic mice

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  6. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  7. Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain.

    Sunshine, A; Olson, N Z; Zighelboim, I; De Castro, A

    1993-11-01

    Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. Analgesia for the first dose was assessed over an 8-hour period. Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose (325 mg acetaminophen plus 5 mg oxycodone) were also assessed for up to 7 days. The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures. A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose. Ketoprofen, 100 mg, was at least as effective as the combination and its effects lasted longer, with the exception of hour 1 when the combination was superior. Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain. PMID:8222498

  8. Possible fatal acetaminophen intoxication with atypical clinical presentation.

    De-Giorgio, Fabio; Lodise, Maria; Chiarotti, Marcello; d'Aloja, Ernesto; Carbone, Arnaldo; Valerio, Luca

    2013-09-01

    Acetaminophen or paracetamol, a commonly used over-the-counter analgesic, is known to elicit severe adverse reactions when taken in overdose, chronically at therapeutic dosage or, sporadically, following single assumptions of a therapeutic dose. Damage patterns including liver damage and, rarely, acute tubular necrosis or a fixed drug exanthema. We present a case of fatal acetaminophen toxicity with postmortem blood concentration 78 μg/mL and unusual clinical features, including a visually striking and massive epidermolysis and rhabdomyolysis, disseminated intravascular coagulation and myocardial ischemia. This case is compared with the most similar previous reports in terms of organ damage, clinical presentation, and cause of death. We conclude that a number of severe patterns of adverse effects to acetaminophen are emerging that were previously greatly underestimated, thus questioning the adequacy of the clinical spectrum traditionally associated with acetaminophen intoxication and leading to the need to review this spectrum and the associated diagnostic criteria. PMID:23822653

  9. Acetaminophen-induced cellulitis-like fixed drug eruption

    Neila Fathallah; Chaker Ben Salem; Raoudha Slim; Lobna Boussofara; Najet Ghariani; Kamel Bouraoui

    2011-01-01

    Acetaminophen is a widely used analgesic drug. Its adverse reactions are rare but severe. An 89-year-old man developed an indurated edematous and erythematous plaque on his left arm 1 day after acetaminophen ingestion. Cellulitis was suspected and antibiotictherapy was started but there was no improvement of the rash; there was a spectacular extension of the lesion with occurrence of flaccid vesicles and blisters in the affected sites. The diagnosis of generalized-bullous-fixed drug eruption ...

  10. Toxic epidermal necrolysis induced by acetaminophen: a case report

    M. C. Gupta; Niti Mittal; Nishikant Sharma

    2013-01-01

    Acetaminophen is a very commonly used analgesic and antipyretic drug across various age groups. Although mild to moderate cutaneous reactions have been reported quite frequently, serious reactions like Stevens –Johnson syndrome and Toxic epidermal necrolysis (TEN) are very rare. We report the case of a 10 year old child who had TEN after ingestion of tablet acetaminophen. This case report highlights the need to be critically aware of this rare and serious adverse effect of this commonly ...

  11. Reversal of acetaminophen toxicity in isolated hamster hepatocytes by dithiothreitol

    The toxicity of acetaminophen in freshly isolated hamster hepatocytes was investigated. Cells exposed to 2.5 mM acetaminophen for 90 min, followed by washing to completely remove unbound acetaminophen, and resuspension in fresh buffer, showed a dramatic decrease in viability over the ensuing 4.5 hr by which time only 4% of the cells could still exclude trypan blue. During the initial 90-min incubation, there was a substantial depletion of glutathione, to 19% of control values, covalent binding of [14C]acetaminophen to cellular proteins, and evidence of morphological changes consistent with some disturbance of the plasma membrane. During subsequent incubation of these cells, covalent binding did not change nor did lipid peroxidation, despite the decrease in viability that occurred. Subsequent incubation of cells exposed to acetaminophen for 90 min in buffer containing 1.5 mM dithiothreitol (DTT), a disulfide-reducing agent, largely prevented the decrease in cell viability and reversed the morphological changes that occurred during the first 90-min incubation. However, there was no change in lipid peroxidation, glutathione content, or covalent binding. It is concluded that acetaminophen interacted with some critical target in the cell, and that this left unchecked, led eventually to the death of the cell. DTT prevented and reversed this effect. The toxicity of acetaminophen, and its reversal by DTT, appear independent of either covalent binding of acetaminophen or lipid peroxidation. In addition, the effect of DTT was independent of the concentration of glutathione, most probably acting by directly reducing oxidized SH-groups in critical enzymes, possibly membrane-bound ATP-dependent Ca2+ translocases

  12. Childhood suicide attempts with acetaminophen in Denmark

    Hedeland, Rikke; Jørgensen, Marianne H; Teilmann, Grete;

    2013-01-01

    Aims: To explore: (1) The relationship between children admitted to our paediatric department as a result of suicide attempts with acetaminophen and their parents and friends. (2) The extent to which the children had attempted to speak to their parents about their problems before their suicide...... attempts. (3) The frequency of self-mutilation among children with suicidal behaviour. (4) The purposes and reasons for childhood suicide attempts. Methods: A retrospective case-control study based on medical records and in-hospital child psychiatric assessments at the Paediatric Department, Hillerød....... There was a significant association between a dissociated parental relationship and 'the feeling of not being heard' (p = 0.004), the discovery of the suicide attempt (p = 0.008), the reasons for the suicide attempt (p = 0.006), academic school problems (p = 0.03), and the child's relationships with...

  13. The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model

    Ben-Shachar Rotem

    2012-12-01

    Full Text Available Abstract Background Acetaminophen (N-acetyl-para-aminophenol is the most widely used over-the-counter or prescription painkiller in the world. Acetaminophen is metabolized in the liver where a toxic byproduct is produced that can be removed by conjugation with glutathione. Acetaminophen overdoses, either accidental or intentional, are the leading cause of acute liver failure in the United States, accounting for 56,000 emergency room visits per year. The standard treatment for overdose is N-acetyl-cysteine (NAC, which is given to stimulate the production of glutathione. Methods We have created a mathematical model for acetaminophen transport and metabolism including the following compartments: gut, plasma, liver, tissue, urine. In the liver compartment the metabolism of acetaminophen includes sulfation, glucoronidation, conjugation with glutathione, production of the toxic metabolite, and liver damage, taking biochemical parameters from the literature whenever possible. This model is then connected to a previously constructed model of glutathione metabolism. Results We show that our model accurately reproduces published clinical and experimental data on the dose-dependent time course of acetaminophen in the plasma, the accumulation of acetaminophen and its metabolites in the urine, and the depletion of glutathione caused by conjugation with the toxic product. We use the model to study the extent of liver damage caused by overdoses or by chronic use of therapeutic doses, and the effects of polymorphisms in glucoronidation enzymes. We use the model to study the depletion of glutathione and the effect of the size and timing of N-acetyl-cysteine doses given as an antidote. Our model accurately predicts patient death or recovery depending on size of APAP overdose and time of treatment. Conclusions The mathematical model provides a new tool for studying the effects of various doses of acetaminophen on the liver metabolism of acetaminophen and

  14. Methodological considerations in the evaluation of analgesic combinations: Acetaminophen (paracetamol) and hydrocodone in postpartum pain

    Beaver, William T.; McMillan, Diane

    1980-01-01

    1 In a double-blind study, 108 postpartum patients received single oral doses of either placebo, acetaminophen (paracetamol) 1000 mg, hydrocodone 10 mg, the combination of acetaminophen plus hydrocodone, or codeine 60 mg.

  15. N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen.

    Dahlin, D C; Miwa, G T; Lu, A Y; Nelson, S. D.

    1984-01-01

    N-acetyl-p-benzoquinone imine (NAPQI) has been proposed as the toxic metabolite of acetaminophen for the past 10 years, although it has never been detected as an enzymatic oxidation product of acetaminophen. We report (i) direct detection of NAPQI formed as an oxidation product of acetaminophen by cytochrome P-450 and cumene hydroperoxide and (ii) indirect evidence that is compelling for NAPQI formation from acetaminophen by cytochrome P-450, NADPH, and NADPH-cytochrome P-450 reductase. Evide...

  16. NQO2 Is a Reactive Oxygen Species Generating Off-Target for Acetaminophen

    Miettinen, Teemu P.; Björklund, Mikael

    2014-01-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In hu...

  17. Effect of excipients on acetaminophen metabolism and its implications for prevention of liver injury

    Ganetsky, Michael; Böhlke, Mark; Pereira, Luis; Williams, David; LeDuc, Barbara; Guatam, Shiva

    2013-01-01

    Acetaminophen poisoning is the most frequent cause of acute hepatic failure in the US. Toxicity requires reductive metabolism of acetaminophen, primarily via CYP2E1. Liquid acetaminophen preparations contain propylene glycol, a common excipient that has been shown to reduce hepatocellular injury in vitro and in rodents. Children are less susceptible to acetaminophen toxicity for unclear reasons. We conducted a pharmacokinetic single-blinded crossover study of 15 healthy adult volunteers compa...

  18. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats

    Attalla Farag El-Kott, PhD; Mashael Mohammed Bin-Meferij, PhD

    2015-01-01

    Background: Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. Objective: To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Methods: Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. Results: The treatment with Arctium lappa extract reduc...

  19. Confusion: acetaminophen dosing changes based on NO evidence in adults.

    Krenzelok, Edward P; Royal, Mike A

    2012-06-01

    Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used? PMID:22530736

  20. MODULATION OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY BY THE XENOBIOTIC RECEPTOR CAR

    We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR-...

  1. Testing of Candidate Icons to Identify Acetaminophen-Containing Medicines

    Saul Shiffman

    2016-01-01

    Full Text Available Adding icons on labels of acetaminophen-containing medicines could help users identify the active ingredient and avoid concomitant use of multiple medicines containing acetaminophen. We evaluated five icons for communication effectiveness. Adults (n = 300 were randomized to view a prescription container label or over-the-counter labels with either one or two icons. Participants saw two icon candidates, and reported their interpretation; experts judged whether these reflected critical confusions that might cause harm. Participants rated how effectively each icon communicated key messages. Icons based on abbreviations of “acetaminophen” (“Ac”, “Ace”, “Acm” were rated less confusing and more effective in communicating the active ingredient than icons based on “APAP” or an abstract symbol. Icons did not result in critical confusion when seen on a readable medicine label. Icon implementation on prescription labels was more effective at communicating the warning against concomitant use than implementation on over-the-counter (OTC labels. Adding an icon to a second location on OTC labels did not consistently enhance this communication, but reduced rated effectiveness of acetaminophen ingredient communication among participants with limited health literacy. The abbreviation-based icons seem most suitable for labeling acetaminophen-containing medications to enable users to identify acetaminophen-containing products.

  2. Tramadol and acetaminophen tablets for dental pain.

    Medve, R. A.; Wang, J.; Karim, R.

    2001-01-01

    The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours before taking supplemental analgesia. Patients assessed overall efficacy (scale, 1-5) upon completion. In all, 1197 patients (age range, 16-46 years) were evaluable for efficacy; treatment groups in each study were similar at baseline. Pain relief was superior to placebo (P < or = .0001) for all treatments. Pain relief provided by tramadol/ APAP was superior to that of tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001) and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes (95% CI, 15-20 minutes) for tramadol/APAP compared with 51 minutes (95% CI, 40-70 minutes) for tramadol, 18 minutes (95% CI, 16-21 minutes) for APAP, and 34 minutes (95% CI, 28-44 minutes) for ibuprofen. Median time to supplemental analgesia and mean overall assessment of efficacy were greater (P < .05) for the tramadol/APAP group (302 minutes and 3.0, respectively) than for the tramadol (122 minutes and 2.0) or APAP (183 minutes and 2

  3. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update.

    Yoon, Eric; Babar, Arooj; Choudhary, Moaz; Kutner, Matthew; Pyrsopoulos, Nikolaos

    2016-06-28

    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways. PMID:27350943

  4. Toxic epidermal necrolysis induced by acetaminophen: a case report

    M. C. Gupta

    2013-12-01

    Full Text Available Acetaminophen is a very commonly used analgesic and antipyretic drug across various age groups. Although mild to moderate cutaneous reactions have been reported quite frequently, serious reactions like Stevens –Johnson syndrome and Toxic epidermal necrolysis (TEN are very rare. We report the case of a 10 year old child who had TEN after ingestion of tablet acetaminophen. This case report highlights the need to be critically aware of this rare and serious adverse effect of this commonly used over the counter drug. [Int J Basic Clin Pharmacol 2013; 2(6.000: 831-832

  5. The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.

    Cooper, S A; Kupperman, A

    1991-01-01

    In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen. PMID:1930699

  6. Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

    Sunshine, A; Zighelboim, I; De Castro, A; Sorrentino, J V; Smith, D S; Bartizek, R D; Olson, N Z

    1989-07-01

    A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain. PMID:2569485

  7. Gastric emptying in rats with acetaminophen-induced hepatitis

    Hessel G.

    1998-01-01

    Full Text Available The objective of this work was to study the gastric emptying (GE of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each. Group I was fed a sucrose diet throughout the experiment (66 h while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each. Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg. Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml than in group IB (87 µg/ml. The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values. The correlation between gastric retention and AST levels was significant (P<0.05 for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.

  8. A zeolite modified carbon paste electrode as useful sensor for voltammetric determination of acetaminophen

    The voltammetric behavior of a carbon paste electrode modified with Co(II)-exchanged zeolite A (Co(II)-A/ZMCPE) for determination of acetaminophen was studied. The proposed electrode showed a diffusion controlled reaction with the electron transfer rate constant (Ks) of 0.44 s−1 and charge transfer coefficient of 0.73 in the absence of acetaminophen. A linear voltammetric response was obtained in the range of 0.1 to 190 μmol L−1 of acetaminophen [r2 = 0.9979, r = 0.9989 (n = 10)] with a detection limit of 0.04 μmol L−1. The method was successfully applied to the analysis of acetaminophen in some drugs. - Highlights: • Modified carbon paste electrode with Co(II)-zeolite A improved the voltammetric current in determination of acetaminophen. • Modified electrode is applicable for acetaminophen in real samples. • The proposed method has good reproducibility and repeatability

  9. Pharmacist and Physician Interpretation of Abbreviations for Acetaminophen Intended for Use in a Consumer Icon

    Saul Shiffman; Helene Cotton; Christina Jessurun; Sembower, Mark A.; Steve Pype; Jerry Phillips

    2015-01-01

    Concomitant use of multiple acetaminophen medications is associated with overdose. To help patients identify acetaminophen medications and thus avoid concomitant use, an icon with an abbreviation for “acetaminophen” has been proposed for all acetaminophen medications. This study assessed pharmacists’ and physicians’ use and interpretation of abbreviations for “acetaminophen”, to identify abbreviations with other meanings that might cause confusion. Physicians (n = 150) reported use and interp...

  10. Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury

    Chen, Wei-Ting; Yang, Chieh-ling; Yin, Mei-chin

    2014-01-01

    Background Protective effects of Houttuynia cordata aqueous extract (HCAE) against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined. Methods HCAE, at 1 or 2 g/L, was added into the drinking water for 4 weeks. Acute liver injury was induced by acetaminophen treatment intraperitoneally (350 mg/kg body weight). Results Acetaminophen treatment significantly depleted hepatic glutathione (GSH) content, increased hepatic malonyldialdehyde (MDA), reactive oxygen species (ROS) and ox...

  11. IV Acetaminophen: Assessment of Medication Utilization Evaluation Data in Peri-operative Pain Management

    Mark A. Malesker; Anne L Bruckner; Hilleman, Daniel E; Brian Loggie

    2015-01-01

    IV acetaminophen has become an accepted component of a multimodal analgesic strategy in perioperative patients. It is currently a branded drug (Ofirmev®) in the United States. The purchase price of the drug is greater than oral and rectal acetaminophen, intravenous ketorolac, and parenteral opioids. As a result, a large number of medication utilization evaluations (MUEs) have been conducted to evaluate the appropriateness of IV acetaminophen use. Many of these MUEs have failed to demonstrate ...

  12. [Acetaminophen-induced hypothermia, an AIDS related side-effect? About 4 cases].

    Denes, Eric; Amaniou, Monique; Rogez, Jean-Philippe; Weinbreck, Pierre; Merle, Louis

    2002-10-01

    Hypothermia is an uncommon side effect of acetaminophen. We report 4 cases of HIV-infected patients who developed hypothermia after intravenous injection of propacetamol (the parenteral formulation of acetaminophen). The mechanism of this hypothermia is unknown. AIDS-induced changes in the metabolism of acetaminophen, could be an explanation. AIDS-associated opportunistic diseases may account for part of the mechanism. These hypothermias occur within 6 hours after the injection, are well tolerated and regress spontaneously. PMID:12486392

  13. Comparing the Efficacy of Intravenous Acetaminophen and Intravenous Meperidine in Pain Relief After Outpatient Urological Surgery

    Kolahdouzan, Khosro; Eydi, Mahmood; Mohammadipour Anvari, Hassan; Golzari, Samad EJ; Abri, Reyhaneh; GHOJAZADEH, Morteza; Ojaghihaghighi, Seyed Hossein

    2014-01-01

    Background: Pain relief after surgery is an essential component of postoperative care. Objectives: The purpose of this study was to compare the efficacy of intravenous acetaminophen and intravenous meperidine in pain relief after outpatient urological surgery. Patients and Methods: In a prospective, randomized, double-blind clinical trial, 100 outpatients of urological surgery were studied in two groups of acetaminophen (A) and meperidine (M). Patients in group A received 1g of acetaminophen ...

  14. Sleep Disruption and Proprioceptive Delirium due to Acetaminophen in a Pediatric Patient

    Carla Carnovale; Marco Pozzi; Andrea Angelo Nisic; Elisa Scrofani; Valentina Perrone; Stefania Antoniazzi; Emilio Clementi; Sonia Radice

    2013-01-01

    We present the case of a 7-year-old boy, who received acetaminophen for the treatment of hyperpyrexia, due to an infection of the superior airways. 13 mg/kg (260 mg) of acetaminophen was administered orally before bedtime, and together with the expected antipyretic effect, the boy experienced sleep disruption and proprioceptive delirium. The symptoms disappeared within one hour. In the following six months, acetaminophen was administered again twice, and the reaction reappeared with similar f...

  15. IV Acetaminophen: Assessment of Medication Utilization Evaluation Data in Peri-operative Pain Management

    Mark A Malesker

    2015-04-01

    Full Text Available IV acetaminophen has become an accepted component of a multimodal analgesic strategy in perioperative patients. It is currently a branded drug (Ofirmev® in the United States. The purchase price of the drug is greater than oral and rectal acetaminophen, intravenous ketorolac, and parenteral opioids. As a result, a large number of medication utilization evaluations (MUEs have been conducted to evaluate the appropriateness of IV acetaminophen use. Many of these MUEs have failed to demonstrate the expected benefits observed with the use of IV acetaminophen in randomized, controlled trials. This review summarizes the major methodological flaws seen in many of these MUEs. The most common flaws of the available MUEs were inclusion of inadequate numbers of patients, failure to adequately define the timing and duration of IV acetaminophen use, and failure to adequately match characteristics of patients receiving IV acetaminophen with control patients. An appropriately designed MUE for IV acetaminophen should take into consideration the identified methodological flaws described in this review. A template for a comprehensive MUE of IV acetaminophen is provided in the review. This template can be modified to meet institution specific criteria applied to the use of IV acetaminophen.

  16. Relationship between serum acetaminophen concentration and N-acetylcysteine-induced adverse drug reactions.

    Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Khan, Halilol Rahman Mohamed; Sawalha, Ansam F; Sweileh, Waleed M; Al-Jabi, Samah W

    2010-09-01

    Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR. PMID:20374238

  17. The effect of acetaminophen administration on its disposition and body stores of sulphate.

    Hendrix-Treacy, S; Wallace, S M; Hindmarsh, K W; Wyant, G M; Danilkewich, A

    1986-01-01

    This investigation was designed to investigate the effects of ingestion of multiple therapeutic doses of acetaminophen on the disposition of the drug and on the cosubstrate, sulfate. Nine healthy volunteers and nine outpatients receiving acetaminophen for chronic pain were involved in the study. Volunteers were given a single 650 mg oral dose of acetaminophen. One week later they were given 650 mg of acetaminophen every six hours for five doses. Patients were maintained on their normal treatment and dosage schedules (600 mg every 3 to 8 h) for the study. In healthy volunteers the half-life of acetaminophen after single and multiple dosing was not significantly different. However, the fraction of acetaminophen recovered in the urine as the sulfate conjugate was less and the glucuronide conjugate greater after multiple dosing than after a single of the drug. There was no difference in the percentage recovered as the parent compound between single and multiple dosing. Serum sulfate levels fluctuated over the 6-h period following administration of single and multiple doses of acetaminophen to volunteers. The mean serum sulfate concentration was less after administration of five sequential 650 mg doses of acetaminophen than after a single dose. The renal clearance of inorganic sulfate showed a corresponding decrease. Unexpectedly, patients on chronic acetaminophen therapy exhibited elevated serum sulfate levels (levels higher than the maximum sulfate concentration seen in volunteers). PMID:3732362

  18. Interaction of white and pink grapefruit juice with acetaminophen (paracetamol) in vivo in mice.

    Dasgupta, Amitava; Reyes, Meredith A; Risin, Semyon A; Actor, Jeffrey K

    2008-12-01

    Grapefruit juice increases bioavailability of a number of drugs because of inhibition of the P-glycoprotein pump and inhibition of intestinal cytochrome P450 3A4 enzyme. However, interaction between acetaminophen (also known as paracetamol in many parts of the world) and grapefruit juice has never been reported. The interaction of grapefruit juice with acetaminophen was examined in an in vivo mouse model. BALB/c mice were fed 200 microL of white grapefruit juice or pink grapefruit juice by oral gavage (three mice in each group) followed by oral delivery of 10, 50, or 100 mg/kg acetaminophen 1 hour later. Blood was withdrawn from the retro-orbital venous plexus at 1 hour and 2 hours after feeding with acetaminophen. The concentrations of acetaminophen in sera of mice were determined by fluorescence polarization immunoassay. White grapefruit juice increased concentrations of acetaminophen in mice both 1 hour and 2 hours after feeding compared to controls. In contrast, pink grapefruit juice increased acetaminophen concentrations 2 hours after feeding compared to controls. Because acetaminophen is almost completely absorbed these effects seems to be related to increased elimination half-life of acetaminophen because of interaction with grapefruit juice. PMID:19053875

  19. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity.

    Owumi, Solomon E; Andrus, James P; Herzenberg, Leonard A; Herzenberg, Leonore A

    2015-08-01

    Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today. PMID:26250417

  20. FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF ACETAMINOPHEN

    Abhay Kumar Mourya et al.

    2012-02-01

    Full Text Available The present research work has been carried out for an optimized formulation of co-processed directly compressible vehicles in the preparation of the Acetaminophen mouth fast dissolving tablets (MFDTs. Acetaminophen was chosen due to its poor compression properties. Di-calcium Phosphate(DCP was incorporated in the neutralized aqueous starch dispersion to prepare co-processed excipient. Co-processed direct compressible DCP and Starch used as co-processed excipient were taken in good formulation ratio such as (25:75 and Cross Povidone used as superdisintegrant. The effects of other superdisintegrants were studied in the best formulation F5. Formulation F5 was found to be optimum compressibility characteristics hardness 3.62±0.40 to 4.68±0.31 kg/cm2 with fast disintegration (10 sec compare to other formulations.

  1. Pre-emptive analgesia with paracetamol (acetaminophen) in postoperative pain

    To evaluate efficacy and safety of preoperative paracetamol for postoperative pain relief. The study population consisted of 40 adult female patients scheduled for tubectomy as an elective surgery who were in ASA class I. Patients were allocated randomly to receive 325mg of acetaminophen orally half an hour before surgery. Pain was assessed by verbal rating scale in three situations (resting, moving and coughing). Data was collection done using the questionnaire and data analysis done using descriptive statistical methods. The patients who received oral paracetamol experienced moderate and mild pain in 50% of the cases when they were in resting position. Feeling mild and moderate pain with movement was in 40% and 60% respectively. While coughing, 100% of the cases felt only moderate pain and none experienced severe pain. Administration of a single dose of acetaminophen in preoperative period is effective for acute postoperative pain relief. (author)

  2. Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions.

    Watanabe, Hideaki; Kamiyama, Taisuke; Sasaki, Shun; Kobayashi, Kae; Fukuda, Kenichiro; Miyake, Yasufumi; Aruga, Tohru; Sueki, Hirohiko

    2016-03-01

    Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN. PMID:26362011

  3. Role of nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver: Nicotinamide effect in acetaminophen-damged liver.

    Mahmoud, Yomna I; Mahmoud, Asmaa A

    2016-06-01

    Acetaminophen is a widely used analgesic and antipyretic agent, which is safe at therapeutic doses. However, overdoses of acetaminophen induce severe oxidative stress, which leads to acute liver failure. Nicotinamide has proven effective in ameliorating many pathological conditions that occur due to oxidative stress. This study verifies the prophylactic and therapeutic effects of nicotinamide against the hepatic pathophysiological and ultrastructural alterations induced by acetaminophen. Wistar rats intoxicated with an acute overdose of acetaminophen (5g/kg b.wt) were given a single dose of nicotinamide (500mg/kg b.wt) either before or after intoxication. Acetaminophen caused significant elevation in the liver functions and lipid peroxidation marker, and decline in the activities of the hepatic antioxidant enzymes. This oxidative injury was associated with hepatic centrilobular necrosis, hemorrage, vacuolar degeneration, lipid accumulation and mitochondrial alterations. Treating intoxicated rats with nicotinamide (500mg/kg) significantly ameliorated acetaminophen-induced biochemical changes and pathological injuries. However, administering the same dose of nicotinamide to healthy animals or prior to acetaminophen-intoxication induced hepatotoxicity. Caution should be taken when administering high doses of NAM because of its possible hepatotoxicity. Considering the wide use of nicotinamide, there is an important need for monitoring nicotinamide tolerance, safety and efficacy in healthy and diseased subjects. PMID:27211843

  4. Acute interstitial nephritis with acetaminophen and alcohol intoxication

    Alexopoulou Iakovina; Fruchter Lauren L; Lau Keith K

    2011-01-01

    Abstract Drug-induced acute interstitial nephritis (AIN) represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well...

  5. Post hemorrhoidectomy pain control: rectal Diclofenac versus Acetaminophen

    Rahimi M

    2009-03-01

    Full Text Available "nBackground: Anal surgeries are prevalent, but they didn't perform as outpatient surgeries because of concerns about postoperative pain. The aim of the present study was to compare the effects of rectal acetaminophen and diclofenac on postoperative analgesia after anal surgeries in adult patients. "nMethods: In a randomized, double-blinded, placebo-controlled study 60 ASA class I or II scheduled for haemorrhoidectomy, anal fissure or fistula repair, were randomized (with block randomization method to receive either a single dose of 650 mg rectal acetaminophen (n=20, 100 mg rectal diclofenac (n=20 or placebo suppositories (n=20 after the operation. The severity of pain, time to first request of analgesic agent after administration of suppositories and complications were compared between three groups. Pain scores were evaluated in patients by Visual Analogue Scale (VAS in 0 (after complete consciousness in recovery, 2, 4, 12 and 24 hours after surgery. The period between administration of the suppositories and the patients' first request to receive analgesic was compared between groups. "nResults: Pain scores were lower significantly in rectal diclofenac than the other groups. The period between administration of the suppositories and the patients' first request to receive analgesic in diclofenac group was 219±73 minutes, was significantly longer compared with placebo (153±47 minutes and acetaminophen (178±64 minutes groups. No complications were reported. "nConclusions: Diclofenac suppository is more effective than acetaminophen suppository in post hemorrhoidectomy pain management.

  6. Post hemorrhoidectomy pain control: rectal Diclofenac versus Acetaminophen

    Rahimi M; Makarem J; Maktobi M

    2009-01-01

    "nBackground: Anal surgeries are prevalent, but they didn't perform as outpatient surgeries because of concerns about postoperative pain. The aim of the present study was to compare the effects of rectal acetaminophen and diclofenac on postoperative analgesia after anal surgeries in adult patients. "nMethods: In a randomized, double-blinded, placebo-controlled study 60 ASA class I or II scheduled for haemorrhoidectomy, anal fissure or fistula repair, were randomized (with block...

  7. Efficacy of Intravenous Acetaminophen after Coronary Artery Bypass Graft Surgery

    Leick AM; Ratliff PD; Shely RN; Lester WC; Short MR

    2015-01-01

    In recent years, a multimodal approach to post-operative pain control consisting of opioid and non-opioid agents administered simultaneously has been used to provide synergistic effects and reduce opioid-related adverse effects. This is a retrospective, cohort study involving coronary artery bypass graft surgery patients who received scheduled intravenous IV acetaminophen 1gm every 6 hours for 4 doses starting at surgery end time with opioids administered as needed versus opioids as monother...

  8. Patterns of Acetaminophen Use Exceeding 4 Grams Daily in a Hospitalized Population at a Tertiary Care Center

    Civan, Jesse M.; Navarro, Victor; Herrine, Steven K.; Riggio, Jeffrey M.; Adams, Paul; Rossi, Simona

    2014-01-01

    Unintentional acetaminophen-induced hepatotoxicity has been increasingly recognized as a significant problem, prompting increased scrutiny and restrictions from the US Food and Drug Administration on products combining acetaminophen with narcotics. Patterns of acetaminophen use have not previously been reported in the hospitalized patient population, which may be especially vulnerable to liver injury. We aimed to quantify the frequency at which acetaminophen dosing exceeded the recommended ma...

  9. The UDP-Glucuronosyltransferase (UGT) 1A Polymorphism c.2042C>G (rs8330) Is Associated with Increased Human Liver Acetaminophen Glucuronidation, Increased UGT1A Exon 5a/5b Splice Variant mRNA Ratio, and Decreased Risk of Unintentional Acetaminophen-Induced Acute Liver FailureS⃞

    Court, Michael H; Freytsis, Marina; Wang, Xueding; Peter, Inga; Guillemette, Chantal; Hazarika, Suwagmani; Duan, Su X.; Greenblatt, David J; Lee, William M.

    2013-01-01

    Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose. In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen-glucuronidating enzymes (UGTs 1A1, 1A6, 1A9, and 2B15). Of th...

  10. Photodegradation of acetaminophen in TiO2 suspended solution

    This study investigated the photocatalytic degradation of acetaminophen (APAP) in TiO2 suspended solution under a 250 W metal halide lamp. The influence of some parameters on the degradation of acetaminophen was studied and described in details, such as initial APAP concentration, initial pH value and TiO2 dosage. After 100 min irradiation, about 95% of APAP is decomposed in the 1.0 g L-1 TiO2 aqueous solution with an initial concentration of 100 μmol L-1. The effect of adsorption at three different pH values has also been analyzed and it has been conducted that pH 3.5, at which APAP was readily adsorbed also degraded at a faster rate. Reaction rate at pH 6.9 and pH 9.5 was 2.84 and 2.96 μM min-1, respectively. Direct hole (h+) oxidation and ipso-substitution was found to be the main initial step for APAP degradation. Main reaction intermediates and products were identified by GC/MS analysis. The mechanism of acetaminophen photocatalytic degradation in TiO2 suspended solution was studied not only experimentally but also theoretically by calculating the frontier electron density of APAP. The results obtained indicated that TiO2 photocatalytic degradation is a highly effective way to remove APAP from wastewater and drinking water without any generation of more toxic products

  11. Acute interstitial nephritis with acetaminophen and alcohol intoxication.

    Fruchter, Lauren L; Alexopoulou, Iakovina; Lau, Keith K

    2011-01-01

    Drug-induced acute interstitial nephritis (AIN) represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis. PMID:21496243

  12. Acute interstitial nephritis with acetaminophen and alcohol intoxication

    Alexopoulou Iakovina

    2011-04-01

    Full Text Available Abstract Drug-induced acute interstitial nephritis (AIN represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis.

  13. Efficacy of Intravenous Acetaminophen after Coronary Artery Bypass Graft Surgery

    Leick AM

    2015-12-01

    Full Text Available In recent years, a multimodal approach to post-operative pain control consisting of opioid and non-opioid agents administered simultaneously has been used to provide synergistic effects and reduce opioid-related adverse effects. This is a retrospective, cohort study involving coronary artery bypass graft surgery patients who received scheduled intravenous IV acetaminophen 1gm every 6 hours for 4 doses starting at surgery end time with opioids administered as needed versus opioids as monotherapy for postoperative pain control. The primary endpoint assessed was total morphine equivalents administered post-operatively in each group with a secondary focus on degree of pain control, total length of stay, ICU length of stay, and time to first bowel movement. The study concludes that the addition of IV acetaminophen to opioids for postoperative pain relief did not produce an opioid sparing effect and paradoxically led to an increase in opioid use. Clinical outcomes including pain control, total length of stay, and ICU length of stay were unaffected by the addition of IV acetaminophen.

  14. Validity of a two-point acetaminophen pharmacokinetic study.

    Scavone, J M; Greenblatt, D J; Blyden, G T; Luna, B G; Harmatz, J S

    1990-01-01

    The pharmacokinetics of a single 650-mg intravenous dose of acetaminophen were determined in 82 volunteers using multiple (13 or more) plasma acetaminophen concentrations measured by high pressure liquid chromatography during 24 h after dosage. Kinetic values from the complete study were compared with kinetic estimates based on only two data points: (a) the 2- and 6-h points only; and (b) the 3 and 6-h points only. For elimination half-life, values from the complete study (mean 2.42 h) were highly correlated (r = 0.87 and 0.84) with methods a and b (means 2.41 and 2.43 h), with regression slopes of 1.00 and 0.99, respectively. For clearance, the complete study values (mean 312 ml/min) were highly correlated (r = 0.97 and 0.97) with method a and b values, but both two-point methods significantly overestimated clearance (means 350 and 355 ml/min) by an average of 13 and 14%, respectively. Results for volume of distribution were similar to those for clearance. Although acetaminophen elimination half-life can be estimated with reasonable precision using a two-point blood-sampling procedure, clearance and volume of distribution values using the two-point method overestimate the actual values. PMID:2305419

  15. Formulation and characterization of acetaminophen nanoparticles in orally disintegrating films.

    Al-Nemrawi, Nusaiba K; Dave, Rutesh H

    2016-01-01

    The purpose of this study was to prepare orally disintegrating films containing nanoparticles loaded with acetaminophen. Nanoparticles were prepared by the emulsion-solvent evaporation method where acetone phase containing acetaminophen and poly(lactide-co-glycolide acid) (PLGA) was added to water phase containing hydroxypropyl methyl cellulose, poly ethylene glycol, polyvinyl alcohol (PVA) and aspartame in a rate of 1.5 drop s(-1) and agitated at 1200 rpm. The size, polydispersity index (PI) and drug entrapment (DE) were measured. The emulsions were cast to form films, which were evaluated physico-mechanically. The effect of different degrees of hydrolization of PVA and polymerization of PLGA and the effect of different ratios of PVA to PLGA was studied. Films with acceptable physico-mechanical properties were further studied. The size and PI of the nanoparticles was dependent on PVA hydrolization, PLGA polymerization and the ratio of PVA to PLGA. All films disintegrated in less than one minute, but acetaminophen was not free in the dissolution media even after six days. These results may indicate that although the nanoparticles released from the films immediately when impressed in solution the drug is sustained in the nanoparticles for longer time, which is to be clarified in future work. PMID:25013958

  16. Acetaminophen-Induced Acute Pancreatitis. A Case Report

    Hisato Igarashi

    2009-09-01

    Full Text Available Context Drug-induced acute pancreatitis is rare but should not be overlooked in a patient who presents with idiopathic acute pancreatitis. More than 100 drugs have been implicated in causing the disease: acetaminophen has been associated with acute pancreatitis in cases where there has been an overdose of drugs; however, the frequency is rare. Case report We report the case of a 35-year-old woman who presented with acute pancreatitis and severe metabolic acidosis after overdosing on a drug containing acetaminophen. She improved dramatically after intensive care; however, she showed recurrent episodes after re-overdosing on the same drug. With her self re-challenge test, she was diagnosed as having acetaminophen-induced pancreatitis and metabolic acidosis. A review of the relevant literature is also presented. Conclusions Drug-induced acute pancreatitis is often challenging for clinicians and a detailed mechanism is unknown. It is very important to rule out drug-induced pancreatitis when treating pancreatitis with an unknown etiology.

  17. Developmental exposure to acetaminophen does not induce hyperactivity in zebrafish larvae.

    Reuter, Isabel; Knaup, Sabine; Romanos, Marcel; Lesch, Klaus-Peter; Drepper, Carsten; Lillesaar, Christina

    2016-08-01

    First line pain relief medication during pregnancy relies nearly entirely on the over-the-counter analgesic acetaminophen, which is generally considered safe to use during gestation. However, recent epidemiological studies suggest a risk of developing attention-deficit/hyperactivity disorder (ADHD)-like symptoms in children if mothers use acetaminophen during pregnancy. Currently, there are no experimental proofs that prenatal acetaminophen exposure causes developmental brain alterations of progeny. Exposure to high acetaminophen concentrations causes liver toxicity, which is well investigated in different model organisms. However, sub-liver-toxic concentrations have not been experimentally investigated with respect to ADHD endophenotypes such as hyperactivity. We used zebrafish to investigate the potential impact of acetaminophen exposure on locomotor activity levels, and compared it to the established zebrafish Latrophilin 3 (Lphn3) ADHD-model. We determined the sub-liver-toxic concentration of acetaminophen in zebrafish larvae and treated wild-type and lphn3.1 knockdown larvae with increasing concentrations of acetaminophen. We were able to confirm that lphn3.1 knockdown alone causes hyperactivity, strengthening the implication of Lphn3 dysfunction as an ADHD risk factor. Neither acute nor chronic exposure to acetaminophen at sub-liver-toxic concentrations in wild-type or lphn3.1 knock-downs increases locomotor activity levels. Together our findings show that embryonic to larval exposure to acetaminophen does not cause hyperactivity in zebrafish larvae. Furthermore, there are no additive and/or synergistic effects of acetaminophen exposure in a susceptible background induced by knock-down of lphn3.1. Our experimental study suggests that there is, at least in zebrafish larvae, no direct link between embryonic acetaminophen exposure and hyperactivity. Further work is necessary to clarify this issue in humans. PMID:27116683

  18. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle

    Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Our recent investigations have focused on the possible involvement of glutathione-derived APAP metabolites in APAP nephrotoxicity and have demonstrated that administration of acetaminophen-cysteine (APAP-CYS) potentiated APAP-induced renal injury with no effects on APAP-induced liver injury. Additionally, APAP-CYS treatment alone resulted in a dose-responsive renal GSH depletion. This APAP-CYS-induced renal GSH depletion could interfere with intrarenal detoxification of APAP or its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) and may be the mechanism responsible for the potentiation of APAP nephrotoxicity. Renal-specific GSH depletion has been demonstrated in mice and rats following administration of amino acid γ-glutamyl acceptor substrates for γ-glutamyl transpeptidase (γ-GT). The present study sought to determine if APAP-CYS-induced renal glutathione depletion is the result of disruption of the γ-glutamyl cycle through interaction with γ-GT. The results confirmed that APAP-CYS-induced renal GSH depletion was antagonized by the γ-glutamyl transpeptidase (γ-GT) inhibitor acivicin. In vitro analysis demonstrated that APAP-CYS is a γ-glutamyl acceptor for both murine and bovine renal γ-GT. Analysis of urine from mice pretreated with acivicin and then treated with APAP, APAP-CYS, or acetaminophen-glutathione identified a γ-glutamyl-cysteinyl-acetaminophen metabolite. These findings are consistent with the hypothesis that APAP-CYS contributes to APAP nephrotoxicity by depletion of renal GSH stores through interaction with the γ-glutamyl cycle

  19. Postoperative pain relief with pentazocine and acetaminophen: comparison with other analgesic combinations and placebo.

    Petti, A

    1985-01-01

    A single-blind, parallel-group study was carried out to evaluate the efficacy and safety of an analgesic combining 650 mg of acetaminophen and 25 mg of pentazocine in 129 patients with moderate postoperative pain. Comparisons were made with a combination containing acetaminophen (300 mg) and codeine (30 mg), a combination containing acetaminophen (650 mg) and propoxyphene napsylate (100 mg), and a placebo. A nurse observer queried patients at regular intervals over a six-hour period concerning the intensity of pain and the degree of pain relief. The scores obtained were used in the calculation of standard measures of analgesic efficacy. Acetaminophen/pentazocine proved to be significantly superior to placebo and equivalent to the other active analgesic combinations. No side effects were reported with acetaminophen/pentazocine, acetaminophen/propoxyphene napsylate, or placebo. One mild side effect was questionably associated with acetaminophen/codeine. This study demonstrates that the combination of acetaminophen and pentazocine is as safe and effective in controlling postoperative pain of moderate severity as other commonly used analgesics. PMID:2870808

  20. Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy

    Thulstrup, Ane Marie; Sørensen, Henrik Toft; Nielsen, Gunnar Lauge;

    1999-01-01

    We studied the association between acetaminophen exposure during pregnancy and the prevalence of congenital abnormalities and fetal growth. Our study included 123 women who had received a prescription of acetaminophen during pregnancy and/or 30 days before conception and 13,329 controls who did n...

  1. 76 FR 2691 - Prescription Drug Products Containing Acetaminophen; Actions To Reduce Liver Injury From...

    2011-01-14

    ... acetaminophen drugs (final rule, 74 FR 19385, April 29, 2009; and technical amendment, 74 FR 61512, November 25...., nonsteroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, and naproxen), at recommended doses... caused by the effects of a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI)...

  2. Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain.

    Johnson, G H; Van Wagoner, J D; Brown, J; Cooper, S A

    1997-01-01

    The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study. PMID:9220215

  3. Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis.

    Yamamoto, Akihiro; Liu, Ming-Yih; Kurogi, Katsuhisa; Sakakibara, Yoichi; Saeki, Yuichi; Suiko, Masahito; Liu, Ming-Cheh

    2015-12-01

    Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo. This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported. PMID:26067475

  4. Acetaminophen hepatotoxicity and HIF-1α induction in acetaminophen toxicity in mice occurs without hypoxia

    HIF-1α is a nuclear factor important in the transcription of genes controlling angiogenesis including vascular endothelial growth factor (VEGF). Both hypoxia and oxidative stress are known mechanisms for the induction of HIF-1α. Oxidative stress and mitochondrial permeability transition (MPT) are mechanistically important in acetaminophen (APAP) toxicity in the mouse. MPT may occur as a result of oxidative stress and leads to a large increase in oxidative stress. We previously reported the induction of HIF-1α in mice with APAP toxicity and have shown that VEGF is important in hepatocyte regeneration following APAP toxicity. The following study was performed to examine the relative contribution of hypoxia versus oxidative stress to the induction of HIF-1α in APAP toxicity in the mouse. Time course studies using the hypoxia marker pimonidazole showed no staining for pimonidazole at 1 or 2 h in B6C3F1 mice treated with APAP. Staining for pimonidazole was present in the midzonal to periportal regions at 4, 8, 24 and 48 h and no staining was observed in centrilobular hepatocytes, the sites of the toxicity. Subsequent studies with the MPT inhibitor cyclosporine A showed that cyclosporine A (CYC; 10 mg/kg) reduced HIF-1α induction in APAP treated mice at 1 and 4 h and did not inhibit the metabolism of APAP (depletion of hepatic non-protein sulfhydryls and hepatic protein adduct levels). The data suggest that HIF-1α induction in the early stages of APAP toxicity is secondary to oxidative stress via a mechanism involving MPT. In addition, APAP toxicity is not mediated by a hypoxia mechanism.

  5. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: j.vandelft@maastrichtuniversity.nl [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques

  6. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques outperformed

  7. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A; Johnston, Zoe C; Chetty, Tarini; Smith, Lee B; McKinnell, Chris; Dean, Afshan; Homer, Natalie Z; Jorgensen, Anne; Camacho-Moll, Maria E; Sharpe, Richard M; Mitchell, Rod T

    2015-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons......, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45......% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the...

  8. Analgesic effect of acetaminophen, phenyltoloxamine and their combination in postoperative oral surgery pain.

    Forbes, J A; Barkaszi, B A; Ragland, R N; Hankle, J J

    1984-01-01

    In this factorial study, 148 outpatients with pain after oral surgery were randomly assigned, on a double-blind basis, a single oral dose of acetaminophen 650 mg, phenyltoloxamine 60 mg, a combination of acetaminophen 650 mg with phenyltoloxamine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medication. Measures of total and peak analgesia were derived from these subjective reports. The acetaminophen effect was significant for every measure of total and peak analgesia. The phenyltoloxamine effect was not significant for any measure of analgesia. Although efficacy was lower for the acetaminophen-phenyltoloxamine combination than for acetaminophen alone, for every variable, the contrast for interaction was not statistically significant. The results of this study differ from those of previous studies in patients with headache and musculoskeletal pain. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic. PMID:6483639

  9. Association of prenatal exposure to acetaminophen and coffee with childhood asthma

    Liu, Xiaoqin; Liew, Zeyan; Olsen, Jørn;

    2016-01-01

    PurposeSome studies have suggested that maternal acetaminophen use during pregnancy is associated with asthma in the offspring, and coffee consumption may modify the toxicity of acetaminophen. We aim to examine whether pregnancy maternal acetaminophen use increases the risk for offspring asthma......, and whether such a potential association could be modified by maternal coffee consumption. MethodsWe included 63 652 live-born singletons enrolled in the Danish National Birth Cohort. Maternal acetaminophen use and coffee consumption during pregnancy were assessed prospectively via the enrolment questionnaire...... and three computer-assisted telephone interviews. Asthma cases were identified by using the Danish National Patient Register and the Danish National Prescription Registry. We estimated the hazard ratios (HRs) for asthma according to prenatal acetaminophen and coffee exposure using Cox proportional hazards...

  10. Spathodea campanulata Extract Attenuates Acetaminophen-Induced Hepatic Injury in Mice

    Phyllis Elsie Dadzeasah

    2013-10-01

    Full Text Available Spathodea campanulata, well known for its traditional medicinal uses was investigated for hepatoprotective activity against acetaminophen-induced hepatic damage in mice. Six groups of mice were pre-treated with 100, 300 and 625 mg/kg of the aqueous extract of Spathodea campanulata stem bark, N-acetyl cysteine (300 mg/kg; p.o or distilled water for 5 days before they were intoxicated with a single dose of acetaminophen (600 mg/kg; p.o. Alanine aminotransferase, Aspartate aminotransferase and total protein levels were measured in serum, glutathione peroxidase, superoxide dismutase and total cytochrome P450 levels were measured in liver homogenate and liver histology was also observed on liver sections. Total liver cytochrome P450 levels in Spathodea campanulata extract, distilled water, ketoconazole or phenobarbital-treated animals were also measured. Significant hepatoprotection was obtained against liver damage induced by acetaminophen as evident from decreased serum levels of Aspartate transaminase, Alanine transaminase and increased levels of total protein in the combined acetaminophen and extract treated groups and the acetaminophen and N-acetylcysteine-treated groups compared to the acetaminophen only controls. The decrease in serum antioxidant enzymes; glutathione peroxidase and superoxide dismutase levels caused by acetaminophen was significantly reversed by the extract. The results correlated well with the histopathology of liver from treated and control animals. The extract also caused considerable inhibition of total CYP450, the enzymes involved in the activation of acetaminophen. The present results indicate that Spathodea campanulata protects the liver against acetaminophen-induced hepatotoxicity by enhancing antioxidant protection capacity and interfering with the bio-activation of acetaminophen.

  11. Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type.

    Kane, Alice E; Mitchell, Sarah J; Mach, John; Huizer-Pajkos, Aniko; McKenzie, Catriona; Jones, Brett; Cogger, Victoria; Le Couteur, David G; de Cabo, Rafael; Hilmer, Sarah N

    2016-01-01

    Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice. PMID:26615879

  12. Selective inhibition of acetaminophen oxidation and toxicity by cimetidine and other histamine H2-receptor antagonists in vivo and in vitro in the rat and in man.

    Mitchell, M C; Schenker, S.; Speeg, K V

    1984-01-01

    Acetaminophen-induced hepatotoxicity results from hepatic enzymatic oxidation of acetaminophen to a toxic, electrophilic intermediate. Acetaminophen is ordinarily eliminated after conjugation with glucuronic acid and sulfate to nontoxic derivatives. Cimetidine has been shown to inhibit the hepatic oxidation of a number of drugs and to protect rats from acetaminophen-induced hepatic necrosis. The aim of this study was to define the mechanism by which cimetidine reduced acetaminophen-induced he...

  13. Selective crystallization of metastable phase of acetaminophen by ultrasonic irradiation

    Mori, Yoichiro; Maruyama, Mihoko; Takahashi, Yoshinori; Ikeda, Kenji; Fukukita, Suguru; Yoshikawa, Hiroshi Y.; Okada, Shino; Adachi, Hiroaki; Sugiyama, Shigeru; Takano, Kazufumi; Murakami, Satoshi; Matsumura, Hiroyoshi; Inoue, Tsuyoshi; Yoshimura, Masashi; Mori, Yusuke

    2015-06-01

    A new method for selective crystallization of the metastable phase (form II) of acetaminophen is described. To obtain form II, we prepared a highly supersaturated solution (σI = 3.7) and then applied ultrasonic irradiation at different frequencies. Without ultrasonic irradiation, spontaneous crystallization did not occur within one month in the highly supersaturated condition (σI = 3.7). When ultrasonic irradiation at 28 kHz was applied, form II preferentially crystallized. Therefore, we conclude that ultrasonic irradiation can be an effective technique for selectively crystallizing the metastable phase.

  14. Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse.

    Novac, Andrei; Iosif, Anamaria M; Groysman, Regina; Bota, Robert G

    2015-01-01

    Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can now be provided with multidisciplinary care that addresses an individual's psychiatric, social, and medical needs, which requires close cooperation between physicians of varying specialties. This report describes a patient who experienced hearing loss from hydrocodone/acetaminophen abuse. PMID:26835162

  15. Activation of LXR Increases Acetaminophen Clearance and Prevents Its Toxicity

    Saini, Simrat P. S.; Zhang, Bin; Niu, Yongdong; Jiang, Mengxi; Gao, Jie; Zhai, Yonggong; Lee, Jung Hoon; Uppal, Hirdesh; Tian, Hui; Tortorici, Michael A.; Poloyac, Samuel M.; Qin, Wenxin; Venkataramanan, Raman; Xie, Wen

    2011-01-01

    Overdose of acetaminophen (APAP), the active ingredient of Tylenol, is the leading cause of drug-induced acute liver failure in the US. As such, it is necessary to develop novel strategies to prevent or manage APAP toxicity. In this report, we revealed a novel function of the liver X receptor (LXR) in preventing APAP-induced hepatotoxicity. Activation of LXR in transgenic mice or by an LXR agonist conferred resistance to the hepatotoxicity of APAP, whereas the effect of LXR agonist on APAP to...

  16. Pharmacist and Physician Interpretation of Abbreviations for Acetaminophen Intended for Use in a Consumer Icon

    Saul Shiffman

    2015-10-01

    Full Text Available Concomitant use of multiple acetaminophen medications is associated with overdose. To help patients identify acetaminophen medications and thus avoid concomitant use, an icon with an abbreviation for “acetaminophen” has been proposed for all acetaminophen medications. This study assessed pharmacists’ and physicians’ use and interpretation of abbreviations for “acetaminophen”, to identify abbreviations with other meanings that might cause confusion. Physicians (n = 150 reported use and interpretation of candidate abbreviations Ac and Acm. Pharmacists (n = 150 interpretations of prescription orders using the candidate abbreviations APAP, Ac, Ace and Acm in typed, handwritten or spoken form, were judged for critical confusions likely to cause patient harm. Critical confusion was rare, except for omission by pharmacists of the acetaminophen dose for Hydrocodone/APAP prescriptions (10%. Ac was in common use to indicate “before meals”, and was interpreted as such, but some physicians (8% said they use Ac to indicate anticoagulant drugs. Most pharmacists (54% interpreted Ace as acetaminophen, and none interpreted it as referring to ACE-inhibitors. Acm was rarely used in prescriptions, had no common interfering meanings, and was often (63% interpreted as acetaminophen, especially when prescribed in combination with an opiate (85%. The data validated concerns about abbreviations in prescribing: all abbreviations resulted in some misinterpretations. However, Acm was rarely misinterpreted, was readily associated with “acetaminophen”, and seemed appropriate for use in a graphic icon to help consumers/patients identify acetaminophen medications.

  17. [Intoxication or false-positive acetaminophen result of toxicological determinations? Two case reports].

    Winnicka, Renata; Kołaciński, Zbigniew; Brzeznicki, Sławomir; Wesołowski, Wiktor; Kucharska, Małgorzata; Krakowiak, Anna

    2013-01-01

    The aim of this study was to show the diagnostic procedure used in the two cases with false-positive serum acetaminophen results in suspected acetaminophen poisoning. The determination of serum acetaminophen were carried out using a UV/VIS spectrophotometer (Specord 40 Analytik Jena), coupled with an analytic computer station WinASPECT. The employed method of determination was based on the acetaminophen reaction with sodium nitrite, which yields yellow colour of solution in the presence of sodium hydrate. The intensity of the yellow colour depends on the concentration of acetaminophen in serum. The relationship between absorbance and concentration was linear at concentrations in the range 50-600 microg/mL, with relative standard deviation of +/- 2.1% and detection limit of 30 microg/mL. To confirm or reject the doubtful results of colorimetric assays, the serums of patients were measured with high performance liquid chromatography with mass spectrometry detection and gas chromatography with mass spectrometry detection. The analysis of presented cases leads to a conclusion that acetaminophen results should be confirmed either by scanning urine for p-aminophenol presence (which is a routine procedure in our laboratory) or by using a different method of measuring acetaminophen serum levels. PMID:24466725

  18. BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury

    It has been recently shown that acute acetaminophen toxicity results in endoplasmic reticulum redox stress and an increase in cells with apoptotic phenotype in liver. Since activation of effector caspases was absent, the relevance of caspase-independent mechanisms in acetaminophen-induced programmed cell death was investigated. BGP-15, a drug with known protective actions in conditions involving redox imbalance, has been co-administered with a single sublethal dose of acetaminophen. Proapoptotic events and outcome of the injury were investigated. ER redox alterations and early ER-stress-related signaling events induced by acetaminophen, such as ER glutathione depletion, phosphorylation of eIF2α and JNK and induction of the transcription factor GADD153, were not counteracted by co-treatment with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus translocation and mitochondrial depolarization. BGP-15 co-treatment attenuated the rate of acetaminophen-induced cell death as assessed by apoptotic index and enzyme serum release. These results reaffirm that acute acetaminophen toxicity involves oxidative stress-induced caspase-independent cell death. In addition, pharmacological inhibition of AIF translocation may effectively protect against or at least delay acetaminophen-induced programmed cell death.

  19. Associations between acetaminophen use during pregnancy and ADHD symptoms measured at ages 7 and 11 years.

    John M D Thompson

    Full Text Available OBJECTIVE: Our aim was to replicate and extend the recently found association between acetaminophen use during pregnancy and ADHD symptoms in school-age children. METHODS: Participants were members of the Auckland Birthweight Collaborative Study, a longitudinal study of 871 infants of European descent sampled disproportionately for small for gestational age. Drug use during pregnancy (acetaminophen, aspirin, antacids, and antibiotics were analysed in relation to behavioural difficulties and ADHD symptoms measured by parent report at age 7 and both parent- and child-report at 11 years of age. The analyses included multiple covariates including birthweight, socioeconomic status and antenatal maternal perceived stress. RESULTS: Acetaminophen was used by 49.8% of the study mothers during pregnancy. We found significantly higher total difficulty scores (Strengths and Difficulty Questionnaire parent report at age 7 and child report at age 11 if acetaminophen was used during pregnancy, but there were no significant differences associated with any of the other drugs. Children of mothers who used acetaminophen during pregnancy were also at increased risk of ADHD at 7 and 11 years of age (Conners' Parent Rating Scale-Revised. CONCLUSIONS: These findings strengthen the contention that acetaminophen exposure in pregnancy increases the risk of ADHD-like behaviours. Our study also supports earlier claims that findings are specific to acetaminophen.

  20. Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol.

    Lim, S P; Andrews, F J; O'Brien, P E

    1995-12-01

    Studies into the mechanism of acetaminophen (APAP)-induced hepatotoxicity have focused mainly at the hepatocellular level. This study aimed to investigate the effect of acetaminophen on the hepatic microvasculature using a vascular casting technique. Acetaminophen was administered at a dose of 650 mg/kg body weight (intraperitoneally) to fasted male Long Evans rats. Microvascular casting was performed at various points after drug administration. Liver casts from control rats showed good patency with normal hepatic microvasculature. Thirty-six hours after overdose with acetaminophen, liver casts showed rounded centrilobular cavities of various sizes, representing regions in which cast-filled sinusoids were absent with relatively normal microvasculature within periportal regions. Evidence of microvascular injury occurred as early as 5 hours after acetaminophen overdose. This injury consisted of changes to centrilobular sinusoids including areas of incomplete filling and dilated centrilobular sinusoids. Misoprostol (a prostaglandin E1 analog) treatment (6 x 25 micrograms/kg) given before and after acetaminophen administration markedly reduced the extent of microvascular injury with only small focal unfilled areas in the casts and a generally intact microvasculature. In conclusion, this study shows that overdosage with APAP resulted in an extensive, characteristic pattern of hepatic microvascular injury in the centrilobular region. The results also suggest that microvascular injury is an early event in the pathogenesis of acetaminophen hepatotoxicity. Misoprostol was found to protect against injury occurring at the microvascular level. PMID:7489988

  1. The effect of acetaminophen nanoparticles on liver toxicity in a rat model

    Esmaeil Biazar

    2010-03-01

    Full Text Available Esmaeil Biazar1, S Mahdi Rezayat2, Naser Montazeri1, Khalil Pourshamsian1, Reza Zeinali3, Azadeh Asefnejad3, Mehdi Rahimi3, Mohammadmajid Zadehzare3, Mehran Mahmoudi3, Rohollah Mazinani3, Mehdi Ziaei31Department of Chemistry, Islamic Azad University, Tonekabon Branch, Mazandaran, Iran; 2Department of Pharmacology, School of Medicine, Tehran University of Medical Science, Tehran, Iran; 3Biomedical Engineering, Islamic Azad University, Research and Science Branch, Tehran, IranAbstract: Acetaminophen, a pain-reliever, is one of the most widely used medications in the world. Acetaminophen with normal dosage is considered a nontoxic drug for therapeutic applications, but when taken at overdose levels it produces liver damage in human and various animal species. By a high energy mechanically activated method, we produced acetaminophen in a nanometer crystalline size (24 nm. Forty-eight hours after injection of crystalline particles with normal and reduced size of our drug, the effect of liver toxicity was compared by determination of liver transferase enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase (ALT. These enzymes were examined by routine colorimetric methods using commercial kits and pathologic investigations. Statistical analysis and pathological figures indicated that ALT delivery and toxicity in reduced size acetaminophen was significantly reduced when compared with normal size acetaminophen. Pathology figures exhibited reduced necrosis effects, especially the confluent necrosis, in the central part of the lobule in the reduced size acetaminophen samples when compared with the normal samples.Keywords: acetaminophen, size reduction, pathological and enzymatic investigations, toxicity

  2. Use of acetaminophen (paracetamol) during pregnancy and the risk of autism spectrum disorder in the offspring.

    Andrade, Chittaranjan

    2016-02-01

    Acetaminophen (paracetamol) is available over the counter in most countries and is widely considered to be safe for use during pregnancy; studies report gestational exposures to acetaminophen that lie in the 46%-65% range. Acetaminophen influences inflammatory and immunologic mechanisms and may predispose to oxidative stress; these and other effects are hypothesized to have the potential to compromise neurodevelopment in the fetal and infant brain. Two ecological studies suggested that population-level trends in the use of acetaminophen were associated with trends in the incidence/prevalence of autism; one of these studies specifically examined acetaminophen use during pregnancy. One large prospective observational cohort study found that gestational exposure to acetaminophen (especially when the duration of exposure was 28 days or more) was associated with motor milestone delay, gross and fine motor impairments, communication impairment, impairments in internalizing and externalizing behaviors, and hyperactivity, all at age 3 years; however, social and emotional developmental behaviors were mostly unaffected. A very recent large cohort study with a 12.7-year follow-up found that gestational exposure to acetaminophen was associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. In the light of existing data associating acetaminophen use during pregnancy and subsequent risk of attention-deficit/hyperactivity disorder, this new finding suggests that the predisposition, if any, is toward the hyperkinetic syndrome rather than to autism. In summary, the empirical data are very limited, but whatever empirical data exist do not support the suggestion that the use of acetaminophen during pregnancy increases the risk of autism in the offspring. PMID:26930528

  3. Plasma concentrations after high-dose (45 mg.kg-1) rectal acetaminophen in children.

    Montgomery, C J; McCormack, J P; Reichert, C C; Marsland, C P

    1995-11-01

    Although the recommended dose of rectal acetaminophen (25-30 mg.kg-1) is twice that for oral administration (10-15 mg.kg-1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured venous plasma acetaminophen concentrations resulting from 45 mg.kg-1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined using a TDxFLx fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 +/- 39 mumol.L-1 (13 +/- 6 micrograms.ml-1) and the time of peak plasma concentration was 198 +/- 70 min (mean +/- SD). At 420 min, the mean plasma concentration was 46 +/- 18 mumol.L-1 (7.0 +/- 0.9 micrograms.ml-1). No plasma concentrations associated with toxicity (> 800 mumol.L-1) were identified. A 45 mg.kg-1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10-15 mg.kg-1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children. PMID:8590508

  4. Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen-induced liver injury in rats)

    Yao, Hsien-Tsung; Yang, Yu-Chi; Chang, Chen-Hui; Yang, Hui-Ting; Yin, Mei-chin

    2015-01-01

    (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.54 %, w/w) for 1 week and were then intraperitoneally injected with acetaminophen (1 g/kg body weight) and killed after 12 h. Concentrations of acetaminophen and its conjugates in plasma an...

  5. Mitogen-activated Protein Kinase Phosphatase (Mkp)-1 Protects Mice against Acetaminophen-induced Hepatic Injury

    Wancket, Lyn M.; Meng, Xiaomei; Rogers, Lynette K.; Liu, Yusen

    2012-01-01

    c-Jun N-terminal kinase (JNK) activation promotes hepatocyte death during acetaminophen overdose, a common cause of drug-induced liver failure. While mitogen-activated protein kinase (MAPK) phosphatase (Mkp)-1 is a critical negative regulator of JNK MAPK, little is known about the role of Mkp-1 during hepatotoxicity. In this study, we evaluated the role of Mkp-1 during acute acetaminophen toxicity. Mkp-1+/+ and Mkp-1−/− mice were dosed ip with vehicle or acetaminophen at 300 mg/kg (for mechan...

  6. Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim

    2016-01-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  7. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections.

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim; Ye, Young-Min

    2016-08-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  8. The analgesic efficacy of intra-articular acetaminophen in an experimental model of carrageenan-induced arthritis

    Arun, Oguzhan; Canbay, Ozgur; Celebi, Nalan; Sahin, Altan; Konan, Ali; Atilla, Pergin; Aypar, Ulku

    2013-01-01

    BACKGROUND: Acetaminophen is one of the most common drugs used for the treatment of pain and fever. OBJECTIVES: To examine the effects of intra-articular (IA) acetaminophen on carrageenan-induced arthritic pain-related behaviour and spinal c-Fos expression in rats. METHODS: The present study was performed using 20 Sprague Dawley rats. Forty microlitres of IA 0.9% NaCl was injected in the control group, and 40 μL of IA carrageenan was injected in the carrageenan group. One hour after carrageenan injection, 400 μg of IA acetaminophen was injected in the IA acetaminophen group, and 400 μg of intraperitoneal (IP) acet-aminophen was injected in the IP acetaminophen group. One day before injection, and 4 h and 8 h after injection, diameters of both knee joints, motility of the rat, paw loading and joint mobility were assessed. After the rats were euthanized, L3 and L4 spinal segments were excised for c-Fos assessment. RESULTS: IA acetaminophen decreased both the severity and distribution of c-Fos expression. IP acetaminophen decreased only the distribution of c-Fos expression. IA acetaminophen decreased knee diameter at 8 h. IA and IP acetaminophen increased rat motility and paw loading scores. Joint mobility scores of IP acetaminophen were similar to saline at 8 h. CONCLUSIONS: Results of the present study indicate an analgesic and/or possible anti-inflammatory effect of IA acetaminophen and provide further evidence on the efficacy of systemic acetaminophen injection in reducing arthritic pain. PMID:24093120

  9. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

    Maria Goretti R. Queiroz

    2008-10-01

    Full Text Available Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae leaf essential oil (EOCz was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o. acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT, serum glutamate oxaloacetate transaminase (GOT activities, that were significantly (p<0.01 elevated in the acetaminophen alone treated animals. Histopathological examinations of liver tissue corroborated well with the biochemical changes. Hepatic steatosis, hydropic degeneration and necrosis were observed in the acetaminophen treated group, while these were completely absent in the standard and EOCz treated groups. In conclusion, these data suggest that the Croton zehntneri essential oil can prevent hepatic injuries from acetaminophen-induced hepatotoxicity in mice.

  10. Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in humans.

    Witter, F R; Woods, A S; Griffin, M D; Smith, C R; Nadler, P; Lietman, P S

    1988-08-01

    In healthy volunteers receiving a single intramuscular dose of 18 X 10(6) U interferon alone or after 24 hours of an 8-day course of prednisone (40 mg/day), aspirin (650 mg every 4 hours), or acetaminophen (650 mg every 4 hours), the magnitude of the biologic response to interferon was quantified by measuring the time course of the induction of 2'-5'-oligoadenylate synthetase and resistance to vesicular stomatitis virus infection in human peripheral blood mononuclear cells. Prednisone decreased the AUC of 2'-5'-oligoadenylate synthetase activity (p less than 0.05), whereas administration of aspirin or acetaminophen did not affect this biologic response. No measurable effect was seen during administration of prednisone, aspirin, or acetaminophen on the duration or intensity of vesicular stomatitis virus yield reduction. The side effects seen with interferon administration at the dose tested were not altered in a clinically meaningful manner by prednisone, aspirin, or acetaminophen. PMID:2456175

  11. Sleep Disruption and Proprioceptive Delirium due to Acetaminophen in a Pediatric Patient

    Carla Carnovale

    2013-01-01

    Full Text Available We present the case of a 7-year-old boy, who received acetaminophen for the treatment of hyperpyrexia, due to an infection of the superior airways. 13 mg/kg (260 mg of acetaminophen was administered orally before bedtime, and together with the expected antipyretic effect, the boy experienced sleep disruption and proprioceptive delirium. The symptoms disappeared within one hour. In the following six months, acetaminophen was administered again twice, and the reaction reappeared with similar features. Potential alternative explanations were excluded, and analysis with the Naranjo algorithm indicated a “probable” relationship between acetaminophen and this adverse reaction. We discuss the potential mechanisms involved, comprising imbalances in prostaglandin levels, alterations of dopamine, and cannabinoid and serotonin signalings.

  12. Sleep Disruption and Proprioceptive Delirium due to Acetaminophen in a Pediatric Patient

    Carnovale, Carla; Pozzi, Marco; Nisic, Andrea Angelo; Scrofani, Elisa; Perrone, Valentina; Antoniazzi, Stefania; Radice, Sonia

    2013-01-01

    We present the case of a 7-year-old boy, who received acetaminophen for the treatment of hyperpyrexia, due to an infection of the superior airways. 13 mg/kg (260 mg) of acetaminophen was administered orally before bedtime, and together with the expected antipyretic effect, the boy experienced sleep disruption and proprioceptive delirium. The symptoms disappeared within one hour. In the following six months, acetaminophen was administered again twice, and the reaction reappeared with similar features. Potential alternative explanations were excluded, and analysis with the Naranjo algorithm indicated a “probable” relationship between acetaminophen and this adverse reaction. We discuss the potential mechanisms involved, comprising imbalances in prostaglandin levels, alterations of dopamine, and cannabinoid and serotonin signalings. PMID:23573447

  13. Protective effect of zinc aspartate against acetaminophen induced hepato-renal toxicity in albino rats

    Zinc is an essential nutrient that is required in humans and animals for many physiological functions, including antioxidant functions. The evidence to date indicates that zinc is an important element that links antioxidant system and tissue damage. Acetaminophen (AP), a widely used analgesic and antipyretic, produces hepatocyte and renal tubular necrosis in human and animals following overdose. In human, AP is one of the most common causes of acute liver failure as a result of accidental or deliberate overdose. Moreover, the initial event in AP toxicity is a toxic metabolic injury with the release of free radicals and subsequent cellular death by necrosis and apoptosis. This study was designed to evaluate the potential protective role of zinc aspartate in case of acetaminophen induced hepato-renal toxicity in rats. A total number of 32 adult male albino rats were divided into 4 equal groups: group I (control group), group II (zinc aspartate treated group), group III (acetaminophen treated group; by a single oral dose of 750 mg/kg body weight) and group IV acetaminophen plus zinc treated group; (zinc aspartate was intraperitoneally given one hour after acetaminophen administration in a dose of 30 mg/kg body weight). Serum levels of: alanine aminotransferase, aspartate aminotransferase, direct bilirubin, blood urea nitrogen, creatinine, uric acid, xanthine oxidase (XO), glutathione (GSH), malonaldehyde (MDA) and nitric oxide (NO) were assessed in all groups. The results of this study showed that treatment with acetaminophen alone (group III) produced a significant increase in serum levels of the liver enzymes and direct bilirubin. Moreover, in the same group there was a significant increase in the blood urea nitrogen and serum creatinine compared to the control group. In addition, there was a significant increase in XO and MDA and a significant decrease in GSH and NO level. Injection of rats with zinc aspartate after acetaminophen treatment could produce a

  14. Associations between Acetaminophen Use during Pregnancy and ADHD Symptoms Measured at Ages 7 and 11 Years

    John M. D. Thompson; Waldie, Karen E; Wall, Clare R.; Murphy, Rinky; Mitchell, Edwin A; ,

    2014-01-01

    Objective Our aim was to replicate and extend the recently found association between acetaminophen use during pregnancy and ADHD symptoms in school-age children. Methods Participants were members of the Auckland Birthweight Collaborative Study, a longitudinal study of 871 infants of European descent sampled disproportionately for small for gestational age. Drug use during pregnancy (acetaminophen, aspirin, antacids, and antibiotics) were analysed in relation to behavioural difficulties and AD...

  15. Undifferentiated altered mental status: a late presentation of toxic acetaminophen ingestion.

    Robey, Thomas E; Melnick, Edward R

    2012-01-01

    Altered mental status is a common undifferentiated presentation in the emergency department. We describe a case of acetaminophen-induced acute liver failure that was diagnosed and treated prior to obtaining definitive historical or laboratory information about the etiology. The physical exam finding of scleral icterus in this case was a key element to rapid identification and treatment of this life-threatening condition. A discussion of appropriate N-acetylcysteine treatment for acute liver failure and acetaminophen intoxication is included. PMID:23326702

  16. Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats

    Shahab Bohlooli; Sadollah Mohammadi; Keyvan Amirshahrokhi; Hafez Mirzanejad-asl; Mohammad Yosefi; Amir Mohammadi-Nei; Mir Mehdi Chinifroush

    2013-01-01

    Objective(s): Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains and beverages. In this study the effect of MSM pretreatment on acetaminophen induced liver damage was investigated. Materials and Methods: Male Sprague Dawley rats were pretreated with 100 mg/kg MSM for one week. On day seven rats were received acetaminophen (850 mg/kg, intraperitoneal). Twenty-four hours later, blood samples were taken to determi...

  17. Effect of Tramadol/Acetaminophen on Motivation in Patients with Chronic Low Back Pain

    Tetsunaga, Tomoko; Tetsunaga,Tomonori; Tanaka, Masato; Nishida, Keiichiro; Takei, Yoshitaka; Ozaki,Toshifumi

    2016-01-01

    Background. The contribution of apathy, frequently recognized in individuals with neurodegenerative diseases, to chronic low back pain (LBP) remains unclear. Objectives. To investigate levels of apathy and clinical outcomes in patients with chronic LBP treated with tramadol-acetaminophen. Methods. A retrospective case-control study involving 73 patients with chronic LBP (23 male, 50 female; mean age 71 years) treated with tramadol-acetaminophen (n=36) and celecoxib (n=37) was performed. All p...

  18. Effect of acetaminophen and fluvastatin on post-dose symptoms following infusion of zoledronic acid

    Silverman, S. L.; Kriegman, A.; Goncalves, J.; Kianifard, F; Carlson, T.; Leary, E.

    2010-01-01

    Summary A randomized, double-blind, placebo-controlled study assessed the efficacy of acetaminophen or fluvastatin in preventing post-dose symptoms (increases in body temperature or use of rescue medication) following a single infusion of the intravenous (IV) bisphosphonate zoledronic acid (ZOL). Acetaminophen, but not fluvastatin, significantly reduced the incidence and severity of post-dose symptoms. Introduction Transient symptoms including myalgia and pyrexia have been reported post-infus...

  19. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation.

    Abernethy, D R; Greenblatt, D J; Ameer, B; Shader, R I

    1985-08-01

    Eleven subjects received acetaminophen (650 mg i.v.) on two occasions in random sequence, with and without concurrent administration of probenecid (500 mg) every 6 hr. Nine subjects similarly received lorazepam (2 mg. i.v.) with and without concurrent probenecid. Acetaminophen half-life was prolonged during probenecid treatment (mean +/- S.E., 4.30 +/- 0.23 vs. 2.51 +/- 0.16 hr; P less than .001) due to markedly decreased clearance (178 +/- 13 vs. 329 +/- 24 ml/min; P less than .001) with no change in volume of distribution (65 +/- 4 vs. 69 +/- 3 l; NS). Urinary excretion of acetaminophen glucuronide during 24 hr was decreased (84 +/- 9 vs. 260 +/- 21 mg of acetaminophen as glucuronide; P less than .001) and acetaminophen sulfate excretion was increased (323 +/- 25 vs. 217 +/- 17 mg of acetaminophen as sulfate; P less than .005) during concurrent probenecid treatment. However, the sum of the two conjugated metabolites was not significantly different (407 +/- 28 vs. 476 +/- 20 mg of acetaminophen as glucuronide plus sulfate excreted per 24 hr; NS). Lorazepam half-life was also prolonged during probenecid treatment (33.0 +/- 3.9 vs. 14.3 +/- 1.08 hr; P less than .001) due to decreased clearance (44.7 +/- 5.4 vs. 80.3 +/- 13.2 ml/min; P less than .001) with no change in volume of distribution (111 +/- 5 vs. 111 +/- 7 l; NS). Formation of the ether glucuronides of acetaminophen and lorazepam is impaired markedly by therapeutic doses of probenecid. Sulfate conjugation is not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4020675

  20. Nootropic activity of acetaminophen against colchicine induced cognitive impairment in rats

    Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan A.; Thiyagarajan, Manisenthilkumar K.; Aiyalu, Rajasekaran; Sreedhar, Remya; Nakamura,Takashi; Watanabe, Kenichi

    2012-01-01

    Alzheimer’s disease is a devastating neurodegenerative disorder, the most common among the dementing illnesses. Acetaminophen has gaining importance in neurodegenerative diseases by attenuating the dopaminergic neurodegeneration in Caenorhabditis elegans model, decreasing the chemokines and the cytokines and increasing the anti apoptotic protein such as Bcl-2 in neuronal cell culture. The low concentration acetaminophen improved the facilitation to find the hidden platform in Morris Water Maz...

  1. A pilot study comparing ketoprofen and acetaminophen with hydrocodone for the relief of postoperative periodontal discomfort.

    Reed, K L; Smith, J. R.; Lie, T.; Adams, D F

    1997-01-01

    The aim of this study was to compare ketoprofen to acetaminophen with hydrocodone (A/H) in a postoperative periodontal pain model. A double-blind protocol was used. Thirty minutes prior to each procedure, subjects were given orally either 100 mg ketoprofen or a placebo tablet. Four hours later, the subjects took either 50 mg ketoprofen (ketoprofen group) or 1000 mg acetaminophen with 10 mg hydrocodone (placebo group). Subjects reported levels of overall discomfort and pain using visual analog...

  2. Protective Effect of Acacia nilotica (L.) against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2013-01-01

    The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, ...

  3. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism

    Jensen, Morten Søndergaard; Rebordosa, Cristina; Thulstrup, Ane Marie;

    2010-01-01

    Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial for...... normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism....

  4. Alterations in the Rat Serum Proteome During Liver Injury from Acetaminophen Exposure

    Merrick, B. Alex; Bruno, Maribel E.; Madenspacher, Jennifer H.; Wetmore, Barbara A.; Foley, Julie; Pieper, Rembert; Zhao, Ming; Makusky, Anthony J.; McGrath, Andrew M.; ZHOU, JEFF X.; Taylor, John; Tomer, Kenneth B.

    2006-01-01

    Changes in the serum proteome were identified during early, fulminant and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, non-injury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 hr to 120 hr. Two-dimensional gel electrophoresis of immunodepleted serum separated about 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum ALT/AST levels and histopatho...

  5. LC-MS/MS method development for quantitative analysis of acetaminophen uptake by the aquatic fungus Mucor hiemalis.

    Esterhuizen-Londt, Maranda; Schwartz, Katrin; Balsano, Evelyn; Kühn, Sandra; Pflugmacher, Stephan

    2016-06-01

    Acetaminophen is a pharmaceutical, frequently found in surface water as a contaminant. Bioremediation, in particular, mycoremediation of acetaminophen is a method to remove this compound from waters. Owing to the lack of quantitative analytical method for acetaminophen in aquatic organisms, the present study aimed to develop a method for the determination of acetaminophen using LC-MS/MS in the aquatic fungus Mucor hiemalis. The method was then applied to evaluate the uptake of acetaminophen by M. hiemalis, cultured in pellet morphology. The method was robust, sensitive and reproducible with a lower limit of quantification of 5pg acetaminophen on column. It was found that M. hiemalis internalize the pharmaceutical, and bioaccumulate it with time. Therefore, M. hiemalis was deemed a suitable candidate for further studies to elucidate its pharmaceutical tolerance and the longevity in mycoremediation applications. PMID:26950900

  6. High-performance liquid chromatographic assay for acetaminophen and phenacetin in the presence of their metabolites in biological fluids

    The authors propose a method in which tracer amounts of a radiolabeled compound are used as the internal standard for the same unlabeled compound in high-performance liquid chromatography. The approach is valuable when a response from the internal standard becomes undesirable due to the presence of interference by the metabolites. The authors tested their approach with phenacetin and its metabolites, 2-hydroxyphenacetin, N-hydroxyphenacetin, phenetidine, acetaminophen sulfate conjugate and acetaminophen glucuronide conjugate in biological fluids with the use of [14C] phenacetin and [3H] acetaminophen as the internal standards, and were able to quantitate both phenacetin and acetaminophen simultaneously. They also tested the alternative approach in which the unlabeled drug was used as internal standard for tracer amounts of the same radiolabeled compound, with phenacetin and acetaminophen as the internal standards for tracer amounts of [14C] phenacetin and [3H] acetaminophen. Again, they were able to quantiate the two tracer radiolabeled compounds simultaneously. (Auth.)

  7. Properties of the radicals formed by one-electron oxidation of acetaminophen - a pulse radiolysis study

    The semi-iminoquinone radical of acetaminophen, which has previously been proposed as a possible hepatotoxic intermediate in the cytochrome P-450 catalysed oxidation of acetaminophen, has been generated and studied by pulse radiolysis. In the absence of other reactive solutes, the radical decays rapidly by second order kinetics with a rate constant (2k2) of (2.2 ± 0.4) x 109 M-1 sec-1. In alkaline solutions the radical deprotonates with a pK of 11.1 ± 0.1 to form a radical-anion. The acetaminophen radical-anion reacts with resorcinol at high pH values, leading to the formation of a transient equilibrium from which the one-electron reduction potential of the semi-iminoquinone radical of acetaminophen is estimated to be + 0.707 ± 0.01 V at pH 7. This value predicts that acetaminophen should be oxidised by thiyl radicals. This was confirmed by pulse radiolysis experiments for reaction of the cysteinyl radical, for which rate constants of 7 x 106 M-1 sec-1 at pH7 and 2.7 x 108 M-1 sec-1 at pH 11.3 were obtained. The reaction of O2 with the acetaminophen semi-iminoquinone radical could not be detected by pulse radiolysis, and alternative mechanisms for superoxide radical formation are discussed. (author)

  8. A zeolite modified carbon paste electrode as useful sensor for voltammetric determination of acetaminophen

    Ahmadpour-Mobarakeh, Leila; Nezamzadeh-Ejhieh, Alireza, E-mail: arnezamzadeh@iaush.ac.ir

    2015-04-01

    The voltammetric behavior of a carbon paste electrode modified with Co(II)-exchanged zeolite A (Co(II)-A/ZMCPE) for determination of acetaminophen was studied. The proposed electrode showed a diffusion controlled reaction with the electron transfer rate constant (K{sub s}) of 0.44 s{sup −1} and charge transfer coefficient of 0.73 in the absence of acetaminophen. A linear voltammetric response was obtained in the range of 0.1 to 190 μmol L{sup −1} of acetaminophen [r{sup 2} = 0.9979, r = 0.9989 (n = 10)] with a detection limit of 0.04 μmol L{sup −1}. The method was successfully applied to the analysis of acetaminophen in some drugs. - Highlights: • Modified carbon paste electrode with Co(II)-zeolite A improved the voltammetric current in determination of acetaminophen. • Modified electrode is applicable for acetaminophen in real samples. • The proposed method has good reproducibility and repeatability.

  9. Comparison of oral nalbuphine, acetaminophen, and their combination in postoperative pain.

    Jain, A K; Ryan, J R; McMahon, F G; Smith, G

    1986-03-01

    This double-blind, randomized, parallel, placebo-controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination. PMID:3512149

  10. Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

    Muncie, H L; King, D E; DeForge, B

    1986-08-01

    Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine. PMID:2942630

  11. Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics.

    Hoffman, D A; Wallace, S M; Verbeeck, R K

    1990-01-01

    The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 microM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 microM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (-51%) and renal clearance (-33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00-14.00 h, 14.00-20.00 h) on Day 4 of the acetaminophen regimen. PMID:2253663

  12. Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood

    Liew, Zeyan; Ritz, Beate; Virk, Jasveer; Olsen, Jørn

    2015-01-01

    Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We...... associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc....... hyperkinetic symptoms (HR = 1.51 95% CI 1.19-1.92), but not with other ASD cases (HR = 1.06 95% CI 0.92-1.24). Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold. Maternal use of acetaminophen in pregnancy was......Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We...

  13. A randomized, placebo-controlled trial to determine the course of aminotransferase elevation during prolonged acetaminophen administration

    Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C.

    2014-01-01

    Background Acetaminophen administration for more than 4 days causes aminotransferase elevation in some subjects. The objective of this randomized, placebo-controlled trial is to describe the course of alanine aminotransferase (ALT) elevation in subjects administered 4 g/day of acetaminophen for at least 16 days. Methods A randomized, placebo controlled trial of acetaminophen (4 g/day) vs placebo. Subjects were healthy volunteers with normal liver enzymes. The primary outcome was the course of...

  14. Direct Protection Against Acetaminophen Hepatotoxicity by Propylthiouracil: IN VIVO AND IN VITRO STUDIES IN RATS AND MICE

    Yamada, Tadataka; Ludwig, Shelly; Kuhlenkamp, John; Kaplowitz, Neil

    1981-01-01

    Hepatotoxicity caused by acetaminophen can be prevented by enzyme-catalyzed conjugation of its reactive metabolite with glutathione (GSH). Since we have shown in previous studies that 6-N-propyl-2-thiouracil (PTU) can substitute for GSH as a substrate for the GSH S-transferases, we examined the possibility that PTU might also protect against acetaminophen hepatotoxicity by direct chemical interaction with the reactive metabolite of acetaminophen. In an in vitro system consisting of [3H]acetam...

  15. Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

    Mitchell, Sarah J.; Huizer-Pajkos, Aniko; Cogger, Victoria C; McLachlan, Andrew J.; Le Couteur, David G; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

    2011-01-01

    We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pas...

  16. Acetaminophen metabolism, cytotoxicity, and genotoxicity in rat primary hepatocyte cultures

    Acetaminophen (APAP) metabolism, cytotoxicity, and genotoxicity were measured in primary cultures of rat hepatocytes. Although 3 mM APAP caused a slight increase in cellular release of lactate dehydrogenase into the culture medium, cellular glutathione concentration (an index of APAP metabolism) was reduced by 50%. APAP at 7 mM was significantly more toxic to these hepatocytes and had a similar but more marked effect on glutathione concentrations. In spite of its cytotoxicity, neither dose of APAP stimulated DNA repair synthesis when monitored by the rate of incorporation of [3H]thymidine into DNA following exposure to APAP. Thus, although APAP has been shown to be both hepato- and nephrotoxic in several in vivo and in vitro systems, the reactive toxic metabolite of APAP is not genotoxic in rat primary hepatocyte cultures

  17. Preparation and electrochemical application of a new biosensor based on plant tissue/polypyrrole for determination of acetaminophen

    Gholamhossein Rounaghi; Roya Mohammadzadeh Kakhki

    2012-10-01

    Banana tissue containing polyphenol oxidase was incorporated into polypyrrole matrix to make a biosensor for the analysis of acetaminophen (ACT). The electrocatalytic behaviour of oxidized acetaminophen was studied at the surface of the biosensor, using various electrochemical methods. The advantages of this biosensor for the determination of acetaminophen are excellent catalytic activity, good detection limit and high exchange current density. The electrochemical and structural properties of the electrode were assessed using cyclic voltammetry, differential voltammetry, chronoamperometric techniques. The analytical properties (sensitivity, p) of this biosensor increased with plant tissue loading. Also this new biosensor was successfully applied for determination of acetaminophen in biologic samples.

  18. Potentiation in the intact rat of the hepatotoxicity of acetaminophen by 1,3-bis(2-chloroethyl)-1-nitrosourea.

    Nakae, D; Oakes, J W; Farber, J L

    1988-12-01

    Studies of the killing of cultured hepatocytes by acetaminophen indicate that the cells are injured by an oxidative stress that accompanies the metabolism of the toxin (J. L. Farber et al. (1988) Arch. Biochem. Biophys. 267, 640-650). The present report documents that the essential features of the killing of cultured hepatocytes by acetaminophen are reproduced in the intact animal. Male rats had no evidence of liver necrosis 24 h after administration of up to 1000 mg/kg of acetaminophen. Induction of mixed function oxidase activity by 3-methylcholanthrene increased the hepatotoxicity of acetaminophen. Inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the hepatotoxicity of acetaminophen in male rats induced with 3-methylcholanthrene. Whereas the pretreatment with BCNU reduced the GSH content by 40%, a comparable depletion of GSH by diethylmaleate did not potentiate the toxicity of acetaminophen. The antioxidant diphenylphenylenediamine (25 mg/kg) and the ferric iron chelator deferoxamine (1000 mg/kg) prevented the liver necrosis produced by 500 mg/kg acetaminophen in rats pretreated with BCNU. Neither protective agent prevented the fall in GSH produced by acetaminophen. It is concluded the conditions of the irreversible injury of cultured hepatocytes by acetaminophen previously reported are not necessarily different from those that obtain in the intact rat with this toxin. PMID:3214175

  19. Immune mechanisms in acetaminophen-induced acute liver failure.

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  20. Formulation and Characterization of Acetaminophen Nanoparticles in Orally Disintegrating Films

    AI-Nemrawi, Nusaiba K.

    The purpose of this study is to prepare acetaminophen loaded nanoparticles to be cast directly, while still in the emulsion form, into Orally Disintegrating Films (ODF). By casting the nanoparticles in the films, we expected to keep the particles in a stable form where the nanoparticles would be away from each other to prevent their aggregation. Once the films are applied on the buccal mucosa, they are supposed to dissolve within seconds, releasing the nanoparticles. Then the nanoparticles could be directly absorbed through the mucosa to the blood stream and deliver acetaminophen there. The oral cavity mucosa is one of the most attractive sites for systemic drug delivery due to its high permeability and blood supply. Furthermore, it is robust and shows short recovery times after stress or damage, and the drug bypasses first pass effect and avoids presystemic elimination in the GI tract. Nanoencapsulation increases drug efficacy, specificity, tolerability and therapeutic index. These Nanocapsules have several advantages in the protection of premature degradation and interaction with the biological environment, enhancement of absorption into a selected tissue, bioavailability, retention time and improvement of intracellular penetration. The most important characteristics of nanoparticles are their size, encapsulation efficiency (EE), zeta potential (surface charge), and the drug release profiles. Unfortunately, nanoparticles tend to precipitate or aggregate into larger particles within a short time after preparation or during storage. Some solutions for this problem were mentioned in literature including lyophilization and spray drying. These methods are usually expensive and give partial solutions that might have secondary problems; such as low re-dispersion efficacy of the lyophilized NPs. Furthermore, most of the formulations of NPs are invasive or topical. Few formulas are available to be given orally. Fast disintegrating films (ODFs) are rapidly gaining interest

  1. Acetaminophen degradation by electro-Fenton and photoelectro-Fenton using a double cathode electrochemical cell

    Highlights: ► The electro-Fenton reactor using a double cathode electrochemical cell was applied. ► The initial Fe2+ concentration was the most significant parameter for the acetaminophen degradation. ► Thirteen intermediates were identified and a degradation pathway was proposed. - Abstract: Acetaminophen is a widely used drug worldwide and is one of the most frequently detected in bodies of water making it a high priority trace pollutant. This study investigated the applicability of the electro-Fenton and photoelectro-Fenton processes using a double cathode electrochemical cell in the treatment of acetaminophen containing wastewater. The Box–Behnken design was used to determine the effects of initial Fe2+ and H2O2 concentrations and applied current density. Results showed that all parameters positively affected the degradation efficiency of acetaminophen with the initial Fe2+ concentration being the most significant parameter for both processes. The acetaminophen removal efficiency for electro-Fenton was 98% and chemical oxygen demand (COD) removal of 43% while a 97% acetaminophen removal and 42% COD removal were observed for the photoelectro-Fenton method operated at optimum conditions. The electro-Fenton process was only able to obtain 19% total organic carbon (TOC) removal while the photoelectro-Fenton process obtained 20%. Due to negligible difference between the treatment efficiencies of the two processes, the electro-Fenton method was proven to be more economically advantageous. The models obtained from the study were applicable to a wide range of acetaminophen concentrations and can be used in scale-ups. Thirteen different types of intermediates were identified and a degradation pathway was proposed.

  2. Acetaminophen degradation by electro-Fenton and photoelectro-Fenton using a double cathode electrochemical cell

    Luna, Mark Daniel G. de [Department of Chemical Engineering, University of the Philippines, 1011 Diliman, Quezon City (Philippines); Environmental Engineering Graduate Program, University of the Philippines, 1011 Diliman, Quezon City (Philippines); Veciana, Mersabel L. [Environmental Engineering Graduate Program, University of the Philippines, 1011 Diliman, Quezon City (Philippines); Su, Chia-Chi [Department of Environmental Resources Management, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Lu, Ming-Chun, E-mail: mmclu@mail.chan.edu.tw [Department of Environmental Resources Management, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer The electro-Fenton reactor using a double cathode electrochemical cell was applied. Black-Right-Pointing-Pointer The initial Fe{sup 2+} concentration was the most significant parameter for the acetaminophen degradation. Black-Right-Pointing-Pointer Thirteen intermediates were identified and a degradation pathway was proposed. - Abstract: Acetaminophen is a widely used drug worldwide and is one of the most frequently detected in bodies of water making it a high priority trace pollutant. This study investigated the applicability of the electro-Fenton and photoelectro-Fenton processes using a double cathode electrochemical cell in the treatment of acetaminophen containing wastewater. The Box-Behnken design was used to determine the effects of initial Fe{sup 2+} and H{sub 2}O{sub 2} concentrations and applied current density. Results showed that all parameters positively affected the degradation efficiency of acetaminophen with the initial Fe{sup 2+} concentration being the most significant parameter for both processes. The acetaminophen removal efficiency for electro-Fenton was 98% and chemical oxygen demand (COD) removal of 43% while a 97% acetaminophen removal and 42% COD removal were observed for the photoelectro-Fenton method operated at optimum conditions. The electro-Fenton process was only able to obtain 19% total organic carbon (TOC) removal while the photoelectro-Fenton process obtained 20%. Due to negligible difference between the treatment efficiencies of the two processes, the electro-Fenton method was proven to be more economically advantageous. The models obtained from the study were applicable to a wide range of acetaminophen concentrations and can be used in scale-ups. Thirteen different types of intermediates were identified and a degradation pathway was proposed.

  3. Effect of acetaminophen on the leukocyte-labeling efficiency of indium oxine In 111

    The effect of acetaminophen on the labeling efficiency of leukocytes with indium oxine In 111 was studied. A blood sample was obtained from eight healthy men before and after they received acetaminophen 650 mg every four hours for 24 hours. After dividing the plasma from each sample into three portions, leukocytes were separated and labeled with indium oxine In 111. In an in vitro study, 200 ml of blood was obtained from one of the men, and the plasma was separated into four portions. Acetaminophen in 95% ethanol was added to three of the plasma fractions to produce acetaminophen concentrations of 4, 20, and 100 micrograms/ml; ethanol was added to the fourth fraction as a control. Each plasma fraction was then subdivided into three aliquots, and leukocytes were labeled as in the in vivo study. Mean leukocyte labeling efficiencies in both studies were calculated from the ratios of leukocyte radioactivity to initial radioactivity in the samples, expressed as percentages. Leukocyte labeling efficiencies before acetaminophen administration ranged from 79 to 85%; after administration, labeling efficiencies ranged from 70 to 87%. No significant differences in mean labeling efficiency before and after acetaminophen administration were noted in any of the subjects. Leukocyte labeling efficiencies in all in vitro plasma fractions were reduced, ranging from 54 to 63%, but no significant differences in labeling efficiency between any of the plasma fractions were found. Using the labeling procedures in this study, exposure of leukocytes from healthy men to acetaminophen in vivo or in vitro does not affect labeling efficiency with indium oxine In 111

  4. Prediction of color changes in acetaminophen solution using the time-temperature superposition principle.

    Mochizuki, Koji; Takayama, Kozo

    2016-07-01

    A prediction method for color changes based on the time-temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l'Eclairage (CIE) LAB color space (a*, b*, L* and ΔE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time-temperature shift factor of a*, b*, L* and ΔE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and ΔE*ab at 40 °C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R(2) values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time. PMID:26559666

  5. Comparison of Acetaminophen with or without Codeine to Ibuprofen on the Postoperative Pain of Pediatric Tonsillectomy

    2011-04-01

    Full Text Available Introduction: Management of pain in children is often inadequate and numerous clinical practice guidelines and policy statements have been published on the subject of pediatric pain. Tonsillectomy is among the most frequent otorhinolaryngologic surgeries, especially in the pediatric age group and after tonsillectomy the patients usually suffer from mild to severe pain for three postoperative days which may limit activity level and intake, leading to dehydration and a prolonged hospital stay. In this study acetaminophen, acetaminophen codeine and ibuprofen have been compared in a single study. Materials and Methods: A randomized, prospective, double-blind study was conducted at the Tabriz pediatric hospital. Patients were selected randomly from the hospitalized patients undergoing tonsillectomy suffering from recurrent tonsillitis or adenotonsillar hypertrophy and assigned to one of three groups (acetaminophen (ACT-acetaminophen codeine (ACT/C-ibuprofen (IBU according to a predetermined randomization code. All the operations were taken place under same conditions by the same surgeon. Objective pain score used for pain assessment and adverse drug reactions were collected on checklists and analyzed using SPSS software. Results: Chi square test results revealed a significant difference between ACT ACT/C IBU groups. Neither acetaminophen nor Ibuprofen at the doses given was able to provide sufficient analgesia. The rate of bleeding in all groups did not show any significant difference according to Pearson-chi-square test (P=0.22. The incidence of anorexia in ACT, ACT/C and IBU groups was 15.7, 7.8 and 25.8 percent, respectively, which showed a significant difference by chi-square test (P=0.045. Conclusion: According to our study it can be concluded that acetaminophen codeine posses more analgesic effect than acetaminophen and ibuprofen in post tonsillectomy pain management in pediatric patients.

  6. Effect of antipyrine coadministration on the kinetics of acetaminophen and lidocaine.

    Blyden, G T; Greenblatt, D J; LeDuc, B W; Scavone, J M

    1988-01-01

    Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received: 1, antipyrine 1.0 g intravenously (i.v.); 2, acetaminophen 650 mg i.v.; 3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml.min-1.kg-1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen VZ was reduced (1.14 vs 1.00 l.kg-1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml.min-1.kg-1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine VZ (2.6 vs 2.7 l.kg-1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml.min-1.kg-1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine. PMID:3197750

  7. TRPV1 in brain is involved in acetaminophen-induced antinociception.

    Christophe Mallet

    Full Text Available BACKGROUND: Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404 by fatty acid amide hydrolase (FAAH in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV(1 in vitro. Pharmacological activation of TRPV(1 in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV(1 in the brain contributes to the analgesic effect of acetaminophen. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV(1 knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E(2 (PGE(2 and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV(1-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV(1 in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test. CONCLUSIONS: This study shows that TRPV(1 in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV(1 in the brain.

  8. Comparison of Intravenous Metoclopramide and Acetaminophen in Primary Headaches: a Randomized Controlled Trial

    Gholamreza Faridaalaee

    2015-05-01

    Full Text Available Introduction: Headache is the most common neurologic symptom among referees to the emergency department (ED, while the best treatment has not yet been found. Therefore, in the present study pain relief effects of metoclopramide and acetaminophen were compared in patients suffered acute primary headache. Methods: This study was a double-blind randomized clinical trial performed in Imam Khomeini Hospital, Urmia, Iran, through July to October 2014.  All adult patients, with acute primary (migraine, tension type and cluster headache referred to the ED were included in this study. Pain Severity was measured with 10 centimeters numeric rating scales. The patients were randomized in to two groups of intravenous (IV metoclopramide (10 milligrams and acetaminophen (1 gram. Pain score, success rate, and complication of drugs were compared within administration time and 15, 30, 60, as well as 120 minutes after medication. Results: 100 patients were equally categorized in to two groups (mean age of 32 ± 13.2 years; 51.2% male. Initial pain score in metoclopramide and acetaminophen groups were 9.1 and 9.4, respectively (p=0.46. IV metoclopramide did not have any analgesic effect at 15 minutes, but had good effect at 30 minutes. While, the analgesic effect of acetaminophen initiated after 15 minutes. After 2 hours, both drugs had good treatment effect on primary headaches (p<0.001. Conclusion: The present study demonstrated that efficacy of metoclopramide for pain relief in primary headaches is lower than acetaminophen.  In this regard, success rate of acetaminophen was 42.0% versus 0% for metoclopramide within 15 minutes. The efficacy of acetaminophen continued until 60 minutes.

  9. Supra-additive effects of tramadol and acetaminophen in a human pain model.

    Filitz, Jörg; Ihmsen, Harald; Günther, Werner; Tröster, Andreas; Schwilden, Helmut; Schüttler, Jürgen; Koppert, Wolfgang

    2008-06-01

    The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6+/-16.2 mA) induced spontaneous acute pain (NRS=6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7+/-4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8+/-4.4%), but a sustained antihyperalgesic effect (34.5+/-14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2+/-5.7% and an enhanced antihyperalgesic effect (41.1+/-14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics. PMID:17709207

  10. Effect of acetaminophen on the leukocyte-labeling efficiency of indium oxine In 111

    Augustine, S.C.; Schmelter, R.F.; Nelson, K.L.; Petersen, R.J.; Qualfe, M.A.

    1983-11-01

    The effect of acetaminophen on the labeling efficiency of leukocytes with indium oxine In 111 was studied. A blood sample was obtained from eight healthy men before and after they received acetaminophen 650 mg every four hours for 24 hours. After dividing the plasma from each sample into three portions, leukocytes were separated and labeled with indium oxine In 111. In an in vitro study, 200 ml of blood was obtained from one of the men, and the plasma was separated into four portions. Acetaminophen in 95% ethanol was added to three of the plasma fractions to produce acetaminophen concentrations of 4, 20, and 100 micrograms/ml; ethanol was added to the fourth fraction as a control. Each plasma fraction was then subdivided into three aliquots, and leukocytes were labeled as in the in vivo study. Mean leukocyte labeling efficiencies in both studies were calculated from the ratios of leukocyte radioactivity to initial radioactivity in the samples, expressed as percentages. Leukocyte labeling efficiencies before acetaminophen administration ranged from 79 to 85%; after administration, labeling efficiencies ranged from 70 to 87%. No significant differences in mean labeling efficiency before and after acetaminophen administration were noted in any of the subjects. Leukocyte labeling efficiencies in all in vitro plasma fractions were reduced, ranging from 54 to 63%, but no significant differences in labeling efficiency between any of the plasma fractions were found. Using the labeling procedures in this study, exposure of leukocytes from healthy men to acetaminophen in vivo or in vitro does not affect labeling efficiency with indium oxine In 111.

  11. Acetaminophen induces a caspase-dependent and Bcl-XL sensitive apoptosis in human hepatoma cells and lymphocytes.

    Boulares, A Hamid; Zoltoski, Anna J; Stoica, Bogdan A; Cuvillier, Olivier; Smulson, Mark E

    2002-01-01

    Acetaminophen is a widely used analgesic and antipyretic drug that exhibits toxicity at high doses to the liver and kidneys. This toxicity has been attributed to cytochrome P-450-generated metabolites which covalently modify target proteins. Recently, acetaminophen, in its unmetabolized form, has been shown to affect a variety of cells and tissues, for instance, testicular and lymphoid tissues and lymphocyte cell lines. The effects on cell viability of acetaminophen at a concentration comparable to that achieved in plasma during acetaminophen toxicity have now been examined with a hepatoma cell line SK-Hep1, primary human peripheral blood lymphocytes and human Jurkat T cells. Acetaminophen reduced cell viability in a time-dependent manner. Staining of cells with annexin-V also revealed that acetaminophen induced, after 8 hr of treatment, a loss of the asymmetry of membrane phospholipids, which is an early event associated with apoptosis. Acetaminophen triggered the release of cytochrome c from mitochondria into the cytosol, activation of caspase-3, 8, and 9, cleavage of poly(ADP-ribose) polymerase, and degradation of lamin B1 and DNA. Whereas cleavage of DNA into internucleosomal fragments was apparent in acetaminophen treated SK-Hep1 and primary lymphocytes, DNA was only degraded to 50-kb fragments in treated Jurkat cells. Overexpression of the antiapoptotic protein Bcl-XL prevented these various apoptotic events induced by acetaminophen in Jurkat cells. Caspase-8 activation was a postmictochondrial event and occurred in a Fas-independent manner. These results demonstrate that acetaminophen induces caspases-dependent apoptosis with mitochondria as a primary target. These results also reiterate the potential role of apoptosis in acetaminophen hepatic and extrahepatic toxicity. PMID:12005112

  12. Metabolite kinetics: formation of acetaminophen from deuterated and nondeuterated phenacetin and acetanilide on acetaminophen sulfation kinetics in the perfused rat liver preparation

    The role of hepatic intrinsic clearance for metabolite formation from various precursors on subsequent metabolite elimination was was investigated in the once-through perfused rat liver preparation. Two pairs of acetaminophen precursors: [14C] phenacetin-d5 and [3H] phenacetin-do, [14C] acetanilide and [3H] phenacetin were delivered by constant flow (10 ml/min/liver) either by normal or retrograde perfusion to the rat liver preparations. The extents of acetaminophen sulfation were compared within the same preparation. The data showed that the higher the hepatocellular activity (intrinsic clearance) for acetaminophen formation, the greater the extent of subsequent acetaminophen sulfation. The findings were explained on the basis of blood transit time and metabolite duration time. Because of blood having only a finite transit time in liver, the longer the drug requires for metabolite formation, the less time will remain for metabolite sulfation and the less will be the degree of subsequent sulfation. Conversely, when the drug forms the primary metabolite rapidly, a longer time will remain for the metabolite to be sulfated in liver to result in a greater degree of metabolite sulfation. Finally, the effects of hepatic intrinsic clearances for metabolite formation and zonal distribution of enzyme systems for metabolite formation and elimination in liver are discussed

  13. Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs

    KuKanich, Butch

    2010-01-01

    The purpose of this study was to determine the pharmacokinetics of codeine and the active metabolites morphine and codeine-6-glucuronide after IV codeine administration and the pharmacokinetics of acetaminophen (APAP), codeine, morphine, and codeine-6-glucuronide after oral administration of combination product containing acetaminophen and codeine to dogs.

  14. Piperine, an active ingredient of black pepper attenuates acetaminophen-induced hepatotoxicity in mice

    Evan Prince Sabina; Annie Deborah Harris Souriyan; Deborah Jackline; Mahaboob Khan Rasool

    2010-01-01

    Objective: To explore the hepatoprotective and antioxidant effects of piperine against acetaminophen-induced hepatotoxicity in mice. Methods: In mice, hepatotoxicity was induced by a single dose of acetaminophen (900 mg/kg b.w. i.p.). Piperine (25 mg/kg b.w. i.p.) and standard drug silymarin (25 mg/kg b.w. i.p.) were given to mice, 30 min after the single injection of acetaminophen. After 4 h, the mice were decapitated. Activities of liver marker enzymes [(aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP)] and inflammatory mediator tumour necrosis factor-alpha (TNF-α) were estimated in serum, while lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase and glutathione) were determined in liver homogenate of control and experimental mice. Results: Acetaminophen induction (900 mg/kg b.w. i.p.) significantly increased the levels of liver marker enzymes, TNF-α, and lipid peroxidation, and caused the depletion of antioxidant status. Piperine and silymarin treatment to acetaminophen challenged mice resulted in decreased liver marker enzymes activity, TNF-α and lipid peroxidation levels with increase in antioxidant status. Conclusions: The results clearly demonstrate that piperine shows promising hepatoprotective effect as comparable to standard drug silymarin.

  15. Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats.

    Paul, Sudip; Islam, Md Aminul; Tanvir, E M; Ahmed, Romana; Das, Sagarika; Rumpa, Nur-E-Noushin; Hossen, Md Sakib; Parvez, Mashud; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-01-01

    Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation. PMID:27034701

  16. Preventive and curative effects of Acalypha indica on acetaminophen-induced hepatotoxicity

    M Mathew

    2011-01-01

    Full Text Available Effect of ethanol extract of the leaves of Acalypha indica (Euphorbiaceae was investigated against acetaminophen-induced hepatic damage. Acetaminophen (paracetamol at the rate of 1 g/kg produced liver damage in rats as manifested by the significant (P<0.001 rise in serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, compared to respective control values. Treatment of rats with acetaminophen led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA. This was associated with a significant reduction in superoxide dismutase (SOD and glutathione (GSH contents. Pretreatment of animals with the plant extract (100 mg/kg orally once daily for 5 days prevented (P<0.01 the acetaminophen-induced rise in serum transaminases (AST and ALT and ALP. Post treatment with five successive doses of the extract (100 mg/kg restricted the hepatic damage induced by the above said Paracetamol (P<0.001. Histological changes around the hepatic central vein were recovered by administration of the drug. Thus, it is evident that these biochemical and histological alterations resulting from acetaminophen administration were inhibited by pre and post treatment with A. indica leaf extract. One notable study of the study was the spontaneous recovery of liver damage within a week after stopping paracetamol. These results indicate that the crude ethanol extract of A. indica exhibits hepatoprotective action through antioxidant effect and validates the traditional use of the plant in hepatic dysfunction.

  17. Rapid onset of Stevens-Johnson syndrome and toxic epidermal necrolysis after ingestion of acetaminophen.

    Kim, Eun-Jin; Lim, Hyun; Park, So Young; Kim, Sujeong; Yoon, Sun-Young; Bae, Yun-Jeong; Kwon, Hyouk-Soo; Cho, You Sook; Moon, Hee-Bom; Kim, Tae-Bum

    2014-01-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but life-threatening, severe cutaneous adverse reactions most frequently caused by exposure to drugs. Several reports have associated the use of acetaminophen with the risk of SJS or TEN. A typical interval from the beginning of drug therapy to the onset of an adverse reaction is 1-3 weeks. A 43-year-old woman and a 60-year-old man developed skin lesions within 3 days after administration of acetaminophen for a 3-day period. Rapid identification of the symptoms of SJS and TEN caused by ingestion of acetaminophen enabled prompt withdrawal of the culprit drug. After administration of intravenous immunoglobulin G, both patients recovered fully and were discharged. These two cases of rapidly developed SJS/TEN after ingestion of acetaminophen highlight the possibility that these complications can develop within only a few days following ingestion of over-the-counter medications such as acetaminophen. PMID:24527413

  18. Protective Effect of Acacia nilotica (L. against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

    Narayanan Kannan

    2013-01-01

    Full Text Available The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT, Aspartate transaminase (AST, Alkaline phosphatase (ALP, total bilirubin, total protein, oxidative stress test (Lipid peroxidation, antioxidant parameter glutathione (GSH, and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model.

  19. Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats

    Paul, Sudip; Islam, Md. Aminul; Tanvir, E. M.; Ahmed, Romana; Das, Sagarika; Rumpa, Nur-E-Noushin; Hossen, Md. Sakib; Parvez, Mashud; Gan, Siew Hua; Khalil, Md. Ibrahim

    2016-01-01

    Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation. PMID:27034701

  20. Satkara (Citrus macroptera Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats

    Sudip Paul

    2016-01-01

    Full Text Available Although Citrus macroptera (Rutaceae, an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

  1. Acetaminophen fails to inhibit ethanol-induced subjective effects in human volunteers.

    Pickworth, W B; Klein, S A; George, F R; Henningfield, J E

    1992-01-01

    In animals, ethanol causes some of its CNS effects by releasing prostaglandins (PG); this is demonstrated by reports that prostaglandin synthetase inhibitors (PGSIs) diminish ethanol-induced effects. However, use of animals in these studies has precluded testing for subjective effects. We studied the interaction of ethanol and acetaminophen, a PGSI, in a double-blind crossover experiment. Six adult males were given no drug or acetaminophen (0, 325, 650, 1300 or 1950 mg) 75 min before ethanol (total dose = 0.625 g/kg; five divided doses). Physiologic, subjective and performance measures were collected. Compared to the no drug condition, ethanol significantly increased ratings of drug "liking," "drunk," "sluggish" and "drug strength" and decreased ratings of "sober." Ethanol increased heart rate and acetaminophen did not diminish or enhance this effect. The failure to antagonize ethanol-induced subjective and physiologic effects by acetaminophen in humans may be due to species differences or inadequate dosage of the PGSI. It is also possible that subjective and certain physiologic effects of ethanol in humans are not mediated by prostaglandin-dependent neural processes. Nevertheless, the finding that at greater than typical analgesic doses, acetaminophen failed to prevent subjective effects of ethanol is of clinical significance. PMID:1539069

  2. Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

    Forbes, J A; Butterworth, G A; Burchfield, W H; Beaver, W T

    1990-01-01

    One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin. PMID:2082317

  3. Investigations of acetaminophen binding to bovine serum albumin in the presence of fatty acid: Fluorescence and 1H NMR studies

    Bojko, B.; Sułkowska, A.; Maciążek-Jurczyk, M.; Równicka, J.; Sułkowski, W. W.

    2009-04-01

    The binding of acetaminophen to bovine serum albumin (BSA) was studied by the quenching fluorescence method and the proton nuclear magnetic resonance technique ( 1H NMR). For fluorescence measurements 1-anilino-9-naphthalene sulfonate (ANS) hydrophobic probe was used to verify subdomain IIIA as acetaminophen's likely binding site. Three binding sites of acetaminophen in subdomain IIA of bovine serum albumin were found. Quenching constants calculated by the Stern-Volmer modified method were used to estimate the influence of myristic acid (MYR) on the drug binding to the albumin. The influence of [fatty acid]/[albumin] molar ratios on the affinity of the protein towards acetaminophen was described. Changes of chemical shifts and relaxation times of the drug indicated that the presence of MYR inhibits interaction in the AA-albumin complex. It is suggested that the elevated level of fatty acids does not significantly influence the pharmacokinetics of acetaminophen.

  4. Role of tumor necrosis factor receptor 1 (p55) in hepatocyte proliferation during acetaminophen-induced toxicity in mice

    Hepatocyte proliferation represents an important part of tissue repair. In these studies, TNF receptor 1 (TNFR1) knockout mice were used to analyze the role of TNF-α in hepatocyte proliferation during acetaminophen-induced hepatotoxicity. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis. This was associated with proliferation of hepatocytes surrounding the damaged areas, which was evident at 24 h. The cell cycle regulatory proteins, cyclin D1 and cyclin A, were also up regulated in hepatocytes. In contrast, in TNFR1-/- mice, which exhibit exaggerated acetaminophen hepatotoxicity, hepatocyte proliferation, and expression of cyclin D1 and cyclin A, as well as the cyclin dependent kinases, Cdk4 and Cdk2, were reduced. The cyclin-dependent kinase inhibitor p21 was also induced in the liver following acetaminophen administration. This was greater in TNFR1-/- mice compared to WT mice. To investigate mechanisms mediating the reduced hepatic proliferative response of TNFR1-/- mice, we analyzed phosphatidyl inositol-3-kinase (PI-3K) signaling. In both WT and TNFR1-/- mice, acetaminophen caused a rapid increase in total PI-3K within 3 h. Acetaminophen also increased phosphorylated PI-3K, but this was delayed 6-12 h in TNFR1-/- mice. Expression of Akt, a downstream target of PI-3K, was increased in both WT and TNFR1-/- mice in response to acetaminophen. However, the increase was greater in WT mice. Acetaminophen-induced expression of phosphorylated STAT3, a key regulator of cytokine-induced hepatocyte proliferation, was also delayed in TNFR1-/- mice relative to WT. These data suggest that TNF-α signaling through TNFR1 is important in regulating hepatocyte proliferation following acetaminophen-induced tissue injury. Delayed cytokine signaling may account for reduced hepatocyte proliferation and contribute to exaggerated acetaminophen-induced hepatotoxicity in TNFR1-/- mice

  5. The immunological and histopathological changes of Tramadol, Tramadol/Acetaminophen and Acetaminophen in male Albino rats "Comparative study"

    Hanan Mostafa Rabei

    2011-10-01

    Full Text Available Tramadol is a synthetic opioid analgesic. It is commonly prescribed for moderate to severe pain, becoming abused more popular among teens in most countries. Paracetamol as anti-inflammatory drugs (acetaminophen (APAP is widely used as an analgesic and antipyretic agent. Meanwhile, tramadol/acetaminophen (tramacet is effective in acute or chronic moderate-to-moderately severe pain. In comparative study, the current investigation threw the light on the effect of over doses of tramadol and/or APAP on the immune function and hepatocytes in adult male Sprague-Dawley rats. Material and methods: Treated rats received oral doses of each drug for 15 consecutive days and after last treatment, they kept three days later for withdrawal studies. The rats were divided into four treatment groups, in the first group, rats received saline and used as control. The second, third and fourth groups treated with tramadol (45 mg/kg, tramadol/APAP (45/450 mg/kg, APAP (450 mg/kg respectively, once a-day at the first week and ending with 90, 90/900, 900 mg/kg at the second week. Rats were sacrificed at the end of the first, second weeks and three days of last treatment. Results: Daily doses of tramadol and /or APAP exposure in rats decreased the cellularity of spleen. Moreover, phagocytic and killing of S. aureus by PMN and macrophage cells caused a highly significant decrease in treated groups. IFN- was reduced in a statistically different treated group of rats. Serum IL-10 was unaffected by any of the treatment regimens but increased only in tramadol/APAP treated rats. Spleen histology exhibited mild pathological alteration with different injures between treated groups. Splenic white pulp accompanied by ill deformed which reflected the reduction of white pulp zones, thickened vasculature in the splenic net work, fibrous trabeculae become prominent feature, where splenic red pulp occupied large areas of the splenic network with predominant edema and megakaryocytes. On

  6. Lysosomal Cholesterol Accumulation Sensitizes To Acetaminophen Hepatotoxicity by Impairing Mitophagy

    Baulies, Anna; Ribas, Vicent; Núñez, Susana; Torres, Sandra; Alarcón-Vila, Cristina; Martínez, Laura; Suda, Jo; Ybanez, Maria D.; Kaplowitz, Neil; García-Ruiz, Carmen; Fernández-Checa, Jose C.

    2015-01-01

    The role of lysosomes in acetaminophen (APAP) hepatotoxicity is poorly understood. Here, we investigated the impact of genetic and drug-induced lysosomal cholesterol (LC) accumulation in APAP hepatotoxicity. Acid sphingomyelinase (ASMase)−/− mice exhibit LC accumulation and higher mortality after APAP overdose compared to ASMase+/+ littermates. ASMase−/− hepatocytes display lower threshold for APAP-induced cell death and defective fusion of mitochondria-containing autophagosomes with lysosomes, which decreased mitochondrial quality control. LC accumulation in ASMase+/+ hepatocytes caused by U18666A reproduces the susceptibility of ASMase−/− hepatocytes to APAP and the impairment in the formation of mitochondria-containing autolysosomes. LC extraction by 25-hydroxycholesterol increased APAP-mediated mitophagy and protected ASMase−/− mice and hepatocytes against APAP hepatotoxicity, effects that were reversed by chloroquine to disrupt autophagy. The regulation of LC by U18666A or 25-hydroxycholesterol did not affect total cellular sphingomyelin content or its lysosomal distribution. Of relevance, amitriptyline-induced ASMase inhibition in human hepatocytes caused LC accumulation, impaired mitophagy and increased susceptibility to APAP. Similar results were observed upon glucocerebrosidase inhibition by conduritol β-epoxide, a cellular model of Gaucher disease. These findings indicate that LC accumulation determines susceptibility to APAP hepatotoxicity by modulating mitophagy, and imply that genetic or drug-mediated ASMase disruption sensitizes to APAP-induced liver injury. PMID:26657973

  7. Chitohexaose protects against acetaminophen-induced hepatotoxicity in mice.

    Barman, P K; Mukherjee, R; Prusty, B K; Suklabaidya, S; Senapati, S; Ravindran, B

    2016-01-01

    Acetaminophen (N-acetyl-para-aminophenol (APAP)) toxicity causes acute liver failure by inducing centrilobular hepatic damage as a consequence of mitochondrial oxidative stress. Sterile inflammation, triggered by hepatic damage, facilitates gut bacterial translocation leading to systemic inflammation; TLR4-mediated activation by LPS has been shown to have a critical role in APAP-mediated hepatotoxicity. In this study, we demonstrate significant protection mediated by chitohexaose (Chtx) in mice challenged with a lethal dose of APAP (400 mg/kg b.w.). Decreased mortality by Chtx was associated with reduced hepatic damage, increased peritoneal migration of neutrophils, decreased mRNA expression of IL-1β as well as inhibition of inflammasome activation in liver. Further, an alternate mouse model of co-administration of a sublethal doses of APAP (200 mg/kg b.w.) and LPS (5 mg/kg b.w.) operating synergistically and mediating complete mortality was developed. Overwhelming inflammation, characterized by increased inflammatory cytokines (TNF-α, IL-1β and so on) in liver as well as in circulation and mortality was demonstrable in this model. Also, Chtx administration mediated significant reversal of mortality in APAP+LPS co-administered mice, which was associated with reduced IL-1β in liver and plasma cytokines in this model. In conclusion, Chtx being a small molecular weight linear carbohydrate offers promise for clinical management of liver failure associated with APAP overdose. PMID:27171266

  8. Increased hepatotoxicity of acetaminophen in Hsp70i knockout mice

    The effect of the inducible forms of 70 kDa heat shock protein (Hsp70i) on acetaminophen (APAP) hepatotoxicity was assessed in an Hsp70i knockout mouse model. Absence of the Hsp70i protein in liver was verified by monitoring Hsp levels in knockout and control mice after heat stress (41.5 oC water bath immersion for 30 min). Hsp70i knockout mice were more susceptible to APAP-induced hepatotoxicity than controls, as indicated by elevated serum alanine aminotransferase activities 24 and 48 h after the APAP dose. Increased APAP hepatotoxicity in knockout mice was verified by morphological evaluation of liver sections. The difference in toxic response to APAP between knockout and control strain mice could not be attributed to differences in APAP bioactivation, assessed by measurement of CYP2E1 and glutathione S-transferase activities, hepatic nonprotein sulfhydryl content, or covalent binding of reactive APAP metabolites to proteins. Pretreatment with transient hyperthermia to produce a general upregulation of Hsps resulted in decreased APAP hepatotoxicity in both the knockout and control strains. Among thermally-pretreated mice, hepatotoxicity of APAP was greater in the knockouts compared with the control strain. These observations suggest that increased Hsp70i expression in response to APAP acts to limit the extent of tissue injury. Results further suggest that other factors related to heat stress can also contribute to protection against APAP toxicity

  9. The determination of acetaminophen using a carbon nanotube:graphite-based electrode

    The oxidation of acetaminophen was studied at a glassy carbon electrode modified with multi-walled carbon nanotubes and a graphite paste. Cyclic voltamety, differential pulse voltammetry and square wave voltammetry at various pH values, scan rates, and the effect of the ratio of nanotubes to graphite were investigated in order to optimize the parameters for the determination of acetaminophen. Square wave voltammetry is the most appropriate technique in giving a characteristic peak at 0. 52 V at pH 5. The porous nanostructure of the electrode improves the surface area which results in an increase in the peak current. The voltammetric response is linear in the range between 75 and 2000 ng. mL-1, with standard deviations between 0. 25 and 7. 8%, and a limit of detection of 25 ng. mL-1. The method has been successfully applied to the analysis of acetaminophen in tablets and biological fluids. (author)

  10. Ethyl pyruvate for the treatment of acetaminophen intoxication: alternative to N-acetylcysteine?

    Wagner, Florian; Asfar, Pierre; Georgieff, Michael; Radermacher, Peter; Wagner, Katja

    2012-01-01

    N-acetylcysteine is the classical antidote for acetaminophen overdose-induced hepatotoxicity, but its efficacy is limited by the need for early and only temporary treatment. Therefore, Yang and colleagues tested the hypothesis of whether ethyl pyruvate--another anti-inflammatory and antioxidant compound, which they had previously shown to protect against liver injury of various other etiologies--may allow circumventing these limitations. While ethyl pyruvate improved liver regeneration when administered early and during a limited period only, the opposite response was present both after delayed as well as prolonged treatment. The authors concluded that prolonged anti-inflammatory treatment is detrimental after acetaminophen intoxication-induced liver damage. On the one hand, this research paper confirms the need for biomarkers to monitor organ recovery after acetaminophen. On the other hand, this paper adds to the ongoing discussion on the usefulness of ethyl pyruvate as a resuscitation fluid in the critically ill. PMID:22348679

  11. Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain.

    Mehlisch, D R; Jasper, R D; Brown, P; Korn, S H; McCarroll, K; Murakami, A A

    1995-01-01

    This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated. PMID:8595637

  12. Carbon Based Electrodes Modified with Horseradish Peroxidase Immobilized in Conducting Polymers for Acetaminophen Analysis

    Cecilia Cristea

    2013-04-01

    Full Text Available The development and optimization of new biosensors with horseradish peroxidase immobilized in carbon nanotubes-polyethyleneimine or polypyrrole nanocomposite film at the surface of two types of transducer is described. The amperometric detection of acetaminophen was carried out at −0.2 V versus Ag/AgCl using carbon based-screen printed electrodes (SPEs and glassy carbon electrodes (GCEs as transducers. The electroanalytical parameters of the biosensors are highly dependent on their configuration and on the dimensions of the carbon nanotubes. The best limit of detection obtained for acetaminophen was 1.36 ± 0.013 μM and the linear range 9.99–79.01 μM for the HRP-SWCNT/PEI in GCE configuration. The biosensors were successfully applied for the detection of acetaminophen in several drug formulations.

  13. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    Daniela Rodrigues

    2012-12-01

    Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.

  14. Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain.

    Turek, M D; Baird, W M

    1988-12-01

    One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind, randomized, parallel study designed to compare the efficacy and safety of single oral doses of ketoprofen (50 and 150 mg), an acetaminophen (650 mg) plus codeine (60 mg) combination, and placebo. From 1 through 4 hours after administration of the study drugs, the mean summed pain intensity difference (SPID) and time-weighted total pain relief (TOPAR) scores for the three active treatments generally were significantly (P less than 0.05) higher than those for placebo but not significantly different from each other. At the 6-hour evaluation, the ketoprofen groups, but not the acetaminophen-codeine group, had higher (P less than 0.05) mean SPID and TOPAR scores than the placebo group, as a result of a shorter duration of pain relief in the acetaminophen-codeine group. The 6-hour TOPAR scores were significantly (P less than 0.05) higher for both ketoprofen groups than for the acetaminophen-codeine group; the ketoprofen 150 mg group also had significantly (P less than 0.05) higher mean 6-hour SPID and global subjective assessment scores. As a result of a higher frequency of somnolence, there was a significantly (P less than 0.05) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen. These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer. PMID:3072354

  15. Fulminate Hepatic Failure in a 5 Year Old Female after Inappropriate Acetaminophen Treatment

    Kasmi, Irena; Sallabanda, Sashenka; Kasmi, Gentian

    2015-01-01

    BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/L. Patient totally recovered within 29 days. CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction.

  16. Spathodea campanulata Extract Attenuates Acetaminophen-Induced Hepatic Injury in Mice

    Phyllis Elsie Dadzeasah; Charles Ansah

    2013-01-01

    Spathodea campanulata, well known for its traditional medicinal uses was investigated for hepatoprotective activity against acetaminophen-induced hepatic damage in mice. Six groups of mice were pre-treated with 100, 300 and 625 mg/kg of the aqueous extract of Spathodea campanulata stem bark, N-acetyl cysteine (300 mg/kg; p.o) or distilled water for 5 days before they were intoxicated with a single dose of acetaminophen (600 mg/kg; p.o). Alanine aminotransferase, Aspartate aminotransferase an...

  17. Fluorescence excitation spectrum and solvent-assisted conformational isomerization (SACI) of jet-cooled acetaminophen

    Sohn, Woon Yong; Kang, Jeong Seok; Lee, So Young; Kang, Hyuk

    2013-08-01

    Fluorescence excitation spectrum of jet-cooled acetaminophen was obtained. When AAP was expanded with a buffer gas containing 0.3-1.1% of water, absorption peaks of the less stable trans conformer was significantly reduced by solvent-assisted conformational isomerization (SACI), which is confirmed by a separately measured UV-UV hole burning spectroscopy. It is also confirmed by quantum mechanical calculation and RRKM calculation that it is energetically and kinetically possible to induce SACI in AAP with water. The SACI mechanism suggests a possible pathway that acetaminophen can adopt an active conformation in vivo, which is need for molecular recognition and drug activity.

  18. Rapid onset of Stevens-Johnson syndrome and toxic epidermal necrolysis after ingestion of acetaminophen

    Kim, Eun-Jin; Lim, Hyun; Park, So Young; Kim, Sujeong; Yoon, Sun-Young; Bae, Yun-Jeong; Kwon, Hyouk-Soo; Cho, You Sook; Moon, Hee-Bom; Kim, Tae-Bum

    2014-01-01

    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but life-threatening, severe cutaneous adverse reactions most frequently caused by exposure to drugs. Several reports have associated the use of acetaminophen with the risk of SJS or TEN. A typical interval from the beginning of drug therapy to the onset of an adverse reaction is 1-3 weeks. A 43-year-old woman and a 60-year-old man developed skin lesions within 3 days after administration of acetaminophen for a 3-da...

  19. Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice

    Hagiya, Yoshifumi; Kamata, Shotaro; Mitsuoka, Saya; Okada, Norihiko; Yoshida, Saori; Yamamoto, Junya; Ohkubo, Rika [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan); Abiko, Yumi [Environmental Biology Laboratory, School of Medicine, University of Tsukuba, Ibaraki 305-8575 (Japan); Yamada, Hidenori [Jobu Hospital for Respiratory Diseases, Maebashi 371-0048 (Japan); Akahoshi, Noriyuki [Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543 (Japan); Kasahara, Tadashi [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan); Kumagai, Yoshito [Environmental Biology Laboratory, School of Medicine, University of Tsukuba, Ibaraki 305-8575 (Japan); Ishii, Isao, E-mail: isao-ishii@umin.ac.jp [Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512 (Japan)

    2015-01-15

    The key mechanism for acetaminophen hepatotoxicity is cytochrome P450 (CYP)-dependent formation of N-acetyl-p-benzoquinone imine, a potent electrophile that forms protein adducts. Previous studies revealed the fundamental role of glutathione, which binds to and detoxifies N-acetyl-p-benzoquinone imine. Glutathione is synthesized from cysteine in the liver, and N-acetylcysteine is used as a sole antidote for acetaminophen poisoning. Here, we evaluated the potential roles of transsulfuration enzymes essential for cysteine biosynthesis, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), in acetaminophen hepatotoxicity using hemizygous (Cbs{sup +/−} or Cth{sup +/−}) and homozygous (Cth{sup −/−}) knockout mice. At 4 h after intraperitoneal acetaminophen injection, serum alanine aminotransferase levels were highly elevated in Cth{sup −/−} mice at 150 mg/kg dose, and also in Cbs{sup +/−} or Cth{sup +/−} mice at 250 mg/kg dose, which was associated with characteristic centrilobular hepatocyte oncosis. Hepatic glutathione was depleted while serum malondialdehyde accumulated in acetaminophen-injected Cth{sup −/−} mice but not wild-type mice, although glutamate–cysteine ligase (composed of catalytic [GCLC] and modifier [GCLM] subunits) became more activated in the livers of Cth{sup −/−} mice with lower K{sub m} values for Cys and Glu. Proteome analysis using fluorescent two-dimensional difference gel electrophoresis revealed 47 differentially expressed proteins after injection of 150 mg acetaminophen/kg into Cth{sup −/−} mice; the profiles were similar to 1000 mg acetaminophen/kg-treated wild-type mice. The prevalence of Cbs or Cth hemizygosity is estimated to be 1:200–300 population; therefore, the deletion or polymorphism of either transsulfuration gene may underlie idiosyncratic acetaminophen vulnerability along with the differences in Cyp, Gclc, and Gclm gene activities. - Highlights: • Cbs{sup +/−}, Cth{sup +/−}, and

  20. Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice

    The key mechanism for acetaminophen hepatotoxicity is cytochrome P450 (CYP)-dependent formation of N-acetyl-p-benzoquinone imine, a potent electrophile that forms protein adducts. Previous studies revealed the fundamental role of glutathione, which binds to and detoxifies N-acetyl-p-benzoquinone imine. Glutathione is synthesized from cysteine in the liver, and N-acetylcysteine is used as a sole antidote for acetaminophen poisoning. Here, we evaluated the potential roles of transsulfuration enzymes essential for cysteine biosynthesis, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), in acetaminophen hepatotoxicity using hemizygous (Cbs+/− or Cth+/−) and homozygous (Cth−/−) knockout mice. At 4 h after intraperitoneal acetaminophen injection, serum alanine aminotransferase levels were highly elevated in Cth−/− mice at 150 mg/kg dose, and also in Cbs+/− or Cth+/− mice at 250 mg/kg dose, which was associated with characteristic centrilobular hepatocyte oncosis. Hepatic glutathione was depleted while serum malondialdehyde accumulated in acetaminophen-injected Cth−/− mice but not wild-type mice, although glutamate–cysteine ligase (composed of catalytic [GCLC] and modifier [GCLM] subunits) became more activated in the livers of Cth−/− mice with lower Km values for Cys and Glu. Proteome analysis using fluorescent two-dimensional difference gel electrophoresis revealed 47 differentially expressed proteins after injection of 150 mg acetaminophen/kg into Cth−/− mice; the profiles were similar to 1000 mg acetaminophen/kg-treated wild-type mice. The prevalence of Cbs or Cth hemizygosity is estimated to be 1:200–300 population; therefore, the deletion or polymorphism of either transsulfuration gene may underlie idiosyncratic acetaminophen vulnerability along with the differences in Cyp, Gclc, and Gclm gene activities. - Highlights: • Cbs+/−, Cth+/−, and especially Cth−/− mice were susceptible to APAP hepatic injury.

  1. Discrepancies between N-Acetyl Cysteine Prescription based on Patient’s History and Plasma Acetaminophen Level

    Fakhreddin Taghaddosi-Nejad

    2012-11-01

    Full Text Available Background: Fatalities from acetaminophen poisoning are common, but they are preventable by timely treatment with N-acetyl cysteine (NAC. In many medical centers, NAC is prescribed in keeping with the ingested dose of the drug as revealed through medical history. It seems to significantly differ from the real indications of NAC administration based on plasma level of acetaminophen. Overtreatment increases adverse drug reactions and it is time- consuming and costly. Methods: Acetaminophen plasma level was checked by HPLC method in 170 admitted patients who had history of acute ingestion of more than 7.5 g acetaminophen within 4 to 24 hours prior to hospital admission. Indications for NAC prescription according to patient’s history and adaptation from acetaminophen plasma level in Romack-Mathew nomogram were matched. Data were analyzed by SPSS software version 16.0. Results: Mean age of the patients was 21.8±6.05 years. In 75.8% of the patients, poisoning had occurred after suicidal attempts. Acetaminophen plasma level was between less than 2 and 265 μg/ml (18.7±28.88, mean± SD. Only in 18 (10.6% cases, overtreatment had been performed. Multiple logistic regression analysis showed that the number of suicidal attempts, number of ingested pills, and time of referral had positive relationships with acetaminophen plasma level. Conclusion: If NAC is prescribed only based on patient's medical history, overtreatment may take place.

  2. Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity

    Neutrophils are recruited into the liver after acetaminophen (AAP) overdose but the pathophysiological relevance of this acute inflammatory response remains unclear. To address this question, we compared the time course of liver injury, hepatic neutrophil accumulation and inflammatory gene mRNA expression for up to 24 h after treatment with 300 mg/kg AAP in C3Heb/FeJ and C57BL/6 mice. Although there was no relevant difference in liver injury (assessed by the increase of plasma alanine aminotransferase activities and the areas of necrosis), the number of neutrophils and the expression of several pro-inflammatory genes (e.g., tumor necrosis factor-α, interleukin-1β and macrophage inflammatory protein-2) was higher in C3Heb/FeJ than in C57BL/6 mice. In contrast, the expression of the anti-inflammatory genes interleukin-10 and heme oxygenase-1 was higher in C57BL/6 mice. Despite substantial hepatic neutrophil accumulation, none of the liver sections from both strains stained positive for hypochlorite-modified proteins, a specific marker for a neutrophil-induced oxidant stress. In addition, treatment with the NADPH oxidase inhibitors diphenyleneiodonium chloride or apocynin or the anti-neutrophil antibody Gr-1 did not protect against AAP hepatotoxicity. Furthermore, although intercellular adhesion molecule-1 (ICAM-1) was previously shown to be important for neutrophil extravasation and tissue injury in several models, ICAM-1-deficient mice were not protected against AAP-mediated liver injury. Together, these data do not support the hypothesis that neutrophils aggravate liver injury induced by AAP overdose

  3. Mechanism of protection by metallothionein against acetaminophen hepatotoxicity

    Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the US. Metallothionein (MT) expression attenuates APAP-induced liver injury. However, the mechanism of this protection remains incompletely understood. To address this issue, C57BL/6 mice were treated with 100 μmol/kg ZnCl2 for 3 days to induce MT. Twenty-four hours after the last dose of zinc, the animals received 300 mg/kg APAP. Liver injury (plasma ALT activities, area of necrosis), DNA fragmentation, peroxynitrite formation (nitrotyrosine staining), MT expression, hepatic glutathione (GSH), and glutathione disulfide (GSSG) levels were determined after 6 h. APAP alone caused severe liver injury with oxidant stress (increased GSSG levels), peroxynitrite formation, and DNA fragmentation, all of which were attenuated by zinc-induced MT expression. In contrast, MT knockout mice were not protected by zinc. Hydrogen peroxide-induced cell injury in primary hepatocytes was dependent only on the intracellular GSH levels but not on MT expression. Thus, the protective effect of MT in vivo was not due to the direct scavenging of reactive oxygen species. Zinc treatment had no effect on the early GSH depletion kinetics after APAP administration, which is an indicator of the metabolic activation of APAP to its reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). However, MT was able to effectively trap NAPQI by covalent binding. We conclude that MT scavenges some of the excess NAPQI after GSH depletion and prevents covalent binding to cellular proteins, which is the trigger for the propagation of the cell injury mechanisms through mitochondrial dysfunction and nuclear DNA damage.

  4. Nilotinib interferes with the signalling pathways implicated in acetaminophen hepatotoxicity.

    Shaker, Mohamed E

    2014-03-01

    Nilotinib, a second-generation tyrosine kinase inhibitor, has been recently approved for the treatment for chronic myeloid leukaemia. The objective of this study was to explore the potential effects of clinically relevant doses of nilotinib against acetaminophen (APAP)-induced hepatotoxicity in mice. To simulate the clinical application in human beings, nilotinib (25 and 50 mg/kg) was administered to mice 2 hr after APAP intoxication (500 mg/kg). The results indicated that nilotinib (25 mg/kg) (i) abolished APAP-induced liver injury and necro-inflammation, (ii) increased hepatic-reduced glutathione (GSH) and its related enzymes synthesis, (iii) suppressed hepatic oxidative/nitrosative stress cascades, (iv) decreased neutrophil accumulation in the liver, and (v) prevented the over-expression of B-cell lymphoma-2 (bcl-2), cyclin-D1 and stem cell factor receptor (c-Kit) proteins in the liver. Although nilotinib (50 mg/kg) acted through the same mechanisms, there was severe depletion in hepatic GSH content by nilotinib itself at that dose level, rather than the potent stimulation observed by using a dose of 25 mg/kg. Consequently, the mortality rate after 18 hr was 100% for nilotinib (50 mg/kg) + APAP (750 mg/kg) versus 60% for APAP (750 mg/kg) and 40% for nilotinib (25 mg/kg) + APAP (750 mg/kg) in the survival analysis experiment. In conclusion, nilotinib can counteract the hepatotoxicity produced by a non-lethal dose of APAP. However, there is a risk of aggravating the mortality for a lethal dose of APAP when nilotinib is co-administered at doses relatively high, or near to the clinical range because of hepatic GSH depletion and c-kit inhibition. PMID:24119297

  5. Acetaminophen Induced Hepatotoxicity in Wistar Rats—A Proteomic Approach

    Soundharrajan Ilavenil

    2016-01-01

    Full Text Available Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups—control, nontoxic (150 mg/kg and toxic dose (1500 mg/kg of APAP—were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD’s PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%, immunity (14%, neurological related (12% and transporter proteins (2%, whereas in non-toxic dose-induced rats they were  oxidative stress (9%, immunity (6%, neurological (14% and transporter proteins (9%. It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database.

  6. Inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin.

    Schwartz, Jules I; Musser, Bret J; Tanaka, Wesley K; Taggart, William V; Mehta, Anish; Gottesdiener, Keith M; Greenberg, Howard E

    2015-09-01

    This double-blind, randomized crossover study assessed the effect of acetaminophen (1000 mg every 8 hours) versus indomethacin (50 mg every 8 hours) versus placebo on cyclooxygenase enzymes (COX-1 and COX-2). Urinary excretion of 2,3-dinor-6-keto-PGF1α, (prostacyclin metabolite, PGI-M; COX-2 inhibition) and 11-dehydro thromboxane B2 (thromboxane metabolite, Tx-M; COX-1 inhibition) were measured after 1 dose and 5 days of dosing. Peak inhibition of urinary metabolite excretion across 8 hours following dosing was the primary end point. Mean PGI-M excretion was 33.7%, 55.9%, and 64.6% on day 1 and 49.4%, 65.1%, and 80.3% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Acetaminophen and indomethacin inhibited PGI-M excretion following single and multiple doses (P = .004 vs placebo). PGI-M excretion inhibition after 1 dose was similar for indomethacin and acetaminophen, but significantly greater with indomethacin after multiple doses (P = .006). Mean Tx-M excretion was 16.2%, 45.2%, and 86.6% on day 1 and 46.2%, 58.4%, and 92.6% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Tx-M excretion inhibition following 1 dose was reduced by acetaminophen (P ≤ .003). Indomethacin reduced Tx-M excretion significantly more than acetaminophen and placebo after single and multiple doses (P ≤ .001). Acetaminophen and indomethacin inhibited COX-1 and COX-2 following a single dose, but acetaminophen was a less potent COX-1 inhibitor than indomethacin. PMID:27137142

  7. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

    Franke RM; Morton T; Devarakonda K

    2015-01-01

    Ryan M Franke, Terri Morton, Krishna Devarakonda Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Abstract: This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crosso...

  8. Improvement of Physico-mechanical Properties of Partially Amorphous Acetaminophen Developed from Hydroalcoholic Solution Using Spray Drying Technique

    Fatemeh Sadeghi; Mansour Torab; Mostafa Khattab; Alireza Homayouni; Hadi Afrasiabi Garekani

    2013-01-01

      Objective(s): This study was performed aiming to investigate the effect of particle engineering via spray drying of hydroalcoholic solution on solid states and physico-mechanical properties of acetaminophen.   Materials and Methods: Spray drying of hydroalcoholic solution (25% v/v ethanol/water) of acetaminophen (5% w/v) in the presence of small amounts of polyninylpyrrolidone K30 (PVP) (0, 1.25, 2.5 and 5% w/w based on acetaminophen weight) was carried out. The properties of spray dried pa...

  9. Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients

    We evaluated the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablet, for the treatment of breakthrough pain in cancer patients. This study was conducted at Changhua Christian Hospital, Changhua, Taiwan from January 2006 to February 2007. The single-center and open-label study enrolled 59 opioid-treated cancer patients with at least moderate breakthrough pain (visual analog scale [VAS] score >/=40mm on a 100-mm scale). The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/acetaminophen. Visual analog scale score at time of pain relief was reported. The mean VAS score when the breakthrough pain episode began (0 minute) was 77.8. Analysis showed significant better mean pain VAS scores at 10, 30, and 60 minutes after the administration of tramadol/acetaminophen (p Tramadol/acetaminophen might be efficacious and safe in the treatment of breakthrough pain in cancer (Author).

  10. Cats Have Nine Lives, but Only One Liver: The Effects of Acetaminophen

    Dewprashad, Brahmadeo

    2009-01-01

    This case recounts the story of a student who gave her cat half of a Tylenol tablet not knowing its potential harmful effects. The cat survives, but the incident motivates the student to learn more about the reaction mechanism underlying the liver toxicity of acetaminophen. The case outlines three possible reaction schemes that would explain the…

  11. Propoxyphene and acetaminophen mixture (Darvocet)--related radiation-induced pneumonitis

    In a patient undergoing radiation therapy for recurrent, metastatic breast cancer, a mixture of propoxyphene and acetaminophen (Darvocet) was given for intercurrent viral infection. Discontinuation of therapy with this medication coincided with appearance of pneumonitis, reminiscent of the steroid withdrawal--related radiation pneumonitis

  12. Effect of Tramadol/Acetaminophen on Motivation in Patients with Chronic Low Back Pain

    Tomoko Tetsunaga

    2016-01-01

    Full Text Available Background. The contribution of apathy, frequently recognized in individuals with neurodegenerative diseases, to chronic low back pain (LBP remains unclear. Objectives. To investigate levels of apathy and clinical outcomes in patients with chronic LBP treated with tramadol-acetaminophen. Methods. A retrospective case-control study involving 73 patients with chronic LBP (23 male, 50 female; mean age 71 years treated with tramadol-acetaminophen (n=36 and celecoxib (n=37 was performed. All patients were assessed using the self-reported questionnaires. A mediation model was constructed using a bootstrapping method to evaluate the mediating effects of pain relief after treatment. Results. A total of 35 (55.6% patients met the criteria for apathy. A four-week treatment regimen in the tramadol group conferred significant improvements in the Apathy scale and numerical rating scale but not in the Rolland-Morris Disability Questionnaire, Pain Disability Assessment Scale, or Pain Catastrophizing Scale. The depression component of the Hospital Anxiety and Depression Scale was lower in the tramadol group than in the celecoxib group. The mediation analysis found that the impact of tramadol-acetaminophen on the change in apathy was not mediated by the pain relief. Conclusions. Tramadol-acetaminophen was effective at reducing chronic LBP and conferred a prophylactic motivational effect in patients with chronic LBP.

  13. Effect of Tramadol/Acetaminophen on Motivation in Patients with Chronic Low Back Pain

    Tetsunaga, Tomoko; Tetsunaga, Tomonori; Tanaka, Masato; Nishida, Keiichiro; Takei, Yoshitaka; Ozaki, Toshifumi

    2016-01-01

    Background. The contribution of apathy, frequently recognized in individuals with neurodegenerative diseases, to chronic low back pain (LBP) remains unclear. Objectives. To investigate levels of apathy and clinical outcomes in patients with chronic LBP treated with tramadol-acetaminophen. Methods. A retrospective case-control study involving 73 patients with chronic LBP (23 male, 50 female; mean age 71 years) treated with tramadol-acetaminophen (n = 36) and celecoxib (n = 37) was performed. All patients were assessed using the self-reported questionnaires. A mediation model was constructed using a bootstrapping method to evaluate the mediating effects of pain relief after treatment. Results. A total of 35 (55.6%) patients met the criteria for apathy. A four-week treatment regimen in the tramadol group conferred significant improvements in the Apathy scale and numerical rating scale but not in the Rolland-Morris Disability Questionnaire, Pain Disability Assessment Scale, or Pain Catastrophizing Scale. The depression component of the Hospital Anxiety and Depression Scale was lower in the tramadol group than in the celecoxib group. The mediation analysis found that the impact of tramadol-acetaminophen on the change in apathy was not mediated by the pain relief. Conclusions. Tramadol-acetaminophen was effective at reducing chronic LBP and conferred a prophylactic motivational effect in patients with chronic LBP.

  14. Croton zehntneri Essential oil prevents acetaminophen-induced acute hepatotoxicity in mice

    Maria Goretti R. Queiroz; José Henrique L. Cardoso; Adriana R. Tomé; Roberto C. P. Lima Jr.; Jamile M. Ferreira; Daniel F. Sousa; Felipe C. Lima; Campos, Adriana R.

    2008-01-01

    Hepatoprotective activity of Croton zehntneri Pax & Hoffman (Euphorbiaceae) leaf essential oil (EOCz) was evaluated against single dose of acetaminophen-induced (500 mg/kg, p.o.) acute hepatotoxicity in mice. EOCz significantly protected the hepatotoxicity as evident from the activities of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT) activities, that were significantly (p

  15. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial : a multicentre, randomised, placebo-controlled, phase III trial

    den Hertog, Heleen M.; van der Worp, H. Bart; van Gemert, H. Maarten A.; Algra, Ate; Kappelle, L. Jaap; Van Gijn, Jan; Koudstaal, Peter J.; Dippel, Diederik W. J.

    2009-01-01

    Background High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing b

  16. Correction: PAIS: paracetamol (acetaminophen in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480

    Kappelle L Jaap

    2008-11-01

    Full Text Available Abstract Background The Paracetamol (Acetaminophen In Stroke (PAIS study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever. The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. Methods Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. Conclusion The protocol change was initiated because of both advances in statistical approaches and to increase the efficiency of the trial by improving statistical power. Trial Registration Current Controlled Trials [ISCRTN74418480

  17. Effect of pretreatment with acetaminophen-propoxyphene for oral surgery pain.

    Liashek, P; Desjardins, P J; Triplett, R G

    1987-02-01

    To determine the effect of pretreatment and multiple doses on postsurgical pain, a study of the relative analgesic efficacy of placebo, acetaminophen 650 mg, and propoxyphene napsylate 100 mg alone and in combination was conducted. Forty-five patients undergoing surgical removal of impacted third molar teeth under local anesthesia were randomly allocated to the four treatment regimens under double-blind conditions. The first oral dose was administered one hour preoperatively and the second dose when the pain became moderate or severe, following the dissipation of the local anesthesia. Pain intensity and pain relief were assessed using standard verbal descriptor scales at 30 minutes and hourly for four hours after the postoperative dose. Measures of total effect, peak effect and duration of their effect were derived from these descriptors. Acetaminophen was no better than placebo. For peak and total effects, propoxyphene alone and the propoxyphene-acetaminophen combination were substantially superior to both placebo and acetaminophen alone. Duration of analgesia was also significantly longer with both propoxyphene-containing treatments. No side effects were reported. The results suggest that pretreatment with a narcotic agonist markedly improves postoperative analgesia. PMID:3468226

  18. An Experiment in Physical Chemistry: Polymorphism and Phase Stability in Acetaminophen (Paracetamol)

    Myrick, Michael L.; Baranowski, Megan; Profeta, Luisa T. M.

    2010-01-01

    Differential scanning calorimetry analyses of two easily prepared polymorphs of acetaminophen (also known as paracetamol) are recorded. The density of the forms can be found in the literature. Rules for heats of transition, heats of fusion, and density, as well as methods for determining the solid-solid transition temperature between the forms,…

  19. A Biomedical Application of Activated Carbon Adsorption: An Experiment Using Acetaminophen and N-Acetylcysteine.

    Rybolt, Thomas R.; And Others

    1988-01-01

    Illustrates an interesting biomedical application of adsorption from solution and demonstrates some of the factors that influence the in vivo adsorption of drug molecules onto activated charcoal. Uses acetaminophen and N-acetylcysteine for the determination. Suggests several related experiments. (MVL)

  20. Effect of acetaminophen on fetal acid-base balance in chorioamnionitis.

    Kirshon, B; Moise, K J; Wasserstrum, N

    1989-12-01

    The effect of antipyretic treatment with acetaminophen on fetal status was examined in eight laboring women febrile with chorioamnionitis. After a fetal heart rate tracing and scalp blood gas level were obtained near maximum maternal fever, a 650-mg acetaminophen suppository was administered. If the temperature remained greater than 101 degrees F, the dose was repeated in one to two hours. The fetal heart rate tracing was analyzed again after the mother's fever was reduced by acetaminophen. All patients delivered within four hours of the first dose. Umbilical artery blood gases were obtained at delivery. Significant improvements in the bicarbonate concentration and base deficit were noted at the time of delivery as compared to the scalp gas at the height of the maternal fever. The fetal heart rate tracings at the height of the maternal fever, characterized by tachycardia, poor variability and late decelerations, changed to a normal heart rate pattern without decelerations when the mother's fever was reduced. Hence, in the laboring gravida with chorioamnionitis, reducing maternal fever with acetaminophen improves fetal status and thereby may reduce the probability of cesarean section for fetal distress. PMID:2621737

  1. Differential effect of cigarette smoking on antipyrine oxidation versus acetaminophen conjugation.

    Scavone, J M; Greenblatt, D J; LeDuc, B W; Blyden, G T; Luna, B G; Harmatz, J S

    1990-01-01

    The effect of cigarette smoking on drug oxidation and conjugation was studied using antipyrine and acetaminophen as marker compounds. For the antipyrine study, healthy cigarette smokers (n = 30) and nonsmoking controls (n = 53) received a single 1.0-gram intravenous dose of antipyrine. For the acetaminophen study, 14 smokers and 15 nonsmokers received a 650-mg intravenous dose of acetaminophen. The clearance of antipyrine was significantly increased (0.93 vs. 0.60 ml/min/kg, p less than 0.0001) and elimination half-life was correspondingly reduced (8.9 vs. 13.0 h, p less than 0.0001) in smokers compared to nonsmoking controls. Total recovery of antipyrine and metabolites excreted in urine did not differ between groups, but there was a significantly increased fractional clearance of antipyrine via formation of 4-hydroxyantipyrine and 3-hydroxymethyl metabolites in smokers. Fractional clearance via formation of norantipyrine did not differ significantly between groups. Comparison of acetaminophen kinetics between smokers and nonsmokers indicated no significant differences in elimination half-life, clearance or volume of distribution. Thus, cigarette smoking is more likely to induce drug oxidation rather than drug conjugation. However, not all oxidative pathways are equally influenced; induction effects of smoking are highly substrate selective and pathway specific. PMID:2345775

  2. Hepatoprotective potential of three sargassum species from Karachi coast against carbon tetrachloride and acetaminophen intoxication

    Khan Hira

    2016-01-01

    Full Text Available Objective: To assess the hepatoprotective effect of ethanol extracts of Sargassum variegatum (S. variegatum, Sargassum tenerrimum (S. tenerrimum and Sargassum binderi occurring at Karachi coast against carbon tetrachloride (CCl4 and acetaminophen intoxication in rats. Methods: Sargassum species were collected at low tide from Buleji beach at Karachi coast. Effect of ethanol extracts of Sargassum spp., on lipid parameter, serum glucose and kidney function was examined. Liver damage in rats was induced by CCl4 or acetaminophen. Rats were administered with ethanol extracts of S. tenerrimum, S. variegatum and Sargassum binderi at 200 mg/kg body weight daily for 14 days separately. Hepatotoxicity was determined in terms of cardiac and liver enzymes and other biochemical parameters. Results: S. variegatum showed highest activity by reducing the elevated level of hepatic enzymes, bilirubin, serum glucose, triglyceride with restoration of cholesterol. Urea and creatinine concentrations were also significantly (P < 0.05 reduced as compared to acetaminophen intoxicated rats. S. tenerrimum and S. variegatum showed moderate activity against CCl4 hepatic toxicity. Conclusions: The protective role of S. variegatum against acetaminophen liver damage and its positive impact on disturbed lipid, glucose metabolism, kidney dysfunction and S. tenerrimum against CCl4 liver toxicity suggest that Sargassum species offer a non-chemical means for the treatment of toxicity mediated liver damage.

  3. Acetaminophen structure-toxicity studies: In vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide

    High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled [3H or 14C]3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of [G-3H]acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAA was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of [ring-3H]3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential

  4. Enhanced photoactivity of graphene/titanium dioxide nanotubes for removal of Acetaminophen

    Highlights: • TiO2 and graphite oxide were used as precursors of titanium dioxide nanotubes and graphene respectively. Titanium dioxide nanotube and graphene (GR-TNT) nanocomposites were synthesized through a simple hydrothermal method. • And its application to removal acetaminophen, degradation efficiency is more than 96%. • The photocatalytic degradation results indicated that the sample with 5% GO in GR-TNT nanocomposites for 3 h had the highest degradation rate. • The degradation intermediates of acetaminophen by the composites were invested by GC-MS and the possible pathways were invested. - Abstract: Acetaminophen is commonly used as an antipyretic or analgesics agent and poses threat to human health. In this research, TiO2 and graphite oxide were used as precursors of titanium dioxide nanotubes and graphene respectively. Titanium dioxide nanotube and graphene (GR-TNT) nanocomposites were synthesized through a hydrothermal method. FT-IR, UV-Vis, XRD, and TGA were used to characterize the catalysts. The acetaminophen degradation rate can reach up to 96% under UV light irradiation for 3 h and with the 5% GR-TNT dosage of 0.1 g L−1. Further experiments were done to probe the mechanism of the photocatalytic reaction catalyzed by the GR-TNT composite. EDTA (hole scavengers) and t-BuOH (radical scavengers) were used to detect the main active oxidative species in the system. The results showed that the holes are the main oxidation species in the photocatalytic process. This study provides a new prospect for acetaminophen degradation by using high efficiency catalysts

  5. Effect of corn silk extract on acetaminophen induced renal damage in mice

    To evaluate the protective role of Corn Silk extract on Acetaminophen induced nephrotoxicity in albino mice. Study Design: Laboratory based randomized controlled trials. Place and Duration of Study: The study was carried out in experimental research laboratory University of Health Sciences and Anatomy department, Lahore. The study duration was one year from February 2012 to February 2013. Material and Methods: Twenty seven male albino mice, 6-8 weeks old weighing 30 + 5 gm, were used; these animals were randomly divided into three groups having nine mice in each group. Group A served as control and was given 16.6ml/kg normal saline intraperitoneally on first day of experiment and was sacrificed on 10th day of the experiment. Group B was treated with acetaminophen 600 mg/kg dissolved in 16.6 ml of normal saline intraperitoneally on 1st day of experiment and was sacrificed after 48 hours. Group C was given acetaminophen at a dose of 600 mg/kg intraperitoneally on first day of experiment and then corn silk extract was given by oral route at a dose of 400 mg/kg for next 8 days. The animals were sacrificed on 10th day of the experiment, the kidneys were removed; 3mm three tissue pieces were fixed in 10% formaline; processed and stained with H and E for histological study. Results: It was observed on microscopic examination that Corn silk extract reduced deleterious effects of acetaminophen on tubules of kidney as evidenced by reduction of tubular vacuolation and necrosis, absence of protein casts, vascular congestion and inflammation. Conclusion: It is concluded from current results that corn silk extract protects acetaminophen induced nephrotoxicity. (author)

  6. Enhanced photoactivity of graphene/titanium dioxide nanotubes for removal of Acetaminophen

    Tao, Hong; Liang, Xiao [School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093 (China); Zhang, Qian [Graduate Institute of Environmental Engineering, National Taiwan University, 10617, Taiwan (China); Chang, Chang-Tang, E-mail: ctchang@niu.edu.tw [Department of Environmental Engineering, National I-Lan University, 26047, Taiwan (China)

    2015-01-01

    Highlights: • TiO{sub 2} and graphite oxide were used as precursors of titanium dioxide nanotubes and graphene respectively. Titanium dioxide nanotube and graphene (GR-TNT) nanocomposites were synthesized through a simple hydrothermal method. • And its application to removal acetaminophen, degradation efficiency is more than 96%. • The photocatalytic degradation results indicated that the sample with 5% GO in GR-TNT nanocomposites for 3 h had the highest degradation rate. • The degradation intermediates of acetaminophen by the composites were invested by GC-MS and the possible pathways were invested. - Abstract: Acetaminophen is commonly used as an antipyretic or analgesics agent and poses threat to human health. In this research, TiO{sub 2} and graphite oxide were used as precursors of titanium dioxide nanotubes and graphene respectively. Titanium dioxide nanotube and graphene (GR-TNT) nanocomposites were synthesized through a hydrothermal method. FT-IR, UV-Vis, XRD, and TGA were used to characterize the catalysts. The acetaminophen degradation rate can reach up to 96% under UV light irradiation for 3 h and with the 5% GR-TNT dosage of 0.1 g L{sup −1}. Further experiments were done to probe the mechanism of the photocatalytic reaction catalyzed by the GR-TNT composite. EDTA (hole scavengers) and t-BuOH (radical scavengers) were used to detect the main active oxidative species in the system. The results showed that the holes are the main oxidation species in the photocatalytic process. This study provides a new prospect for acetaminophen degradation by using high efficiency catalysts.

  7. Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults

    Carroll, Chad C; Dickinson, Jared M; Lemoine, Jennifer K;

    2011-01-01

    Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance...... training. Thirty-six individuals were randomly assigned to a Placebo (67±2y), Acetaminophen (64±1y; 4000mg(.)d(-1)), or Ibuprofen (64±1y; 1200mg(.)d(-1)) group in a double-blind manner and completed 12-weeks of knee extensor resistance-training. Before and after training in vivo patellar tendon properties...... this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the Acetaminophen group (3%, p0.05) with training in the Placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the Acetaminophen group, tendon deformation and strain...

  8. Validation Thin Layer Chromatography for the Determination of Acetaminophen in Tablets and Comparison with a Pharmacopeial Method

    Pyka, Alina; Budzisz, Marika; Dołowy, Małgorzata

    2013-01-01

    Adsorption thin layer chromatography (NP-TLC) with densitometry has been established for the identification and the quantification of acetaminophen in three leading commercial products of pharmaceutical tablets coded as brand: P1 (Product no. 1), P2 (Product no. 2), and P3 (Product no. 3). Applied chromatographic conditions have separated acetaminophen from its related substances, namely, 4-aminophenol and and 4′-chloroacetanilide. UV densitometry was performed in absorbance mode at 248 nm. The presented method was validated by specificity, range, linearity, accuracy, precision, detection limit, quantitative limit, and robustness. The TLC-densitometric method was also compared with a pharmacopeial UV-spectrophotometric method for the assay of acetaminophen, and the results confirmed statistically that the NP-TLC-densitometric method can be used as a substitute method. It could be said that the validated NP-TLC-densitometric method is suitable for the routine analysis of acetaminophen in quantity control laboratories. PMID:24063006

  9. Validation Thin Layer Chromatography for the Determination of Acetaminophen in Tablets and Comparison with a Pharmacopeial Method

    Alina Pyka

    2013-01-01

    Full Text Available Adsorption thin layer chromatography (NP-TLC with densitometry has been established for the identification and the quantification of acetaminophen in three leading commercial products of pharmaceutical tablets coded as brand: P1 (Product no. 1, P2 (Product no. 2, and P3 (Product no. 3. Applied chromatographic conditions have separated acetaminophen from its related substances, namely, 4-aminophenol and and 4′-chloroacetanilide. UV densitometry was performed in absorbance mode at 248 nm. The presented method was validated by specificity, range, linearity, accuracy, precision, detection limit, quantitative limit, and robustness. The TLC-densitometric method was also compared with a pharmacopeial UV-spectrophotometric method for the assay of acetaminophen, and the results confirmed statistically that the NP-TLC-densitometric method can be used as a substitute method. It could be said that the validated NP-TLC-densitometric method is suitable for the routine analysis of acetaminophen in quantity control laboratories.

  10. Effect of Momordica charantia (bitter melon on serum glucose level and various protein parameters in acetaminophen intoxicated rabbits

    Kanwal Zahra

    2012-02-01

    Full Text Available Aim: Liver function tests, including total plasma proteins, albumin, bilirubin and glucose were analyzed to find out the hepatocurative and hepatoprotective effects of Momordica charantia. Method: The study was divided into two categories. In first category, the livers of rabbits were intoxicated with acetaminophen, and then Momordica fruit extract was given to observe its hepatocurative effects. Results: The results indicated significant changes in concentrations of the parameters in acetaminophen-challenged rabbits. In the second category, treatment was started by giving Momordica fruit extract dose orally for 10 days and 15 days to two groups of rabbits, respectively. Then, livers of rabbits were damaged with acetaminophen and hepatoprotective effects of Momordica were observed. Conclusion: The results showed that the animals treated with Momordica fruit extract experienced less liver damage due to acetaminophen intoxication, indicating that Momordica has hepatoprotective properties. [J Intercult Ethnopharmacol 2012; 1(1.000: 7-12