Outcomes from massive paracetamol overdose: a retrospective observational study.

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Marks, Daniel J B; Dargan, Paul I; Archer, John R H; Davies, Charlotte L; Dines, Alison M; Wood, David M; Greene, Shaun L

2017-06-01

This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAP pl ) and treatment nomogram thresholds at those time points (APAP t ) provides a useful assessment tool. This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l -1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAP pl :APAP t ratio (based on a treatment line through 100 mg l -1 at 4 h), and time to acetylcysteine. Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAP pl :APAP t  ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort. © 2016 The British Pharmacological Society.

Body Position Modulates Gastric Emptying and Affects the Post-Prandial Rise in Plasma Amino Acid Concentrations Following Protein Ingestion in Humans

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Andrew M. Holwerda

2016-04-01

Full Text Available Dietary protein digestion and amino acid absorption kinetics determine the post-prandial muscle protein synthetic response. Body position may affect gastrointestinal function and modulate the post-prandial rise in plasma amino acid availability. We aimed to assess the impact of body position on gastric emptying rate and the post-prandial rise in plasma amino acid concentrations following ingestion of a single, meal-like amount of protein. In a randomized, cross-over design, eight healthy males (25 ± 2 years, 23.9 ± 0.8 kg·m−2 ingested 22 g protein and 1.5 g paracetamol (acetaminophen in an upright seated position (control and in a −20° head-down tilted position (inversion. Blood samples were collected during a 240-min post-prandial period and analyzed for paracetamol and plasma amino acid concentrations to assess gastric emptying rate and post-prandial amino acid availability, respectively. Peak plasma leucine concentrations were lower in the inversion compared with the control treatment (177 ± 15 vs. 236 ± 15 mmol·L−1, p < 0.05, which was accompanied by a lower plasma essential amino acid (EAA response over 240 min (31,956 ± 6441 vs. 50,351 ± 4015 AU; p < 0.05. Peak plasma paracetamol concentrations were lower in the inversion vs. control treatment (5.8 ± 1.1 vs. 10.0 ± 0.6 mg·L−1, p < 0.05. Gastric emptying rate and post-prandial plasma amino acid availability are significantly decreased after protein ingestion in a head-down tilted position. Therefore, upright body positioning should be considered when aiming to augment post-prandial muscle protein accretion in both health and disease.

Paracetamol degradation in aqueous solution by non-thermal plasma

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Baloul, Yasmine; Aubry, Olivier; Rabat, Hervé; Colas, Cyril; Maunit, Benoît; Hong, Dunpin

2017-08-01

This study deals with paracetamol degradation in water using a non-thermal plasma (NTP) created by a dielectric barrier discharge (DBD). The effects of the NTP operating conditions on the degradation were studied, showing that the treatment efficiency of the process was highly dependent on the electrical parameters and working gas composition in the reactor containing the aqueous solution. A conversion rate higher than 99% was reached with an energy yield of 12 g/kWh. High resolution mass spectrometry (HRMS) measurements showed that the main species produced in water during the process were nitrogen compounds, carboxylic acids and aromatic compounds. Contribution to the topical issue "The 15th International Symposium on High Pressure Low Temperature Plasma Chemistry (HAKONE XV)", edited by Nicolas Gherardi and Tomáš Hoder

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

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Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.

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Krekels, Elke H J; van Ham, Saskia; Allegaert, Karel; de Hoon, Jan; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

2015-09-01

Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol-glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants.

DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL

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Almakaeva L.G.

2016-06-01

Full Text Available The intravenous form of paracetamol compared with oral more reliably supports effective drug concentration in blood plasma that promotes a higher therapeutic effect. Recent studies have confirmed that the use of the intravenous form of paracetamol to deal with postoperative pain multimodal analgesia modes results in reducing the frequency and quantity of opioids administered , and, as a consequence, its associated side effects. The drug Paracetamol , infusion solution 10 mg / ml to 100 ml glass bottles is a drug - generic . His qualitative and quantitative composition is developed from the study of literature data about the drug - similar to " Perfalhan , 10 mg / ml solution for infusion in 100 mL " company Bristol - Myers Squibb, France and experimental work. The aim of our study is development and support of the national composition of the infusion of the drug on the basis of paracetamol, selection of excipients that provide stability of the active substances. Materials and methods. The object of the study was the substance of paracetamol manufactured by Zhejiang Kangle Pharmaceutical Co. , Ltd, China. During the work conducted qualitative and quantitative monitoring sample preparation for indicators of stability: pH content of the active ingredient , transparency, color, impurities , contamination by the methods described in the SFU [and nor- ral documentation to the drug . One potential factor of instability is the effect of paracetamol oxygen, due to the presence in the molecule of paracetamol and -NH possibility of oxidation. Results and Discussion. Paracetamol is derived atsetamina . Substance acetylation are p - aminophenol with acetic anhydride . Saturated aqueous solution has a pH of paracetamol - ment about 6 . Paracetamol is a crystalline white powder , sparingly soluble in water, soluble in 96% alcohol, very slightly soluble in metilenhloride . . Active substance enters in comparison drug in the concentration of 10 mg/ml. Stable

A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose

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Kalsi SS

2011-12-01

Full Text Available Sarbjeet S Kalsi1,2, Paul I Dargan2–4, W Stephen Waring5, David M Wood2–41Emergency Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3King’s Health Partners, London, UK; 4King’s College London, London, UK; 5York Teaching Hospital NHS Foundation Trust, York, UKAbstract: Paracetamol (acetaminophen poisoning is common throughout the world. The management of nonstaggered (acute paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although

Photodegradation of Paracetamol in Nitrate Solution

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Meng, Cui; Qu, Ruijuan; Liang, Jinyan; Yang, Xi

2010-11-01

The photodegradation of paracetamol in nitrate solution under simulated solar irradiation has been investigated. The degradation rates were compared by varying environmental parameters including concentrations of nitrate ion, humic substance and pH values. The quantifications of paracetamol were conducted by HPLC method. The results demonstrate that the photodegradation of paracetamol followed first-order kinetics. The photoproducts and intermediates of paracetamol in the presence of nitrate ions were identified by extensive GC-MS method. The photodegradation pathways involving. OH radicals as reactive species were proposed.

Photodegradation of Paracetamol in Nitrate Solution

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Cui, Meng; Ruijuan, Qu; Jinyan, Liang; Xi, Yang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China)

2010-11-24

The photodegradation of paracetamol in nitrate solution under simulated solar irradiation has been investigated. The degradation rates were compared by varying environmental parameters including concentrations of nitrate ion, humic substance and pH values. The quantifications of paracetamol were conducted by HPLC method. The results demonstrate that the photodegradation of paracetamol followed first-order kinetics. The photoproducts and intermediates of paracetamol in the presence of nitrate ions were identified by extensive GC-MS method. The photodegradation pathways involving. OH radicals as reactive species were proposed.

Photodegradation of Paracetamol in Nitrate Solution

International Nuclear Information System (INIS)

Meng Cui; Qu Ruijuan; Liang Jinyan; Yang Xi

2010-01-01

The photodegradation of paracetamol in nitrate solution under simulated solar irradiation has been investigated. The degradation rates were compared by varying environmental parameters including concentrations of nitrate ion, humic substance and pH values. The quantifications of paracetamol were conducted by HPLC method. The results demonstrate that the photodegradation of paracetamol followed first-order kinetics. The photoproducts and intermediates of paracetamol in the presence of nitrate ions were identified by extensive GC-MS method. The photodegradation pathways involving. OH radicals as reactive species were proposed.

Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

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Trettin, Arne; Böhmer, Anke; Suchy, Maria-Theresia; Probst, Irmelin; Staerk, Ulrich; Stichtenoth, Dirk O.; Frölich, Jürgen C.

2014-01-01

Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans. PMID:24799980

Paracetamol decreases steady-state exposure to lamotrigine by induction of glucuronidation in healthy subjects

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Gastrup, Sandra; Stage, Tore Bjerregaard; Fruekilde, Palle Bach Nielsen

2016-01-01

AIM: Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug-drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy...... volunteers to quantify the effect of 4-day treatment of paracetamol on the metabolism of steady-state lamotrigine. METHODS: Twelve healthy, male volunteers participated in an open-label, sequential interaction study. Lamotrigine was titrated to steady state (100 mg daily) over 36 days, and blood and urine...... sampling was performed in a non-randomised order with and without paracetamol (1 g four times daily). The primary endpoint was change in steady-state area under the plasma concentration-time curve of lamotrigine. Secondary endpoints were changes in total apparent oral clearance, renal clearance...

Clinical Pharmacology of Paracetamol in Neonates: A Review

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Gian Maria Pacifici, MD, PhD

2015-12-01

Paracetamol clearance is lower in neonates than in children and adults. After metabolic conversion, paracetamol is subsequently eliminated by the renal route. The main metabolic conversions are conjugation with glucuronic acid and with sulphate. In the urine of neonates sulphated paracetamol concentration is higher than the glucuronidated paracetamol level, suggesting that sulfation prevails over glucuronidation in neonates. A loading dose of 20 mg/kg followed by 10 mg/kg every 6 hours of intravenous paracetamol is suggested to achieve a compartment concentration of 11 mg/L in late preterm and term neonates. Aiming for the same target concentration, oral doses are similar with rectal administration of 25 to 30 mg/kg/d in preterm neonates of 30 weeks’ gestation, 45 mg/kg/d in preterm infants of 34 weeks’ gestation, and 60 mg/kg/d in term neonates are suggested. The above-mentioned paracetamol doses for these indications (pain, fever are well tolerated in neonates, but do not result in a significant increase in liver enzymes, and do not affect blood pressure and have limited effects on heart rate. In contrast, the higher doses suggested in extreme preterm neonates to induce closure of the patent ductus arteriosus have not yet been sufficiently evaluated regarding efficacy or safety. Moreover, focussed pharmacovigilance to explore the potential causal association between paracetamol exposure during perinatal life and infancy and subsequent atopy is warranted.

Degradation of paracetamol in aqueous solutions by TiO2 photocatalysis.

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Yang, Liming; Yu, Liya E; Ray, Madhumita B

2008-07-01

In this study, photo/photocatalytic oxidation of common analgesic and antipyretic drug, paracetamol (acetaminophen), was investigated to determine the optimal operating conditions for degradation in water. UVA (365 nm) radiation alone degraded negligible amount of paracetamol, whereas paracetamol concentration decreased substantially under an irradiation of UVC (254 nm) with marginal changes in total organic carbon (TOC). In the presence of TiO2, much faster photodegradation of paracetamol and effective mineralization occurred; more than 95% of 2.0mM paracetamol was degraded within 80 min. The degradation rate constant decreased with an increase in the initial concentration of paracetamol, while it increased with light intensity and oxygen concentration. The degradation rate also increased with TiO2 loading until a concentration of 0.8 g L(-1). The degradation rate slowly increased between pH 3.5 and 9.5, but significantly decreased with increasing pH between 9.5 and 11.0. Based on the experimental data, a kinetic equation describing paracetamol photocatalytic degradation with various process parameters is obtained.

Interaction of paracetamol and 125I-paracetamol with surface groups of activated carbon. Theoretical and experimental study

International Nuclear Information System (INIS)

Daniel Hernandez-Valdes; Ulises Jauregui-Haza; Carlos Enriquez-Victorero; Melvin Arias

2015-01-01

The selection of activated carbon (AC) filters for water decontamination is currently carried out empirically. The low concentrations of drugs in the environment make the radioisotope labeling a valuable tool for physical and chemical studies of the adsorption process. A theoretical study of paracetamol and 125 I-paracetamol adsorption onto AC was performed to evaluate the interactions between pollutants and surface groups (SG) of AC. Paracetamol was labeled with 125 I and adsorption isotherms were obtained using radioanalytical and spectrophotometric techniques. The radioanalytical method overestimates the paracetamol adsorption. The validity of the chosen approach for qualitative assessment of SG influence over the adsorption process was demonstrated. (author)

Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia.

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Kim, Dong-Wook; Tan, Eugene Y; Jin, Yu; Park, Sahee; Hayes, Michael; Demirhan, Eren; Schran, Horst; Wang, Yanfeng

2011-02-01

The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML). Patients (n = 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2-8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses. The area under the plasma concentration-time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co-administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone. The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

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Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: risk of liver toxicity.

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Pingili, Ravindra Babu; Pawar, A Krishnamanjari; Challa, Siva R

2015-01-01

Intestinal P-glycoprotein (P-gp) and drug-metabolizing enzymes (DMEs) play an important role in the first-pass-metabolism (FPM) and pharmacokinetics (PK) of majority of drugs. Paracetamol is primarily metabolized by conjugation reactions and a little amount (∼15%) undergoes cytochrome P450 (CYP2E1)-mediated oxidative metabolism produces a hepatotoxic metabolite, N-acetyl-p-benzoquinonimine (NAPQI). Quercetin and chrysin are naturally occurring flavonoids, reported as modulators of P-gp and DMEs. Therefore, the objective of this study was to evaluate the effects of quercetin and chrysin on the pharmacokinetics of paracetamol using rats and non-everted gut sacs in vitro. Paracetamol was given orally (100 mg/kg) to rats alone and in combination with quercetin (5, 10 and 20 mg/kg) and chrysin (50, 100 and 200 mg/kg) once daily for 21 consecutive days. Blood samples were collected on the 1st day in single dose pharmacokinetic study (SDS) and on the 21st day in multiple pharmacokinetic studies (MDS). The plasma concentrations of paracetamol were determined by HPLC and PK parameters were calculated by using Kinetica (Version 5.1). The maximum plasma concentration (Cmax) and area under the curve (AUC0-12) of paracetamol was significantly increased by quercetin and chrysin co-administration in SDS and MDS. In non-everted rat gut sac method, the absorption of paracetamol was increased by presence of P-gp inhibitors (verapamil, quinidine and ketoconazole), quercetin and chrysin (50 μg/mL). Our findings suggested that the quercetin and chrysin might be inhibited the P-gp and metabolism of paracetamol; thereby increased the systemic exposure of paracetamol. Further studies are needed to evaluate whether the quercetin or chrysin are involved in the formation of NAPQI by CYP2E1 or not on isolated rat hepatocytes or using cell lines.

Degradation of paracetamol by pure bacterial cultures and their microbial consortium.

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Zhang, Lili; Hu, Jun; Zhu, Runye; Zhou, Qingwei; Chen, Jianmeng

2013-04-01

Three bacterial strains utilizing paracetamol as the sole carbon, nitrogen, and energy source were isolated from a paracetamol-degrading aerobic aggregate, and assigned to species of the genera Stenotrophomonas and Pseudomonas. The Stenotrophomonas species have not included any known paracetamol degraders until now. In batch cultures, the organisms f1, f2, and fg-2 could perform complete degradation of paracetamol at concentrations of 400, 2,500, and 2,000 mg/L or below, respectively. A combination of three microbial strains resulted in significantly improved degradation and mineralization of paracetamol. The co-culture was able to use paracetamol up to concentrations of 4,000 mg/L, and mineralized 87.1 % of the added paracetamol at the initial of 2,000 mg/L. Two key metabolites of the biodegradation pathway of paracetamol, 4-aminophenol, and hydroquinone were detected. Paracetamol was degraded predominantly via 4-aminophenol to hydroquinone with subsequent ring fission, suggesting new pathways for paracetamol-degrading bacteria. The degradation of paracetamol could thus be performed by the single isolates, but is stimulated by a synergistic interaction of the three-member consortium, suggesting a possible complementary interaction among the various isolates. The exact roles of each of the strains in the consortium need to be further elucidated.

Degradation of paracetamol by Pseudomonas aeruginosa strain HJ1012.

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Hu, Jun; Zhang, Li L; Chen, Jian M; Liu, Yu

2013-01-01

Pseudomonas aeruginosa strain HJ1012 was isolated on paracetamol as a sole carbon and energy source. This organism could completely degrade paracetamol as high as 2200 mg/L. Following paracetamol consumption, a CO₂ yield rate up to 71.4% proved that the loss of paracetamol was mainly via mineralization. Haldane's equation adequately described the relationship between the specific growth rate and substrate concentration. The maximum specific growth rate and yield coefficient were 0.201 g-Paracetamol/g-VSS·h and 0.101 mg of biomass yield/mg of paracetamol consumed, respectively. A total of 8 metabolic intermediates was identified and classified into aromatic compounds, carboxylic acids, and inorganic species (nitrite and nitrate ions). P-aminophenol and hydroquinone are the two key metabolites of the initial steps in the paracetamol catabolic pathway. Paracetamol is degraded predominantly via p-aminophenol to hydroquinone with subsequent ring fission, suggesting partially new pathways for paracetamol-degrading bacteria.

Improving degradation of paracetamol by integrating gamma radiation and Fenton processes.

Science.gov (United States)

Cruz-González, Germán; Rivas-Ortiz, Iram B; González-Labrada, Katia; Rapado-Paneque, Manuel; Chávez-Ardanza, Armando; Nuevas-Paz, Lauro; Jáuregui-Haza, Ulises J

2016-10-14

Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters.

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.

Science.gov (United States)

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 slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

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Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

2015-03-01

1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

Predicting outcome of paracetamol poisoning by using 14C-aminopyrine breath test

International Nuclear Information System (INIS)

Saunders, J.B.; Wright, N.; Lewis, K.O.

1980-01-01

The 14 C-aminopyrine ( 14 C-amidopyrine) breath test, carried out within 24 to 36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14 C0 2 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage. (author)

Risk prediction of hepatotoxicity in paracetamol poisoning.

Science.gov (United States)

Wong, Anselm; Graudins, Andis

2017-09-01

Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment. Similarly, there would be benefit in early identification of those with a low likelihood of developing hepatotoxicity, as this group may be safely treated with an abbreviated acetylcysteine regimen. To review the current literature related to risk prediction tools that can be used to identify patients at increased risk of hepatotoxicity. A systematic literature review was conducted using the search terms: "paracetamol" OR "acetaminophen" AND "overdose" OR "toxicity" OR "risk prediction rules" OR "hepatotoxicity" OR "psi parameter" OR "multiplication product" OR "half-life" OR "prothrombin time" OR "AST/ALT (aspartate transaminase/alanine transaminase)" OR "dose" OR "biomarkers" OR "nomogram". The search was limited to human studies without language restrictions, of Medline (1946 to May 2016), PubMed and EMBASE. Original articles pertaining to the theme were identified from January 1974 to May 2016. Of the 13,975 articles identified, 60 were relevant to the review. Paracetamol treatment nomograms: Paracetamol treatment nomograms have been used for decades to help decide the need for acetylcysteine, but rarely used to determine the risk of hepatotoxicity with treatment. Reported paracetamol dose and concentration: A dose ingestion >12 g or serum paracetamol concentration above the treatment thresholds on the paracetamol nomogram are associated with a greater risk of hepatotoxicity. Paracetamol elimination half

Retrospective study of paracetamol poisoning in children aged zero to six years found no cases of liver injury

DEFF Research Database (Denmark)

Dan-Nielsen, S; Bisgaard, A S; Jans, S R

2018-01-01

AIM: This study focused on children aged zero to six years with suspected single-dose paracetamol poisoning, which has not been investigated in Denmark. We evaluated the incidence of liver injuries and the use of activated charcoal and N-acetylcysteine treatment. METHODS: Our retrospective study.......67 ± 1.05 years. Activated charcoal treatment was given in 87% of cases, but only 15% of the children received treatment within one hour of the suspected paracetamol poisoning. Although 80% of the children received N-acetylcysteine treatment, only one case (0.5%) had a toxic plasma paracetamol level...... children aged zero to six years with suspected paracetamol poisoning. Vomiting or abdominal pain was associated with elevated plasma paracetamol levels. No liver injuries were reported....

[Paracetamol (acetaminophen) use in neonatology: a (re)appreciation of an old drug].

Science.gov (United States)

Langhendries, J-P

2015-10-01

In neonates, paracetamol is mainly used for its analgesic action. This drug is actually preferred by neonatologists because of its broad therapeutic index. Recently, it has been demonstrated that paracetamol is also an anti-cyclooxygenase (COX) medication through its inhibitory action on the peroxidase arm of central and peripheral COX (Boutaud et al., 2002; Toussaint et al., 2010; Graham et al., 2013; Hinz et al., 2008; Hinz and Brune, 2011). As such, this drug interferes with the synthesis of prostaglandins. This inhibition of peroxidase is, however, limited to a low concentration of arachidonic acid (AA) (around 2μM, in vitro) when the plasmatic concentration of paracetamol is experimentally 10μM, actually within the same range as compared to the therapeutic concentrations in vivo. This may partly explain its low anti-inflammatory effect as compared to ibuprofen and indomethacin, which exert their inhibition on COX whatever the AA concentrations are. This new well-demonstrated action of paracetamol on peripheral COX-2 of intact cells could explain recent observations making this drug a potential alternative in treating patent ductus arteriosus. However, the higher dosages that have been claimed by some authors in this indication still remain to be validated. This inhibition that paracetamol shows on the physiological synthesis of prostaglandins E2 (PGE2) could also explain some long-term immune deviations because the physiological concentration of PGE2 is a well-known actor in the genesis of immune homeostasis in the submucosal area. Indeed, recent epidemiology studies have pointed out immune deviations in children repeatedly exposed to paracetamol earlier in life. Consequently, this is actually the new discovery of an old drug. From these new data on paracetamol, a more focused pharmacovigilance on the long-term effects of paracetamol repeatedly given in the early stage should be urgently initiated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Enhanced degradation of paracetamol by UV-C supported photo-Fenton process over Fenton oxidation.

Science.gov (United States)

Manu, B; Mahamood, S

2011-01-01

For the treatment of paracetamol in water, the UV-C Fenton oxidation process and classic Fenton oxidation have been found to be the most effective. Paracetamol reduction and chemical oxygen demand (COD) removal are measured as the objective functions to be maximized. The experimental conditions of the degradation of paracetamol are optimized by the Fenton process. Influent pH 3, initial H(2)O(2) dosage 60 mg/L, [H(2)O(2)]/[Fe(2+)] ratio 60 : 1 are the optimum conditions observed for 20 mg/L initial paracetamol concentration. At the optimum conditions, for 20 mg/L of initial paracetamol concentration, 82% paracetamol reduction and 68% COD removal by Fenton oxidation, and 91% paracetamol reduction and 82% COD removal by UV-C Fenton process are observed in a 120 min reaction time. By HPLC analysis, 100% removal of paracetamol is observed at the above optimum conditions for the Fenton process in 240 min and for the UV-C photo-Fenton process in 120 min. The methods are effective and they may be used in the paracetamol industry.

Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

Science.gov (United States)

Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

2013-01-01

Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

Interventions for paracetamol (acetaminophen) overdose.

Science.gov (United States)

Chiew, Angela L; Gluud, Christian; Brok, Jesper; Buckley, Nick A

2018-02-23

benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software. We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more

[A patient who refused treatment after self-poisoning with paracetamol

NARCIS (Netherlands)

Kramers, C.; Jansman, F.G.A.; Droogleever Fortuyn, H.A.

2006-01-01

Two patients, a 20-year-old man and a 33-year-old woman, were admitted with paracetamol poisoning. Both patients refused treatment initially but eventually complied. The man had a paracetamol concentration of 47.5 mg/l 2.5-5.0 h after ingestion, so antidote treatment was not considered necessary.

Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

Science.gov (United States)

Wong, Anselm; Sivilotti, Marco L A; Gunja, Naren; McNulty, Richard; Graudins, Andis

2018-03-01

Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.

Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine.

Science.gov (United States)

Coulson, James; Thompson, John Paul

2010-02-01

The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

Science.gov (United States)

Hayward, Kelly L; Powell, Elizabeth E; Irvine, Katharine M; Martin, Jennifer H

2016-02-01

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. © 2015 The British Pharmacological Society.

A simple assay of paracetamol based on dried blood

African Journals Online (AJOL)

User

Dried blood spots in Guthrie cards are a reliable means of blood sampling suitable for pharmacoki- netic analysis in .... pers were then packed in plastic bags and stored at. 4ºC in the ..... of paracetamol and its metabolites in urine, plasma and ...

Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

Science.gov (United States)

Acheampong, Paul; Thomas, Simon H L

2016-10-01

To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases. © 2016 The British Pharmacological Society.

Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development.

Science.gov (United States)

Holm, Jacob Bak; Chalmey, Clementine; Modick, Hendrik; Jensen, Lars Skovgaard; Dierkes, Georg; Weiss, Tobias; Jensen, Benjamin Anderschou Holbech; Nørregård, Mette Marie; Borkowski, Kamil; Styrishave, Bjarne; Martin Koch, Holger; Mazaud-Guittot, Severine; Jegou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

2015-11-01

Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairs male reproductive development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Interventions for paracetamol (acetaminophen) overdoses

DEFF Research Database (Denmark)

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....

A simple assay of paracetamol based on dried blood spot suitable ...

African Journals Online (AJOL)

Dried blood spots in Guthrie cards are a reliable means of blood sampling suitable for pharmacoki-netic analysis in children. The aim of this study was to develop a simple and reliable bioanalytical method to measure the concentration of paracetamol in dried blood spots. Paracetamol was ex-tracted from dry blood spots by ...

Combined paracetamol and amitriptyline adsorption to activated charcoal

DEFF Research Database (Denmark)

Hoegberg, Lotte Christine Groth; Groenlykke, Thor Buch; Abildtrup, Ulla

2010-01-01

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix......® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed...... dose (0.080 g) to all samples. Drug concentrations in the liquid phase were analyzed using high-performance liquid chromatography (HPLC)/UV-detection. Results. Q(m), amitriptyline, were 0.49 g/g Carbomix® and 0.70 g/g Norit Ready-To-Use, and Q(m), paracetamol, were 0.63 g/g Carbomix® and 0.72 g/g Norit...

A New Sensor Based on Graphite Screen Printed Electrode Modified With Cu-Nanocomplex for Determination of Paracetamol

Directory of Open Access Journals (Sweden)

Hadi Beitollai

2017-01-01

Full Text Available Paracetamol is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of paracetamol can cause hepatic toxicity and kidney damage. Hence, the determination of paracetamol receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the paracetamol based on screen-printed modified electrode (SPE with Cu nanocomplex (Cu in pH=7.0. The paracetamol is not stable in strong acidic and strong alkaline media, and is hydrolyzed and hydroxylated. However, it is stable in intermediate pHs due to the dimerization of paracetamol. The kinetics of the paracetamol oxidation was briefly studied and documented in the schemes. In addition, the characterization of Cu nanocomplex was probed by Fourier transform infrared spectroscopy (FT-IR, X-ray diffraction (XRD, scanning electron microscopy (SEM, and energy dispersive X-ray spectroscopy (EDX. Moreover, the voltammetry determined the paracetamol with the linear concentration ranging from 10.0 to 1000.0 μM and the lower detection limit of 1.0 μM. This method was also successfully used to detect the concentration of paracetamol in pharmaceutical formulations and urine samples.

Electrocatalytic Study of Paracetamol at a Single-Walled Carbon Nanotube/Nickel Nanocomposite Modified Glassy Carbon Electrode

Directory of Open Access Journals (Sweden)

Koh Sing Ngai

2015-01-01

Full Text Available A rapid, simple, and sensitive method for the electrochemical determination of paracetamol was developed. A single-walled carbon nanotube/nickel (SWCNT/Ni nanocomposite was prepared and immobilized on a glassy carbon electrode (GCE surface via mechanical attachment. This paper reports the voltammetry study on the effect of paracetamol concentration, scan rate, pH, and temperature at a SWCNT/Ni-modified electrode in the determination of paracetamol. The characterization of the SWCNT/Ni/GCE was performed by cyclic voltammetry. Variable pressure scanning electron microscopy (VPSEM and energy dispersive X-ray (EDX spectrometer were used to examine the surface morphology and elemental profile of the modified electrode, respectively. Cyclic voltammetry showed significant enhancement in peak current for the determination of paracetamol at the SWCNT/Ni-modified electrode. A linear calibration curve was obtained for the paracetamol concentration between 0.05 and 0.50 mM. The SWCNT/Ni/GCE displayed a sensitivity of 64 mA M−1 and a detection limit of 1.17 × 10−7 M in paracetamol detection. The proposed electrode can be applied for the determination of paracetamol in real pharmaceutical samples with satisfactory performance. Results indicate that electrodes modified with SWCNT and nickel nanoparticles exhibit better electrocatalytic activity towards paracetamol.

GUIDELINES FOR PARACETAMOL POISONING TREATMENT

Directory of Open Access Journals (Sweden)

Lucija Sarc

2014-04-01

Full Text Available Paracetamol overdose results in an accumulation of the reactive, hepatotoxic metabolite N-acetyl-p-benzoquinoneimin (NAPKQI which can cause serious liver injury. Recognition of paracetamol overdose, hepatotoxicity risk estimation and early treatment are crutial in paracetamol poisoniong management. In ingestion of potential hepatotoxic dose of paracetamol decontamination and early treatment with N-acetylcysteine (NAC are indicated. Both, 20-hours intravenous and 72-hurs oral regimes of NAC administration are successful. By antidote regime selection we should consider patient condition and time after paracetamol overdose. In severe hepatotoxicity, criteria for liver transplantation should be regularly evaluated and mechanisms for liver transplantation must be activated in time. 

Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.

Science.gov (United States)

Cook, Sarah F; Stockmann, Chris; Samiee-Zafarghandy, Samira; King, Amber D; Deutsch, Nina; Williams, Elaine F; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-11-01

This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CL formation ) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CL formation for all metabolites increased with weight; CL formation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CL formation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CL formation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CL formation increased paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

Effect of paracetamol on the plasma protein binding of quinine ...

African Journals Online (AJOL)

The co-administration of antimalarial and antipyretic drugs is a common practice in the treatment of malaria. Paracetamol, which is a majorly used antipyretic drug, has proved useful in the management of some common feverish effects such as pains and headache associated with most antimalarial drugs. This study was ...

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

Science.gov (United States)

Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2016-12-01

The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum. Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC). The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels. The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS). Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Diffusion coefficients of paracetamol in aqueous solutions

International Nuclear Information System (INIS)

Ribeiro, Ana C.F.; Barros, Marisa C.F.; Veríssimo, Luís M.P.; Santos, Cecilia I.A.V.; Cabral, Ana M.T.D.P.V.; Gaspar, Gualter D.; Esteso, Miguel A.

2012-01-01

Highlights: ► Mutual diffusion coefficients of paracetamol in aqueous dilute solutions. ► Influence of the thermodynamic factors on the variation of their mutual diffusion coefficients. ► Estimation of the mutual limiting diffusion coefficients of the molecular, D m 0 , and ionized forms, D ± 0 , of this drug. - Abstract: Binary mutual diffusion coefficients measured by the Taylor dispersion method, for aqueous solutions of paracetamol (PA) at concentrations from (0.001 to 0.050) mol·dm −3 at T = 298.15 K, are reported. From the Nernst–Hartley equation and our experimental results, the limiting diffusion coefficient of this drug and its thermodynamic factors are estimated, thereby contributing in this way to a better understanding of the structure of such systems and of their thermodynamic behaviour in aqueous solution at different concentrations.

Interventions for paracetamol (acetaminophen) overdose

DEFF Research Database (Denmark)

Chiew, Angela L; Gluud, Christian; Brok, Jesper

2018-01-01

BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various...... of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best...... was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol...

Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

Science.gov (United States)

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

2011-06-14

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children

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Falgun Indravadan Vyas

2014-01-01

Full Text Available Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05; however, the difference was not clinically significant (<1΀C. The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1 st h (P = 0.04. Highest fall of temperature was noted in the 1 st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated.

Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

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Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

2017-06-01

The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

Population prevalence of high dose paracetamol in dispensed paracetamol/opioid prescription combinations: an observational study

Science.gov (United States)

2012-01-01

Background Paracetamol (acetaminophen) is generally considered a safe medication, but is associated with hepatotoxicity at doses above doses of 4.0 g/day, and even below this daily dose in certain populations. Methods The Nova Scotia Prescription Monitoring Program (NSPMP) in the Canadian province of Nova Scotia is a legislated organization that collects dispensing information on all out-of-hospital prescription controlled drugs dispensed for all Nova Scotia residents. The NSPMP provided data to track all paracetamol/opioids redeemed by adults in Nova Scotia, from July 1, 2005 to June 30, 2010. Trends in the number of adults dispensed these prescriptions and the numbers of prescriptions and tablets dispensed over this period were determined. The numbers and proportions of adults who filled prescriptions exceeding 4.0 g/day and 3.25 g/day were determined for the one-year period July 1, 2009 to June 30, 2010. Data were stratified by sex and age (paracetamol/opioid prescription was lower in each successive one-year period. From July 2009 to June 2010, one in 12 adults (n = 59,197) filled prescriptions for over 13 million paracetamol/opioid tablets. Six percent (n = 3,786) filled prescriptions that exceeded 4.0 g/day and 18.6% (n = 11,008) exceeded 3.25 g/day of paracetamol at least once. These findings exclude non-prescription paracetamol and paracetamol–only prescribed medications. Conclusions A substantial number of individuals who redeem prescriptions for paracetamol/opioid combinations may be at risk of paracetamol-related hepatotoxicity. Healthcare professionals must be vigilant when prescribing and dispensing these medications in order to reduce the associated risks. PMID:22709372

Simultaneous determination of paracetamol, 4-Aminophenol, 4-Chloroacetanilid, Benzyl alcohol,Benzaldehyde and EDTA by HPLC methodin paracetamol injection ampoule

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Ali Merrikhi Khosroshahi

2016-06-01

Full Text Available Paracetamol that is known as acetaminophen have the most consume as an analgesic and antipyretic drug in the world. That is formulated in single compound or mixture at many forms such as tablets, syrups, suspensions and drops. The last form is intravenous injections. Paracetamol derived from 4-minophenol which is synthesized by acylated the P-acetaminophenol and acetic anhydride. 4-aminophenol is the main impurity at manufacturing of paracetamol which could produce by hydrolysis during storage or synthesis under normal conditions (temperature, pH, etc.. Also, 4-chloroacetanilid may be observed as an impurity in the raw material of paracetamol synthesis. Benzyl alcohol is a preservative that used in Paracetamol for injection. It will be very important if there are analytical techniques to measuring paracetamol and its degradation products accurately and easily. Undoubtedly the most important and widely used, separation technique is chromatography. There are several reports about separation and quantitative determination of paracetamol lonely or simultaneous determination of paracetamol and 4-aminophenol. In this paper investigated simultaneous determination of paracetamol, 4-aminophenol, 4-chloroacetanilid, benzyl alcohol, benzaldehyde, and EDTA in paracetamol for injection ampoules by high performance liquid chromatography. By changing the ratio of mixing methanol and acetonitrile as mobile phase at the wavelength of 215 nm and pH=3 separation of all compounds were completely done.

Quality control of the paracetamol drug by chemometrics and imaging spectroscopy in the near infrared region

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Baptistao, Mariana; Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

2011-09-01

In this work, it was used imaging spectroscopy and chemometric tools for the development and analysis of paracetamol and excipients in pharmaceutical formulations. It was also built concentration maps to study the distribution of the drug in the tablets surface. Multivariate models based on PLS regression were developed for paracetamol and excipients concentrations prediction. For the construction of the models it was used 31 samples in the tablet form containing the active principle in a concentration range of 30.0-90.0% (w/w) and errors below to 5% were obtained for validation samples. Finally, the study of the distribution in the drug was performed through the distribution maps of concentration of active principle and excipients. The analysis of maps showed the complementarity between the active principle and excipients in the tablets. The region with a high concentration of a constituent must have, necessarily, absence or low concentration of the other one. Thus, an alternative method for the paracetamol drug quality monitoring is presented.

Treatment with paracetamol in infants

DEFF Research Database (Denmark)

Arana, A; Morton, N S; Hansen, Tom Giedsing

2001-01-01

Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has become the most widely used analgesic and antipyretic in children. However, there is a wide discrepancy between the extent to which paracetamol is used and the limited available pharmacological data in small infants. The purpose...... of this article is to present a review of the current literature regarding the use of paracetamol in neonates and infants with a particular emphasis on pharmacological issues....

Acetanilide and paracetamol pharmacokinetics before and during phenytoin administration: genetic control of induction?

Science.gov (United States)

Cunningham, J L; Evans, D A

1981-01-01

1 Steady state plasma concentrations (SSPCs) of acetanilide (AA) and its metabolite, paracetamol (PL), were studied in 27 healthy volunteer subjects before and at the end of an 11-day exposure to phenytoin (DPH). Plasma concentrations of DPH were estimated. Plasma concentrations of DPH varied from 5.1 to 20.4 microgram ml-1 (mean +/- s.e.mean 12.2 +/- 0.9). 2 The SSPC of AA before exposure to DPH varied from 0.06 to 0.67 microgram ml-1 (mean +/- s.e.mean 0.24 +/- 0.02), and following exposure from 0.03 to 0.47 microgram ml-1 (mean +/- s.e.mean 0.15 +/- 0.02). 3 The SSPC of PL before exposure to DPH varied from 1.2 to 4.4 microgram ml-1 (mean +/- s.e.mean 2.7 +/- 0.13), and following exposure from 1.1 to 3.8 microgram ml-1 (mean +/- s.e.mean 2.2 +/- 0.13). 4 SSPCs of AA and of PL decreased significantly during DPH administration (P less than 0.01 for AA, P less than 0.001 for PL). 5 Correlations were observed between the SSPCs of the drugs measured, suggesting a common influence on their kinetics. 6 Similarity was observed between the changes in plasma levels of AA and PL following DPH ingestion. There was, however, wide inter-subject variability in this regard. In some subjects no change was observed even though they had DPH demonstrable in their plasma. Consequently it may be speculated that the effects of DPH may be under genetic control. PMID:7272175

Characteristics and outcomes of paracetamol poisoning cases at a general hospital in Northern Malaysia.

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Mohd Zain, Z; Fathelrahman, A I; Ab Rahman, A F

2006-02-01

Paracetamol is available as an over-the-counter medication in many countries including Malaysia. This drug has been implicated in many poisoning cases admitted to hospitals throughout the country. We conducted a three-year retrospective review of 165 medical records of patients admitted to the Penang General Hospital for acute paracetamol poisoning. Cases were identified according to the discharge diagnosis documented in their medical records. Acute paracetamol poisoning occurred in all major ethnic groups. About 70 percent of our patients were female. There was minimal involvement of children. Admissions were more likely to be due to deliberate ingestions rather than accidental poisoning. In most cases, serum concentrations data plotted on the Rumack-Matthew nomogram predicted the majority of cases to be unlikely to be hepatotoxic, which were consistent with their mild clinical courses. Patients who acutely ingested more than 140 mg/kg or predicted to be hepatotoxic, based on their serum concentrations, had a significantly longer hospital stay. Although acute paracetamol poisoning was common, the outcome was generally good.

Toxicological effects of paracetamol on the clam Ruditapes philippinarum: exposure vs recovery.

Science.gov (United States)

Nunes, Bruno; Nunes, Joana; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

2017-11-01

Exposure of wild organisms to anthropogenic substances never follows a definite time-course and pulsed events can often determine biological responses to such chemicals, confounding the interpretation of toxicological data. This is the case of specific chemicals such as pharmaceutical drugs, which are commonly released by sewage systems into sensitive areas, including estuaries. The presence and amount of these chemicals in the wild can be modulated by events such as dilution due to heavy rain, floods, or by varying patterns of domestic water use (daily vs. seasonal). The present study aimed to obtain additional data about the toxicity of paracetamol towards the marine clam species Ruditapes philippinarum, following realistic modes of exposure. Thus, the toxicity assessment was made after an acute exposure to different concentrations of paracetamol, followed by a recovery period. The adopted toxicological endpoints included energy-related parameters (glycogen content, GLY; protein content, PROT; electron transport system activity, ETS), activity of antioxidant and biotransformation enzymes (superoxide dismutase, SOD; glutathione peroxidase, GPx; Glutathione-S-transferases, GSTs), levels of reduced glutathione (GSH), neurotoxicity (cholinesterases activity, ChEs), and indicators of oxidative damage (lipid peroxidation, LPO). The here obtained results showed an increase in SOD and GPx activities after exposure. In organisms exposed to the highest concentration tested it was also possible to observe a significant increase in GSTs activity. However, these alterations in the antioxidant defence system were not able to prevent the occurrence of oxidative stress in exposed organisms. Furthermore, exposure to paracetamol induced neurotoxicity in clams, with a concentration-dependent ChEs inhibition along the exposure concentrations. Exposure to paracetamol also led to an increase of GLY content which resulted from metabolic activity depression along the increasing exposure

Release Properties of Paracetamol Granulationa Formulated with ...

African Journals Online (AJOL)

Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

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Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

2013-11-01

Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

Leukosit Ayam Pedaging setelah Diberikan Paracetamol

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. Suriansyah

2016-03-01

Full Text Available Penelitian ini bertujuan untuk mengetahui profil hematologi (total leukosit dan diferensial leukosit pada ayam pedaging yang diberikan paracetamol dalam pakan mulai umur 14 – 35 hari, Penelitian ini menggunakan Rancangan acak lengkap yaitu P0 (kelompok ayam pedaging yang hanya diberi pakan standar SB-11, P? (pakan standar SB-11 dan paracetamol 1 g/kg pakan, P? (pakan standar SB-11 dan paracetamol 2 g/kg pakan, P? (pakan standar SB-11 dan paracetamol 4 g/kg pakan masing-masing kelompok terdiri dari enam ekor ayam pedaging. Pengambilan darah pada vena brachialis dilakukan sebelum diberikan perlakuan dan pada hari ke 21 setelah diberikan perlakuan. Hasil penelitian menunjukkan bahwa pemberian paracetamol dosis 1-4 g/kg pakan tidak berpengaruh nyata terhadap total leukosit (P>0,05 akan tetapi hanya berpengaruh nyata terhadap monosit (P

Paracetamol for feverish children: parental motives and experiences

DEFF Research Database (Denmark)

Jensen, J.F.; Tonnesen, L.L.; Söderström, Margareta

2010-01-01

OBJECTIVE: The sale of paracetamol products for children is increasing, and more children are accidentally given overdoses, even though the use of paracetamol against fever is still under discussion. This study explores Danish parents' use of paracetamol for feverish children and their motives fo...... their GP for advice on fever treatment, paracetamol is sometimes given to children on vague indications. Clearer information for parents on when to give paracetamol as fever treatment may help regulate its use...

The Assessment of Liver Reserve Function by Spectrophotometry based on Determination of Phenacetin and Paracetamol.

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Ren, Rui; Ma, Yongmei; Ma, Wanshan; Lu, Sumei

2015-01-01

To establish a technical system for assessing liver reserve function based on spectrophotometry by detection of phenacetin and paracetamol in blood samples. Taking detected contents of phenacetin and paracetamol by high performance liquid chromatography (HPLC) as standard, which was proved to be able to detect drug concentrations with high resolution and accuracy, we established a technical system based on the spectrophotometric technique to assay phenacetin and paracetamol, including the color system, the maximum absorption wavelength, the influence factors of color system, and the optimal conditions for hydrolysis. Then we verified our established system compared with that under HPLC by recovery test. This study established a technical system to detect phenacetin and paracetamol in blood samples using spectrophotometry. Mainly, 3 mol/L hydrochloric acid (HCl) was added to samples for hydrolysis for 30 minutes, then, adding 0.02% 1,2-naphthoquinone-4-sulfonate (NQS), 1% cetyltrimethyl ammonium bromide (CTA) and 2% sodium hydroxide (or 3% sodium carbonate) (ratio of 1:6:1:2 or 3), and the absorbance was measured at 500 nm and 570 nm to calculate their concentrations. Using an established spectrophotometric system to detect phenacetin and paracetamol in blood samples could assess liver reserve function, which was proved comparable with HPLC in resolution and repeatability.

First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid

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Sharma CV

2017-11-01

Full Text Available Chhaya V Sharma,1 Jamie H Long,2 Seema Shah,1 Junia Rahman,1 David Perrett,3 Samir S Ayoub,4 Vivek Mehta1 1Pain & Anaesthesia Research Centre, St Bartholomew’s and The Royal London Hospitals, Barts Health NHS Trust, London, UK; 2Barts & The London School of Medicine, Queen Mary University of London, London, UK; 3BioAnalytical Science, Barts & The London School of Medicine, Queen Mary University of London, London, UK; 4School of Health, Sport and Bioscience, Medicines Research Group, University of East London, London, UK Abstract: Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404. AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic ­neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L–1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L–1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of

Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism.

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Goday Arno, Albert; Farré, Magí; Rodríguez-Morató, Jose; Ramon, Jose M; Pérez-Mañá, Clara; Papaseit, Esther; Civit, Ester; Langohr, Klaus; Lí Carbó, Marcel; Boix, David Benaiges; Nino, Olga Castañer; Le Roux, Juana Antonia Flores; Pera, Manuel; Grande, Luis; de la Torre, Rafael

2017-12-01

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).

Granule properties of paracetamol made with Bombax ceiba gum ...

African Journals Online (AJOL)

Bombax ceiba gum was extracted from the calyx of the Bombax flower using both hot and cold water extraction method. The gum was used as binder to prepare paracetamol granules in concentrations of 1, 1.5, 2, and 3 %. Acacia gum was used to prepare the standard at the same concentrations. The granule properties of ...

Degradation of paracetamol and other constituents in Perfalgan®

African Journals Online (AJOL)

was used to calculate the penetration of paracetamol in Perfalgan® into the lipid layer. Results: The ..... Molar ratio derived by 1H NMR. Molecular weight .... injection volume and sample concentration were used in all the experiments this is ...

A novel approach for estimating ingested dose associated with paracetamol overdose.

Science.gov (United States)

Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

2016-04-01

In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

Effect of Solution pH on the Adsorption of Paracetamol on Chemically Modified Activated Carbons

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Valentina Bernal

2017-06-01

Full Text Available Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo was obtained by treating the GAC with a boiling solution of 6 M nitric acid, so to generate a greater number of oxygenated surface groups. In addition, a reduced activated carbon (GACr was obtained by heating the GAC at 1173 K, to remove the oxygenated surface groups. Paracetamol adsorption was higher for GACr due to the lower presence of oxygenated surface functional groups. Moreover, adsorption was highest at neutral pH. The magnitude of the interactions between paracetamol molecules and activated carbons was studied by measuring the immersion enthalpies of activated carbons in solution of paracetamol at different concentrations and pH values and by calculating the interaction enthalpy. The highest value was obtained for GACr in a paracetamol solution of 1000 mg L−1 at pH 7, confirming that paracetamol adsorption is favoured on basic activated carbons at pH values near to neutrality. Finally, the Gibbs energy changes confirmed the latter result, allowing explaining the different magnitudes of the interactions between paracetamol and activated carbons, as a function of solution pH.

Effect of quercetin on paracetamole-induced liver disjunction in irradiated rats

International Nuclear Information System (INIS)

Hedayat, I.S.

2005-01-01

Nowadays, increasing attention has been given to the role of free radicals generated through oxidation stress. Persons subjected to radiation, such as radiotherapy, consuming analgesic drugs such as paracetamole which accumulates at relatively high concentration in liver, are in need to be investigated to explore the synergetic effects of these stresses. Many radical scavengers, interestingly naturally occurring antioxidants, have been found to be effective in inhibiting the oxidative damage Quercetin, the well known phenolic compound widely present in the plant kingdom, has been investigated for its possible protection effect against gamma irradiation and paracetamole-induced hepatic damage. Data revealed serious effects of oral administration of sublethal dose of paracetamole (500 mg/kg) and/or exposure to 6 Gy whole body gamma irradiation on liver. This damage is reflected by increased hepatic levels of MDA, carbonyl content and ALT activity, associated by decrease in hepatic SOD, catalase and GSH when compared with respective control values. The combination of quercetin with paracetamole and/or gamma irradiation have clearly reduced liver damage. It was noticed that the restoration of peroxides and carbonyls rates has occurred. Quercetin seems to act by activation of the turnover of SOD, catalase and GSH and permitting the capitation of reactive metabolites of paracetamole as well as its ability in quenching free radicals induced by exposure of rats to gamma irradiation, thus improving regeneration in the biological tissues

Pharmacokinetics of rectal paracetamol after repeated dosing in children

DEFF Research Database (Denmark)

Hahn, T W; Henneberg, S W; Holm-Knudsen, R J

2000-01-01

Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

Science.gov (United States)

Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2015-09-01

The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

Science.gov (United States)

Gedeborg, Rolf; Svennblad, Bodil; Holm, Lennart; Sjögren, Hans; Bardage, Carola; Personne, Mark; Sjöberg, Gunilla; Feltelius, Nils; Zethelius, Björn

2017-05-01

To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies.

Science.gov (United States)

El-Khuffash, Afif; Jain, Amish; Corcoran, David; Shah, Prakesh S; Hooper, Christopher W; Brown, Naoko; Poole, Stanley D; Shelton, Elaine L; Milne, Ginger L; Reese, Jeff; McNamara, Patrick J

2014-09-01

We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA). Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy. Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P 1 µmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.

Lack of respiratory depression in paracetamol-codeine combination overdoses.

Science.gov (United States)

Heppell, Simon P E; Isbister, Geoffrey K

2017-06-01

Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone. We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression. From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score depression, with only two given naloxone and none intubated for

Morphological effect of BiVO4 catalysts on degradation of aqueous paracetamol under visible light irradiation.

Science.gov (United States)

Hu, Changying; Xu, Jie; Zhu, Yaqi; Chen, Acong; Bian, Zhaoyong; Wang, Hui

2016-09-01

Morphological effect of bismuth vanadate (BiVO4) on visible light-driven catalytic degradation of aqueous paracetamol was carefully investigated using four monoclinic BiVO4 catalysts. The catalysts with different morphologies were controllably prepared by a hydrothermal method without any additions. The prepared catalysts were fully characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis diffuse reflectance spectroscopy (DRS). Under the visible light irradiation, these catalysts with different morphology were investigated to degrade aqueous paracetamol contaminant. The degradation effects were evaluated based on the catalyst morphology, solution pH, initial paracetamol concentration, and catalyst dosage. Cube-like BiVO4 powders exhibited excellent photocatalytic performance. The optimal photocatalytic performance of the cube-like BiVO4 in degrading paracetamol was achieved.

One-pot synthesis of a graphene oxide coated with an imprinted sol–gel for use in electrochemical sensing of paracetamole

International Nuclear Information System (INIS)

Luo, Jing; Cong, Jiaojiao; Fang, Ruixue; Fei, Xiaoma; Liu, Xiaoya

2014-01-01

A route is described for the preparation of a composite consisting of graphene oxide and a molecularly imprinted sol–gel polymer (GO/MIPs) through one-pot room temperature polymerization in aqueous solution. The material was obtained by mixing graphene oxide with the monomers (phenyltriethoxysilane and tetramethoxysilane) and the template paracetamole, followed by sol–gel copolymerization and extraction. The monomer and template concentrations and the incubation time were optimized. The composite was characterized by FTIR, TGA, XRD, Raman spectroscopy and SEM. It was then deposited as a thin film acting as a molecular recognition element on a glassy carbon electrode to obtain an electrochemical sensor for paracetamole. The electrode displayed an excellent recognition capacity toward paracetamole compared to its analogs. The peak current is linearly proportional to the concentration of paracetamole in the 0.1 μM to 80 μM range, and the detection limit is 20 nM (at an SNR of 3). Hence, this electrode possesses a wider response range and lower detection limit compared to most previously reported electrochemical sensors for paracetamole. It also exhibits excellent stability and has been successfully used to determine paracetamole in tablets and spiked human urine samples. (author)

Intercalation of paracetamol into the hydrotalcite-like host

International Nuclear Information System (INIS)

Kovanda, František; Maryšková, Zuzana; Kovář, Petr

2011-01-01

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg–Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals. - Graphical abstract: Molecular simulations showed disordered arrangement of paracetamol molecules in the interlayer; most of the interlayer water molecules are located near the hydroxide sheets.▪ Highlights: ► Paracetamol was intercalated in Mg–Al hydrotalcite-like host by rehydration/reconstruction procedure. ► Paracetamol phenolic groups interact with positively charged sites in hydroxide sheets. ► Molecular simulations showed disordered arrangement of guest molecules in the interlayer. ► Slower release of paracetamol intercalated in the hydrotalcite-like host was observed.

Paracetamol for feverish children: parental motives and experiences

DEFF Research Database (Denmark)

Jensen, J.F.; Tonnesen, L.L.; Söderström, Margareta

2010-01-01

OBJECTIVE: The sale of paracetamol products for children is increasing, and more children are accidentally given overdoses, even though the use of paracetamol against fever is still under discussion. This study explores Danish parents' use of paracetamol for feverish children and their motives...

Paracetamol in the environment and its degradation by microorganisms.

Science.gov (United States)

Wu, Shijin; Zhang, Lili; Chen, Jianmeng

2012-11-01

Paracetamol (4'-hydroxyacetanilide, N-acetyl-p-aminophenol, acetaminophen, and paracetamol) is a widely used over-the-counter analgesic and antipyretic drug. Paracetamol and structural analogs are ubiquitous in the natural environment and easily accumulate in aquatic environment, which have been detected in surface waters, wastewater, and drinking water throughout the world. Paracetamol wastewater is mainly treated by chemical oxidation processes. Although these chemical methods may be available for treating these pollutants, the harsh reaction conditions, the generation of secondary pollutants, and the high operational cost associated with these methods have often made them not a desirable choice. Biodegradation of paracetamol is being considered as an environmentally friendly and low-cost option. The goal of this review is to provide an outline of the current knowledge of biodegradation of paracetamol in the occurrence, degrading bacteria, and proposed metabolic/biodegrading pathways, enzymes and possible intermediates. The comprehensive understanding of the metabolic pathways and enzyme systems involved in the utilization of paracetamol means will be helpful for optimizing and allowing rational design of biodegradation systems for paracetamol-contaminated wastewater.

The effect of paracetamol on 5 fluorouracil and bovine serum albumin interaction: A biophysical study

Science.gov (United States)

Dahiya, Vandana; Pal, Samanwita

2018-05-01

Serum Albumin is a major carrier protein and its binding with drugs is important to examine the change in pharmacokinetic properties due to interaction amongst drugs. In the present study we have attempted to understand the relevant drug-drug interaction (DDI) between two common drugs viz, paracetamol, an anti-inflammatory and fluorouracil, an anti-cancer drug. In-vitro spectroscopic methods viz., fluorescence quenching and UV-vis absorption have been employed for the drug-bovine serum albumin (BSA) complexes studies. The binding parameters and quenching constants have been determined for BSA-Paracetamol and BSA-5Fluorouracil complex according to literature models. It is also predicted from the quenching studies that BSA-5Fluorouracil is a stronger complex than BSA-Paracetamol. On the other hand paracetamol can alter binding affinity of 5Fluorouracil towards BSA. Hence it becomes clear that although the drugs could be administered simultaneously but they influence each other's binding with protein in a concentration dependent fashion. Further these results also indicate that availability of free 5Fluorouracil in blood may increase in presence of paracetamol.

Availability of Paracetamol Sold Over-the-Counter in Europe

DEFF Research Database (Denmark)

Morthorst, Britt Reuter; Erlangsen, Annette; Nordentoft, Merete

2018-01-01

Due to the risk of hepatotoxicity when excessive amounts of paracetamol are consumed, Poisons Information Centers (PICs) frequently receive paracetamol-related enquiries. This study examined how widely pack size restrictions of paracetamol sold over-the-counter have been implemented in Europe...... and also availability of paracetamol through non-pharmacy outlets and their possible associations with frequency of poisoning enquiries. A cross-sectional European multicentre questionnaire study was performed using a questionnaire to identify the extent and nature of paracetamol pack size restrictions......, non-pharmacy outlet sales and the frequency of paracetamol-related enquiries to PICs. In total, 21 European countries participated. All PICs provided telephone hotline services. In 14 (67%) countries, pack size restrictions had been implemented in pharmacies (range: 8-30 grams). No significant...

Acute liver failure in a term neonate after repeated paracetamol administration

Directory of Open Access Journals (Sweden)

Fabio Bucaretchi

2014-03-01

Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

Paracetamol - toxicity and microbial utilization. Pseudomonas moorei KB4 as a case study for exploring degradation pathway.

Science.gov (United States)

Żur, Joanna; Wojcieszyńska, Danuta; Hupert-Kocurek, Katarzyna; Marchlewicz, Ariel; Guzik, Urszula

2018-09-01

Paracetamol, a widely used analgesic and antipyretic drug, is currently one of the most emerging pollutants worldwide. Besides its wide prevalence in the literature only several bacterial strains able to degrade this compound have been described. In this study, we isolated six new bacterial strains able to remove paracetamol. The isolated strains were identified as the members of Pseudomonas, Bacillus, Acinetobacter and Sphingomonas genera and characterized phenotypically and biochemically using standard methods. From the isolated strains, Pseudomonas moorei KB4 was able to utilize 50 mg L -1 of paracetamol. As the main degradation products, p-aminophenol and hydroquinone were identified. Based on the measurements of specific activity of acyl amidohydrolase, deaminase and hydroquinone 1,2-dioxygenase and the results of liquid chromatography analyses, we proposed a mechanism of paracetamol degradation by KB4 strain under co-metabolic conditions with glucose. Additionally, toxicity bioassays and the influence of various environmental factors, including pH, temperature, heavy metals at no-observed-effective-concentrations, and the presence of aromatic compounds on the efficiency and mechanism of paracetamol degradation by KB4 strain were determined. This comprehensive study about paracetamol biodegradation will be helpful in designing a treatment systems of wastewaters contaminated with paracetamol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Paracetamol and salicylic acid removal from contaminated water by microalgae.

Science.gov (United States)

Escapa, C; Coimbra, R N; Paniagua, S; García, A I; Otero, M

2017-12-01

The biomass growth, pharmaceutical removal and light conversion efficiency of Chlorella sorokiniana under the presence of paracetamol (PC) and salicylic acid (SaC) were assessed and compared at two different concentrations of these pharmaceuticals (I: 25 mg l -1 , II: 250 mg l -1 ). Microalgae were resistant to these concentrations and, moreover, their growth was significantly stimulated (p ≤ 0.05) under these drugs (biomass concentration increased above 33% PCI, 35% SaCI, 13% PCII and 45% SaCII, as compared with the respective positive controls). At the steady state of the semicontinuous culture, C. sorokiniana showed removal efficiencies above 41% and 69% for PCI and PCII, respectively; and above 93% and 98% for SaCI and SaCII, respectively. Under an irradiance of 370 μE m -2  s -1 , higher quantum yields were reached by microalgae under the presence of drugs, either at dose I or II, than by the respective positive controls. These results point to C. sorokiniana as a robust strain for the bioremediation of paracetamol and salicylic acid concentrated wastewaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipid profile and atherogenic predictor indices of albino rabbits administered coconut water as antidote to paracetamol overdose

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Chidi Uzoma Igwe

2016-11-01

Full Text Available Objective: To investigate the effects of coconut water intake on lipid profile and atherogenic predictor indices of albino rabbits overdosed with paracetamol using standard methods. Methods: Thirty-five albino rabbits weighing between 800–1200 g and aged between 2 and 3 months, were divided into 7 groups (I–VII of 5 animals each. Groups I, II and III were orally administered distilled water (20 mL/kg body weight, coconut water (20 mL/kg body weight and paracetamol (1000 mg/kg body weight respectively, for 7 days. Groups IV and V were administered coconut water (20 mL/kg body weight and silymarin (35 mg/kg body weight, respectively, for 6 days, then paracetamol (1000 mg/kg body weight on the 7th day. Groups VI and VII were administered distilled water for 6 days, paracetamol on the 7th day, then coconut water and silymarin, respectively, after 3 h. Results: The results showed that paracetamol overdose significantly reduced (P < 0.05 the mean body weight of the animals, increased the concentrations of serum total cholesterol, triacylglycerol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol and the atherogenic predictor indices but reduced the serum high density lipoprotein cholesterol concentration of the animals relative to the control. The observed changes in the lipid profile and atherogenic predictor indices were countered more by post- than pre-treatment with coconut water and silymarin. Conclusions: The results indicated that coconut water acted as an effective antidote to paracetamol overdose-induced lipid abnormality in animals.

Estimation of paracetamol in urine to assess the diurnal variation

Directory of Open Access Journals (Sweden)

Mithun Chandro Bhowmik

2018-05-01

Full Text Available The aim of the present study was to evaluate the diurnal variation of the pharmacokinetics of paracetamol by estimating the urinary free paracetamol level after single oral administration of paracetamol (500 mg tablet to 24 healthy male volunteers (students of a Medical College. The volunteers were given paracetamol tablet at 0800, 1400 and 2000 hours in three different days (two weeks apart and the urine samples of the volunteers were collected at just before and four hours after paracetamol administration. The samples were analyzed for free paracetamol using HPLC. The mean age was 21.1 ± 1.3 years and the body weight was 63.9 ± 10.9 kg. Three peaks were detected in the HPLC and one of them was identified for free paracetamol (RT= 4.7 min. The urine volume was nearly similar in all three times. After administration at 0800 hour, total free paracetamol excretion was significantly more than at 1400 and 2000 hours (p<0.001. The present study indicates that the dose reduction of paracetamol is required at morning than the afternoon or evening dose. 

Effects of an Agaricus blazei Aqueous Extract Pretreatment on Paracetamol-Induced Brain and Liver Injury in Rats

Directory of Open Access Journals (Sweden)

Andréia A. Soares

2013-01-01

Full Text Available The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma but also in terms of functional and metabolic parameters (e.g., gluconeogenesis. Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products.

Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

Science.gov (United States)

Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

2014-03-01

Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

Efficacy and pharmacokinetics of intravenous paracetamol in the critically ill patient

NARCIS (Netherlands)

Samson, A.D.; Hunfeld, N.G.; Touw, D.J.; Melief, P.H.

2009-01-01

Introduction: Paracetamol (PCM) is a drug with analgesic and antipyretic properties. Despite its frequent use, little is known about its efficacy and pharmacokinetics (PK) when intravenously administered in the critically ill patient. A previous study suggests that therapeutic concentrations are not

PANSAID - PAracetamol and NSAID in combination

DEFF Research Database (Denmark)

Thybo, Kasper Højgaard; Hägi-Pedersen, Daniel; Wetterslev, Jørn

2017-01-01

compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA. METHODS: PANSAID is a placebo-controlled, parallel four-group, multicentre trial with centralised computer......-generated allocation sequence and allocation concealment and with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients and statisticians. Patients are randomised to four groups: (A) paracetamol 1 g × 4 and ibuprofen 400 mg × 4, (B) paracetamol 1 g × 4 and placebo, (C......) placebo and ibuprofen 400 mg × 4 and (D) paracetamol 0.5 g × 4 and ibuprofen 200 mg. The two co-primary outcomes are 24-h consumption of morphine and number of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest...

Simultaneous determination of paracetamol, 4-Aminophenol, 4-Chloroacetanilid, Benzyl alcohol,Benzaldehyde and EDTA by HPLC methodin paracetamol injection ampoule

OpenAIRE

Ali Merrikhi Khosroshahi; Fereydoon Aflaki; Nader Saemiyan; Assem Abdollahpour; Ramin Asgharian

2016-01-01

Paracetamol that is known as acetaminophen have the most consume as an analgesic and antipyretic drug in the world. That is formulated in single compound or mixture at many forms such as tablets, syrups, suspensions and drops. The last form is intravenous injections. Paracetamol derived from 4-minophenol which is synthesized by acylated the P-acetaminophenol and acetic anhydride. 4-aminophenol is the main impurity at manufacturing of paracetamol which could produce by hydrolysis during sto...

Hyperamylasaemia and acute pancreatitis in paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2004-01-01

BACKGROUND: Hyperamylasaemia and even acute pancreatitis have been reported in patients with paracetamol poisoning. AIMS: To describe the incidence, clinical characteristics, and prognostic implications of hyperamylasaemia in paracetamol poisoning. PATIENTS: Six hundred and two patients transferred...... to a specialized unit with severe paracetamol poisoning and 212 unselected patients admitted from the local region. METHODS: Retrospective study based on hospital charts. The optimum threshold of serum amylase to discriminate non-survivors was identified. RESULTS: An elevated serum amylase (>100 U/L) occurred...... in 28 of the unselected patients (13%), in 218 of the transferred patients (36%), and in 118 of 148 patients (80%) with fulminant hepatic failure. Only 33 cases of paracetamol-associated acute pancreatitis were diagnosed. A threshold serum amylase of 150 U/L to discriminate non-survivors had sensitivity...

PANSAID-PAracetamol and NSAID in combination

DEFF Research Database (Denmark)

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel

2017-01-01

BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary...... publication to prevent outcome reporting bias and data-driven analysis results. METHODS/DESIGN: The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen...... of paracetamol and ibuprofen used in a perioperative setting. TRIAL REGISTRATION: ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015....

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

DEFF Research Database (Denmark)

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....

A graphene-based electrochemical sensor for sensitive detection of paracetamol

Energy Technology Data Exchange (ETDEWEB)

Kang, Xinhuang; Wang, Jun; Wu, Hong; Liu, Jun; Aksay, Ilhan A.; Lin, Yuehe

2010-05-15

An electrochemical sensor based on the electrocatalytic activity of functionalized graphene for sensitive detection of paracetamol is presented. The electrochemical behaviors of paracetamol on graphene-modified glassy carbon electrodes (GCEs) were investigated by cyclic voltammetry and square-wave voltammetry. The results showed that the graphene-modified electrode exhibited excellent electrocatalytic activity to paracetamol. A quasi-reversible redox process of paracetamol at the modified electrode was obtained, and the over-potential of paracetamol decreased significantly compared with that at the bare GCE. Such electrocatalytic behavior of graphene is attributed to its unique physical and chemical properties, e.g., subtle electronic characteristics, attractive π–π interaction, and strong adsorptive capability. The sensor shows great promise for simple, sensitive, and quantitative detection of paracetamol.

Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen poisoning.

Directory of Open Access Journals (Sweden)

Oliver W Morgan

2007-04-01

Full Text Available Paracetamol (acetaminophen poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide.We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations, aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003. Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol

Overdosed prescription of paracetamol (acetaminophen) in a teaching hospital.

Science.gov (United States)

Charpiat, B; Henry, A; Leboucher, G; Tod, M; Allenet, B

2012-07-01

Paracetamol is the most commonly used analgesic and antipyretic. Reviews of hospital use of paracetamol are scarce. Little is known about the appropriateness of the dose of paracetamol prescribed for hospitalized adults. The aim of this study was to report on the nature and the frequency of the overdosed prescription of paracetamol observed in adult patients over a 4.5-year period in a teaching hospital. Prescription analysis by pharmacists was performed once a week in six medical and three surgical departments and daily in a post-emergency unit. In cases of prescription error, the pharmacist notified the physician through an electronic alert when a computerized prescription order entry system was available or otherwise by face-to-face discussion. For each drug-related problem detected, the pharmacists recorded relevant details in a database. From October 2006 to April 2011, 44,404 prescriptions were reviewed and 480 alerts related to the overdosed prescription of paracetamol were made (1% of analyzed prescriptions). The extent of errors of dosage was within the intervals [90-120 mg/kg/d] and greater than 120 mg/kg/d for 87 and 11 patients respectively, who were prescribed a single non-combination paracetamol containing product. Sixty alerts concerned co-prescription of at least two paracetamol containing products with similar frequency for computerized (1.4/1000) or handwritten (1.2/1000) prescriptions. Prescriptions of paracetamol for hospitalized adults frequently exceed the recommended dosage. These results highlight the need for increased awareness of unintentional paracetamol overdose and support the initiation of an educational program aimed at physicians and nurses. Copyright © 2012. Published by Elsevier Masson SAS.

Intercalation of paracetamol into the hydrotalcite-like host

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Kovanda, František; Maryšková, Zuzana; Kovář, Petr

2011-12-01

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg-Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals.

Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations.

Science.gov (United States)

Karaś-Ruszczyk, Katarzyna; Kuczyńska, Julita; Sienkiewicz-Jarosz, Halina; Kurkowska-Jastrzębska, Iwona; Bienkowski, Przemyslaw; Restel, Magdalena; Samochowiec, Jerzy; Mierzejewski, Pawel

2017-06-01

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy. Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography-tandem mass spectrometry with positive ionization. Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed). The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.

Evaluation of standard haemodynamic tests of autonomic function and HbA1c as predictors of delayed gastric emptying in patients with type 1 diabetes mellitus.

LENUS (Irish Health Repository)

Lydon, A

2012-02-03

We examined the relation between chronic glycaemic control (using glycosylated haemoglobin), haemodynamic autonomic function and rate of gastric emptying in 16 patients with type 1 diabetes mellitus. Gastric emptying was measured using a paracetamol absorption technique. Parameters of gastric emptying include area under the plasma paracetamol concentration time curve. Patients were classified as diabetic autonomic neuropathy positive or negative using five standardized haemodynamic reflex tests. Area under the plasma paracetamol concentration time curve in the neuropathy positive (10.36 (4.5) mmol.-1. min) and negative (9.84 (3.0) mmol.-1. min) groups were similar (.P.=0.42) using unpaired Student\\'s.t. -tests. Glycosylated haemoglobin concentration and area under the plasma paracetamol concentration time curve (.n.=16) demonstrated a Pearson\\'s correlation co-efficient of 0.24. Neither tests of haemodynamic autonomic function, nor concentration of glycosylated haemoglobin, are predictive of diabetic gastroparesis.

Missed paracetamol (acetaminophen) overdose due to confusion regarding drug names.

Science.gov (United States)

Hewett, David G; Shields, Jennifer; Waring, W Stephen

2013-07-01

Immediate management of drug overdose relies upon the patient account of what was ingested and how much. Paracetamol (acetaminophen) is involved in around 40% of intentional overdose episodes, and remains the leading cause of acute liver failure in many countries including the United Kingdom. In recent years, consumers have had increasing access to medications supplied by international retailers via the internet, which may have different proprietary or generic names than in the country of purchase. We describe a patient that presented to hospital after intentional overdose involving 'acetaminophen' purchased via the internet. The patient had difficulty recalling the drug name, which was inadvertently attributed to 'Advil', a proprietary non-steroidal anti-inflammatory drug. The error was later recognised when the drug packaging became available, but the diagnosis of paracetamol overdose and initiation of acetylcysteine antidote were delayed. This case illustrates the benefit of routinely measuring paracetamol concentrations in all patients with suspected poisoning, although this is not universally accepted in practice. Moreover, it highlights the importance of the internet as a source of medications for intentional overdose, and emphasises the need for harmonisation of international drug names to improve patient safety.

Solubility and degradation of paracetamol in subcritical water

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Emire Zuhal

2017-01-01

Full Text Available In this study, solubility and degradation of paracetamol were examined using subcritical water. Effect of temperature and static time was investigated during solubility process in subcritical water at constant pressure (50 bar. Experimental results show that temperature and static time have crucial effect on the degradation and solubility rates. Maximum mole fraction for solubility of paracetamol was obtained at 403 K as (14.68 ± 0.74×103. Approximation model for solubility of paracetamol was proposed. O2 and H2O2 were used in degradation process of paracetamol. Maximum degradation rate was found as 68.66 ± 1.05 and 100 ± 0.00 % using O2 and H2O2, respectively.

Powder compression properties of paracetamol, paracetamol hydrochloride, paracetamol cocrystals and coformers.

Science.gov (United States)

Persson, Ann-Sofie; Ahmed, Hamzah; Velaga, Sitaram; Alderborn, Göran

2018-03-31

The objective was to study the relationship between crystal structure, particle deformation properties and tablet-forming ability for the monoclinic form of paracetamol (PRA), two cocrystals and a salt crystal of PRA in addition to two coformers (oxalic acid and 4,4'-bipyridine). Thus, the structure - property - performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery. plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as cThe rystals containing slip planes. In addition, crystals containing slip-planes displayed both high and low plasticity. The mechanical properties could neither be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity stiffness. Furthermore, the elastic deformation could not explain the tablet forming ability. It was concluded that no relationship between structure - property - performance for paracetamol and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship an improved knowledge of crystallographic structure and inter-particle bonding during compaction is needed. Copyright © 2018. Published by Elsevier Inc.

Potential protective effect of honey against paracetamol-induced hepatotoxicity.

Science.gov (United States)

Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

2012-11-01

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

Plasma Glutamine Concentrations in Liver Failure.

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Gunnel Helling

Full Text Available Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.Four different groups of patients were studies; chronic liver failure (n = 40, acute on chronic liver failure (n = 20, acute fulminant liver failure (n = 20, and post-hepatectomy liver failure (n = 20. Child-Pugh and Model for End-stage Liver Disease (MELD scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100, severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

The effect of food and ice cream on the adsorption capacity of paracetamol to high surface activated charcoal

DEFF Research Database (Denmark)

Høgberg, Lotte Christine Groth; Angelo, Helle Riis; Christophersen, Anne Bolette

2003-01-01

, the reductions compared to control (Hoegberg et al. 2002) varied between 11% and 26%. Even though a reduction in drug adsorption to activated charcoal was observed when food mixture or ice cream was added, the remaining adsorption capacity of both types of activated charcoal theoretically was still able......The effect of added food mixture (as if food was present in the stomach of an intoxicated patient) or 4 different types of ice cream (added as a flavouring and lubricating agent) on the adsorption of paracetamol (acetaminophen) to 2 formulations of activated charcoal was determined in vitro......, and paracetamol were mixed with either food mixture or ice cream followed by one hr incubation. The maximum adsorption capacity of paracetamol to activated charcoal was calculated using Langmuirs adsorption isotherm. Paracetamol concentration was analyzed using high pressure liquid chromatography. In the presence...

Paracetamol-induced spindle disturbances in V79 cells with and without expression of human CYP1A2

DEFF Research Database (Denmark)

Jensen, K G; Poulsen, H E; Doehmer, J

1996-01-01

Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2) was transfected with human CYP1A2. This enzyme catalyses the oxidative formation of the reactive paracetamol metabolite, NAPQI, believed...... to initiate hepatoxicity by covalent binding to proteins after overdose. In the native V79 cell line paracetamol increased c-mitosis frequency in a concentration dependent manner from 8.7 + or - 3.5% (control) to 66 + or - 18% at 20 mM. A significant increase to 13.3 + or - 3.5% was first seen at 2.5 m......M in the native cell line (Pparacetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4 + or - 5.0% and 19.0 + or - 3...

Plasma fibronectin concentrations in morbidly obese patients

DEFF Research Database (Denmark)

Dejgaard, A; Andersen, T; Christoffersen, Pernille Yde

1984-01-01

Plasma fibronectin concentrations and liver morphology were investigated in 45 morbidly obese subjects (median overweight 88%) and in 42 normal weight controls, matched for sex and age. A significantly (P less than 0.01) raised plasma fibronectin concentration (median 464 mg/l, range 276-862 mg...... in their liver biopsies (r = 0.33, P less than 0.05). Significantly (P less than 0.05) elevated plasma fibronectin concentrations even in obese subjects without hepatic fatty change indicate that liver fat accumulation is no prerequisite of the obesity-related elevation of plasma fibronectin. Raised plasma...

Anaphylaxis following intravenous paracetamol: the problem is the solution.

Science.gov (United States)

Jain, S S; Green, S; Rose, M

2015-11-01

Paracetamol is a ubiquitous analgesic and antipyretic that is widely administered, including by anaesthetists. Immediate hypersensitivity reactions to intravenous paracetamol are particularly rare. We report two cases involving four separate episodes of anaphylaxis to intravenous paracetamol in different perioperative settings without a past history of intolerance to the oral form. The allergological investigations are described, during which it became evident that both patients were allergic to an excipient (mannitol) present in the formulation and that neither was allergic to the principal agent (paracetamol). The importance of referral and investigation of perioperative drug reactions is underscored by these two cases.

Intravenous paracetamol overdose in a paediatric patient

NARCIS (Netherlands)

Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

2013-01-01

BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

Intake of paracetamol and risk of asthma in adults

DEFF Research Database (Denmark)

Thomsen, Simon Francis; Kyvik, Kirsten Ohm; Skadhauge, Lars

2008-01-01

Intake of paracetamol has been associated with development of asthma. The aim of this study was to address a possible association between intake of paracetamol and risk of adult-onset asthma. Using a multidisciplinary postal questionnaire survey concerning health and lifestyle we prospectively...... studied 19,349 adult twins enrolled in the nationwide Danish Twin Registry. There was a higher prevalence of new-onset asthma in subjects who reported frequent intake of paracetamol at baseline compared with subjects without this determinant (12.0% vs. 4.3%), OR = 3.03 (1.51-6.11), p = 0.005. The result...... remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema, and intake of medications other than paracetamol, OR = 2.16 (1.03-4.53), p = 0.041. Frequent intake of paracetamol is an independent risk factor for adult-onset asthma....

Dielectric spectroscopy in aqueous solutions of paracetamol over the frequency range of 20 Hz to 2 MHz at 293.15 K temperature

Science.gov (United States)

Pandit, T. R.; Rana, V. A.

2018-05-01

Frequency domain dielectric relaxation spectroscopy plays an important role in the study of pharmaceutical drug molecules. The complex relative dielectric permittivity ɛ*(ω) = ɛ' - j ɛ" of aqueous solutions of paracetamol in the frequency range of 20 Hz to 2 MHz at a temperature range of 293.15 K are measured with the help of Agilent precision LCR meter E4980A along with four terminal liquid test fixture Agilent 16452A. Data of complex relative permittivity are used to calculate loss tangent for all concentrations of paracetamol in distilled water. Electrode polarization relaxation time has been calculated for all solutions. Effect of variation of concentrations of paracetamol in distilled water on these dielectric parameters is discussed.

Determinação espectrofotométrica simultânea de paracetamol e ibuprofeno em formulações farmacêuticas usando calibração multivariada Simultaneous spectrophotometric determination of paracetamol and ibuprofen in pharmaceutical formulations by multivariate calibration

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Marcelo M. Sena

2007-02-01

Full Text Available A simple method was proposed for determination of paracetamol and ibuprofen in tablets, based on UV measurements and partial least squares. The procedure was performed at pH 10.5, in the concentration ranges 3.00-15.00 µg ml-1 (paracetamol and 2.40-12.00 µg ml-1 (ibuprofen. The model was able to predict paracetamol and ibuprofen in synthetic mixtures with root mean squares errors of prediction of 0.12 and 0.17 µg ml-1, respectively. Figures of merit (sensitivity, limit of detection and precision were also estimated. The results achieved for the determination of these drugs in pharmaceutical formulations were in agreement with label claims and verified by HPLC.

Paracetamol suppository induced allergic contact dermatitis

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Rangaraj Murugaiyan

2016-01-01

Full Text Available Paracetamol, a para-aminophenol derivative given systemically can produce allergic reactions and has been reported so far, but allergic reaction due to suppositories is very rare. A 4 month old male child brought by his mother with complaints of raised dark coloured skin lesions over the perianal region for the past 3 days. The child had history of (H/o of fever for 4 days back for which paracetamol suppository was prescribed following which the child developed the lesion over the perianal region On examination a well defined hyperpigmented plaque of size 5*3 cms extending from anal verge posteriorly and anteriorly upto the beginning of scrotum with lateral extensions from the centre to the gluteals. In our case, the paracetamol suppository used caused an allergic reaction which made the child very irritable and the child developed an allergic contact dermatitis in the site where the suppository was kept and the surrounding area. We report this case because paracetamol suppository as such without preservative causing allergic contact dermatitis has not been reported so far and the treating doctor should keep in mind such type of reactions that might occur when used.

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.

Science.gov (United States)

Tsaganos, Thomas; Tseti, Ioulia K; Tziolos, Nikolaos; Soumelas, Georgios-Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani; Giamarellos-Bourboulis, Evangelos J

2017-04-01

No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

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Das S

2011-06-01

Full Text Available Suvadra Das, Partha Roy, Runa Ghosh Auddy, Arup MukherjeeDepartment of Chemical Technology, University of Calcutta, Kolkata, West Bengal, IndiaAbstract: Silymarin (Sm is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany. Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 µmol/g in hepatic tissue due to Smnps.Keywords: silymarin, paracetamol, nanoparticle, glutathione, mouse hepatotoxicity

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial.

Science.gov (United States)

Ortiz, Mario I; Murguía-Cánovas, Gabriela; Vargas-López, Laura C; Silva, Rodolfo; González-de la Parra, Mario

2016-10-24

Dysmenorrhea is caused by the discharge of prostaglandins into the uterine tissue; therefore, non-steroidal anti-inflammatory drugs (NSAIDs) are the established initial therapy for dysmenorrhea. Dysmenorrhea therapy may include the administration of drug monotherapy or combination therapy. However, clinical scientific evidence on the efficacy of medications with two or three drugs combined is scarce or nonexistent. To evaluate and compare the efficacy and safety of two oral fixed-dose combinations for the relief of the symptoms of primary dysmenorrhea among Mexican women. One of the combinations is widely used in Mexico (paracetamol, pyrilamine and pamabrom) and the selected comparison was a medication with naproxen sodium, paracetamol and pamabrom based on the pathophysiology of primary dysmenorrhea. This was a single-centre, double blind, experimental, parallel group, randomized trial. Female patients with primary dysmenorrhea, older than 17 years and with pain intensity greater than 45 mm on a visual analogue scale, were included. The patients were then randomized to receive tablets with naproxen sodium, paracetamol and pamabrom or tablets with paracetamol, pyrilamine and pamabrom for one menstrual cycle. Patient evaluations of symptomatology and pain intensity were recorded throughout one menstrual period. Descriptive and inferential statistical analyses were utilized. An intention-to-treat population of 91 women, with a mean age of 21.3 ± 3.2 years, received paracetamol, pyrilamine and pamabrom tablets, and 98 participants, with a mean age of 21.0 ± 3.2 years, received naproxen sodium, paracetamol and pamabrom tablets. The participants’ assessments of pain on the Visual Analogue Scale during the menstrual cycle demonstrated a significant reduction in both treatment groups (p0.05). The results showed that both drug combinations were not different in reducing dysmenorrheic pain. Likewise, both treatments were well tolerated. Therefore, both treatments may be

Concomitant overdosing of other drugs in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, Lars E; Dalhoff, Kim

2002-01-01

AIMS: Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome...... of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

Effects of Methionine Containing Paracetamol Formulation on ...

African Journals Online (AJOL)

Effects of Methionine Containing Paracetamol Formulation on Serum Vitamins and Trace Elements in Male Rats. AA Iyanda, JI Anetor, DP Oparinde, FAA Adeniyi. Abstract. Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a ...

Colorimetric determination of a paracetamole in raw material and in pharmaceutical dosage forms

International Nuclear Information System (INIS)

Usifoh, C.O; Adelusi, S.A.; Adebambo, R.F.

2002-01-01

A rapid, accurate and simple method is proposed for the determination of p-acetaminophen (paracetamole) in raw material, tablets and syrups. The method is based on measuring the intensity of the yellow color that developed when acute acetaminophen is allowed to react with p-dimethylaminobenzaldehyde in 2M HCl after heating. The color which absorbs in the visible region of gamma 450 nm is stable for several hours and the intensity is directly proportional to the concentration of the drug, that is, Beer lambert law is obeyed. The method can be used to analyse paracetamole in raw material and in pharmaceutical dosage forms. (author)

Simultaneous determination of paracetamol and penicillin V by square-wave voltammetry at a bare boron-doped diamond electrode

International Nuclear Information System (INIS)

Švorc, Ľubomír; Sochr, Jozef; Tomčík, Peter; Rievaj, Miroslav; Bustin, Dušan

2012-01-01

Highlights: ► Unmodified BDD electrode = sensitive electrochemical sensor for drugs determination. ► No special pretreatment of samples except simple dilution. ► Selective method, common compounds present in urine do not interfere in high excess. ► Simultaneous determination of PAR and PEN has yet not been published in literature. - Abstract: A simple, sensitive and selective square-wave voltammetry method for simultaneous determination of paracetamol and penicillin V on a bare (unmodified) boron-doped diamond electrode has been developed. The good potential separation of about 0.35 V between the oxidation peak potentials of both drugs present in mixture was found. It was found by cyclic voltammetry that paracetamol gave quasireversible wave and penicillin V provided irreversible oxidation peak. The effect of supporting electrolyte, pH and scan rate on voltammetric response of both drugs was studied to select the optimum experimental conditions. The optimal conditions for quantitative simultaneous determination were obtained in acetate buffer solution at pH 5.0. The oxidation peak of paracetamol and penicillin V showed a systematic increase in peak currents with increase of their concentration. The calibration curves for the simultaneous determination of paracetamol and penicillin V exhibited the good linear responses within the concentration range from 0.4 to 100 μM for both drugs. The detection limit was established to 0.21 and 0.32 μM for paracetamol and penicillin V, respectively. The method proved the good sensitivity, repeatability (RSD of 1.5 and 2.1% for mixture solution of 10 μM PCM and PEN) and selectivity when influence of interferents commonly existing in human urine was negligible. The practical analytical utility of proposed method was demonstrated by simultaneous determination of paracetamol and penicillin V in human urine samples, with results similar to those obtained using a high-performance liquid chromatography method as an

Evaluation of Palm Oil-Based Paracetamol Suppositories by ...

African Journals Online (AJOL)

Methods: The suppository base was prepared by mixing hydrogenated palm oil and palm kernel ... DSC can be used to predict drug release in paracetamol suppository formulations. Keywords: Palm oil, Liquefaction time, Paracetamol, Suppositories, Thermal analysis. ..... Drug Evaluation & Research (CDER), Food and.

The impact of current tobacco use on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2003-01-01

BACKGROUND: Tobacco smoke contains a number of substances that are capable of inducing cytochrome P450. Consequently, current tobacco use may enhance the hepatotoxicity from a paracetamol overdose by increasing the oxidative metabolism of paracetamol. AIM: To evaluate, by multivariate analysis......: Current tobacco use was very frequent in patients admitted with paracetamol poisoning. It was an independent risk factor of severe hepatotoxicity, acute liver failure and death following paracetamol overdose......., the effect of current tobacco use on the morbidity and mortality from paracetamol-induced hepatotoxicity. METHODS: A retrospective study was carried out on the basis of the hospital charts of 602 patients admitted with single-dose paracetamol poisoning for whom information on current tobacco use...

Oral paracetamol (acetaminophen) for cancer pain.

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Wiffen, Philip J; Derry, Sheena; Moore, R Andrew; McNicol, Ewan D; Bell, Rae F; Carr, Daniel B; McIntyre, Mairead; Wee, Bee

2017-07-12

Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Non-opioid drugs are commonly used to treat mild to moderate cancer pain, and are recommended for this purpose in the WHO cancer pain treatment ladder, either alone or in combination with opioids.A previous Cochrane review that examined the evidence for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005. This review, and another on NSAIDs, updates the evidence. To assess the efficacy of oral paracetamol (acetaminophen) for cancer pain in adults and children, and the adverse events reported during its use in clinical trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to March 2017, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind, studies of five days' duration or longer, comparing paracetamol alone with placebo, or paracetamol in combination with an opioid compared with the same dose of the opioid alone, for cancer pain of any intensity. Single-blind and open studies were also eligible for inclusion. The minimum study size was 25 participants per treatment arm at the initial randomisation. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Three studies in adults satisfied the inclusion criteria, lasting up to one week; 122 participants were randomised initially, and 95 completed treatment. We found no studies in children. One study was parallel-group, and

Long-term toxicological effects of paracetamol in rats

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S.K. Majeed,

2013-06-01

Full Text Available The analgesic and antipyretic properties of paracetamol were first described in 1893, then it has been widely available as a non-prescription drug, with a therapeutic profile that reflects widespread safety and efficacy as well as paracetamol became the most widely used analgesic and antipyretic in children. It is the most frequently used over-the counter medicine in young children and is nearly universally used in infants. The drug is used by millions of children every day. The study was designed to study the toxicological effect of therapeutic dose of paracetamol after oral administration for three months in laboratory rats (Rattus norvegicous on the heart, kidney and liver. Results showed oral administration of the paracetamol for three months in laboratory rats showed that this drug has a severe damaging effect on most of the vital organs in the body like kidney, liver and heart.

Intentional and accidental paracetamol poisoning in childhood – a retrospective analysis

Directory of Open Access Journals (Sweden)

Katarzyna Kominek

2015-04-01

Full Text Available Paracetamol is one of the most commonly used analgesics and antipyretics available without limits as preparations of the OTC group (over the counter drugs. Overdose and poisoning with this drug always brings about the risk of acute hepatic failure. The objective of the study was a retrospective evaluation of patients hospitalized in the Paediatric Clinic during the period 2004–2012 due to poisoning with paracetamol.The analysis covered 44 patients hospitalized in the Paediatric Clinic during 2004–2012 due to poisoning with paracetamol. Patients were divided into three groups: intentional poisonings, accidental poisonings, and drug overdose.During the period of the study, 44 patients aged 2.1–17.1, poisoned with paracetamol, were hospitalized. Among these patients there were 30 (68.2% cases of intentional poisonings, 10 (22.7% of accidental poisonings, and only 4 patients (9.1% were children hospitalized after a paracetamol overdose. The majority of patients in all groups were females (93.3%.Paracetamol intoxication may occur after exceeding a single allowable dose, in the case of intentional poisoning, more rarely after exceeding the daily dose, in the case of intense pain complaints, or in the treatment of persistent fever.Based on the analysis performed, an increase was observed in the frequency of poisoning with paracetamol, especially intentional poisoning. Unlimited access to paracetamol as an OTC drug should be reconsidered.

Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver failure have an early monocytopenia.

Science.gov (United States)

Moore, J K; MacKinnon, A C; Man, T Y; Manning, J R; Forbes, S J; Simpson, K J

2017-02-01

Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome. On admission, patients with worst outcomes after POD-ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a 'cytokine storm' and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes. Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non-paracetamol-induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention. © 2016 John Wiley & Sons Ltd.

The effect of regular medication on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2002-01-01

BACKGROUND: Patients admitted with paracetamol overdose frequently receive one or more types of regular medication that may affect the outcome of the paracetamol intoxication. AIM: To describe the use of regular medication in patients with paracetamol poisoning and to evaluate its effects...... on morbidity and mortality. METHODS: Seven hundred and thirty-seven consecutive patients admitted with paracetamol poisoning were studied and the use of regular medication was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, severe hepatic dysfunction and severe...... hepatocellular injury was evaluated by multivariate analysis. RESULTS: Regular medication was received by 332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives (51 cases), beta-agonists (40 cases), opioid...

Voltammetric sensing of paracetamole, dopamine and 4-aminophenol at a glassy carbon electrode coated with gold nanoparticles and an organophillic layered double hydroxide

International Nuclear Information System (INIS)

Yin, H.; Shang, K.; Meng, X.; Ai, S.

2011-01-01

A differential pulse voltammetric method was developed for the simultaneous determination of paracetamole, 4-aminophenol and dopamine at pH 7.0 using a glassy carbon electrode (GCE) coated with gold nanoparticles (AuNPs) and a layered double hydroxide sodium modified with dodecyl sulfate (SDS-LDH). The modified electrode displays excellent redox activity towards paracetamole, and the redox current is increased (and the corresponding over-potential decreased) compared to those of the bare GCE, the AuNPs-modified GCE, and the SDS-LDH-modified GCE. The modified electrode enables the determination of paracetamole in the concentration range from 0.5 to 400 μM, with a detection limit of 0.13 μM (at an S/N of 3). The sensor was successfully applied to the simultaneous determination of paracetamole and dopamine, and of paracetamole and 4-aminophenol, respectively, in pharmaceutical tablets and in spiked human serum samples. (author)

Plasma concentration of acetylcholine in young women

International Nuclear Information System (INIS)

Kawashima, K.; Oohata, H.; Fujimoto, K.; Suzuki, T.

1987-01-01

A sensitive and specific radioimmunoassay was applied to the determination of acetylcholine (ACh) in plasma. The concentration of ACh in plasma sampled from 32 young women was 456.1+-53.1 (mean +-S.E.M.) pg/ml. No significant correlations were observed between plasma concentrations of ACh and acetylcholinesterase (AChE) activity, or gonadal hormones. These data demonstrate that an amount of ACh measurable by radioimmunoassay is present in plasma and plasma ACh is not regulated by AChE activity and the menstrual cycle in young women. The origin and physiological as well as pathophysiological significance of ACh in plasma remain to be clarified. 13 refs. (Author)

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

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Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

Radiolysis of paracetamol in dilute aqueous solution

International Nuclear Information System (INIS)

Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

2012-01-01

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O 2 is c.a. 10%. The efficiency is 2–3 times higher in the presence of O 2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily. - Highlights: ► Paracetamol is easily degraded in aqueous solution by low dose irradiation. ► Main degradation products are hydroxylated molecules, acetamide and hydroquinone. ► Toxicity of solutions goes through a maximum as a function of dose.

Radiolysis of paracetamol in dilute aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Szabo, Laszlo [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Budapest University of Technology and Economics, Budapest (Hungary); Toth, Tuende [Budapest University of Technology and Economics, Budapest (Hungary); Homlok, Renata [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Takacs, Erzsebet [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Wojnarovits, Laszlo [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary)

2012-09-15

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O{sub 2} is c.a. 10%. The efficiency is 2-3 times higher in the presence of O{sub 2} due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily. - Highlights: Black-Right-Pointing-Pointer Paracetamol is easily degraded in aqueous solution by low dose irradiation. Black-Right-Pointing-Pointer Main degradation products are hydroxylated molecules, acetamide and hydroquinone. Black-Right-Pointing-Pointer Toxicity of solutions goes through a maximum as a function of dose.

Plasma concentrations of misonidazole

Energy Technology Data Exchange (ETDEWEB)

Notter, G; Rylander, U; Turesson, I

1980-10-01

The plasma concentrations of misonidazole doses between 0.6 and 2.0 g/m/sup 2/ were analyzed in respect to the variation within the same patient and between different patients. Peak plasma levels were observed after 2 hours. The mean plasma levels of misonidazole only at 3 hours were 23.8, 47.0 and 76.5 ..mu..g/ml after misonidazole doses of 0.6, 1.2 g/m/sup 2/, respectively. The half-life of misonidazole only was found to be 8.2 hours for women and 10.5 for men. Good linearity between plasma levels and drug doses was observed after administration of different single doses to the same patient within the dose range 0.6 to 2.0 g/m/sup 2/.

Paracetamol (acetaminophen): a blessing or a hidden curse?

Science.gov (United States)

Whitehouse, M W; Butters, D E

2014-02-01

This Journal has recently published a splendid review of all you need to know about paracetamol (Graham et al. 2013), an analgesic widely used in the long-term management of arthritis. It clearly presents the science and hard facts. This commentary, by contrast, discusses some aspects of the metapharmacology of paracetamol; particularly by asking questions of how we might extract more benefit and suffer less adverse reactions when using this analgesic in the context of non-transient inflammation. As both a drug and a toxin, paracetamol exemplifies how beneficial and/or deleterious responses may be conditioned by circumstances (disease stress, nutritional status, fasting, etc.).

Paracetamol (acetaminophen) for prevention or treatment of pain in newborns.

Science.gov (United States)

Ohlsson, Arne; Shah, Prakeshkumar S

2016-10-07

Newborn infants have the ability to experience pain. Hospitalised infants are exposed to numerous painful procedures. Healthy newborns are exposed to pain if the birth process consists of assisted vaginal birth by vacuum extraction or by forceps and during blood sampling for newborn screening tests. To determine the efficacy and safety of paracetamol for the prevention or treatment of procedural/postoperative pain or pain associated with clinical conditions in neonates. To review the effects of various doses and routes of administration (enteral, intravenous or rectal) of paracetamol for the prevention or treatment of pain in neonates. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 9 May 2016), Embase (1980 to 9 May 2016), and CINAHL (1982 to 9 May 2016). We searched clinical trials' databases, Google Scholar, conference proceedings, and the reference lists of retrieved articles. We included randomised and quasi-randomised controlled trials of paracetamol for the prevention/treatment of pain in neonates (≤ 28 days of age). Two review authors independently extracted data from the articles using pre-designed forms. We used this form to decide trial inclusion/exclusion, to extract data from eligible trials and to request additional published information from authors of the original reports. We entered and cross-checked data using RevMan 5 software. When noted, we resolved differences by mutual discussion and consensus. We used the GRADE approach to assess the quality of evidence. We included nine trials with low risk of bias, which assessed paracetamol for the treatment of pain in 728 infants. Painful procedures studied included heel lance, assisted vaginal birth, eye examination for retinopathy of prematurity assessment and postoperative care. Results of individual studies could not be combined in meta-analyses as the painful

Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice.

Science.gov (United States)

Fleischmann, Thea; Arras, Margarete; Sauer, Mareike; Saleh, Lanja; Rülicke, Thomas; Jirkof, Paulin

2017-04-01

Embryo transfer (ET) in mice is a key technique in biomedical research, and is carried out mostly via surgery by transferring founder embryos into pseudo-pregnant recipient females. To cover post-operative analgesic requirements in surrogate mothers, oral self-administration of painkillers has several advantages, but its effectiveness has also been criticized as voluntary ingestion of the drug can be uncertain. Additionally, concerns about potential negative side effects of analgesics on embryo viability and development have been raised. In this regard, we investigated the impact of orally administered analgesia by comparing the outcome of ET with and without paracetamol in the drinking water (3.5mg/ml) of surrogate mothers. Water intake increased significantly when paracetamol, as a sweet-tasting formulation (children's syrup), was added to the drinking water. Measurements of paracetamol concentrations in blood serum confirmed reasonable drug uptake. Success rate of ETs and the body weight of newborn offspring were not different whether paracetamol was administered for two days after surgery or not. In conclusion, paracetamol in drinking water was consumed voluntarily in substantial doses, without detectable side-effects, by freshly operated surrogate mothers, and can therefore be recommended as a feasible method for providing analgesic treatment for surgical ET in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paracetamol potentiates the antidepressant-like and anticompulsive-like effects of fluoxetine.

Science.gov (United States)

Manna, Shyamshree S S; Umathe, Sudhir N

2015-04-01

Recent studies suggest the possible involvement of serotonergic and endocannabinoid systems in analgesic, anxiolytic, and anticonvulsant-like actions of paracetamol. Considering the fact that these systems play intricate roles in affective disorders, we investigated the effects of paracetamol in depression-like and compulsion-like behavior. Swiss mice (20-22 g) were subjected to forced swim, tail suspension, or marble-burying tests after an injection of paracetamol either alone or in the presence of AM251 (a CB1 antagonist), fenclonine (pCPA: a 5-HT synthesis inhibitor), AM404 (anandamide uptake inhibitor) or fluoxetine. Paracetamol dose dependently (50-400 mg/kg) decreased depressive and compulsive behaviors. These effects were comparable to those of fluoxetine (5, 10, or 20 mg/kg) and AM404 (10 or 20 mg/kg). Interestingly, fenclonine pretreatment completely abolished the effects of a 50 mg/kg dose of paracetamol. However, similar effects were not observed in AM251-pretreated mice at the same dose. In contrast, AM251 completely antagonized the effects of the 400 mg/kg dose, which was otherwise partially blocked in fenclonine-treated mice. Similar sets of results were observed with fluoxetine and AM404. Thus, it appears that paracetamol-induced antidepressant-like and anticompulsive effects may, at least partially, involve both the serotonergic and the endocannabinoid system. In addition, coadministration of paracetamol and fluoxetine/AM404 at subeffective doses produced synergistic effects, indicating that subthreshold doses of fluoxetine and paracetamol may enable better management in depression and obsessive-compulsive disorder comorbid patients.

Prescription Use of Paracetamol and Risk for Ovarian Cancer in Denmark

DEFF Research Database (Denmark)

Baandrup, Louise; Friis, Søren; Dehlendorff, Christian

2014-01-01

It has been suggested that paracetamol reduces the risk for ovarian cancer. We examined the association between prescription use of paracetamol and ovarian cancer risk in a nationwide case-control study nested within the Danish female population. Case patients (n = 3471) were all women with a first......% confidence intervals (CIs) for ovarian cancer associated with use of paracetamol or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). All statistical tests were two-sided. Use of paracetamol was associated with a reduced odds ratio for ovarian cancer (OR = 0.82; 95% CI = 0.74 to 0.92; P ...) compared with nonuse, and the odds ratio decreased further with long-term (≥10 years), high-intensity paracetamol use (OR = 0.45; 95% CI = 0.24 to 0.86; P = .02). Use of nonaspirin NSAIDs was not associated with ovarian cancer risk....

Paracetamol removal in subsurface flow constructed wetlands

Science.gov (United States)

Ranieri, Ezio; Verlicchi, Paola; Young, Thomas M.

2011-07-01

SummaryIn this study two pilot scale Horizontal Subsurface Flow Constructed Wetlands (HSFCWs) near Lecce, Italy, planted with different macrophytes ( Phragmites australis and Typha latifolia) and an unplanted control were assessed for their effectiveness in removing paracetamol. Residence time distributions (RTDs) for the two beds indicated that the Typha bed was characterized by a void volume fraction (porosity) of 0.16 and exhibited more ideal plug flow behavior (Pe = 29.7) than the Phragmites bed (Pe = 26.7), which had similar porosity. The measured hydraulic residence times in the planted beds were 35.8 and 36.7 h when the flow was equal to 1 m 3/d. The Phragmites bed exhibited a range of paracetamol removals from 51.7% for a Hydraulic Loading Rate (HLR) of 240 mm/d to 87% with 120 mm/d HLR and 99.9% with 30 mm/d. The Typha bed showed a similar behavior with percentages of removal slightly lower, ranging from 46.7% (HLR of 240 mm/d) to >99.9% (hydraulic loading rate of 30 mm/d). At the same HLR values the unplanted bed removed between 51.3% and 97.6% of the paracetamol. In all three treatments the paracetamol removal was higher with flow of 1 m 3/d and an area of approx. 7.5 m 2 (half bed) than in the case of flow equal to 0.5 m 3/d with a surface treatment of approx. 3.75 m 2. A first order model for paracetamol removal was evaluated and half lives of 5.16 to 10.2 h were obtained.

Determinação espectrofotométrica por injeção em fluxo de paracetamol (acetaminofeno em formulações farmacêuticas

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Aniceto Clezio

2002-01-01

Full Text Available A flow injection spectrophotometric procedure is proposed for the determination of paracetamol (acetaminophen in pharmaceutical formulations. Powdered and liquid samples were previously dissolved/diluted in 0.05 mol L-1 hydrochloric acid solution and a volume of 250 µL was injected directly into a carrier stream of this same acid solution, flowing at 2.5 mL min-1. Paracetamol reacts with sodium hypochlorite forming N-acetyl-p-benzoquinoneimine which then reacts with sodium salicylate in sodium hydroxide solution yielding a blue indophenol dye which was measured at 640 nm in the pH range of 9.5-10.0. Paracetamol was determined in pharmaceutical products in the 1.0 to 100.0 mg L-1 (3.3x10-6 a 6.6x10-4 mol L-1 concentration range, with a detection limit of 0.5 mg L-1 (1.6x10-6 mol L-1. The recovery of this analyte in five samples ranged from 98.0 to 103.6 %. The analytical frequency was 80 determinations per hour and the RSDs were less than 1% for paracetamol concentrations of 25.0, 50.0 and 75.0 mg L-1 (n=10. A paired t-test showed that all results obtained for paracetamol in commercial formulations using the proposed flow injection procedure and a spectrophotometric batch procedure agree at the 95% confidence level.

Plasma magnesium concentration in patients undergoing coronary artery bypass grafting.

Science.gov (United States)

Kotlinska-Hasiec, Edyta; Makara-Studzinska, Marta; Czajkowski, Marek; Rzecki, Ziemowit; Olszewski, Krzysztof; Stadnik, Adam; Pilat, Jacek; Rybojad, Beata; Dabrowski, Wojciech

2017-05-11

[b]Introduction[/b]. Magnesium (Mg) plays a crucial role in cell physiology and its deficiency may cause many disorders which often require intensive treatment. The aim of this study was to analyse some factors affecting preoperative plasma Mg concentration in patients undergoing coronary artery bypass grafting (CABG). [b]Materials and method[/b]. Adult patients scheduled for elective CABG with cardio-pulmonary bypass (CPB) under general anaesthesia were studied. Plasma Mg concentration was analysed before surgery in accordance with age, domicile, profession, tobacco smoking and preoperative Mg supplementation. Blood samples were obtained from the radial artery just before the administration of anaesthesia. [b]Results. [/b]150 patients were studied. Mean preoperative plasma Mg concentration was 0.93 ± 0.17 mmol/L; mean concentration in patients - 1.02 ± 0.16; preoperative Mg supplementation was significantly higher than in patients without such supplementation. Moreover, intellectual workers supplemented Mg more frequently and had higher plasma Mg concentration than physical workers. Plasma Mg concentration decreases in elderly patients. Patients living in cities, on average, had the highest plasma Mg concentration. Smokers had significantly lower plasma Mg concentration than non-smokers. [b]Conclusions. [/b]1. Preoperative magnesium supplementation increases its plasma concentration. 2. Intellectual workers frequently supplement magnesium. 3. Smoking cigarettes decreases plasma magnesium concentration.

Quantification of acetaminophen (paracetamol) in human plasma and urine by stable isotope-dilution GC-MS and GC-MS/MS as pentafluorobenzyl ether derivative.

Science.gov (United States)

Trettin, Arne; Zoerner, Alexander A; Böhmer, Anke; Gutzki, Frank-Mathias; Stichtenoth, Dirk O; Jordan, Jens; Tsikas, Dimitrios

2011-08-01

We report on the quantitative determination of acetaminophen (paracetamol; NAPAP-d(0)) in human plasma and urine by GC-MS and GC-MS/MS in the electron-capture negative-ion chemical ionization (ECNICI) mode after derivatization with pentafluorobenzyl (PFB) bromide (PFB-Br). Commercially available tetradeuterated acetaminophen (NAPAP-d(4)) was used as the internal standard. NAPAP-d(0) and NAPAP-d(4) were extracted from 100-μL aliquots of plasma and urine with 300 μL ethyl acetate (EA) by vortexing (60s). After centrifugation the EA phase was collected, the solvent was removed under a stream of nitrogen gas, and the residue was reconstituted in acetonitrile (MeCN, 100 μL). PFB-Br (10 μL, 30 vol% in MeCN) and N,N-diisopropylethylamine (10 μL) were added and the mixture was incubated for 60 min at 30 °C. Then, solvents and reagents were removed under nitrogen and the residue was taken up with 1000 μL of toluene, from which 1-μL aliquots were injected in the splitless mode. GC-MS quantification was performed by selected-ion monitoring ions due to [M-PFB](-) and [M-PFB-H](-), m/z 150 and m/z 149 for NAPAP-d(0) and m/z 154 and m/z 153 for NAPAP-d(4), respectively. GC-MS/MS quantification was performed by selected-reaction monitoring the transition m/z 150 → m/z 107 and m/z 149 → m/z 134 for NAPAP-d(0) and m/z 154 → m/z 111 and m/z 153 → m/z 138 for NAPAP-d(4). The method was validated for human plasma (range, 0-130 μM NAPAP-d(0)) and urine (range, 0-1300 μM NAPAP-d(0)). Accuracy (recovery, %) ranged between 89 and 119%, and imprecision (RSD, %) was below 19% in these matrices and ranges. A close correlation (r>0.999) was found between the concentrations measured by GC-MS and GC-MS/MS. By this method, acetaminophen can be reliably quantified in small plasma and urine sample volumes (e.g., 10 μL). The analytical performance of the method makes it especially useful in pediatrics. Copyright © 2011 Elsevier B.V. All rights reserved.

Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

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Enrica Migliore

Full Text Available Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR and 95% confidence intervals (CI were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10 [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache revealed no increased risk of wheezing in children.The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.

The impact of current tobacco use on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2003-01-01

BACKGROUND: Tobacco smoke contains a number of substances that are capable of inducing cytochrome P450. Consequently, current tobacco use may enhance the hepatotoxicity from a paracetamol overdose by increasing the oxidative metabolism of paracetamol. AIM: To evaluate, by multivariate analysis......, the effect of current tobacco use on the morbidity and mortality from paracetamol-induced hepatotoxicity. METHODS: A retrospective study was carried out on the basis of the hospital charts of 602 patients admitted with single-dose paracetamol poisoning for whom information on current tobacco use...... was available. RESULTS: In patients admitted with paracetamol poisoning, the rate of current daily tobacco use of 70% (424 of 602 patients) was considerably higher than the rate of 31% in the background population (chi-squared test: P

Eficacia de la asociación paracetamol-metamizol vs. paracetamol-dexketoprofeno en manejo de dolor agudo postoperatorio

OpenAIRE

García Ramiro, M.; Alonso Guardo, L.; Matilla Álvarez, A.; Bartol Sevillano, R.; Vaquero Roncero, L. M.; Muriel Villoria, C.

2013-01-01

Objetivo: El uso de fármacos con mecanismos diferentes combinados entre sí para el tratamiento del dolor, en concreto del dolor agudo postoperatorio, forma parte fundamental de un tipo de analgesia llamada multimodal. El objetivo de este trabajo es evaluar la eficacia de la asociación de paracetamol más metamizol y compararla con la asociación de paracetamol más dexketoprofeno en dolor agudo postoperatorio. Métodos: Diseñamos un estudio prospectivo de intervención en el que se incluyeron 42 p...

Pre-treatment by n-hexane extract of Phyllanthus niruri can alleviate paracetamol-induced damage of the rat liver

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Md Jalaluddin Iqbal

2007-03-01

Full Text Available The present study aimed to obtain and evaluate remedy against viral hepatitis with Phyllanthus niruri (Bhui amla. Viral infection and toxic doses of paracetamol produce similar pattern of hepatotoxicity. Hepatotoxicity was induced by administering paracetamol (750 mg/kg body weight, single dose intraperitoneal into one group (group P of rats. Propylene glycol (vehicle was administered (2 ml into another group (group V of rats. 4 groups of P. niruri extract-pretreated (200 mg/kg body weight/day for 7 days rats were administered the same single dose of paracetamol on the 7th day. Extract of P. niruri were obtained through ethanol (E, hexane (H, dichloromethane (D and butane (B. Rat groups were V, P, E + P, H + P, D + P and B + P. Each group consisted of 6 rats and were sacrificed on the 9th day. Parameters for evaluation were biochemical (serum ALT, serum AST, serum ALP, serum bilirubin, hepatic reduced glutathione concentrations and hepatic histology. Propylene glycol (group V appeared non-toxic to the liver while significant degrees of centrilobuler hepatotoxicity was observed in group P paracetamol-treated rats. The E + P group suggested significant improvements in the serum parameters but these parameters appeared better alleviated in the H + P group. Hepatic reduced glutathione concentrations were replenished to the control level in both E + P and H + P groups. Hepatic histology supported biochemical and other observations in the P, E + P and H + P groups. Lesser degrees of alleviations were observed in the D + P and B + P groups. However, the hexane extract-pretreated group (H + P appeared to provide the most significant hepatoprotection against paracetamol induced hepatotoxicity in the rat. Titration of the dose following isolation of the active ingredient might offer complete alleviation.

Pre-treatment by n-hexane extract of Phyllanthus niruri can alleviate paracetamol-induced damage of the rat liver

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Md. Jalaluddin Iqbal, Fawzia Z. Dewan, S.A.R.Chowdhury, M.I.R. Mamun,

2007-06-01

Full Text Available The present study aimed to obtain and evaluate remedy against viral hepatitis with Phyllanthus niruri (Bhui amla. Viral infection and toxic doses of paracetamol produce similar pattern of hepatotoxicity. Hepatotoxicity was induced by administering paracetamol (750 mg/kg body weight, single dose intraperitoneal into one group (group P of rats. Propylene glycol (vehicle was administered (2 ml into another group (group V of rats. Four groups of P. niruri extract-pretreated (200 mg/kg body weight/day for 7 days rats were administered the same single dose of paracetamol on the 7th day. Extract of P. niruri were obtained through ethanol (E, hexane (H, dichloromethane (D and butane (B. Rat groups were V, P, E + P, H + P, D + P and B + P. Each group consisted of 6 rats and were sacrificed on the 9th day. Parameters for evaluation were biochemical (serum ALT, serum AST, serum ALP, serum bilirubin, hepatic reduced glutathione concentrations and hepatic histology. Propylene glycol (group V appeared non-toxic to the liver while significant degrees of centrilobuler hepatotoxicity was observed in group P paracetamol-treated rats. The E + P group suggested significant improvements in the serum parameters but these parameters appeared better alleviated in the H + P group. Hepatic reduced glutathione concentrations were replenished to the control level in both E + P and H + P groups. Hepatic histology supported biochemical and other observations in the P, E + P and H + P groups. Lesser degrees of alleviations were observed in the D + P and B + P groups. However, the hexane extract-pretreated group (H + P appeared to provide the most significant hepatoprotection against paracetamol induced hepatotoxicity in the rat. Titration of the dose following isolation of the active ingredient might offer complete alleviation.

The Effect of Preemptive Lornoxicam, Paracetamol and Paracetamol Lornoxicam Combinations on the Quality of Patient-Controlled Analgesia After Abdominal Surgery

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Aysenur Coskun

2013-10-01

Full Text Available Aim: We investigated total fentanyl dose, its side effects and the quality of Patient Controlled Analgesia (PCA using preemptive paracetamol, lornoxicam and their combination after abdominal surgery. Material and Method: After approval of the Hospital Ethic Committee of Atatürk University, Erzurum, Turkey, The study included 120 ASA I or II, patients aged between 18 to 70 years, scheduled to undergo elective abdominal surgery (midline incision surgery. Patients were randomly divided into four groups. In all cases, anesthesia was induced with 2mg/kg propofol and 0.6mg/kg rocuronium. Anesthesia was maintained by using 1-1.5% sevoflurane in 60% 40% nitrous oxide - O2. Group control (Group C, n=30: received intravenous (i.v. fentanyl through Patient Controlled Analgesia (PCA Group Lornoxicam (Group L, n=30: a one-time 8mg dose of i.v. lornoxicam was added, which was completed approximately 30 minutes before intubation.; Group paracetamol (Group P, n=30: received 1g i.v. paracetamol before intubation, followed by every 6 hours for a total of four times. Group lornoxicam and paracetamol (Group PL, n=30: received 8mg i.v. lornoxicam before intubation, and 1g i.v. paracetamol before intubation every 6 hours for a total of 4 times. During the postoperative 2, 4, 8, 12 and 24 hours, visual analogue scale (VAS, sedation, and nausea-vomiting scores, patient satisfaction, incidence of side effects and total amount of fentanyl used were recorded. Results: Total postoperative fentanyl consumption was significantly higher in GC than of the other groups. At 2, 8, 12, 24. hours, fentanyl consumption was found to be significantly lower in GL than that in GC. In GPL, fentanyl consumption was significantly lower than in GC at all time points. Discussion: We observed that preemptive 8 mg lornoxicam decreased PCA fentanyl consumption but a combination of lornoxicam and paracetamol was not superior to lornoxicam alone.

N-Acetyl-4-aminophenol (paracetamol), N-acetyl-2-aminophenol and acetanilide in urine samples from the general population, individuals exposed to aniline and paracetamol users.

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Dierkes, Georg; Weiss, Tobias; Modick, Hendrik; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger M

2014-01-01

Epidemiological studies suggest associations between the use of N-acetyl-4-aminophenol (paracetamol) during pregnancy and increased risks of reproductive disorders in the male offspring. Previously we have reported a ubiquitous urinary excretion of N-acetyl-4-aminophenol in the general population. Possible sources are (1) direct intake of paracetamol through medication, (2) paracetamol residues in the food chain and (3) environmental exposure to aniline or related substances that are metabolized into N-acetyl-4-aminophenol. In order to elucidate the origins of the excretion of N-acetyl-4-aminophenol in urine and to contribute to the understanding of paracetamol and aniline metabolism in humans we developed a rapid, turbulent-flow HPLC-MS/MS method with isotope dilution for the simultaneous quantification of N-acetyl-4-aminophenol and two other aniline related metabolites, N-acetyl-2-aminophenol and acetanilide. We applied this method to three sets of urine samples: (1) individuals with no known exposure to aniline and also no recent paracetamol medication; (2) individuals after occupational exposure to aniline but no paracetamol medication and (3) paracetamol users. We confirmed the omnipresent excretion of N-acetyl-4-aminophenol. Additionally we revealed an omnipresent excretion of N-acetyl-2-aminophenol. In contrast, acetanilide was only found after occupational exposure to aniline, not in the general population or after paracetamol use. The results lead to four preliminary conclusions: (1) other sources than aniline seem to be responsible for the major part of urinary N-acetyl-4-aminophenol in the general population; (2) acetanilide is a metabolite of aniline in man and a valuable biomarker for aniline in occupational settings; (3) aniline baseline levels in the general population measured after chemical hydrolysis do not seem to originate from acetanilide and hence not from a direct exposure to aniline itself and (4) N-acetyl-2-aminophenol does not seem to be

Consumer concerns about paracetamol: a retrospective analysis of a medicines call centre.

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Lau, Stephanie M; McGuire, Treasure M; van Driel, Mieke L

2016-06-08

To identify consumer information needs about paracetamol, the most commonly used analgesic and antipyretic worldwide. Retrospective analysis of medicines questions from the public. Australian consumer medicines call centre. Callers to National Prescribing Service Medicines Line between September 2002 and June 2010 (n=123 217). Enquiry profile: demographics, enquiry type and concurrent medicines included in paracetamol calls; question themes derived from subset of call narratives. Paracetamol comprised part of the enquiry in 5.2% of calls (n=6367). The caller age distribution for paracetamol calls was skewed towards a younger cohort, with 45.2% made by those aged 25-44 vs 37.5% in 'rest of calls'. Significantly more paracetamol-related calls were made for a child (23.7%) compared with 'rest of calls' (12.7%, pConsumers have many concerns about the use of paracetamol that may be under-recognised by healthcare providers, with the nature of enquiries differing across life stages. These concerns are not adequately addressed by available consumer information. Improving access to targeted information about paracetamol would promote the safe and effective use of this common medicine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Relevancy of paracetamol and Breastfeeding Post Infant Vaccination: A Systematic Review

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Nurain Suleiman

2018-03-01

Full Text Available Background: Paracetamol may be used as an antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain post-vaccination in infants. The use of paracetamol during fever may be or may not be recommended since it may alter the natural human body immune response, although it may reduce fever and fussiness. Objectives: The aims of this study are to describe the effectiveness of breastfeeding in reducing pain and paracetamol in reducing fever and pain post infant vaccination. Methods: Data sources and study selection was conducted by electronic searching of six databases. Manual reference checks of all articles on paracetamol and breastfeeding post infant vaccination published in the English language between 1978 and 2017. Two levels of screening were used on 9614 citations, which include screening of abstracts and titles followed by full text screening. The data synthesis were tabulated into study characteristics, quality, and effects. Results: Systematic review of breastfeeding included three studies from 9614 database searches found significant benefit from breastfeeding in pain scores and the duration of crying, as well as behavioural changes. None of the studies stated the detriment of breastfeeding before, during, and after immunization. Systematic review of paracetamol effectiveness included four studies from 1177 database searches found significant benefit from prophylaxis paracetamol in fever, one study found significant benefit from prophylaxis paracetamol in fussiness, and one study’s results were found to be not significant. Two studies on evaluating the safety of prophylactic paracetamol in 2009 found that antibody responses to several antigens were significantly reduced, and the other study in 1988 found that antibody titres to DTP bacteria of placebo and PCM did not differ significantly. Conclusions: The relevancy of giving paracetamol post all types of vaccination may be questionable

Radiolysis of paracetamol in dilute aqueous solution

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Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

2012-09-01

Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O2 is c.a. 10%. The efficiency is 2-3 times higher in the presence of O2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily.

Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

DEFF Research Database (Denmark)

Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

2016-01-01

BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including...

SIMULTANEOUS DETERMINATION OF PARACETAMOL AND IBUPROFENE MIXTURES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

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Sophi Damayanti

2010-06-01

Full Text Available Analytical method for the determination of paracetamol and ibuprofene mixtures has been developed by High Performance Liquid Chromatography using C-18 column and acetinitrile - phosphate buffer pH = 4.5 (75:25 containing 0.075% sodium hexanesulfunate as a mobile phase. The detector was set at 215 nm. Using such conditions, retention time for paracetamol and ibuprofen was 4.89 and 7.11 min, respectively. The recovery for paracetamol and ibuprofen was found to be 101.07± 0.73% and 102.02 ± 1.58%, respectively. The detector limits of the method was 1.30 and 1.60 μg/mL with the relative standard deviation (RSD 0.74 and 1.52% for paracetamol and ibuprofen, respectively.   Keywords: paracetamol, ibuprofen, multi-component, validation, HPLC.

A sensitive electrochemical sensor for paracetamole based on a glassy carbon electrode modified with multiwalled carbon nanotubes and dopamine nanospheres functionalized with gold nanoparticles

International Nuclear Information System (INIS)

Liu, Xue; Wang, Ling-Ling; Wang, Ya-Ya; Zhang, Xiao-Yan

2014-01-01

We describe an electrochemical sensor for paracetamole that is based on a glassy carbon electrode modified with multiwalled carbon nanotubes and dopamine nanospheres functionalized with gold nanoparticles. The functionalized nanospheres were prepared by a chemical route and characterized by scanning electron microscopy. The well-dispersed gold nanoparticles were anchored on the dopamine nanosphere via a chemical reduction of the gold precursor. The stepwise fabrication of the modified electrode and its electrochemical response to paracetamole were evaluated using electrochemical impedance spectroscopy and cyclic voltammetry. The modified electrode displayed improved electrocatalytic activity towards paracetamole, a lower oxidation potential (371 mV), and a larger peak current when compared to a bare electrode or other modified electrodes. The kinetic parameters governing the electro-oxidation of paracetamole were studied, and the analytical conditions were optimized. The peak current was linearly related to the concentration of paracetamole in 0.8–400 μM range, and the detection limit was 50 nM (at an SNR of 3). The method was successfully applied to the determination of paracetamole in spiked human urine samples and gave recoveries between 95.3 and 105.2 %. (author)

PULMONARY AND LIVER DAMAGE DURING TREATMENT WITH ACETAMINOPHEN (PARACETAMOL

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L. I. Dvoretski

2016-01-01

Full Text Available This is a case report of pulmonary damage in the form of intestinal pneumonitis with severe respiratory failure during administration of acetaminophen (paracetamol. In addition, significant increase of ALT and AST levels without clinical signs of liver damage was observed in this patient. After glucocorticoids administration regression of radiological abnormal findings in the lungs along with normalization of liver enzymes values were registered. The rarity of interstitial pneumonitis induced by acetaminophen (paracetamol, especially in combination with liver damage, is emphasized. The presented patient history is the first case report of drug-induced hepatopulmonary syndrome during acetaminophen (paracetamol administration.

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy.

Science.gov (United States)

Unal, Ciğdem; Cakan, Türkay; Baltaci, Bülent; Başar, Hülya

2013-10-01

[corrected] We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl) due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Visual Analog Scale (VAS) scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12(th) h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml) in group paracetamol (72.3 ± 38.0 ml) and dexketoprofen trometamol (69.3 ± 24.1 ml) was significantly lower than group placebo (129.3 ± 22.6 ml) (P dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Dexketoprofen trometamol and Paracetamol didn't cause significant change on pain scores, but increased patients' comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not recommended.

What do we (not) know about how paracetamol (acetaminophen) works?

Science.gov (United States)

Toussaint, K; Yang, X C; Zielinski, M A; Reigle, K L; Sacavage, S D; Nagar, S; Raffa, R B

2010-12-01

Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Target biomarker profile for the clinical management of paracetamol overdose

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Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

The effect of regular medication on the outcome of paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2002-01-01

hepatocellular injury was evaluated by multivariate analysis. RESULTS: Regular medication was received by 332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives (51 cases), beta-agonists (40 cases), opioid......, neuroleptics, paracetamol, oral contraceptives, beta-agonists or anticonvulsants in the multivariate analysis. CONCLUSIONS: Regular medication with psychotropic medication, analgesics, oral contraceptives, beta-agonists or anticonvulsants was frequent in patients admitted with paracetamol poisoning. Medication...

Overdosed paracetamol (acetaminophen) prescriptions and subsequent pharmacist interventions in French hospitals.

Science.gov (United States)

Charpiat, B; Bedouch, P; Rose, F X; Juste, M; Roubille, R; Conort, O; Allenet, B

2013-11-01

Little is known about the manner in which hospital pharmacists intervene for overdosed paracetamol prescriptions. The aim of this retrospective study was to describe the number and nature of pharmacists' interventions (PIs) for overdosed paracetamol adult prescriptions in hospitals. We studied PIs that had been documented by pharmacists on the French Society of Clinical Pharmacy website tool between 2007 and 2010. We identified PIs that were related to paracetamol-containing prescriptions of one brand name only (type 1) particularly for patients with body weight ≤ 50 kg who were prescribed 4 g/day, and PIs that concerned the co-prescription of two paracetamol-containing products (type 2). Among 60 hospitals, seven did not report any paracetamol overdose-related PIs. Of the 53 hospitals that had at least one PI, 16 did not report any type 1 PIs. Bodyweight, liver disease, cirrhosis and chronic alcoholism were absent recorded criterion by most of the hospitals included in this study. Previously published studies have highlighted that the most frequent PIs are type 1, especially for patients whose body weight is ≤ 50 kg. We observed a broad variability in the number or type of PI that were related to overdosed paracetamol prescriptions compared with the total of all recorded types of PI. These data suggest that a significant number of hospital pharmacists are unaware of the risks that adult patients with low body weight are exposed to when receiving four grams paracetamol/day over several days. Pharmacist educational programs are needed. Copyright © 2013. Published by Elsevier Masson SAS.

BN and BN oxide nanosheets based nanosensor for paracetamol adsorption: a first principles simulation

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Miguel Castro

2014-04-01

Full Text Available The effects that the adsorption of the paracetamol molecule produce on the structural and electronic properties of boron nitride (hBNNs; B27N27H18 and boron nitride oxide (hBNONs; B27N27H17 + O + (OH3 + COOH hexagonal symmetry nanosheets were studied by means of Density Functional Theory. The generalized gradient approximation proposed by Heyd—Scuseria—Ernzerhof ((HSEh1PBE―GGA was used in concert with 6-31G(d basis sets. Several candidate structures, 9 and 13 for the hBNNs―Paracetamol and BNONs―Paracetamol interactions, respectively, were used for the geometry optimization procedure. The results show that in the lowest energy absorption site the paracetamol molecule reaches a parallel orientation to the surface of the nanosheets, producing physisorption for hBNNs―Paracetamol and chemisorption for BNONs―Paracetamol. Besides, the adsorption process yields an increase of the polarity opening the possibility for the solubility and dispersion of these compounds. The paracetamol molecule promotes also a decrease of the reactivity parameter, which is crucial for biological applications of these systems. Referred to pristine hBNNs and BNONs, the work functions of hBNNs-Paracetamol and BNONs―Paracetamol are diminished. That is, these functionalized 2D systems yields appropriate conditions for field emission and they may be used as sensors of such pharmaceutical compound.

The relation between paracetamol use and asthma

DEFF Research Database (Denmark)

Shaheen, S; Potts, J; Gnatiuc, L

2008-01-01

Studies from the UK and the USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking.As part of a multi-centre case-control study organised by the GA(2)LEN network we have examined whether frequent paracetamol use is associated...... with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms in the last 12 months across 12 European centres. All cases and controls were selected from...... the same population defined by age (20-45 years) and place of residence.In a random effects meta-analysis, after controlling for confounders, the adjusted odds ratio for asthma associated with weekly use of paracetamol, compared with less frequent use, was 2.87 (95% CI: 1.49 to 5.37), P=0...

Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

Science.gov (United States)

Yue, Yong; Collaku, Agron; Liu, Dongzhou J

2018-01-01

Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

Science.gov (United States)

Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

2012-01-01

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

Effects of co-administration of chloroquine with paracetamol or ...

African Journals Online (AJOL)

The effects of co-administration of oral chloroquine with paracetamol or with ibuprofen on renal function were studied using 6 groups of New Zealand White rabbits. Group 1, the control group received only feed and water. The other groups (Groups 2-6) either received single therapies of paracetamol (10 mg/kg of body ...

Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers

DEFF Research Database (Denmark)

Gude, Anne-Bolette Jill; Hoegberg, Lotte Christine Groth; Riis Angelo, Helle

2010-01-01

The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated...... whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross-over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol...... was administered, followed 1 hr later by an activated charcoal-Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration-time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25-g dose was found...

Measurement of plasma adenosine concentration: methodological and physiological considerations

International Nuclear Information System (INIS)

Gewirtz, H.; Brown, P.; Most, A.S.

1987-01-01

This study tested the hypothesis that measurements of plasma adenosine concentration made on samples of blood obtained in dipyridamole and EHNA (i.e., stopping solution) may be falsely elevated as a result of ongoing in vitro production and accumulation of adenosine during sample processing. Studies were performed with samples of anticoagulated blood obtained from anesthesized domestic swine. Adenosine concentration of ultra filtrated plasma was determined by HPLC. The following parameters were evaluated: (i) rate of clearance of [ 3 H]adenosine added to plasma, (ii) endogenous adenosine concentration of matched blood samples obtained in stopping solution alone, stopping solution plus EDTA, and perchloric acid (PCA), (iii) plasma and erythrocyte endogenous adenosine concentration in nonhemolyzed samples, and (iv) plasma adenosine concentration of samples hemolyzed in the presence of stopping solution alone or stopping solution plus EDTA. We observed that (i) greater than or equal to 95% of [ 3 H]adenosine added to plasma is removed from it by formed elements of the blood in less than 20 s, (ii) plasma adenosine concentration of samples obtained in stopping solution alone is generally 10-fold greater than that of matched samples obtained in stopping solution plus EDTA, (iii) deliberate mechanical hemolysis of blood samples obtained in stopping solution alone resulted in substantial augmentation of plasma adenosine levels in comparison with matched nonhemolyzed specimens--addition of EDTA to stopping solution prevented this, and (iv) adenosine content of blood samples obtained in PCA agreed closely with the sum of plasma and erythrocyte adenosine content of samples obtained in stopping solution plus EDTA

Degradation of Paracetamol by Photolysis Using C-N-codoped TiO2

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Vanny Yulia Safitri

2017-11-01

Full Text Available Paracetamol is generally used as analgesic and antipyretic drugs. Contamination paracetamol in the environment can occur because of waste material disposal from production site and immediate disposal of household that cause water pollution. Paracetamol is degraded by photolysis method under irradiation 10 watt UV-light (λ=365 nm, visible-light (Philips LED 13 watt 1400 lux and solar-light with and without addition C-N-codoped TiO2catalyst. The solution is analyzed by UV-Vis spectrophotometer at λ 200-400 nm. Optimum weight of C-N-codoped TiO2 catalyst obtained is 20 mg under UV-light photolysis. Paracetamol 4 mg/L is degraded 45.48% after 120 minutes under UV-light irradiation without catalyst, and increases to be 69.31% by using 20 mg catalyst. While degradation percentage of paracetamol is 16.96 % without catalyst, the percentage increases to be 34.29% after using 20 mg catalyst for 120 minutes photolysis under visible-light. Degradation of paracetamol by solar light achieves only 12.27% in absance of catalyst for 120 minutes irradiation, but it increases significantly until 70.39% in presence of 20 mg catalyst.

Plasma concentration of ionized calcium in healthy iguanas.

Science.gov (United States)

Dennis, P M; Bennett, R A; Harr, K E; Lock, B A

2001-08-01

To measure plasma concentration of ionized calcium in healthy green iguanas. Prospective study. 9 juvenile and 21 (10 male, 11 female) adult iguanas. Blood samples were obtained from each iguana, and plasma calcium, glucose, phosphorus, uric acid, total protein, albumin, globulin, potassium, and ionized calcium concentrations, aspartate transaminase (AST) activity, and pH were measured. Heparinized blood was used for measurement of ionized calcium concentration and blood pH. A CBC was also performed to assess the health of the iguanas. Significant differences were not detected among the 3 groups (juveniles, males, and females) with regard to ionized calcium concentration. Mean ionized calcium concentration measured in blood was 1.47 +/- 0.105 mmol/L. Significant differences were detected between juveniles and adults for values of phosphorus, glucose, total protein, albumin, globulin, and AST activity. Ionized calcium concentration provides a clinical measurement of the physiologically active calcium in circulation. Evaluation of physiologically active calcium in animals with suspected calcium imbalance that have total plasma calcium concentrations within reference range or in gravid animals with considerably increased total plasma calcium concentrations is vital for determining a therapeutic plan. Accurate evaluation of calcium status will provide assistance in the diagnosis of renal disease and seizures and allow for better evaluation of the health status of gravid female iguanas.

Acetaminophen/paracetamol: A history of errors, failures and false decisions.

Science.gov (United States)

Brune, K; Renner, B; Tiegs, G

2015-08-01

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect 'epidemy' (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound. © 2014 European Pain Federation - EFIC®

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

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Castellote José

2011-07-01

Full Text Available Abstract Background Acute liver injury (ALI induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8 and of 10 per million paracetamol users-year (95% CI 4.3-19.4. Conclusions Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

Low plasma triiodothyronine concentrations and outcome in preterm infants.

Science.gov (United States)

Lucas, A; Rennie, J; Baker, B A; Morley, R

1988-01-01

A major association has been found between low plasma triiodothyronine concentrations in preterm neonates and their later developmental outcome. Plasma triiodothyronine concentration was measured longitudinally in 280 preterm infants below 1850 g birth weight. Babies whose lowest recorded concentration was less than 0.3 nmol/l had, at 18 months' corrected age, 8.3 and 7.4 point disadvantages in Bayley mental and motor scales and a 8.6 point disadvantage on the academic scale of Developmental Profile II, even after adjusting for a range of antenatal and neonatal factors known to influence later development. Low concentrations of triiodothyronine were strongly associated with infant mortality, but not after adjusting for the presence of respiratory illness. There was no association between plasma triiodothyronine concentrations and somatic growth up to 18 months, and no association with necrotising enterocolitis or later cerebral palsy. Data on postnatal changes in plasma triiodothyronine concentrations are presented for reference purposes. While cited reference ranges for plasma triiodothyronine concentration appear suitable for well infants above 1500 g birth weight, smaller or ill babies often have very low values for many weeks. Our data are relevant to the debate on endocrine 'replacement' treatment in premature babies. PMID:2461683

An assessment of the quality of various brands of paracetamol ...

African Journals Online (AJOL)

To assess the seriousness of the global counterfeiting problem, we quantified the amount of active ingredient present in paracetamol tablets by various official and non-official methods. Eight brands of Paracetamol 500mg tablets were assessed using the quality control parameters of weight uniformity, active ingredient ...

The majority of sick children receive paracetamol during the winter

DEFF Research Database (Denmark)

Ertmann, Ruth; Møller, Janne Julie; Waldorff, Frans Boch

2012-01-01

Even though fever is a common symptom in childhood, it often worries parents and they may try to reduce discomfort by giving the child paracetamol, which is currently the most commonly sold over-the-counter medicine. The objective of this study was to investigate parent-administered paracetamol...

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

Science.gov (United States)

Derry, Sheena; Moore, R Andrew

2013-04-30

This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010 for the original review, and to 13 February 2013 for the update. Two clinical trials registers (ClinicalTrials.gov and gsk-clinicalstudyregister.com) were also searched on both occasions. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared with placebo or other active treatment. Searches for the update identified one additional study for inclusion. Eleven studies (2942 participants, 5109 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12 (19% response with paracetamol, 10% with placebo), 5.0 (56% response with paracetamol, 36% with placebo) and 5.2 (39% response with paracetamol, 20% with placebo) for 2-hour pain-free and 2- and 1

Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids.

Science.gov (United States)

Sherry, Christina L; Oliver, Jeffery S; Renzi, Lisa M; Marriage, Barbara J

2014-08-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. © 2014 American Society for Nutrition.

Paracetamol (acetaminophen) poisoning.

Science.gov (United States)

Park, B Kevin; Dear, James W; Antoine, Daniel J

2015-10-19

Paracetamol directly causes around 150 deaths per year in UK. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 127 studies. After deduplication and removal of conference abstracts, 64 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 46 studies and the further review of 18 full publications. Of the 18 full articles evaluated, one systematic review was updated and one RCT was added at this update. In addition, two systematic reviews and three RCTs not meeting our inclusion criteria were added to the Comment sections. We performed a GRADE evaluation for three PICO combinations. In this systematic overview we categorised the efficacy for six interventions, based on information about the effectiveness and safety of activated charcoal (single or multiple dose), gastric lavage, haemodialysis, liver transplant, methionine, and acetylcysteine.

Plasma catecholamine and serum gastrin concentrations during sham feeding

DEFF Research Database (Denmark)

Bekker, Carsten; Andersen, D; Kronborg, O

1983-01-01

Plasma adrenaline, plasma noradrenaline and serum gastrin concentrations were measured before and after sham feeding in eight patients with duodenal ulcer and in four normal subjects. No significant change in the concentrations was observed after sham feeding. In three patients with duodenal ulce...... groups. It is concluded that sympathetic nervous activity and serum gastrin concentrations are not influenced by sham feeding in contrast to the influence of insulin hypoglycemia....... an insulin test resulted in a 25-fold rise in plasma adrenaline. The ulcer patients showed significantly higher levels of plasma adrenaline and plasma noradrenaline than the normal subjects both before and after sham feeding, and this difference was probably not caused only by age difference in the two...

Quality control and stability study of 100 mg/ml paracetamol oral drops

International Nuclear Information System (INIS)

Garcia Penna, Caridad M.; Montes de Oca Porto, Yanet; Salomon Izquierdo, Suslebys

2013-01-01

Paracetamol is an effective analgesic and antipyretic drug of the non-steroidal anti-inflammatory drug group. Paracetamol oral drops are indicated for use in infant population aged up to 5 years to relieve fever, headache, toothache and symptomatic relief of common cold. To validate two analytical methods for the quality control and the stability study and to study the stability of 100 mg/ml Paracetamol oral drops made in Cuba

Determination of particle concentrations in multitemperature plasmas

International Nuclear Information System (INIS)

Richley, E.; Tuma, D.T.

1982-01-01

The use of the multitemperature Saha equation (MSE) of Prigogine 1 and Patapov 2 for calculating particle concentrations in plasmas is shown to be an invalid procedure. Errors greater than one order of magnitude in the electron density in high-pressure argon and nitrogen electric arc plasmas can be easily incurred by using the multitemperature Saha equation. The alternative kinetic method for calculating concentrations is shown to be based on firm concepts. Simpliying procedures and computational techniques for calculating concentrations with the kinetic method are illustrated with examples

Naproxen, paracetamol and pamabrom versus paracetamol, pyrilamine and pamabrom in primary dysmenorrhea: a randomized, double-blind clinical trial

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Mario I. Ortiz

2016-10-01

Full Text Available Resumen INTRODUCCIÓN La dismenorrea primaria es causada por la descarga de las prostaglandinas en el tejido uterino. Por lo tanto, los fármacos antiinflamatorios no esteroideos son la terapia inicial para la dismenorrea. El tratamiento para la dismenorrea puede incluir la administración de monoterapia o la combinación de fármacos. Sin embargo, la evidencia clínica científica sobre la eficacia de los medicamentos con dos o tres fármacos combinados es escasa o ausente. OBJETIVO Evaluar y comparar la eficacia y seguridad de dos combinaciones, en dosis fija y oral para el alivio de los síntomas de la dismenorrea primaria en mujeres mexicanas. Basados en la fisiopatología de la dismenorrea primaria, se utilizó una combinación comercializada en México de paracetamol, pirilamina y pamabrom. El comparador seleccionado fue un medicamento que contiene naproxeno sódico, paracetamol y pamabrom. MÉTODOS Se realizó un estudio en un solo centro, a doble ciego, experimental, paralelo y aleatorizado. Las pacientes con dismenorrea primaria que se incluyeron fueron mayores de 17 años de edad y con una intensidad del dolor mayor a 45 milímetros en una escala visual analógica. Las pacientes fueron aleatorizadas para recibir tabletas con naproxeno sódico, paracetamol y pamabrom o tabletas con paracetamol, pirilamina y pamabrom para un ciclo menstrual. Se evaluó la intensidad de la sintomatología y el dolor de las pacientes a lo largo de un período menstrual. Se utilizó análisis estadístico descriptivo e inferencial. RESULTADOS Se incluyó una población con intención de tratar de 91 mujeres, con una edad media de 21,3 ± 3,2 años la cual recibió tabletas de paracetamol, pirilamina y pamabrom. Otras 98 participantes, con una edad media de 21,0 ± 3,2 años, recibieron tabletas de naproxeno sódico, paracetamol y pamabrom. Las evaluaciones de dolor de las participantes con la escala visual analógica durante el ciclo menstrual demostraron

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants.

Science.gov (United States)

Ohlsson, Arne; Shah, Prakeshkumar S

2018-04-06

In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can be treated surgically; or medically with one of two prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that paracetamol may be an alternative for the closure of a PDA. An association between prenatal or postnatal exposure to paracetamol and later development of autism or autism spectrum disorder has been reported. To determine the effectiveness and safety of intravenous or oral paracetamol compared with placebo or no intervention, intravenous indomethacin, intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for treatment of an echocardiographically diagnosed PDA in preterm or low birth weight infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 6 November 2017), Embase (1980 to 6 November 2017), and CINAHL (1982 to 6 November 2017). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. We included RCTs in which paracetamol was compared to no intervention, placebo or other agents used for closure of PDA irrespective of dose, duration and mode of administration in preterm (≤ 34 weeks' postmenstrual age) infants. We both reviewed the search results and made a final selection of potentially eligible articles by discussion. We included studies of both prophylactic and therapeutic use of paracetamol. We performed data collection and analyses in accordance with the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence for the following outcomes when data were available: failure of ductal closure after the first course of treatment; neurodevelopmental impairment

COMPARISON OF THE EFFECTS OF INTERCOSTAL NERVE BLOCK WITH ROPIVACAINE AND INTRAVENOUS PARACETAMOL INFUSION TO INTRAVENOUS PARACETAMOL INFUSION ALONE FOR PAIN CONTROL AFTER OPEN CHOLECYSTECTOMY

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Somnath Dey

2017-11-01

Full Text Available BACKGROUND Postoperative pain after open cholecystectomy is associated with respiratory dysfunction, increased stress response and prolonged hospital stay. We compare intravenous paracetamol (7.5 mg/kg plus intercostal nerve block with local anaesthetic ropivacaine 0.5% to intravenous paracetamol (15 mg/kg on pain control after open cholecystectomy. MATERIALS AND METHODS 140 patients, who underwent for open cholecystectomy, were randomly divided into two groups of 70. The patients were randomly allocated to any of the following two groups depending upon the drug used for analgesia (Group P or Group I Intravenous paracetamol 15 mg/kg was given to patients of group P and paracetamol 7.5 mg/kg with Intercostal nerve block in right side 6-10 intercostal nerves with 2 ml local anaesthetic ropivacaine 0.5% in each space was given to patients of group I just after intubation before incision. When the patients were transferred to postoperative recovery room, intensity of pain was recorded by response from the patients using 100 mm linear visual analogue scale ranging from 0 to 100. The pain scoring was done in the immediate postoperative period (when the patient was able to communicate in the post anaesthesia care unit, at 30 minutes, 1 hr. then hourly up to 24 hrs. till patient complained of pain with VAS score 40 or more. RESULTS The severity of pain in VAS score was lower in immediate postoperative period, at 30 minutes, 1 hour and 2 hours postoperatively in group I than the group P and those were statistically significant (p<0.001. Duration of analgesia also significantly lower in group I. Mean duration of analgesia in group P is 161.9 ± 42.6 min and in group I is 241.3 ± 44.2 min (p<0.001. CONCLUSION Adding Intercostal nerve block to intravenous infusion of Paracetamol infusion (7.5 mg/kg is better than sole intravenous infusion of Paracetamol (15 mg/kg in controlling pain severity even after reducing dose of paracetamol after open

Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

Science.gov (United States)

Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

2014-01-01

Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

Science.gov (United States)

Brandlistuen, Ragnhild Eek; Ystrom, Eivind; Nulman, Irena; Koren, Gideon; Nordeng, Hedvig

2013-01-01

Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy. Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age. PMID:24163279

Paracetamol treatment for patent ductus arteriosus: practice and attitudes in Australia and New Zealand.

Science.gov (United States)

Dowd, L A; Wheeler, B J; Al-Sallami, H S; Broadbent, R S; Edmonds, L K; Medlicott, N J

2018-04-03

To describe the current clinical practices and attitudes of neonatologists towards paracetamol treatment of PDA in Australia (AU) and New Zealand (NZ). A web-based survey of all neonatologists registered under the 2017 Australia New Zealand Neonatal Network (ANZNN) was conducted. The response rate for the survey was 67%, (141/210). Of those respondents, 37% stated their unit had a written policy outlining how to treat patent ductus arteriosus (PDA). Of the written policies, 53% mentioned paracetamol treatment. The majority of the respondents (70%) have prescribed paracetamol for PDA closure. When comparing between countries, 79% of AU respondents had compared with 44% of NZ respondents. Successful ductal closure in the infants who received paracetamol was anecdotally reported by 61% of respondents. The main reasons for clinicians not prescribing paracetamol were due to preferential NSAID use (61%) and lack of evidence to indicate efficacy (49%). Many neonatologists in AU and NZ have prescribed paracetamol for PDA closure. However, considerable practice variations exist. The results from this study suggest there may be a role for paracetamol in the treatment of PDA, however, further research is required to clarify the optimal use and provide evidence of efficacy.

Decreased maternal plasma apelin concentrations in preeclampsia.

Science.gov (United States)

Bortoff, Katherine D; Qiu, Chunfang; Runyon, Scott; Williams, Michelle A; Maitra, Rangan

2012-01-01

Preeclampsia is a hypertensive disorder that complicates 3-7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case-control study of pregnant women. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. preclampsia and other hypertensive maternal disorders.

[Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain].

Science.gov (United States)

Kuntz, D; Brossel, R

1996-09-07

A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups. The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

Reduced plasma concentrations of vitamin B6 and increased ...

African Journals Online (AJOL)

Reduced plasma concentrations of vitamin B6 and increased plasma concentrations of the neurotoxin 3-hydroxykynurenine are associated with nodding syndrome: a case control study in Gulu and Amuru districts, Northern Uganda.

Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

Science.gov (United States)

Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

2015-08-01

Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

Degradation of Paracetamol by Photolysis Using C-N-codoped TiO2

OpenAIRE

Vanny Yulia Safitri; Adlis Santoni; Diana Vanda Wellia; Khoiriah Khoiriah; Safni Safni

2017-01-01

Paracetamol is generally used as analgesic and antipyretic drugs. Contamination paracetamol in the environment can occur because of waste material disposal from production site and immediate disposal of household that cause water pollution. Paracetamol is degraded by photolysis method under irradiation 10 watt UV-light (λ=365 nm), visible-light (Philips LED 13 watt 1400 lux) and solar-light with and without addition C-N-codoped TiO2catalyst. The solution is analyzed by UV-Vis spectrophotomete...

Radioimmunoassay of plasma myoglobin concentrations in normal persons

Energy Technology Data Exchange (ETDEWEB)

Milanov, S.; Milkov, V. (Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

1982-01-01

Plasma myoglobin concentrations by radioimmunoassay in 53 normal persons (29 women and 24 men) with ages ranging from 19 to 76 years. The average values for myoglobin concentrations in the plasma of 29 women, aged 19 to 76 years, are 4a.09 +- 4.51 ng/ml, while in 24 healthy men, aged 20 to 74 years, they are 54.39 +-4.68 ng/ml. The obtained results for the plasma myoglobin level in men are higher than the ones recorded in women at statistical significance p<0.05. In the group under study the plasma myoglobin values disclose also age-related differences, although lacking statistical significance (p>0.10).

Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids123

Science.gov (United States)

Sherry, Christina L.; Oliver, Jeffery S.; Renzi, Lisa M.; Marriage, Barbara J.

2014-01-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2–3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4–6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose–supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. PMID:24899160

Combined paracetamol and amitriptyline adsorption to activated charcoal

DEFF Research Database (Denmark)

Hoegberg, Lotte Christine Groth; Groenlykke, Thor Buch; Abildtrup, Ulla

2010-01-01

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix......® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed...... Ready-To-Use. The tested pH differences had minor effect on the adsorption. The mixed-drug adsorption showed about 40% Q(m) reduction of each drug with increasing amounts of drug/g AC, but the total gram of drug adsorbed to AC was increased compared to one-drug conditions. Conclusion. The adsorption...

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2012-01-01

AIMS Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P = 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P = 0.009). CONCLUSIONS Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres. PMID:22106945

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy

Directory of Open Access Journals (Sweden)

Çiğdem Ünal

2013-01-01

Full Text Available Backround: We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Materials and Methods: Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Results: Visual Analog Scale (VAS scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12 th h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml in group paracetamol (72.3 ± 38.0 ml and dexketoprofen trometamol (69.3 ± 24.1 ml was significantly lower than group placebo (129.3 ± 22.6 ml (P < 0.001. Global satisfaction scores of the patients in group placebo was significantly lower than group dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Conclusion: Dexketoprofen trometamol and Paracetamol didn′t cause significant change on pain scores, but increased patients′ comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not

REVIEW ARTICLE – Intravenous paracetamol in pediatrics: A global perspective

Directory of Open Access Journals (Sweden)

Muzammil Irshad, MBBS

2012-12-01

Full Text Available Intravenous (IV Paracetamol is an excellent post operative analgesic and antipyretic in children. Efficacy and tolerability of IV Propacetamol have been established in pediatric practice. It is believed that paracetamol works by inhibiting cyclooxygenase-2 (COX-2 enzymes. Studies bring to light that therapeutic doses of IV acetaminophen are effective and tolerable in children with least chances of hepatotoxicity. However, overdose toxicity has been reported in children and drug induced hypotension in febrile critically ill patients. Therapeutic doses according to body weight of neonates and children can be administered in hospital settings. Special education of health care staff regarding precise dose and solution is necessary to assess the role of IV paracetamol preparation in pediatric practice.

Plasma carnitine concentrations after chronic alcohol intoxication 

Directory of Open Access Journals (Sweden)

Alina Kępka

2013-05-01

Full Text Available Background: Carnitine transports fatty acids from the cytoplasm to the mitochondrial matrix, where the fatty acids are oxidized. Chronic alcohol consumption reduces the concentration of carnitine and interferes with oxidative processes occurring in the cell.Aim: The assessment of carnitine concentrations in plasma of chronically intoxicated alcohol dependent persons in a 49-day abstinence period.Material/Methods: The study included 31 patients (5 women and 27 men aged from 26 to 60 years (44.6± 8.9 and 32 healthy subjects (15 women and 17 men aged 22-60 years (39.8± 9.4. The patients’ alcohol dependence ranged from 2 to 30 years (13.6± 7.5. Examined subjects consumed 75-700 g of ethanol/day (226.9± 151.5. Plasma concentrations of free and total carnitine were measured three times: at the first (T0, 30th (T30 and 49th (T49 day of hospital detoxification. Free (FC and total (TC carnitine were determined by the spectrophotometric method. Plasma acylcarnitine (AC concentration was calculated from the difference between TC and FC; then the AC/FC ratio was calculated. To determine statistically significant differences for related variables, Student’s t-test was used.Results: At T0, alcoholics had significantly lower concentration of FC and TC (p < 0.05 in plasma, as compared to the control group. In comparison to controls, at T30, plasma TC and FC (p < 0.01 as well as AC (p < 0.001 were reduced. The lowest concentration of TC, FC and AC (p < 0.001was found at T49. The ratio of AC/FC at T0 had a tendency to be higher in alcoholics than in the control group (p = 0.05, whereas at T49 it was significantly lower in alcoholics as compared to the control subjects (p < 0.05.Conclusions: Chronic alcohol intoxication causes a plasma deficiency of carnitine. Forty-nine days of abstinence showed a significant decrease in the concentration of TC, FC and AC. Further research is necessary to clarify whether a low level of plasma carnitine

Bioanalytical method development and validation for determination of metoprolol tartarate and hydrochlorothiazide using HPTLC in human plasma

Directory of Open Access Journals (Sweden)

Ambadas Ranganath Rote

2013-12-01

Full Text Available A simple, sensitive, rapid and economic chromatographic method has been developed for determination of metoprolol tartarate and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The analytical technique used for method development was high-performance thin-layer chromatography. HPTLC Camag with precoated silica gel Plate 60F254 (20 cm×10 cm at 250 µm thicknesses (E. Merck, Darmstadt, Germany was used as the stationary phase. The mobile phase used consisted of chloroform: methanol: ammonia (9:1:0.5v/v/v. Densitometric analysis was carried out at a wavelength of 239 nm. The rf values for hydrochlorothiazide, paracetamol and metoprolol tartarate were 0.13±0.04, 0.28±0.05, 0.48±0.04, respectively. Plasma samples were extracted by protein precipitation with methanol. Concentration ranges of 200, 400, 600, 800, 1000, 1200 ng/mL and 2000, 4000, 6000, 8000, 10000, 12000 ng/mL of hydrochlorothiazide and metoprolol tartarate, respectively, were used with plasma for the calibration curves. The percent recovery of metoprolol tartarate and hydrochlorothiazide was found to be 77.30 and 77.02 %, respectively. The stability of metoprolol tartarate and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (-20 ºC on a bench for 24 hours and post-preparatively for 48 hours. The proposed method was validated statistically and proved suitable for determination of metoprolol tartarate and hydrochlorothiazide in human plasma.

Paracetamol for pain relief after surgical removal of lower wisdom teeth

NARCIS (Netherlands)

Weil, K.; Hooper, L.; Afzal, Z.; Esposito, M.; Worthington, H.V.; van Wijk, A.J.; Coulthard, P.

2008-01-01

Background: Paracetamol has been commonly used for the relief of postoperative pain following oral surgery. In this review we investigated the optimal dose of paracetamol and the optimal time for drug administration to provide pain relief, taking into account the side effects of different doses of

Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?

Directory of Open Access Journals (Sweden)

Kalsi SS

2011-10-01

Full Text Available Sarbjeet S Kalsi1,2, David M Wood2–4, W Stephen Waring5, Paul I Dargan2–4 1Emergency Department, 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London; 3King's Health Partners, 4King's College London, London; 5York Teaching Hospital NHS Foundation Trust, York, UK Abstract: Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI. In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as “high-risk” after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose. Keywords

Analgesic activity of fixed dose combinations of paracetamol with diclofenac sodium and paracetamol with tramadol on different pain models in healthy volunteers - A randomized double blind crossover study

Directory of Open Access Journals (Sweden)

Sachidanand Tripathi

2012-01-01

Conclusion: Paracetamol with tramadol combination was more effective than paracetamol with diclofenac sodium combination on the radiant heat model. In human pain models, there is an incomplete understanding of mechanisms and activated pathways are not precisely determined that needs further evaluation.

Increased plasma fibronectin concentrations in obesity

DEFF Research Database (Denmark)

Andersen, T; Dejgaard, A; Astrup, A

1987-01-01

In 23 morbidly obese patients we investigated the influence of a large weight loss (30.6 kg, range 17.5-90.8) on the plasma fibronectin concentrations. Further, changes in plasma fibronectin were related to serum insulin levels and to liver biochemistry. Between the measurements patients had been...... treated with an intermittent very-low-calorie formula diet sufficient in respect to protein, minerals and vitamins. They were investigated in weight-stable states. Before weight reduction, 14 patients (61%, 95% confidence limits 39-80%) had elevated plasma fibronectin levels. Plasma fibronectin decreased...... (medians 1.22 and 0.59 mumol/l before and after weight loss, p less than 0.01) and was after weight loss within the normal range in 14 patients. The change in plasma fibronectin was unassociated with the magnitude of the weight loss as well as with the reduction of overweight. The resulting plasma...

Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

Science.gov (United States)

Schoenmakers, I; Kooistra, H S; Okkens, A C; Hazewinkel, H A; Bevers, M M; Mol, J A

1997-01-01

The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

Risk factors contributing to a low darunavir plasma concentration

NARCIS (Netherlands)

Daskapan, Alper; Stienstra, Ymkje; Kosterink, Jos G.W.; Bierman, Wouter F.W.; van der Werf, Tjip S.; Touw, Daan J.; Alffenaar, Jan Willem C.

Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till

Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

DEFF Research Database (Denmark)

Jepsen, P; Schmidt, L E; Larsen, F S

2010-01-01

The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

Plasma concentrations of endothelin in patients with abnormal vascular reactivity

International Nuclear Information System (INIS)

Predel, H.G.; Meyer-Lehnert, H.; Baecker, A.; Stelkens, H.; Kramer, H.J.

1990-01-01

We measured circulating concentrations of endothelin in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radioimmunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects, in patients with diabetes mellitus type I, in patients with mild to moderate essential hypertension and in non-dialyzed patients with stable chronic renal failure. Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0±0.6 pg/ml, 4.7±0.2 pg/ml and 6.5±1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6±2.9 pg/ml. No correlations were observed between serum creatinine concentrations ranging from 124 to 850 μmol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin

Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents.

Science.gov (United States)

Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr; Williams, David G; Eccleston, Christopher

2017-08-02

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Paracetamol (acetaminophen) is one of the most widely used analgesics in both adults and children. The recommended dosage in the UK, Europe, Australia, and the USA for children and adolescents is generally 10 to 15 mg/kg every four to six hours, with specific age ranges from 60 mg (6 to 12 months old) up to 500 to 1000 mg (over 12 years old). Paracetamol is the only recommended analgesic for children under 3 months of age. Paracetamol has been proven to be safe in appropriate and controlled dosages, however potential adverse effects of paracetamol if overdosed or overused in children include liver and kidney failure. To assess the analgesic efficacy and adverse events of paracetamol (acetaminophen) used

Effect of paracetamol injection on the analgesic effect of tramadol in ...

African Journals Online (AJOL)

Five dogs each were randomly treated with 30mg/kg paracetamol (treatment KXDTA) intravenously or equal volume of normal saline (treatment KXDTS) to evaluate if paracetamol potentiate the analgesic effects of tramadol during the intra-operative period. Thirty minutes later, both groups were treated with 3mg/kg tramadol ...

Safety of Oral Paracetamol – Analysis of Data from a Spontaneous ...

African Journals Online (AJOL)

Purpose: To determine the safety of oral coated paracetamol tablets 500 mg and oral suspension 120 mg/5 mL produced by Hasco-Lek Poland. Methods: We analyzed sales volume and data obtained from the monitoring of spontaneous reports on the adverse effects of paracetamol collected in the period between ...

Altering plasma sodium concentration rapidly changes blood pressure during haemodialysis.

Science.gov (United States)

Suckling, Rebecca J; Swift, Pauline A; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

2013-08-01

Plasma sodium is increased following each meal containing salt. There is an increasing interest in the effects of plasma sodium concentration, and it has been suggested that it may have direct effects on blood pressure (BP) and possibly influences endothelial function. Experimental increases of plasma sodium concentration rapidly raise BP even when extracellular volume falls. Ten patients with end-stage renal failure established on haemodialysis were studied during the first 2 h of dialysis without fluid removal during this period. They were randomized to receive haemodialysis with (i) dialysate sodium concentration prescribed to 135 mmol/L and (ii) 145 mmol/L in random order in a prospective, single-blinded crossover study. BP measurements and blood samples were taken every 30 min. Pre-dialysis sitting BP was 137/76 ± 7/3 mmHg. Lower dialysate sodium concentration (135 mmol/L) reduced plasma sodium concentration [139.49 ± 0.67 to 135.94 ± 0.52 mmol/L (P area under the curve (AUC) 15823.50 ± 777.15 (mmHg)min] compared with 145 mmol/L [AUC 17018.20 ± 1102.17 (mmHg)min], mean difference 1194.70 ± 488.41 (mmHg)min, P < 0.05. There was a significant positive relationship between change in plasma sodium concentration and change in systolic BP. This direct relationship suggests that a fall of 1 mmol/L in plasma sodium concentration would be associated with a 1.7 mmHg reduction in systolic BP (P < 0.05). The potential mechanism for the increase in BP seen with salt intake may be through small but significant changes in plasma sodium concentration.

[Intentional paracetamol intoxication in children

NARCIS (Netherlands)

Bisschops, L.L.; Bisschops, W.A.; Vroegop, M.P.; Rossum, L.K. van; Kramers, C.

2011-01-01

As paracetamol is widely used and easily available acetaminophen auto-intoxication is frequently seen. In the majority of patients no complications will occur, but in a small group it may lead to liver damage and death. Children are less susceptible to complications than adults. Cornerstone of

Application of Response Surface Methodology for Optimization of Paracetamol Particles Formation by RESS Method

International Nuclear Information System (INIS)

Sabet, J.K.; Ghotbi, C.; Dorkoosh, F.

2012-01-01

Ultrafine particles of paracetamol were produced by Rapid Expansion of Supercritical Solution (RESS). The experiments were conducted to investigate the effects of extraction temperature (313-353 K), extraction pressure (10-18 MPa), pre expansion temperature (363-403 K), and post expansion temperature (273-323 K) on particles size and morphology of paracetamol particles. The characterization of the particles was determined by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Liquid Chromatography/Mass Spectrometry (LC-MS) analysis. The average particle size of the original paracetamol was 20.8 μm, while the average particle size of paracetamol after nan onization via the RESS process was 0.46 μm depending on the experimental conditions used. Moreover, the morphology of the processed particles changed to spherical and regular while the virgin particles of paracetamol were needle-shape and irregular. Response surface methodology (RSM) was used to optimize the process parameters. The extraction temperature, 347 K; extraction pressure, 12 MPa; pre expansion temperature, 403?K; and post expansion temperature, 322 K was found to be the optimum conditions to achieve the minimum average particle size of paracetamol.

Paracetamol. Ny viden om virkningsmekanismer samt smertelindrende og antiinflammatorisk effekt sammenlignet med ikke-steroide antiinflammatorika

DEFF Research Database (Denmark)

Handberg, G

2000-01-01

Paracetamol is usually termed a peripheral analgesic from the common belief that its site of action is near the injury. In this review a possible central action is summarised. Furthermore the analgesic effect of paracetamol is compared to non-steroidal anti-inflammatory drugs and the possible anti......-inflammatory effect of paracetamol is discussed....

Oral fixed drug combination analgesic tramadol/paracetamol: Benefits for patients and budgets

NARCIS (Netherlands)

M.J.C. Nuijten (Mark); B.P. Nautrup (Barbara Poulsen); H. Liedgens (Hiltrud)

2006-01-01

textabstractAlthough pain can present in many different ways, acute, subacute and chronic pain are frequently used and helpful categories that cover a wide range of pain phenomena. This paper reviews five cost-minimization studies of tramadol/paracetamol compared with codeine/paracetamol,

A study of the changes during heating of paracetamol.

Science.gov (United States)

de Wet, F N; Gerber, J J; Lötter, A P; van der Watt, J G; Dekker, T G

1998-05-01

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of paracetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the formation of either of the two morphs. To study the cooling rate required for production of form II, paracetamol samples were melted in a differential scanning calorimeter, cooled at three specific rates, and melted again. In all of the samples, cooling resulted in the glassy form followed by recrystallization and the melting of form II. On the hot-stage microscope both forms were produced in one sample. Standardizing conditions for prediction of the resulting form remains a problem. There seems to be a great deal of overlap of the two forms' transition phases, which would make it difficult to force the crystallization of one form by keeping the solution or melt at a specific temperature. The thermal behavior of paracetamol during the heating and cooling phases must be understood in order to manipulate the process. A video camera mounted on a hot-stage microscope was used to follow the changes during heating and cooling of both forms. Nucleation, crystal growth, habit transformation, sublimation, and the final melt are shown on snap shots taken from the video.

Radiolytic degradation of paracetamol in dilute aqueous solution

International Nuclear Information System (INIS)

Szabo, L.; Toth, T.; Homlok, R.; Takacs, E.; Wojnarovits, L.

2011-01-01

Complete text of publication follows. Paracetamol or with name acetaminophen is widely used as analgesic and antipyretic drug. Due to its heavy use it is regularly detected in the surface waters. The degradation of the compound formerly was studied in several advanced oxidation processes (UV/H 2 O 2 , UV/TiO 2 , electrochemical oxidation, ozonation). Here we report on the radiolytic degradation. In the experimental work we combined a wide variety of techniques. For the investigation of the intermediates pulse radiolysis, for end-product experiments (decolouration, mineralization) gamma irradiation were used together with UV-Vis spectroscopy, HPLC separation (with diode array and MS-MS detection), chemical oxygen demand, total organic carbon content and toxicity measurements. · OH radicals are the main oxidative species during irradiation. They add to the aromatic ring producing hydroxycyclohexadienyl type radicals. These radicals either transform to hydroxy-paracetamol stable products in several reaction steps, or after water elimination transform to semi-iminoquinone radical. The reaction of hydroxycyclohexadienyl radicals with O 2 yields peroxi radicals. The latter radicals may eliminate HO 2 · or undergo ring opening and transformation, first to different carboxylic acids, and finally (mineralization) to CO 2 , H 2 O and NH 3 or NO 2 . Paracetamol has a relatively low toxicity. In 10 -3 mol dm -3 DCF solution after irradiation some products (e.g. hydroquinone, acetamide) are more toxic than paracetamol. By increasing the dose the toxicity suddenly decreases. It seems that the toxic products are highly sensitive to irradiation treatment.

High-pressure high-temperature phase diagram of organic crystal paracetamol

Science.gov (United States)

Smith, Spencer J.; Montgomery, Jeffrey M.; Vohra, Yogesh K.

2016-01-01

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped heating diamond anvil. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in five different experiments. Solid state phase transitions from monoclinic Form I  →  orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II  →  unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. This new data is combined with previous ambient temperature high-pressure Raman and x-ray diffraction data to create the first HPHT phase diagram of paracetamol.

High-pressure high-temperature phase diagram of organic crystal paracetamol

International Nuclear Information System (INIS)

Smith, Spencer J; Montgomery, Jeffrey M; Vohra, Yogesh K

2016-01-01

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped heating diamond anvil. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in five different experiments. Solid state phase transitions from monoclinic Form I  →  orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II  →  unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. This new data is combined with previous ambient temperature high-pressure Raman and x-ray diffraction data to create the first HPHT phase diagram of paracetamol. (paper)

Conformational and vibrational reassessment of solid paracetamol

Science.gov (United States)

Amado, Ana M.; Azevedo, Celeste; Ribeiro-Claro, Paulo J. A.

2017-08-01

This work provides an answer to the urge for a more detailed and accurate knowledge of the vibrational spectrum of the widely used analgesic/antipyretic drug commonly known as paracetamol. A comprehensive spectroscopic analysis - including infrared, Raman, and inelastic neutron scattering (INS) - is combined with a computational approach which takes account for the effects of intermolecular interactions in the solid state. This allows a full reassessment of the vibrational assignments for Paracetamol, thus preventing the propagation of incorrect data analysis and misassignments already found in the literature. In particular, the vibrational modes involving the hydrogen-bonded Nsbnd H and Osbnd H groups are correctly reallocated to bands shifted by up to 300 cm- 1 relatively to previous assignments.

Plasma and skin vitamin E concentrations in canine atopic dermatitis.

Science.gov (United States)

Plevnik Kapun, Alja; Salobir, Janez; Levart, Alenka; Tavčar Kalcher, Gabrijela; Nemec Svete, Alenka; Kotnik, Tina

2013-01-01

Altered homeostasis of vitamin E has been demonstrated in human atopic dermatitis. Data on plasma and skin vitamin E concentrations in canine atopic dermatitis (CAD) are not available. To determine vitamin E concentrations in plasma and skin of atopic dogs. Vitamin E concentrations in plasma and full-thickness skin biopsies of 15 atopic dogs were related to CAD extent and severity index (CADESI-03) scores and compared to the equivalent concentrations in 17 healthy dogs. Statistically significant differences of measured parameters between the two groups were determined by the nonparametric Mann Whitney U test and correlations between CADESI-03 scores and vitamin E concentrations were evaluated by the Spearman rank test. A value of P vitamin E were significantly lower in atopic dogs than in healthy dogs, with median values of 29.8 and 52.9 μmol/L, respectively. Skin vitamin E values did not differ significantly between patients and healthy controls. The median concentration of skin vitamin E in atopic dogs was higher than that in healthy dogs. No significant correlations were found between CADESI-03 score and plasma vitamin E or skin vitamin E concentrations. Significantly lower plasma vitamin E concentrations in atopic dogs than in healthy controls indicate altered homeostasis of vitamin E in CAD. Further investigation into vitamin E supplementation in CAD is warranted.

Relationship between the concentrations of plasma phospholipid stearic acid and plasma lipoprotein lipids in healthy men.

Science.gov (United States)

Li, D

2001-01-01

This study investigated the correlation between the plasma phospholipid (PL) saturated fatty acid (SFA) concentration (as a surrogate marker of SFA intake) and plasma lipid and lipoprotein lipid concentrations in 139 healthy Australian men aged 20-55 years old with widely varying intakes of saturated fat (vegans, n=18; ovolacto vegetarians, n=43; moderate meat eaters, n=60; high meat eaters, n=18). Both the ovolacto vegetarian and vegan groups demonstrated significant decreases in plasma total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations compared with both the high-meat-eater and moderate-meat-eater groups. Total SFA and individual SFA [palmitic acid (16:0), stearic acid (18:0) and arachidic acid (20:0)] in the plasma PL were significantly lower in both the ovolacto vegetarian and vegan groups than in both the high- and moderate-meat-eater groups, while myristic acid (14:0) was significantly lower in the vegans than in the high-meat-eaters. Bivariate analysis of the results showed that the plasma PL stearic acid concentration was strongly positively correlated with plasma TC (P<0.0001), LDL-C (P<0.0001) and triacylglycerol (P<0.0001), with r(2) values of 0.655, 0.518 and 0.43 respectively. In multiple linear regression, after controlling for potential confounding factors (such as exercise, dietary group, age, body mass index, plasma PL myristic acid, palmitic acid and arachidic acid, and dietary total fat, saturated fat, cholesterol, carbohydrate and fibre intake), the plasma PL stearic acid concentration was still strongly positively correlated with plasma TC (P<0.0001) and LDL-C (P=0.006) concentrations. Based on the present data, it would seem appropriate for the population to reduce their dietary total SFA intake rather than to replace other SFA with stearic acid.

SEGURIDAD DEL PARACETAMOL EN CUBA. 2003 - 2008

Directory of Open Access Journals (Sweden)

Ashley Chao Cardeso

2010-01-01

Full Text Available n observational, descriptive and retrospective study was realized to characterize the behavior of the adverse reactions related to paracetamol, including in the data base of the National Coordinating Unit of Pharmacovigilance, in the period included from January of the 2003 to December of the 2008.Once identified the main's adverse reactions associated to the use of paracetamol and organs' systems more affected it was determined his distribution by sex and groups of ages. In addition, severity and causality were classified accordantly to the avoidable reactions and their causes.Of the 612 notified reactions, the cutaneous eruptions were those of greater quantity (52.2%, corresponding this result with the system of organs more affected, then it was the skin (54.4%. Feminine sex and the group of age between the 16 and 39 years, presented/displayed the majors percents of undesirable effects, with 62.9% and 30.2%, respectively. The behavior, as far as severity and causality, was not different from what it was reported in other studies because the slight reactions predominated (56.7% and probable (80.2%. As far as the avoidable, the 69.1% of the reactions were catalogued like no avoidable, in as much, the errors in the indication of paracetamol constituted the main evitable cause.

Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain.

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Heiskanen, Tarja; Langel, Kaarina; Gunnar, Teemu; Lillsunde, Pirjo; Kalso, Eija A

2015-10-01

Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R(2) = 0.628 and 0.700, respectively), but not morphine (R(2) = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Plasma concentrations of midazolam during continuous subcutaneous administration in palliative care.

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Bleasel, M D; Peterson, G M; Dunne, P F

1994-01-01

We have investigated the steady-state plasma concentrations of midazolam during continuous subcutaneous administration in palliative care. Using a sensitive gas chromatography with electron capture detector assay, plasma concentrations of midazolam were measured in 11 patients (median age 68 years; range 47-82 years; six females) receiving the drug by continuous subcutaneous infusion (median rate 20 mg/day; range 10-60 mg/day). While not significant, the infusion rate tended to decrease with increasing age of the patient (Spearman's p = -0.51; p = 0.11). The steady-state plasma concentration range was 10-147 ng/ml, with a median of 30 ng/ml. Infusion rates and plasma concentrations of midazolam were correlated (Spearman's p = 0.71; p < 0.05). No other significant relationships were found between plasma concentrations and the variables of age, sex and liver function.

Photocatalytic degradation of paracetamol: intermediates and total reaction mechanism.

Science.gov (United States)

Moctezuma, Edgar; Leyva, Elisa; Aguilar, Claudia A; Luna, Raúl A; Montalvo, Carlos

2012-12-01

The advanced oxidation of paracetamol (PAM) promoted by TiO(2)/UV system in aqueous medium was investigated. Monitoring this reaction by HPLC and TOC, it was demonstrated that while oxidation of paracetamol is quite efficient under these conditions, its mineralization is not complete. HPLC indicated the formation of hydroquinone, benzoquinone, p-aminophenol and p-nitrophenol in the reaction mixtures. Further evidence of p-nitrophenol formation was obtained following the reaction by UV-vis spectroscopy. Continuous monitoring by IR spectroscopy demonstrated the breaking of the aromatic amide present in PAM and subsequent formation of several aromatic intermediate compounds such as p-aminophenol and p-nitrophenol. These aromatic compounds were eventually converted into trans-unsaturated carboxylic acids. Based on these experimental results, an alternative deacylation mechanism for the photocatalytic oxidation of paracetamol is proposed. Our studies also demonstrated IR spectroscopy to be a useful technique to investigate oxidative mechanisms of pharmaceutical compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review

DEFF Research Database (Denmark)

Hyllested, M; Jones, S; Pedersen, J L

2002-01-01

BACKGROUND: Quantitative reviews of postoperative pain management have demonstrated that the number of patients needed to treat for one patient to achieve at least 50% pain relief (NNT) is 2.7 for ibuprofen (400 mg) and 4.6 for paracetamol (1000 mg), both compared with placebo. However, direct...... comparisons between paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been extensively reviewed. The aims of this review are (i) to compare the analgesic and adverse effects of paracetamol with those of other NSAIDs in postoperative pain, (ii) to compare the effects of combined...... paracetamol and NSAID with those of either drug alone, and (iii) to discuss whether the adverse effects of NSAIDs in short-term use are justified by their analgesic effects, compared with paracetamol. METHODS: Medline (1966 to January 2001) and the Cochrane Library (January 2001) were used to perform...

Intoxicación suicida por paracetamol Suicidal poisoning with paracetamol

OpenAIRE

J. Blanco Pampín; N. Morte Tamayo

2002-01-01

La intoxicación por paracetamol es un hecho verdaderamente infrecuente, debido sobre todo al elevado rango terapéutico que posee. Los efectos letales de su ingestión a menudo son el resultado de las complicaciones que originan, aunque por efecto directo del fármaco (intoxicación aguda) se producen tanto en suicidios como a causa de sobredosis en búsqueda de analgesia (intoxicación medicamentosa accidental). El presente artículo expone el caso de una mujer joven con antecedentes psiquiátricos,...

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

Science.gov (United States)

Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

2015-11-01

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed

Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury

DEFF Research Database (Denmark)

Schmidt, Lars E; Knudsen, Tore Tveit; Dalhoff, Kim

2002-01-01

Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients with paraceta......Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients...... with paracetamol poisoning without signs of hepatocellular injury. Prothrombin index had been recorded before, and serially during, acetylcysteine treatment in 87 patients. After initiation of treatment, prothrombin index decreased (mean 0.33, 95% CI 0.29-0.38) in all patients, and was strongly associated...... with the start of acetylcysteine infusion. In patients with uncomplicated paracetamol poisoning, a fall in this index might be misinterpreted as a sign of liver failure, leading to prolonged treatment time....

Determinação de paracetamol em produtos farmacêuticos usando um biossensor de pasta de carbono modificado com extrato bruto de abobrinha (Cucurbita pepo

Directory of Open Access Journals (Sweden)

Vieira Iolanda Cruz

2003-01-01

Full Text Available Crude extracts of several vegetables such as peach (Prunus persica, yam (Alocasia macrorhiza, manioc (Manihot utilissima, artichoke (Cynara scolymus L, sweet potato (Ipomoea batatas (L. Lam., turnip (Brassica campestre ssp. rapifera, horseradish (Armoracia rusticana and zucchini (Cucurbita pepo were investigated as the source of peroxidase (POD: EC 1.11.1.7. Among those, zucchini (Cucurbita pepo crude extract was found to be the best one. This enzyme in the presence of hydrogen peroxide catalyses the oxidation of paracetamol to N-acetyl-p-benzoquinoneimine which the electrochemical reduction back to paracetamol was obtained at a peak potential of fraction three-quarters0.10V. A cyclic voltammetric study was performed by scanning the potential from + 0.5 to fraction three-quarters 0.5 V. The recovery of paracetamol from two samples ranged from 97.3 to 106% and a rectilinear calibration curve for paracetamol concentration from 1.2x10-4 to 2.5x10-3 mol L-1 (r=0.9965 were obtained. The detection limit was 6.9x10-5 mol L-1 and the relative standard deviation was less than 1.1% for a solution containing 2.5x10-3 mol L-1 paracetamol and 2.0x10-3 mol L-1 hydrogen peroxide (n=12. The results obtained for paracetamol in pharmaceutical products using the proposed biosensor and Pharmacopoeial procedures are in agreement at the 95% confidence level.

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants

Science.gov (United States)

Fisher, B.G.; Thankamony, A.; Hughes, I.A.; Ong, K.K.; Dunger, D.B.; Acerini, C.L.

2016-01-01

STUDY QUESTION What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8–14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER Intrauterine paracetamol exposure during 8–14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8–14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE Paracetamol exposure during 8–14

Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Magnus, Maria C; Karlstad, Øystein; Håberg, Siri E; Nafstad, Per; Davey Smith, George; Nystad, Wenche

2016-04-01

Paracetamol exposure has been positively associated with asthma development. The relative importance of prenatal vs infant exposure and confounding by indication remains elusive. We examined the association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication. We used information from the Norwegian Mother and Child Cohort Study, including 53169 children for evaluation of current asthma at 3 years, 25394 for current asthma at 7 years and 45607 for dispensed asthma medications at 7 years in the Norwegian Prescription Database. We calculated adjusted relative risks (adj. RR) and 95% confidence intervals (CI) using log-binomial regression. There were independent modest associations between asthma at 3 years with prenatal paracetamol exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years. This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Our findings suggest that the associations could not be fully explained by confounding by indication. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Concomitant overdosing of other drugs in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, Lars E; Dalhoff, Kim

2002-01-01

of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal...... was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more...... favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity...

Plasma fibronectin concentrations in patients with liver diseases

DEFF Research Database (Denmark)

Gluud, C; Dejgaard, A; Clemmensen, I

1983-01-01

age- and sex-matched healthy controls in patients with chronic persistent or chronic active hepatitis (n = 7), primary biliary cirrhosis (n = 8), alcoholic fatty liver (n = 9), alcoholic hepatitis (n = 10), and alcoholic cirrhosis (n = 16). Patients with acute viral hepatitis (type A (n = 2); type B...... (n = 7); type non A, non B (n = 1] had significantly (P less than 0.01) raised plasma fibronectin concentrations (median 506 mg/l (range 339-804] compared to controls (median 399 mg/l (range 304-462]. Morbidly obese patients with fatty liver (n = 11) had significantly (P less than 0.001) raised......Plasma, obtained just prior to diagnostic liver biopsy in 71 patients with various liver diseases, was examined by electroimmunoassay using immunoglobulin against human fibronectin and purified plasma fibronectin as standard. The plasma fibronectin concentration was not significantly different from...

Fetal plasma erythropoietin concentration in severe growth retardation.

Science.gov (United States)

Snijders, R J; Abbas, A; Melby, O; Ireland, R M; Nicolaides, K H

1993-02-01

The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

DEFF Research Database (Denmark)

Rasmussen, M L; Dierking, G; Lech, K

2008-01-01

BACKGROUND: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy. METHODS: One hundred...... and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg...... or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation...

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

2004-01-01

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg....../kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin...

Radiolytic degradation of paracetamol in dilute aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Szabo, L [Hungarian Academy of Sciences, Budapest (Hungary). Inst. of Isotopes; Budapest University of Technology and Economics, Budapest (Hungary); Toth, T [Budapest University of Technology and Economics, Budapest (Hungary); Homlok, R; Takacs, E; Wojnarovits, L [Hungarian Academy of Sciences, Budapest (Hungary). Inst. of Isotopes

2011-07-01

Complete text of publication follows. Paracetamol or with name acetaminophen is widely used as analgesic and antipyretic drug. Due to its heavy use it is regularly detected in the surface waters. The degradation of the compound formerly was studied in several advanced oxidation processes (UV/H{sub 2}O{sub 2}, UV/TiO{sub 2}, electrochemical oxidation, ozonation). Here we report on the radiolytic degradation. In the experimental work we combined a wide variety of techniques. For the investigation of the intermediates pulse radiolysis, for end-product experiments (decolouration, mineralization) gamma irradiation were used together with UV-Vis spectroscopy, HPLC separation (with diode array and MS-MS detection), chemical oxygen demand, total organic carbon content and toxicity measurements. {sup {center_dot}O}H radicals are the main oxidative species during irradiation. They add to the aromatic ring producing hydroxycyclohexadienyl type radicals. These radicals either transform to hydroxy-paracetamol stable products in several reaction steps, or after water elimination transform to semi-iminoquinone radical. The reaction of hydroxycyclohexadienyl radicals with O{sub 2} yields peroxi radicals. The latter radicals may eliminate HO{sub 2}{sup {center_dot}} or undergo ring opening and transformation, first to different carboxylic acids, and finally (mineralization) to CO{sub 2}, H{sub 2}O and NH{sub 3} or NO{sub 2}. Paracetamol has a relatively low toxicity. In 10{sup -3} mol dm{sup -3} DCF solution after irradiation some products (e.g. hydroquinone, acetamide) are more toxic than paracetamol. By increasing the dose the toxicity suddenly decreases. It seems that the toxic products are highly sensitive to irradiation treatment.

Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol

Science.gov (United States)

Yehia, Ali M.; Mohamed, Heba M.

2016-01-01

Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients' interference.

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants

NARCIS (Netherlands)

E.H.J. Krekels (Elke); S. Van Ham (Saskia); K.M. Allegaert (Karel); J.N. de Hoon; D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

2015-01-01

textabstractPurpose: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling

Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

Energy Technology Data Exchange (ETDEWEB)

Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

1971-09-15

The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility

DEFF Research Database (Denmark)

Holm, Jacob Bak; Mazaud-Guittot, Severine; Danneskiold-Samsøe, Niels Banhos

2016-01-01

in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers......, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect...... of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels...

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

Science.gov (United States)

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

Plasma procalcitonin concentrations are increased in dogs with sepsis

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Goggs, Robert; Milloway, Matthew; Troia, Roberta; Giunti, Massimo

2018-01-01

Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1–164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2–63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis. PMID:29682292

Concentration of plasma haptoglobin and symptomatic cerebral vasospasm after subarachnoid hemorrhage

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FAN Yi-mu

2013-08-01

Full Text Available The relation of plasma haptoglobin concentration to symptomatic cerebral vasospasm (SCVS after subarachnoid hemorrhage (SAH was investigated. The plasma concentration of haptoglobin was analyzed by enzyme-linked immunosorbent assay (ELISA. SCVS was determined by aggravated headache, deteriorated conscious state a few days after ictus or by new neurologic impairment and new ischemic injuries on repeated CT scans. The mean concentration of plasma haptoglobin in 19 patients with SCVS was (0.29 ± 0.14 g/L, whereas it was (0.78 ± 0.48 g/L in 24 patients without SCVS. These findings may suggest that plasma haptoglobin concentration seems to be associated with the development of SCVS after SAH.

Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

International Nuclear Information System (INIS)

Abd El Rahman, N.A.

2012-01-01

L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

International Nuclear Information System (INIS)

Elson, E.M.; Ridley, N.T.F.

2000-01-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Paracetamol as a prophylactic analgesic for hysterosalpingography: A double blind randomized controlled trial

Energy Technology Data Exchange (ETDEWEB)

Elson, E.M.; Ridley, N.T.F

2000-09-01

AIM: To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG). DESIGN: A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded. RESULTS: Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations. CONCLUSION: Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic

Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults.

Science.gov (United States)

Stephens, Guy; Derry, Sheena; Moore, R Andrew

2016-06-16

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria

Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations.

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McGregor, D O; Dellow, W J; Lever, M; George, P M; Robson, R A; Chambers, S T

2001-06-01

Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity. Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression. Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy. DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants.

Science.gov (United States)

Ohlsson, Arne; Shah, Prakeshkumar S

2015-03-11

In preterm newborns, the ductus arteriosus frequently fails to close and the infants require medical or surgical closure of the patent ductus arteriosus (PDA). A PDA can be treated surgically or medically with one of two prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that paracetamol may be an alternative for the closure of a PDA. Concerns have been raised that in neonatal mice paracetamol may cause adverse effects on the developing brain, and an association between prenatal exposure to paracetamol and later development of autism or autism spectrum disorder has been reported. To determine the efficacy and safety of intravenous or oral paracetamol compared with placebo or no intervention, intravenous indomethacin, intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for closure of a PDA in preterm or low-birth-weight infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, EMBASE and CINAHL. We searched abstracts from the meetings of the Pediatric Academic Societies and the Perinatal Society of Australia and New Zealand. We searched clinicaltrials.gov; controlled-trials.com; anzctr.org.au; World Health Organization International Clinical Trials Registry Platform at who.int/ictrp for ongoing trials and the Web of Science for articles quoting identified randomised controlled trials. We searched the first 200 hits on Google Scholar(TM) to identify grey literature. All searches were conducted in December 2013. A repeat search of MEDLINE in August 2014 did not identify any new trials. We identified two randomised controlled trials (RCTs) that compared oral paracetamol to oral ibuprofen for the treatment of an echocardiographically diagnosed PDA in infants born preterm (≤ 34 weeks postmenstrual age (PMA)). We performed data collection and analyses in accordance with the

Estimation of the growth kinetics for the cooling crystallisation of paracetamol and ethanol solutions

Science.gov (United States)

Mitchell, Niall A.; Ó'Ciardhá, Clifford T.; Frawley, Patrick J.

2011-08-01

This work details the estimation of the growth kinetics of paracetamol in ethanol solutions for cooling crystallisation processes, by means of isothermal seeded batch experiments. The growth kinetics of paracetamol crystals were evaluated in isolation, with the growth rate assumed to be size independent. Prior knowledge of the Metastable Zone Width (MSZW) was required, so that supersaturation ratios of 1.7-1.1 could be induced in solution without the occurrence of nucleation. The technique involved the utilisation of two in-situ Process Analytical Techniques (PATs), with a Focused Beam Reflectance Measurement (FBRM ®) utilised to ensure that negligible nucleation occurred and an Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) probe employed for online monitoring of solute concentration. Initial Particle Size Distributions (PSDs) were used in conjunction with desupersaturation profiles to determine the growth rate as a function of temperature and supersaturation. Furthermore, the effects of seed loading and size on the crystal growth rate were investigated. A numerical model, incorporating the population balance equation and the method of moments, was utilised to describe the crystal growth process. Experimental parameters were compared to the model simulation, with the accuracy of the model validated by means of the final product PSDs and solute concentration.

RP-HPLC-DAD method for the determination of phenylepherine, paracetamol, caffeine and chlorpheniramine in bulk and marketed formulation

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A.P. Dewani

2014-11-01

Full Text Available A simple, specific and accurate isocratic RP-HPLC-DAD method was developed for the simultaneous determination of phenylephrine, paracetamol, caffeine and chlorpheniramine in bulk and tablet dosage form. The four contents are present in variable concentrations and have variable chromatographic behavior making the process of analysis very difficult. For present studies a reversed-phase C-18 column (150 mm × 4.5 mm i.d., particle size 5 μm with mobile phase consisting of acetonitrile, methanol and 10 Mm phosphate buffer 16:22:62 (v/v (pH of buffer 2.5 ± 0.02, adjusted with ortho phosphoric acid was used. The flow rate was 1.0 ml/min and eluents were monitored at 280 nm. The mean retention times of phenylephrine, paracetamol, caffeine and chlorpheniramine were found to be 1.8, 3.1, 5.2 and 10.9 min, respectively. The method was validated in terms of linearity, range, specificity, accuracy, precision and robustness. The proposed method was successfully applied to the estimation of phenylephrine, paracetamol, caffeine and chlorpheniramine in combined tablet dosage form.

Patients' knowledge about paracetamol (acetaminophen): a study in a French hospital emergency department.

Science.gov (United States)

Boudjemai, Y; Mbida, P; Potinet-Pagliaroli, V; Géffard, F; Leboucher, G; Brazier, J-L; Allenet, B; Charpiat, B

2013-07-01

Paracetamol is the most widely used analgesic and antipyretic drug. In France, little is known concerning patients' knowledge and beliefs about paracetamol. To determine how much outpatients attending an emergency department know about paracetamol. A semi-structured questionnaire was applied to patients consulting for non-severe medical or traumatic conditions. Thirty-three (45%) of 73 participating patients knew that paracetamol was the active ingredient of the medication they used to reduce pain and/or fever. Three patients thought 2g was the maximum recommended single dose; 25% thought that a delay between two doses ≤ 3 hours was recommended and 15% thought the maximum daily dose was > 4 g. While 8% cited liver toxicity as a side effect, 38% did not believe an excessive dose could be fatal. Two patients correctly answered all questions and five gave no correct answer. Outpatients attending an emergency department (ED) have poor knowledge about paracetamol. This situation is disturbing and our results may serve as an eye opener to healthcare professionals. They emphasize the need for research programs with the following objectives: a) to determine the actual content of the message delivered by healthcare professionals; b) to study conditions under which this message is issued; c) to analyze how patients understand key messages and what their behavioral response is. In ED patients, the level of knowledge about paracetamol is insufficient to ensure its safe use in ambulatory care. Further studies are needed to determine the causes and to permit better patient education. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Evaluation of the Analgesic Efficacy of Dexketoprofen Added to Paracetamol.

Science.gov (United States)

Ceyhan, Dilek; Bilir, Ayten; Güleç, Mehmet Sacit

2016-12-01

Multimodal analgesic methods are preferred for the treatment of postoperative pain; as a result, the additive effects of analgesics are provided while probable side effects are avoided. The current study aimed to compare the effects of the combination of dexketoprofen and paracetamol with regard to postoperative pain therapy. Ninety-six patients who underwent non-malignant gynaecological laparotomy operations were included in this study. Patients were randomized into 3 groups. Group D received 50 mg intravenous dexketoprofen 15 minutes before the end of the operation and 8 and 16 hours after the operation. Group P received 1 g intravenous paracetamol and Group DP received the combination of 500 mg paracetamol and 25 mg dexketoprofen at the same time intervals. All patients received morphine infusion after operation. Total morphine consumption at 24 hours, visual analog scale, patient satisfaction and side effects were investigated. Comparison of the visual analog scale scores revealed that the Group DP presented lower scores at 24th hours compared to the other groups; and the difference between Group DP and Group D was statistically significant. Total morphine consumption was not significantly different between the three groups. The minimum number of side effects was observed in the Group DP. Co-administration of paracetamol, dexketoprofen and morphine provided good analgesia and fewer side effects in gynaecological abdominal surgery.

Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

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Lalić Tijana

2013-01-01

Full Text Available Introduction: Primary aldosteronism (PA is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR, is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28% than with adrenal tumors (46,72%. Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child

DEFF Research Database (Denmark)

Petersen, Tanja Gram; Liew, Zeyan; Nybo Andersen, Anne-Marie

2018-01-01

Background: It has been debated whether mild analgesics, mainly paracetamol, adversely affect aspects of neurodevelopment. We examined whether mother's use of paracetamol, aspirin or ibuprofen in pregnancy is associated with increased risk of cerebral palsy (CP) in the child. Method: We included...... registers. We estimated the average causal effect of analgesics on risk of CP using marginal structural models with stabilized inverse probability weights. Results: Paracetamol use was reported in 49% of all pregnancies, aspirin in 3% and ibuprofen in 4%. Prenatal exposure to paracetamol ever in pregnancy......% CI: 1.0-2.5). Children ever prenatally exposed to aspirin in pregnancy had an elevated risk of bilateral spastic CP (aOR 2.4, 95% CI: 1.1-5.3) compared with unexposed. Conclusion: We observed an increased risk of spastic CP in children prenatally exposed to paracetamol and aspirin. Although we...

Paracetamol use (and/or misuse in children in Enugu, South-East, Nigeria

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Obu Herbert A

2012-07-01

Full Text Available Abstract Background Paracetamol (also known as acetaminophen is the commonest available analgesic and anti-pyretic. It is readily accessed from pharmacy, patent medicine and provision shops as over the counter drug making it a potential drug of abuse, especially in children. We sought to find its use and/or misuse in children seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital (UNTH Ituku-Ozalla, Enugu. Objective To determine the dosage, formulation, and frequency of paracetamol administration to children by caregivers and factors associated with its use and/or misuse. Method An observational prospective study involving 231 children and their caregivers seen at the paediatric outpatient clinic of the University of Nigeria Teaching Hospital, Ituku - Ozalla, Enugu between June and November 2011 was undertaken. Data on paracetamol use before presentation to the clinic, in addition to demographic and other data were obtained from the caregivers using a structured questionnaire. Ethical consent for the study was obtained from the Hospital Ethics and Research Committee and informed consent was further obtained from the caregivers of the children. Results A total of 231 children aged six weeks to 16 years and their caregivers participated in this study. The mean ages of the children and their caregivers were 3.8 and 33.9 years, respectively. One hundred and thirty three of the children studied were males while 98 were females. Most of the children (75.6% received paracetamol at home before presenting. Paracetamol tablet alone or in combination with the syrup was mostly used (60% and this observation was made across all age groups. The commonest reason for using paracetamol tablet instead of the syrup was that it was more effective. Most caregivers relied on past experience (71.2% rather than on enclosed information leaflet to decide the appropriate dosage. Half of the children also received other medications

Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period.

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Chou, Doris; Abalos, Edgardo; Gyte, Gillian M L; Gülmezoglu, A Metin

2013-01-31

Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative births (ventouse or forceps assisted births). To determine the efficacy of a single administration of paracetamol (acetaminophen) systemic drugs used in the relief of acute postpartum perineal pain We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 6 November 2012. Randomised controlled trials (RCTs) assessing paracetamol (acetaminophen) in a single dose compared with placebo for women with early postpartum perineal pain. We excluded quasi-RCTs and cross-over studies. Two review authors assessed each paper for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. We did not identify any new trials from the updated search so the results remain unchanged as follows.We have included 10 studies describing two dosages of paracetamol. Of these, five studies (526 women) assessed 500 mg to 650 mg and six studies (841 women) assessed 1000 mg of paracetamol. We chose to use random-effects meta-analyses because of the heterogeneity in dosage used. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context.More women experienced pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89, 10 studies, 1279 women). In addition, there were significantly fewer women having additional pain relief with paracetamol compared with placebo (RR 0.34, 95% CI 0.21 to 0.55, eight studies, 1132 women). Both the 500 mg to 650 mg and 1000 mg doses were effective in providing more pain relief than placebo.Maternal and neonatal potential adverse drug effects were not assessed in

Low plasma adiponectin concentrations do not predict weight gain in humans

DEFF Research Database (Denmark)

Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

2002-01-01

Low concentrations of plasma adiponectin, the most abundant adipose-specific protein, are observed in obese individuals and predict the development of type 2 diabetes. Administration of adiponectin to rodents prevented diet-induced weight gain, suggesting a potential etiologic role of hypoadipone......Low concentrations of plasma adiponectin, the most abundant adipose-specific protein, are observed in obese individuals and predict the development of type 2 diabetes. Administration of adiponectin to rodents prevented diet-induced weight gain, suggesting a potential etiologic role...... of hypoadiponectinemia in the development of obesity. Our aim was to prospectively examine whether low plasma adiponectin concentrations predict future weight gain in Pima Indians, explaining the predictive effect of adiponectin on the development of type 2 diabetes. We measured plasma adiponectin concentrations in 219...... nondiabetic Pima Indians (112 M/107 F, age 31 +/- 9 years, body weight 96 +/- 20 kg [mean +/- SD]) in whom body weight and height were measured and BMI calculated at baseline and follow-up. Cross-sectionally, plasma adiponectin concentrations were negatively associated with body weight (r = -0.28, P = 0...

Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial

NARCIS (Netherlands)

Grubben, M.J.; Boers, G.H.; Blom, H.J.; Broekhuizen, R.; Jong, de R.; Rijt, van L.; Katan, M.B.

2000-01-01

Background: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. Objective: We studied the effect of coffee consumption on plasma

Paracetamol, 3-monoalkyl- and 3,5-dialkyl-substituted derivatives. Antioxidant activity and relationship between lipid peroxidation and cytotoxicity

NARCIS (Netherlands)

Van de Straat, R; Bijloo, G.J.; Vermeulen, N P

1988-01-01

The analgesic drug paracetamol is known to cause lipid peroxidation and hepatotoxicity after overdosage. In this paper, the relationship between lipid peroxidation and toxicity in freshly isolated hepatocytes was studied using paracetamol and three 3-monoalkyl-substituted derivatives of paracetamol.

Intraocular pressure-lowering effect of oral paracetamol and its in vitro corneal penetration properties

Directory of Open Access Journals (Sweden)

Mohamed N

2013-01-01

Full Text Available Nabiel Mohamed, David MeyerDivision of Ophthalmology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South AfricaBackground: Several studies have confirmed the ability of cannabinoids to reduce intraocular pressure. Experimental data recently demonstrated unequivocally that the analgesic effect of paracetamol is due to its indirect action on cannabinoid receptors. The question then arises as to whether paracetamol can reduce intraocular pressure via its effect on intraocular cannabinoid receptors.Methods: A 2-week, prospective, randomized, controlled, single-center, parallel-group pilot study was carried out to determine the efficacy and safety of paracetamol 1 g orally administered every 6 hours in adult patients with primary or secondary open angle glaucoma as compared with topical levobunolol 0.5% twice a day. Patient well-being was closely monitored throughout the study and focused on hepatic safety in accordance with Drug-Induced Liver Injury Network criteria. The in vitro diffusion kinetics of acetaminophen in a phosphate-buffered solution in rabbit and human corneas was also investigated, with the view to a topical application.Results: Eighteen adult patients were enrolled in the study, with nine in the topical levobunolol group and nine in the oral paracetamol group. In the levobunolol group, the mean reduction in intraocular pressure at day 7 was 7.5 mmHg (P < 0.008 and at day 14 was 9.1 mmHg (P < 0.005, from a mean baseline intraocular pressure of 29.6 mmHg. The corresponding figures for the paracetamol group were 8.8 mmHg (P < 0.0004 at day 7 and 6.5 mmHg (P < 0.004 at day 14, from a mean baseline intraocular pressure of 29.4 mmHg. Both study regimens were well tolerated. No serious treatment-related adverse events were reported in either of the treatment groups. Liver function tests, systolic/diastolic blood pressure, or heart rate remained unchanged in both groups during the 2 weeks of the study. In

Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol.

Science.gov (United States)

Miranda, Hugo F; Puig, Margarita M; Dursteler, Christian; Prieto, Juan Carlos; Pinardi, Gianni

2007-02-01

The antinociceptive activity of dexketoprofen was studied in mice using the acetic acid writhing test (acute tonic pain), the tail flick test (acute phasic pain) and the formalin assay (inflammatory pain). Isobolographic analysis was used to study the antinociceptive interactions between morphine and paracetamol co-administered with dexketoprofen. In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen. In the tail flick test, the curves were parallel with similar efficacy and potency. The administration of morphine or paracetamol in both tests resulted in dose-response curves not parallel with that of dexketoprofen, which showed a potency between morphine and paracetamol. In the formalin assay, the antinociceptive activity of morphine during phase I was 122, 295 and 1695 times higher than dexketoprofen, ketoprofen and paracetamol, respectively. Isobolographic analysis demonstrated that the combination of sub-analgesic doses of dexketoprofen with morphine or with paracetamol was strongly synergic in all three tests. Synergistic drug combinations should improve effective pharmacological treatment of pain, minimizing drug specific adverse effects. These findings are undoubtedly worthy of additional controlled clinical trials in severe pain syndromes.

Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial

NARCIS (Netherlands)

Grubben, M. J.; Boers, G. H.; Blom, H. J.; Broekhuizen, R.; de Jong, R.; van Rijt, L.; de Ruijter, E.; Swinkels, D. W.; Nagengast, F. M.; Katan, M. B.

2000-01-01

An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. We studied the effect of coffee consumption on plasma homocysteine in a crossover

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

Science.gov (United States)

Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

2015-01-01

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K

2001-01-01

AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC...... 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann......-Whitney: P = 0.00006). CONCLUSIONS: Asthma must be considered a risk factor in the development of side-effects to NAC. However, the side-effects are easily managed and there is no reason to withhold NAC from any patient with paracetamol poisoning. Paracetamol itself seems to offer some protection against...

Pathogen Inactivated Plasma Concentrated: Preparation and Uses

Science.gov (United States)

2004-09-01

of decontamination, porcine parvovirus (PPV) was selected as a model virus; B19 is the form that infects humans. PPV is an interesting pathogen...ultrasound to cold plasma. The ultrasound generates pure ice crystals, which are then removed to leave concentrated plasma. Testing: Porcine parvovirus ...energy to “burn” any proteins that they encounter. Furthermore, as they react, they also produce multiple other reactive oxygen species (ROS) that are

Wel of geen paracetamol bij kinderen met koorts? [Risks and benefits of paracetamol in children with fever

NARCIS (Netherlands)

de Bont, E.G.P.M.; Brand, P.L.P.; Dinant, G.J.; van Well, G.T.J.; Cals, J.W.L.

2014-01-01

Worldwide, paracetamol is the most commonly used antipyretic for children and the drug of first choice for reducing fever named in the majority of practice guidelines. However, whether or not it is necessary or desirable to treat fever is questionable. The provision of accurate information on the

Plasma ascorbic acid concentrations in prevalent patients with end-stage renal disease on hemodialysis.

Science.gov (United States)

Sirover, William D; Liu, Yuguan; Logan, Amanda; Hunter, Krystal; Benz, Robert L; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Weisberg, Lawrence S; Handelman, Garry J

2015-05-01

To determine the prevalence of vitamin C (ascorbic acid [AA]) deficiency in patients with end-stage renal disease, the effect of supplemental AA on plasma AA concentrations, and the extrinsic and intrinsic factors that affect plasma AA concentrations in this patient population. In study 1, we compared the effect of hemodialysis (HD) on plasma AA concentrations between patients with low and high pre-HD AA concentrations. In study 2, we analyzed kinetic and nonkinetic factors for their association with increased plasma AA concentrations in patients on maintenance HD. Study 1 was performed in a single outpatient HD clinic in Cherry Hill, New Jersey. Study 2 was performed in 4 outpatient HD clinics in Southern New Jersey. In study 1, we collected plasma samples from 8 adult patients on maintenance HD at various time points around their HD treatment and assayed them for AA concentration. In study 2, we enrolled 203 adult patients and measured pre-HD plasma AA concentrations. We ascertained supplemental AA use and assessed dietary AA intake. In study 1, plasma AA concentrations were compared during the intradialytic and interdialytic period. In study 2, pre-HD plasma AA concentrations were correlated with supplement use and demographic factors. Study 1 showed that over the course of a single HD treatment, the plasma AA concentration decreased by a mean (±standard deviation) of 60% (±6.6). In study 2, the median pre-HD plasma AA concentration was 15.7 μM (interquartile range, 8.7-66.8) in patients who did not take a supplement and 50.6 μM (interquartile range, 25.1-88.8) in patients who did take a supplement (P HD plasma AA concentration ≥30 μM. HD depletes plasma AA concentrations, and AA supplementation allows patients to achieve higher plasma AA concentrations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.

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Ong, Cliff K S; Seymour, Robin A; Lirk, Phillip; Merry, Alan F

2010-04-01

There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models. A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality using a validated scale. Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively. The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found between experimental groups. Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with either drug alone.

Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats.

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Mast, Carole; Pourpe, Charlène; Voyard, Guillaume; Rémond, Didier; Migné, Carole; Centeno, Delphine; Dardevet, Dominique; Savary-Auzeloux, Isabelle; Papet, Isabelle

2017-12-01

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma

DEFF Research Database (Denmark)

Køstner, Anne Helene; Ellegaard, Mai-Britt Bjørklund; Christensen, Ib Jarle

2015-01-01

effective antitumor immune response. The purpose of this retrospective study was to examine the potential role of the IL-2-induced fever in melanoma patients treated with or without paracetamol in two consecutive cohorts. One hundred and seventy-nine patients with metastatic melanoma treated with a modified...... decrescendo regimen of IL-2 and Interferon (IFN) between 2004 and 2010 were retrospectively studied. 87 patients treated before 2007 received paracetamol as part of the treatment schedule, and 92 patients treated after 2007 did not receive paracetamol routinely. Body temperature was analyzed as dichotomized...

Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation.

Science.gov (United States)

Cook, Sarah F; Roberts, Jessica K; Samiee-Zafarghandy, Samira; Stockmann, Chris; King, Amber D; Deutsch, Nina; Williams, Elaine F; Allegaert, Karel; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-01-01

The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset. Nonlinear mixed-effects models were constructed from paracetamol concentration-time data in NONMEM 7.2. Potential covariates included body weight, gestational age, postnatal age, postmenstrual age, sex, race, total bilirubin, and estimated glomerular filtration rate. An external dataset was used to test the predictive performance of the model through calculation of bias, precision, and normalized prediction distribution errors. The model-building dataset included 260 observations from 35 neonates with a mean gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well-described by a one-compartment model with first-order elimination. Weight predicted paracetamol clearance and volume of distribution, which were estimated as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and 2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation), respectively, at the mean subject weight of 2.30 kg. An external evaluation was performed on an independent dataset that included 436 observations from 60 neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median prediction error was 10.1 % [95 % confidence interval (CI) 6.1-14.3] and the median absolute prediction error was 25.3 % (95 % CI 23.1-28.1). Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging from extreme preterm to full-term gestational status. External evaluation suggested that these findings should be generalizable to other similar patient populations.

Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids 1 2 3

OpenAIRE

Sherry, Christina L.; Oliver, Jeffery S.; Renzi, Lisa M.; Marriage, Barbara J.

2014-01-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2–3 mo postpartum. Lutein is the dominant carotenoid in t...

Association of antioxidant nutraceuticals and acetaminophen (paracetamol: Friend or foe?

Directory of Open Access Journals (Sweden)

Mohamed Abdel-Daim

2018-04-01

Full Text Available Acetaminophen (paracetamol or APAP is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results from the murine models of APAP-induced hepatotoxicity showed amelioration of liver damage with nutraceuticals coadministration, as well as reductions in tissue markers of oxidative stress, and serum levels of hepatic enzymes, bilirubin, cholesterol, triglycerides and inflammatory cytokines. On the other hand, both increased and decreased APAP plasma levels have been reported, depending on the nutraceutical type and route of administration. For example, studies showed that repeated administration of flavonoids causes down-regulation of cytochrome P450 enzymes and up-regulation of uridine diphosphate glucuronosyltransferases (UGT. Moreover, nutraceuticals can alter the levels of APAP metabolites, such as mercapturate glucuronide, sulfate and cysteine conjugates. Overall, the reviewed in vivo studies indicate that interactions between APAP and nutraceuticals or plant foods exist. However, the majority of data come from animal models with doses of phytochemicals far from dietary ones. Human studies should investigate gene-diet interactions, as well as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP. Keywords: Acetaminophen, Antioxidants, Food-drug interaction, Nutraceuticals, Paracetamol

Increased plasma proline concentrations are associated with sarcopenia in the elderly.

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Toyoshima, Kenji; Nakamura, Marie; Adachi, Yusuke; Imaizumi, Akira; Hakamada, Tomomi; Abe, Yasuko; Kaneko, Eiji; Takahashi, Soiciro; Shimokado, Kentaro

2017-01-01

Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years) were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids. Twenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia. The plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia.

Increased plasma proline concentrations are associated with sarcopenia in the elderly.

Directory of Open Access Journals (Sweden)

Kenji Toyoshima

Full Text Available Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles.A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids.Twenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia.The plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia.

Plasma bupivacaine concentrations following orbital injections in cats.

Science.gov (United States)

Shilo-Benjamini, Yael; Pypendop, Bruno H; Newbold, Georgina; Pascoe, Peter J

2017-01-01

To determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats. Randomized, crossover, experimental trial with a 2 week washout period. Six adult healthy cats, aged 1-2 years, weighing 4.6 ± 0.7 kg. Cats were sedated by intramuscular injection of dexmedetomidine (36-56 μg kg -1 ) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography-mass spectrometry. Bupivacaine maximum plasma concentration (C max ) and time to C max (T max ) were determined from the data. The bupivacaine median (range) C max and T max were 1.4 (0.9-2.5) μg mL -1 and 17 (4-60) minutes, and 1.7 (1.0-2.4) μg mL -1 , and 28 (8-49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05-0.21 μg mL -1 . In healthy cats, at doses up to 2 mg kg -1 , bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension. Copyright © 2016 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Plasma leptin concentration in donkeys.

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Díez, E; López, I; Pérez, C; Pineda, C; Aguilera-Tejero, E

2012-01-01

Donkeys appear to be more predisposed than large breed horses to suffer from hyperlipemia. The reason for that predisposition is unknown but anorexia is a consistent feature of the disease. Leptin, a protein synthesized in fat tissue, is one of the major inhibitors of appetite in mammals. We hypothesized that donkeys could have elevated plasma leptin concentrations compared to horses. Blood samples were obtained from 50 donkeys for measurement of leptin, triglycerides (TGs), glucose, and insulin. Glucose/insulin ratio, modified insulin to glucose ratio, and reciprocal of the square root of insulin were calculated. Based on their body condition score (BCS), donkeys were classified as lean (n = 18), normal (n = 16), or overweight (n = 16). The results were compared with reference values from our laboratory and with a group of horses (n = 25) used as an internal control. Values of both leptin and TGs in donkeys were above the horse reference range and also significantly higher than those of the control horses: leptin (11.2 ± 1.7 versus 5.8 ± 0.5 µg/L, p donkeys had leptin (19.3 ± 2.9 µg/L) and TG (1.3 ± 0.2 mmol/L) concentrations that were significantly (p donkeys. A significant positive correlation (p Donkeys have higher plasma leptin concentrations than horses and leptin is correlated with BCS.

[Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds].

Science.gov (United States)

Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

2000-02-01

The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Worldwide research productivity of paracetamol (acetaminophen) poisoning: a bibliometric analysis (2003-2012).

Science.gov (United States)

Zyoud, S H; Al-Jabi, S W; Sweileh, W M

2015-01-01

There is a lack of data concerning the evaluation of scientific research productivity in paracetamol poisoning from the world. The purposes of this study were to analyse the worldwide research output related to paracetamol poisoning and to examine the authorship pattern and the citations retrieved from the Scopus database for over a decade. Data were searched for documents with specific words regarding paracetamol poisoning as 'keywords' in the title or/and abstract. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product (GDP) per capita. There were 1721 publications that met the criteria during study period from the world. All retrieved documents were published from 72 countries. The largest number of articles related to paracetamol poisoning was from the United States (US; 30.39%), followed by India (10.75%) and the United Kingdom (UK; 9.36%). The total number of citations at the time of data analysis was 21,109, with an average of 12.3 citations per each documents and median (interquartile range) of 4 (1-14). The h-index of the retrieved documents was 57. After adjusting for economy and population power, India (124.2), Nigeria (18.6) and the US (10.5) had the highest research productivity. Countries with large economies, such as the UK, Australia, Japan, China and France, tended to rank relatively low after adjustment for GDP over the entire study period. Our study demonstrates evidence that research productivity related to paracetamol poisoning has increased rapidly during the recent years. The US obviously dominated in research productivity. However, certain smaller country such as Nigeria has high scientific output relative to their population size and GDP. A highly noticeable increase in the contributions of Asia-Pacific and Middle East regions to scientific literature related to paracetamol poisoning was also

Plasma brain natriuretic peptide concentrations in patients with valvular heart disease

Science.gov (United States)

Stewart, Ralph A; Lee, Mildred; Gabriel, Ruvin; Van Pelt, Niels; Newby, David E; Kerr, Andrew J

2016-01-01

Objective Plasma brain natriuretic peptide (BNP) concentrations predict prognosis in patients with valvular heart disease (VHD), but it is unclear whether this directly relates to disease severity. We assessed the relationship between BNP and echocardiographic measures of disease severity in patients with VHD. Methods Plasma BNP concentrations were measured in patients with normal left ventricular (LV) systolic function and isolated VHD (mitral regurgitation (MR), n=33; aortic regurgitation (AR), n=39; aortic stenosis (AS), n=34; mitral stenosis (MS), n=30), and age-matched and sex-matched controls (n=39) immediately prior to exercise stress echocardiography. Results Compared with controls, patients with VHD had elevated plasma BNP concentrations (MR median 35 (IQR 23–52), AR 34 (22–45), AS 31 (22–60), MS 58 (34–90); controls 24 (16–33) pg/mL; p<0.01 for all). LV end diastolic volume index varied by valve lesion; (MR (mean 77±14), AR (91±28), AS (50±17), MS (43±11), controls (52±13) mL/m2; p<0.0001). There were no associations between LV volume and BNP. Left atrial (LA) area index varied (MR (18±4 cm2/m2), AR (12±2), AS (11±3), MS (19±6), controls (11±2); p<0.0001), but correlated with plasma BNP concentrations: MR (r=0.42, p=0.02), MS (r=0.86, p<0.0001), AR (r=0.53, p=0.001), AS (r=0.52, p=0.002). Higher plasma BNP concentrations were associated with increased pulmonary artery pressure and reduced exercise capacity. Despite adverse cardiac remodelling, 81 (60%) patients had a BNP concentration within the normal range. Conclusions Despite LV remodelling, plasma BNP concentrations are often normal in patients with VHD. Conversely, mild elevations of BNP occur with LA dilatation in the presence of normal LV. Plasma BNP concentrations should be interpreted with caution when assessing patients with VHD. PMID:27175283

[Effect of paracetamol (acetaminophen) on blood pressure in patients with coronary heart disease].

Science.gov (United States)

Sudano, I; Roas, S; Flammer, A J; Noll, G; Ruschitzka, F

2012-06-06

Analgesic drugs, non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) in particular, belong to the most widely prescribed therapeutic agents. Beside their efficacy in pain relief, these drugs were recently linked to increased cardiovascular risk. Indeed, epidemiological and clinical studies showed that non-selective non-steroidal anti-inflammatory drugs, as well as selective cyclooxygenase-2 inhibitors both may increase blood pressure and cardiovascular events. However, the effect of paracetamol (acetaminophen) on blood pressure and cardiovascular health should not be neglected, too. Unfortunately, long-term randomized controlled trials appropriately powered to evaluate cardiovascular outcomes are lacking. This review summarizes the available data about the effect of paracetamol in particular, on blood pressure and other cardiovascular outcomes.

Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2g starting dose following third molar surgery

DEFF Research Database (Denmark)

Juhl, Gitte Irene; Nørholt, Sven E.; Tønnesen, Else Kirstine

2006-01-01

BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3......-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated...... over 8h. Laboratory tests were performed before and 48h after drug administration. RESULTS: Two hundred and ninety seven patients (132=IV paracetamol 2g; 132=IV paracetamol 1g; 33=placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior...

PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

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Day Richard O

2010-07-01

Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

High-Pressure High-Temperature Phase Diagram of the Organic Crystal Paracetamol

Science.gov (United States)

Smith, Spencer; Montgomery, Jeffrey; Vohra, Yogesh

High-pressure high-temperature (HPHT) Raman spectroscopy studies have been performed on the organic crystal paracetamol in a diamond anvil cell utilizing boron-doped diamond as heating anvil. The HPHT data obtained from boron-doped diamond heater is cross-checked with data obtained using a standard block heater diamond anvil cell. Isobaric measurements were conducted at pressures up to 8.5 GPa and temperature up to 520 K in a number of different experiments. Solid state phase transitions from monoclinic Form I --> orthorhombic Form II were observed at various pressures and temperatures as well as transitions from Form II --> unknown Form IV. The melting temperature for paracetamol was observed to increase with increasing pressures to 8.5 GPa. Our previous angle dispersive x-ray diffraction studies at the Advanced Photon Source has confirmed the existence of two unknown crystal structures Form IV and Form V of paracetamol at high pressure and ambient temperature. The phase transformation from Form II to Form IV occurs at ~8.5 GPa and from Form IV to Form V occurs at ~11 GPa at ambient temperature. Our new data is combined with the previous ambient temperature high-pressure Raman and X- ray diffraction data to create the first HPHT phase diagram of paracetamol. Doe-NNSA Carnegie DOE Alliance Center (CDAC) under Grant Number DE-NA0002006.

Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: A birth cohort study

DEFF Research Database (Denmark)

Rebordosa, Cristina; Kogevinas, Manolis; Sørensen, Henrik T

2008-01-01

BACKGROUND: Paracetamol use has been associated with increased prevalence of asthma in children and adults, and one study reported an association between pre-natal exposure to paracetamol and asthma in early childhood. METHODS: To examine if pre-natal exposure to paracetamol is associated...... with the risk of asthma or wheezing in early childhood, we selected 66 445 women from the Danish National Birth Cohort for whom we had information on paracetamol use during pregnancy and who participated in an interview when their children were 18-months-old and 12 733 women whose children had reached the age...... of 7 and estimated the prevalence of physician-diagnosed asthma and wheezing at the ages of 18 months and 7 years. We also linked our population to the Danish National Hospital Registry to record all hospitalizations due to asthma up to age of 18 months. RESULTS: Paracetamol use during any time...

Comparison of Patient-Controlled Analgesia Using Morphine With and Without Paracetamol in Postoperative Pain Control

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Mehryar Taghavi Gilani

2016-04-01

Full Text Available Introduction: Postoperative pain control plays a pivotal role in reducing postoperative complications, hospitality time, and increasing satisfaction. This study aimed to evaluate the effect of paracetamol on the pain and complications caused by gastrectomy. Materials and Methods: This randomized prospective study was conducted on 60 patients (two same group who were candidate for gastrectomy in Imam Reza Hospital of Mashhad, Iran during August-September 2015. The first group received Patient-Controlled Analgesia (PCA with morphine only, and in the second group, paracetamol (1 gram infused with morphine every six hours. Level of pain, morphine intake, and side effects were evaluated in both groups. Results:No significant difference was observed in the four-scale score of pain in the patients (morphine group: 0.64±0.1, morphine-paracetamol group: 0.6±0.1 (P=0.72. During the first 24 hours after the surgery, the morphine group had lower consciousness level (2.3±0.2 compared to the morphine-paracetamol group (1.7±0.3 (P=0.001. Moreover, infusion of paracetamol with morphine to control the pain after gastrectomy reduced the need for morphine analgesia. Morphine intake was 21.4±7.7 in morphine group, while it was 14.3±5.8 in the morphine-paracetamol group within the first 24 hours after the surgery (P=0.001. However, this level had no significant effect on postoperative complications such as itching, nausea, and arterial oxygen saturation. Conclusion: According to the results of this study, intravenous paracetamol (one gram administered every six hours with PCA using morphine could decrease morphine intake leading to better consciousness level during the first 24 hours after gastrectomy without further complications.

Effectiveness of tramadol/paracetamol compared with etoricoxib as ...

African Journals Online (AJOL)

paracetamol combination when compared with etoricoxib as postoperative analgesia following day care surgery. Design: This was a prospective, randomised, single-blind study. Setting and subjects: Sixty-two patients were randomised to receive ...

Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke.

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Gonzalez-Valcarcel, Jaime; Sissani, Leila; Labreuche, Julien; Bousser, Marie-Germaine; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; Steg, Philippe Gabriel; Vicaut, Eric; Amarenco, Pierre

2016-04-01

The presumed safety of paracetamol in high-cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial. We performed 2 nested case-control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. 12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5-145) days for paracetamol and 9 (5-30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04-1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26-2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05-1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06-2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45-2.62). There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding. http://www.isrctn.com. Unique identifier: ISRCTN66157730. © 2016 American Heart Association, Inc.

[Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories].

Science.gov (United States)

Wagner, G; Sand, C; Sachse, M M

2015-03-01

A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

Do plasma concentrations of apelin predict prognosis in patients with advanced heart failure?

Science.gov (United States)

Dalzell, Jonathan R; Jackson, Colette E; Chong, Kwok S; McDonagh, Theresa A; Gardner, Roy S

2014-01-01

Apelin is an endogenous vasodilator and inotrope, plasma concentrations of which are reduced in advanced heart failure (HF). We determined the prognostic significance of plasma concentrations of apelin in advanced HF. Plasma concentrations of apelin were measured in 182 patients with advanced HF secondary to left ventricular systolic dysfunction. The predictive value of apelin for the primary end point of all-cause mortality was assessed over a median follow-up period of 544 (IQR: 196-923) days. In total, 30 patients (17%) reached the primary end point. Of those patients with a plasma apelin concentration above the median, 14 (16%) reached the primary end point compared with 16 (17%) of those with plasma apelin levels below the median (p = NS). NT-proBNP was the most powerful prognostic marker in this population (log rank statistic: 10.37; p = 0.001). Plasma apelin concentrations do not predict medium to long-term prognosis in patients with advanced HF secondary to left ventricular systolic dysfunction.

Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

Science.gov (United States)

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-04-01

Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP.

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Ogunjimi, Abayomi Tolulope; Alebiowu, Gbenga

2014-04-01

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr's index, Hausner's ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength-friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.

Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

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Sarah J. Mitchell

2011-01-01

Full Text Available Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit.

Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

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Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

2014-01-01

In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, pplatelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women.

Science.gov (United States)

Piazza, Cateno; Privitera, Maria Giovanna; Melilli, Barbara; Incognito, Tiziana; Marano, Maria Rosa; Leggio, Gian Marco; Roxas, Matilde Amico; Drago, Filippo

2007-09-01

Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation

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Ines Tofe

2018-02-01

Full Text Available BackgroundStandard medical treatment for patent ductus arteriosus (PDA closure has been indomethacin/ibuprofen or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous paracetamol for closing PDA in preterm neonates presenting contraindication to ibuprofen or ibuprofen had failed and no candidates for surgical ligation because of huge instability.Materials and methodsWe conducted a retrospective case series study in a neonatal intensive care unit from a tertiary hospital. 9 preterm infants ≤32 weeks of gestational age with hemodynamically significant PDA (hsPDA were enrolled. They received 15 mg/kg/6h intravenous paracetamol for ductal closure. Demographic data and transaminase levels before and after treatment were collected.Results30 preterm babies were diagnosed of hsPDA. 11/30 received ibuprofen with closure in 81.1%. 9 received intravenous paracetamol mainly due to bleeding disorders or thrombocytopenia. Successful closure on paracetamol was achieved in seven of nine babies (77.7%. There was a significant increase in transaminase levels in two patients. They required no treatment for normalization.ConclusionParacetamol is an effective option in closure PDA. It should be a first-line therapeutic option when there are contraindications for ibuprofen treatment. Transaminases must be checked during treatment.

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

DEFF Research Database (Denmark)

Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn

2014-01-01

, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial.

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Dan Dang

Full Text Available TRIAL DESIGN: Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. METHODS: One hundred and sixty infants (gestational age ≤ 34 weeks with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80 or ibuprofen (n = 80. After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. RESULT: The ductus was closed in 65 (81.2% infants of the paracetamol group compared with 63 (78.8% of the ibuprofen group. The 95% confidence interval of the difference between these groups was [-0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. CONCLUSION: This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-12002177.

Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

Science.gov (United States)

Moore, R A; Derry, S; Wiffen, P J; Straube, S; Aldington, D J

2015-10-01

Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICC®.

Some mechanisms involved in the radiosensitization of E. coli B/r by paracetamol

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Shenoy, M A; Gopalakrishna, K [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

1977-06-01

Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to /sup 60/Co gamma rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining.

Some mechanisms involved in the radiosensitization of E.coli B/r by paracetamol

International Nuclear Information System (INIS)

Shenoy, M.A.; Gopalakrishna, K.

1977-01-01

Paracetamol, a widely-used analgesic and antipyretic drug, sensitized E.coli B/r to 60 Co gamma-rays under hypoxic conditions. Part of the sensitizing effect has been shown to be due to an electron adduct of the drug. Paracetamol inhibited both post-irradiation DNA and protein syntheses. The targets involved in the inhibition of post-irradiation DNA synthesis have been shown to be different in the presence of the sensitizer. Increased DNA degradation after irradiation was also observed when E.coli B/r were irradiated in the presence of the drug. The presence of paracetamol during hypoxic irradiation of E.coli B/r resulted in the enhancement of DNA single-strand scissions with no apparent effect on their rejoining. (author)

Acute liver failure in a term neonate after repeated paracetamol administration

OpenAIRE

Bucaretchi, Fabio; Fernandes, Carla Borrasca; Branco, Maira Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araujo; Porta, Gilda

2014-01-01

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL)...

Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

DEFF Research Database (Denmark)

Mathiesen, O; Wetterslev, Jørn; Kontinen, V K

2014-01-01

with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects...... of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality...

Changes in the pattern of paracetamol use in the periconception period in a Danish cohort

DEFF Research Database (Denmark)

Ersbøll, Anne S; Hedegaard, Mette; Damm, Peter

2015-01-01

Paracetamol is the most commonly used over-the-counter drug in pregnancy. It is generally considered to be safe, but prolonged antenatal exposure has been associated with offspring short- and long-term morbidity. Our aim was to describe the pattern of paracetamol use with a focus on frequent...... ingestion (more than once a week), 3 months before and in early pregnancy. In this cohort, 8650 pregnant women responded to a web-based clinical questionnaire that included questions about drug use. Paracetamol was the most used drug before and in early pregnancy (35.2% and 6.5% of respondents, respectively......). The proportion of frequent users decreased from 3.9% before to 0.9% in early pregnancy. Frequent paracetamol use was associated with smoking, co-morbidities, body mass index ≥ 25 kg/m(2), unplanned pregnancy, no education and inability to understand Danish. A significant decrease in the proportion of women...

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

Science.gov (United States)

Bardanzellu, Flaminia; Neroni, Paola; Fanos, Vassilios

2017-01-01

In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment. PMID:28828381

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

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Flaminia Bardanzellu

2017-01-01

Full Text Available In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA, resulting in the condition of Patent Ductus Arteriosus (PDA, represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment.

Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism.

Science.gov (United States)

Kuczera, Piotr; Adamczak, Marcin; Więcek, Andrzej

2016-11-15

Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/β-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT). In 58 hemodialysed patients with sHPT (PTH > 300 pg/ml) plasma sclerostin and serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. Serum PTH concentration decreased after 3 and 6 month of treatment from 1138 (931-1345) pg/ml to 772 (551-992) pg/ml and to 635 (430-839) pg/ml, respectively. Mean serum calcium and phosphate concentrations remained stable. Plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.66 (1.35-1.96) ng/ml, to 1.77 (1.43-2.12) ng/ml and to 1.87 (1.50-2.25) ng/ml, respectively. In 42 patients with cinacalcet induced serum PTH decrease plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.51 (1.19-1.84) ng/ml to 1.59 (1.29-1.89) ng/ml and to 1.75 (1.42-2.01) ng/ml, respectively. Contrary, in the 16 patients without cinacalcet induced serum PTH decrease plasma sclerostin concentration was stable. Plasma sclerostin concentrations correlated inversely with serum PTH concentrations at the baseline and also after 6 months of treatment. 1. In hemodialysed patients with secondary hyperparathyroidism treatment with cinacalcet increases plasma sclerostin concentration 2. This effect seems to be related to decrease of serum PTH concentration.

Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized with etorphine.

Science.gov (United States)

Haga, Henning A; Wenger, Sandra; Hvarnes, Silje; Os, Oystein; Rolandsen, Christer M; Solberg, Erling J

2009-11-01

To investigate plasma lactate concentrations of etorphine-immobilized moose in relation to environmental, temporal and physiological parameters. Prospective clinical study. Fourteen female and five male moose (Alces alces), estimated age range 1-7 years. The moose were darted from a helicopter with 7.5 mg etorphine per animal using projectile syringes and a dart gun. Once immobilized, the moose were approached, a venous blood sample was obtained and vital signs including pulse oximetry were recorded. Diprenorphine was administered to reverse the effects of etorphine. Timing of events, ambient temperature and snow depth were recorded. Blood samples were cooled and centrifuged before plasma was harvested and frozen. The plasma was thawed later and lactate analysed. Data were analysed using descriptive statistics and regression analysis. All animals recovered uneventfully and were alive 12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/- 2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow depth and negatively to time from induction of immobilization to blood sampling. The model that best described the variability in plasma lactate concentrations used induction time (time from firing the dart to the moose being immobilized). The second best model included induction time and snow depth. Plasma lactate concentrations in these etorphine-immobilized moose were in the range reported for other immobilized wild ruminants. Decreasing induction time, which may be related to a more profound etorphine effect, and increasing snow depth possibly may increase plasma lactate concentrations in etorphine-immobilized moose.

Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

Science.gov (United States)

Sjoukes, Alies; Venekamp, Roderick P; van de Pol, Alma C; Hay, Alastair D; Little, Paul; Schilder, Anne Gm; Damoiseaux, Roger Amj

2016-12-15

Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate

Het gebruik van paracetamol bij patiënten met levercirrose en het risico op hepatotoxiciteit

NARCIS (Netherlands)

Weersink, R.A.; Borgsteede, S.D.; Okel, E.; Pras, N.; Van Putten, A.W.

2016-01-01

OBJECTIVE: To study the safety and the optimal dose of paracetamol as an analgesic in patients with liver cirrhosis. DESIGN AND METHODS: In a literature search all pharmacokinetic and clinical studies concerning paracetamol use in patients with liver cirrhosis were retrieved, as well as review

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

NARCIS (Netherlands)

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.

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

Effect of Postural Change on Plasma Insulin Concentration in Normal Volunteer

Energy Technology Data Exchange (ETDEWEB)

Sung, Ho Kyung; Koh, Joo Whan; Joo, Jong Koo; Kim, Jin Yong; Lee, Jang Kyu [Korea Atomic Research Institute, Seoul (Korea, Republic of)

1974-03-15

The concentrations of some blood constituents are known to be influenced by the postural change. The blood glucose and insulin concentrations were measured, first, in the supine, and then (30 minutes later) in the erect positions under the fasting state. The effects of a duretic, furose-mide, were also studied under the same condition for 5 consecutive days. The materials were 5 healthy volunteers aging 20-29 years old with out any diabetic past, or family histories. The blood glucose was measured by the Nelson's method, and plasma insulin by the radioimmunoassay method. Following are the results; 1) The plasma insulin concentration in the erect position is slightly higher than in the supine position, however, the increase is statistically insignificant because of the notable individual variations in the values of the supine position. 2) Four out of 5 cases show the increase of about 80% of plasma insulin in the erect position, which is statistically significant if analyzed on the basis of frequency distribution. 3) The blood glucose concentration showed no postural changes. 4) The increase of the plasma insulin concentration in the erect position seems to the result of limited extra vasation of insulin in the lower extremities.

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

Science.gov (United States)

Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-04-01

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

Comparative in-vitro analysis of different brands of paracetamol tablets available in Nepal

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Ganesh Man Singh Thakuri

2016-08-01

Full Text Available Objective: To examine the physico-chemical parameters of commercially available local and multinational brands of paracetamol tablets in Nepal. Methods: Different five paracetamol brands were explored by testing various parameters according to standard methods. The studied parameters included weight variation, friability, disintegration, dissolution and assay. The limits of the official test were referenced from official guidelines of Indian Pharmacopoeia (IP and British Pharmacopoeia (BP. All brands were tested according to their pharmacopoeial claim and methods for these tests were successfully conducted to find out their qualities. Those methods were economic and authentic. Results: Requirements of weight variation and friability value were complied by all brands. Fifteen minutes of disintegration time were also complied by all the brands according to the BP/IP recommendation for uncoated tablets. All brands showed not less than 80% drug release in 45 min as per BP and not less than 85% in 30 min as per IP. Content of each brand was found to be within the range of 95%–105%. The present findings suggested that about every paracetamol brand which was accessible in Nepali market encountering the IP/BP requirements. Conclusions: Although the physico-chemical examinations such as weight variation, friability, disintegration, dissolution and assay were detected varying brand wise, but were found interior to defined limits. Being an over-the-counter drug, the consumption of paracetamol is too high. Therefore, it is important for each brand to be genuine, good manufactured and well marketed. So, additional exploration over the quality of paracetamol is compulsory for safe human consumption.

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study

Science.gov (United States)

Molloy, Phillip; Chambers, Ruth; Cork, Tania

2016-01-01

Objective To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. Methods Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a ‘flu remedy preparation also containing paracetamol, in 54 shops. Results Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32×500 mg paracetamol in conjunction with a paracetamol-containing ‘flu preparation; while 98% shops sold 16×paracetamol 500 mg along with a paracetamol-containing ‘flu remedy, with no questions asked of the shopper or advice given. Discussion MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses. PMID:26781508

Fatal cerebral blødning på grund af mulig interaktionmellem paracetamol og warfarin

DEFF Research Database (Denmark)

Vinsand Naver, Signe; Papina, Maria; Jimenez Solem, Espen

2015-01-01

This is a case report of an 83-year-old man in warfarin treatment with stable international normalised ratio (INR) after aortic valve replacement and atrial fibrillation. Due to back pain he took paracetamol (acetaminophen) 4 g/day, morphine 30 mg/day and diclofenac as rescue medication for two...... paracetamol and warfarin are discussed....

Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose.

Science.gov (United States)

Phillpotts, Simon; Tash, Elliot; Sen, Sambit

2014-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intravenous paracetamol and patent ductus arteriosus closure in preterm infants

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Rizky Adriansyah

2017-08-01

Full Text Available Background Indomethacin and ibuprofen are the drugs of choice for closure of patent ductus arteriosus (PDA in preterm infants. However, intravenous preparations are of limited availability in Indonesia. Circumstantial evidence has shown that intravenous paracetamol may be an alternative therapy for PDA closure in premature infants. Objective To evaluate the effect of intravenous paracetamol on PDA closure in preterm infants. Methods A before-and-after study was conducted between May and August 2014 in Cipto Mangunkusumo General Hospital, Jakarta in preterm infants with hemodynamically significant PDAs, as established by echocardiography using the following criteria: duct diameter >1.4 mm/kg, left atrium to aorta ratio >1.4, and mean velocity in the left pulmonary artery >0.42 m/s or mean diastolic velocity in the left pulmonary artery >0.2 m/s. Subjects, aged 2 and 7 days, received intravenous paracetamol (15 mg/kg every six hours for 3 days. Paired T-test was used to compare pre-intervention PDA diameter to those assessed at 24 hours after the intervention and at 14 days of life. Results Twenty-nine subjects had a mean gestational age of 30.8 weeks and mean birth weight of 1,347 grams. Nineteen (65.5% patients had closed PDAs at the day 14 evaluation, 1 experienced PDA reopening, and 9 had failed PDA closure. No liver toxicity was identified. Mean duct diameters before, 24 hours after the intervention, and at 14 days of life were 3.0, 0.9, and 0.6 mm, respectively (P<0.0001. Conclusion Intravenous paracetamol seems to be reasonably effective for PDA closure in preterm infants.

Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations

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Anja T. Umbach

2016-11-01

Full Text Available Background/Aims: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH2D3 formation and mineral metabolism, is stimulated by store-operated Ca2+ entry (SOCE, which is accomplished by the pore forming Ca2+ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands. The present study thus explored whether annexin A7 impacts on FGF23 plasma levels. Methods: Comparisons were made between gene targeted mice lacking functional annexin A7 (Anx7-/- and their wild type littermates (Anx7+/+. Serum C-terminal-FGF23, intact FGF23, 1,25(OH2D3 and PTH concentrations were measured by ELISA or EIA. The serum and urinary phosphate concentrations were measured by colorimetry, the serum Ca2+ concentration and the urinary Ca2+ concentration by flame photometry. Results: Serum C-terminal FGF23 levels and corticosterone levels were significantly higher and serum 1,25(OH2 D3 and PTH levels were significantly lower in Anx7-/- than in Anx7+/+ mice. Water intake was slightly but significantly higher in Anx7-/- mice than in Anx7+/+ mice. No significant difference was observed between Anx7-/- and Anx7+/+ mice in urinary fluid excretion, plasma Ca2+ concentration, plasma phosphate concentration and urinary Ca2+ output. The urinary phosphate output was significantly lower in Anx7-/- mice than in Anx7+/+ mice. Conclusion: Annexin A7 deficiency upregulates FGF23 plasma levels, an effect paralleled by increased corticosterone plasma levels, as well as decreased 1,25(OH2 D3 and PTH plasma levels.

[Risk of acute hepatic insufficiency in children due to chronic accidental overdose of paracetamol (acetaminophen)

NARCIS (Netherlands)

Hameleers-Snijders, P.; Hogeveen, M.; Smeitink, J.A.M.; Kramers, C.; Draaisma, J.M.T.

2007-01-01

Two girls aged 4 and 3 years, respectively, experienced acute liver failure due to accidental ingestion of supratherapeutic doses of paracetamol (90 mg/kg/day or more). Recognition of chronic paracetamol intoxication as a cause of acute hepatic failure is often delayed. It is important to consider

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth

NARCIS (Netherlands)

Bailey, E.; Worthington, H.V.; van Wijk, A.; Yates, J.M.; Coulthard, P.; Afzal, Z.

2013-01-01

Background Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

Science.gov (United States)

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

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

A comparative study of ibuprofen with paracetamol versus oxyphenbutazone with analgin combination in ophthalmic practice

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Roy I

1988-01-01

Full Text Available A total of 200 patients of either sex with various ophthalmic inflammatory disorders of surgical and non-surgical types were treated with ibuprofen with paracetamol 1 tablet tid. or a combination of oxyphenbutazone and analgin-1 tablet t. i. d. for 7 days/ Patients in the ibuprofen with Paracetamol group recorded a signifi-cantly greater reduction in pain scores; on day 1 and 2 and in swelling scores on day 2, 5 and 7 as compared to patients receiving the combination of ox yphenbutazone and analgin. A significantly lesserr number of patients in the ibuprofen with paraeetamol group required escape analgesics. Seventy six per cent of patients in the Ibuprofen with paracetamol group were judged as showing a Very good - Good, response to treatment as against 55 per cent in the oxvphenbutazone-analgin group. It is concluded that ibuprofen with Paracetamol is superior in efficacy and a safer alternative to a combination of oxyphenbutazone and analgin.

Stability-Indicating RP-HPLC Method for Analysis of Paracetamol and Tramadol in a Pharmaceutical Dosage Form

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Rajesh M. Kamble

2012-01-01

Full Text Available A simple, isocratic, rapid and accurate reversed phase high performance liquid chromatography method was developed for the quantitative determination of paracetamol and tramadol in commercial medicinal tablets. The chromatographic separation was achieved on an Intersil C18 (250 mm x 4.6 mm, 5μm column using water pH 3.4 with orthophosphoric acid: methanol (60:40, v/v as a mobile phase, and UV detection at 228 nm. The chromatographic resolutions between paracetamol and tramadol were found greater than five. The linear range for paracetamol and tramadol were 20.8–39.0 μg/ml and 2.4–4.5 μg/ ml was obtained with correlation coefficients ≥0.999 for each analyte. The retention time were found to be 2.1 and 3.9 min for tramadol and paracetamol respectively. Paracetamol and tramadol was subjected to stress conditions (hydrolysis (acid, base oxidation, photolysis and thermal degradation and the stressed samples were analyzed by use of the method. The major degradation was observed in acid and minor in base, thermal, oxidation and photolysis. The forced degradation studies prove the stability indicating power of the method.

Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

LENUS (Irish Health Repository)

Cronin, C C

2012-02-03

Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

Plasma carotenoid concentrations in relation to acute respiratory infections in elderly people

NARCIS (Netherlands)

Graat, J.M.; Kok, F.J.; Schouten, E.G.

2004-01-01

A high plasma carotenoid concentration could improve the immune response and result in decreased risk of infectious diseases. However, data on the relationship of plasma carotenoid concentration with acute respiratory infections, which occur frequently in elderly people, are scarce. We investigated,

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

Science.gov (United States)

Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

2015-10-05

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.

Biosensor-based real-time monitoring of paracetamol photocatalytic degradation.

Science.gov (United States)

Calas-Blanchard, Carole; Istamboulié, Georges; Bontoux, Margot; Plantard, Gaël; Goetz, Vincent; Noguer, Thierry

2015-07-01

This paper presents for the first time the integration of a biosensor for the on-line, real-time monitoring of a photocatalytic degradation process. Paracetamol was used as a model molecule due to its wide use and occurrence in environmental waters. The biosensor was developed based on tyrosinase immobilization in a polyvinylalcohol photocrosslinkable polymer. It was inserted in a computer-controlled flow system installed besides a photocatalytic reactor including titanium dioxide (TiO2) as photocatalyst. It was shown that the biosensor was able to accurately monitor the paracetamol degradation with time. Compared with conventional HPLC analysis, the described device provides a real-time information on the reaction advancement, allowing a better control of the photodegradation process. Copyright © 2015 Elsevier Ltd. All rights reserved.

The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

Science.gov (United States)

Craig, D G; Zafar, S; Reid, T W D J; Martin, K G; Davidson, J S; Hayes, P C; Simpson, K J

2012-06-01

The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients. © 2012 Blackwell Publishing Ltd.

Low plasma taurine concentration in Newfoundland dogs is associated with low plasma methionine and cyst(e)ine concentrations and low taurine synthesis.

Science.gov (United States)

Backus, Robert C; Ko, Kwang Suk; Fascetti, Andrea J; Kittleson, Mark D; Macdonald, Kristin A; Maggs, David J; Berg, John R; Rogers, Quinton R

2006-10-01

Although taurine is not dietarily essential for dogs, taurine deficiency and dilated cardiomyopathy (DCM) are sporadically reported in large-breed dogs. Taurine status and husbandry were examined in 216 privately owned Newfoundlands, a giant dog breed with high incidence of idiopathic DCM (1.3-2.5%). Plasma taurine concentration was positively correlated (P ine (r = 0.37) and methionine (r = 0.35) concentrations and was similar across age, sex, neutering status, body weight, and body-condition scores. Plasma taurine concentration was low (ine, tryptophan, and alpha-amino-n-butyric acid concentrations than the other dogs (P ine and blood glutathione, lower (P < 0.01) de novo taurine synthesis (59 +/- 15 vs. 124 +/- 27 mg x kg(-0.75) x d(-1)), and greater (P < 0.05) fecal bile acid excretion (1.7 +/- 0.2 vs. 1.4 +/- 0.2 micromol/g). Newfoundlands would appear to have a higher dietary sulfur amino acid requirement than Beagles, a model breed used in nutrient requirement determinations.

Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants?

Science.gov (United States)

Sancak, Selim; Gokmen Yildirim, Tulin; Topcuoglu, Sevilay; Yavuz, Taner; Karatekin, Guner; Ovali, Fahri

2016-01-01

To compare the efficacy of oral and intravenous paracetamol for closure of hemodynamically significant patent ductus arteriosus (HSPDA) in very low birth weight (VLBW) preterm infants. Eighteen VLBW infants with HSPDA treated with either intravenous (n = 10) or oral (n = 8) paracetamol at 60 mg/kg/d for three consecutive days were analysed retrospectively. Ductal closure rate and evaluation of liver function tests were the major outcomes. After two courses of treatment, HSPDA closure rate was higher in oral paracetamol group than that in the intravenous paracetamol group (88% versus 70%), but it was not statistically significant (p = 0.588). Liver function tests were normal after the treatment. Although it was not statistically significant, the cumulative closure rates were higher in oral paracetamol group than those in the intravenous group. Larger trials are needed to confirm these data.

Energy conversion and concentration in a high-current gaseous discharge: Dense plasma spheromak in plasma focus experiments

International Nuclear Information System (INIS)

Kukushkin, A.B.; Rantsev-Kartinov, V.A.; Terentiev, A.R.

1995-01-01

Experimental results are presented which verify the possibility of the self-generated transformation of the magnetic field in plasma focus discharges to give a closed, spheromak-like magnetic configuration (SLMC). The energy conversion mechanism suggests a possibility of further concentrating the plasma power density by means of natural compressing the SLMC-trapped plasma by the residual magnetic field of the plasma focus discharge

Changes in plasma potassium concentration during carbon dioxide pneumoperitoneum

DEFF Research Database (Denmark)

Perner, A; Bugge, K; Lyng, K M

1999-01-01

Hyperkalaemia with ECG changes had been noted during prolonged carbon dioxide pneumoperitoneum in pigs. We have compared plasma potassium concentrations during surgery in 11 patients allocated randomly to undergo either laparoscopic or open appendectomy and in another 17 patients allocated randomly...... to either carbon dioxide pneumoperitoneum or abdominal wall lifting for laparoscopic colectomy. Despite an increasing metabolic acidosis, prolonged carbon dioxide pneumoperitoneum resulted in only a slight increase in plasma potassium concentrations, which was both statistically and clinically insignificant....... Thus hyperkalaemia is unlikely to develop in patients with normal renal function undergoing carbon dioxide pneumoperitoneum for laparoscopic surgery....

Comparison between Infusion Pumps: Fentanyl/Ketamine and Fentanyl/Paracetamol in Pain control Following Tight and Leg Surgeries

Directory of Open Access Journals (Sweden)

Behnam Mahmoodiyeh

2016-08-01

Full Text Available Background: Adjuvants such as ketamine, promethazine and paracetamol could bring up patients satisfaction and control harmful effects of opioids besides lessening their needed doses, as seen by fentanyl/paracetamol and fentanyl/ketamine combination before. The current study headed to compare paracetamol and ketamine in addition to fentanyl applied by infusion pumps in order to pain relief following major surgery.Methods: Through a double blinded randomized clinical trial, patients between18 and 65 with elective surgery for tight or leg fractures with ASA Class 1 and 2 referring to a university hospital in Arak, a town in central region of Iran, were recruited and used infusion pump for their postoperative pain control. The participants were divided into cases and controls regarding using ketamine/fentanyl (KF or paracetamol/fentanyl (PF infusion pumps.Results: The mean pain score was totally 3.87 with higher value in KF (5.06 and lower in PF (4.5 immediately after finishing surgery and getting conscious when started using infusion pump. There was no statistical difference between the groups in this regard. Concerning the side effects of the applied medications, blood pressure and heart rate had no differences comparing the groups.Conclusion: This study showed that paracetamol used in infusion pump can be brilliant in pain control after major surgeries like what done in lower extremities and joint replacement while lessens opioid use. Although paracetamol was more effective than ketamine in the current trial, more qualified studies at bigger size and in other fields of surgery beside orthopedic ones would be useful to support the effects if applicable.Keywords: Infusion pump, Ketamine, Paracetamol, Fentanyl, Postoperative pain

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

Science.gov (United States)

Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-01-01

Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

Tramadol-Paracetamol Combination for Postoperative Pain Relief in Elective Single-level Microdisectomy Surgery.

Science.gov (United States)

Dogar, Samie A; Khan, Fauzia A

2017-04-01

The tramadol and paracetamol combination is used frequently for postoperative pain management. The literature on the use of this combination for vertebral surgery is limited. Our objective was to compare a combination of paracetamol 1 g and a lower dose of tramadol (1 mg/kg: group 1T) with a combination of paracetamol 1 g and a higher dose of tramadol (1.5 mg/kg: group 1.5T) for postoperative pain after microdisectomy surgery. Our main outcome measure was Visual Analogue Scale pain scores for 4 hours postoperatively. This prospective randomized triple-blind clinical trial was conducted at Aga Khan University Hospital, Karachi. Ninety-four patients aged between 18 and 50 years scheduled for elective single-level microdisectomy were allocated randomly into 1 of 2 groups. Twenty minutes before the end of the surgery, patients received the study drugs. There was no significant demographic difference between groups. None of the patients experienced severe pain (VAS>6). There was no significant difference in the mean pain score between groups. The mean score at 4 hours was 2.17 (1.38) in group 1.5T and 1.74 (1.37) in group 1T. The difference was not statistically significant (P=0.14). In group 1.5T, 13 patients reported having nausea and vomiting compared with 2 patients in group 1T. This was a statistically significant difference (P=0.004). The sedation score was similar between groups. The combination of low-dose tramadol (1 mg/kg) and paracetamol has comparable analgesia and a decreased incidence of nausea and vomiting compared with the higher dose of tramadol (1.5 mg/kg) and paracetamol combination.

Paracetamol vs dexketoprofen for perineal pain relief after episiotomy or perineal tear.

Science.gov (United States)

Akil, A; Api, O; Bektas, Y; Yilmaz, A Onan; Yalti, S; Unal, O

2014-01-01

A randomised controlled trial was conducted to investigate efficacy of paracetamol and dexketoprofen trometamol for perineal pain relief after perineal repair. Subjects were randomly assigned to receive two doses of either 50 mg of intravenous dexketoprofen trometamol via slow i.v. infusion (Group I, n = 49) or 1,000 mg of paracetamol via intravenous infusion (Group II, n = 46). The main outcome measure was a VAS (visual analogue scale) for pain recorded at 1 h (VAS 1). A total of 82 patients were included in the final analysis (Group I, n = 41; Group II, n = 41). There was no difference among groups in terms of pain scores at the beginning (VAS 0). The pain was decreased in 70% of the patients in Group I and in 62% of the patients in Group II (p = 0.502). Both paracetamol and dexketoprofen are effective in perineal pain relief after episiotomy or perineal tear repair.

Low-Dose Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-Resistant or Contraindicated Preterm Infants: Three Cases Reports.

Science.gov (United States)

Matsumura, Shun; Oshima, Ayumi; Fujinuma, Sumie; Tanaka, Kosuke; Nagano, Nobuhiko; Miyake, Fuyu; Masutani, Satoshi; Tamura, Masanori; Ueda, Keiko; Namba, Fumihiko

2017-10-01

Background  Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases  Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion  The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

A novel composite electrode based on tungsten oxide nanoparticles and carbon nanotubes for the electrochemical determination of paracetamol

International Nuclear Information System (INIS)

Baytak, Aysegul Kutluay; Duzmen, Sehriban; Teker, Tugce; Aslanoglu, Mehmet

2015-01-01

An electrochemical sensor was prepared by the modification of a glassy carbon electrode (GCE) with a composite of nanoparticles of tungsten oxide (WO 3 ) and carbon nanotubes (CNTs) for the quantification of paracetamol (PR). Energy dispersive X-ray analysis (EDX) and scanning electron microscopy (SEM) were performed for the characterization of the nanocomposite layer. Compared with a bare GCE and a GCE modified with CNTs, the proposed electrode (WO 3 NPs/CNTs/GCE) exhibited a well-defined redox couple for PR and a marked enhancement of the current response. The experimental results also showed that ascorbic acid (AA) did not interfere with the selective determination of PR. The proposed electrode was used for the determination of PR in 0.1 M phosphate buffer solution (PBS) at pH 7.0 using square wave voltammetry (SWV). The peak current increased linearly with the concentration of PR in the range of 1.0 × 10 −9 –2.0 × 10 −7 M. The detection limit (LOD) was 5.54 × 10 −11 M (based on 3 S b /m). The proposed voltammetric sensor provided long-time stability, improved voltammetric behavior and good reproducibility for PR. The selective, accurate and precise determination of PR makes the proposed electrode of great interest for monitoring its therapeutic use. - Highlights: • A voltammetric nanosensor was prepared using nanoparticles of WO 3 and CNTs. • A selective quantification of paracetamol was carried out in the presence of AA. • A linear plot was obtained for current responses versus concentrations over the range from 1.0 × 10 −9 to 2.0 × 10 −7 M. • A detection limit of 554 pM was obtained for paracetamol using the proposed nanosensor. • An accurate quantification makes the proposed nanosensor of great interest for public health

Efectos tóxicos del paracetamol en la salud humana y el ambiente

Directory of Open Access Journals (Sweden)

Rosa Leonor Acevedo-Barrios

2017-06-01

Full Text Available En este artículo se detallan los efectos tóxicos del paracetamol en la salud humana y el ambiente, detallando las generalidades del paracetamol APAP. El metabolismo del APAP y factores potenciales que influyen en su toxicidad, pasando por estudios de toxicidad y por último el destino ambiental. El paracetamol es un analgésico de uso común, presenta alta hidrosolubilidad, eliminándose hasta un 90% por gluconación o sulfación; pero su metabólito N-acetil-para-benzoilquinoneimina en ocasiones se expulsa por medio de las heces y orina, volviéndose un compuesto toxico persistente. Se observan efectos crónicos principalmente en organismos acuáticos, a través de la exposición a diferentes concentraciones de APAP durante un prolongado período de tiempo.

Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

Science.gov (United States)

Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

2014-11-01

Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

LENUS (Irish Health Repository)

Espinoza, Jimmy

2012-02-01

OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal manifestations of preeclampsia, but the possible signaling mechanisms remain unclear. This study compares the fetal plasma concentrations of adenosine from normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary data analysis included normal pregnancies (n = 27) and patients with preeclampsia (n = 39). Patients with preeclampsia were subclassified into patients with (n = 25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV). RESULTS: Fetal plasma concentrations of adenosine were significantly higher in patients with preeclampsia (1.35 +\\/- 0.09 mumol\\/L) than in normal pregnancies (0.52 +\\/- 0.06 mumol\\/L; P < .0001). Fetal plasma concentrations of adenosine in patients with preeclampsia with abnormal UADV (1.78 +\\/- 0.15 mumol\\/L), but not with normal UADV (0.58 +\\/- 0.14 mumol\\/L), were significantly higher than in normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia have high fetal plasma concentrations of adenosine.

Inclusion of Paracetamol into β-cyclodextrin nanocavities in solution and in the solid state

Science.gov (United States)

El-Kemary, Maged; Sobhy, Saffaa; El-Daly, Samy; Abdel-Shafi, Ayman

2011-09-01

We report on steady-state UV-visible absorption and emission characteristics of Paracetamol, drug used as antipyretic agent, in water and within cyclodextrins (CDs): β-CD, 2-hydroxypropyl- β-CD (HP- β-CD) and 2,6-dimethyl- β-CD (Me- β-CD). The results reveal that Paracetamol forms a 1:1 inclusion complex with CD. Upon encapsulation, the emission intensity enhances, indicating a confinement effect of the nanocages on the photophysical behavior of the drug. Due to its methyl groups, the Me- β-CD shows the largest effect for the drug. The observed binding constant showing the following trend: Me- β-CD > HP- β-CD > β-CD. The less complexing effectiveness of HP- β-CD is due to the steric effect of the hydroxypropyl-substituents, which can hamper the inclusion of the guest molecules. The solid state inclusion complex was prepared by co-precipitation method and its characterization was investigated by Fourier transform infrared spectroscopy, 1H NMR and X-ray diffractometry. These approaches indicated that Paracetamol was able to form an inclusion complex with CDs, and the inclusion compounds exhibited different spectroscopic features and properties from Paracetamol.

Paracetamol (acetaminophen) efficacy and safety in the newborn.

Science.gov (United States)

Cuzzolin, Laura; Antonucci, Roberto; Fanos, Vassilios

2013-02-01

Neonates can perceive pain, therefore an adequate analgesic therapy is a major issue not only from an ethical perspective but also to improve short- and long-term outcome. Fever during the neonatal period requires hospitalization and needs a treatment with an antipyretic agent because of the high risk of severe complications. Paracetamol (acetaminophen), the most commonly prescribed drug in paediatric patients for its analgesic and antipyretic effects, is the only agent recommended for use as an antipyretic in the newborn and has been recently proposed as a supplement therapy to opioids for postoperative analgesia. This article aims to give an updated overview on the use of paracetamol in newborns by presenting its pharmacological profile (mechanism of action, pharmacokinetics), recommendations for dosing regimens (oral or rectal administration: 25-30 mg/kg/day in preterm neonates of 30 weeks' gestation, 45 mg/kg/day in preterm neonates of 34 weeks' gestation, 60 mg/kg/day in term neonates; i.v. administration: indicatively 20-40 mg/kg/day depending on gestational age, with some differences among various guidelines) and clinical uses (more commonly as analgesic/antipyretic by oral or rectal route, but also i.v. in anaesthesia for postoperative analgesia and painful procedures in Neonatal Intensive Care Units). Moreover, drug tolerability is discussed in the light of its potential hepatotoxicity and the unique characteristics of the newborn patient. By analyzing the available literature and the dosing guidelines, a mismatch exists between the current clinical use of paracetamol and the recommendations, suggesting a cautious approach particularly in extremely preterm neonates.

Oral Paracetamol for Patent Ductus Arteriosus Rescue Closure.

Science.gov (United States)

Pharande, Pramod; Watson, Hadley; Tan, Kenneth; Sehgal, Arvind

2018-01-01

The objective of this study was to ascertain the efficacy of oral paracetamol in closing a symptomatic patent ductus arteriosus (PDA) when used as 'rescue' option. After obtaining ethics approval, a retrospective appraisal of the data from April 2014 to July 2015 was performed. Infants who were administered oral paracetamol either after unsuccessful therapy with ibuprofen or where it was considered contraindicated were included. A previously published echocardiographic scoring schema to stratify for ductal disease severity was used. Using univariate analysis, characteristics of infants with successful closure were compared with partial (a priori reduction in composite score by ≥ 50% of pretreatment) or no closure. Twenty infants with gestation age and birthweight of 25.7 ± 1.5 weeks and 724.1 ± 143 g, respectively, were studied. Complete closure was noted in 10 (50%) infants with additional four infants showing a significant reduction in haemodynamic shunting. Gestational age at birth and at therapy, chronological age at therapy, birthweight and total fluid intake were comparable between the two groups. The pre-therapy composite score had a significant association with successful closure (the higher the echocardiographic score, the lesser the closure). Concomitant furosemide therapy and late-onset sepsis had a high likelihood ratio of unsuccessful closure (11.01 [2-tailed, p = 0.005] and 5.3 [2-tailed, p = 0.07]), respectively. Oral paracetamol may be a possible therapeutic option in premature infants where therapy with first-line agents is unsuccessful or contraindicated. Concomitant sepsis and furosemide administration may affect successful therapy.

Paracetamol poisoning among immigrants in a department of hepatology

DEFF Research Database (Denmark)

Schmidt, L E; Dalhoff, K P

2001-01-01

INTRODUCTION: An increased incidence of suicides and suicidal behaviour among immigrants has been described in other countries. In Denmark, misuse of paracetamol is suspected in some foreign-born minority groups, although no data have been produced to substantiate this suspicion. METHODOLOGY......: A retrospective study of the incidence of paracetamol poisoning in patients admitted to a specialised department of hepatology from 1994 to 1999 was carried out. RESULTS: Of a total of 580 patients, 56 (9.7%; 95%-confidence interval 7.2-12.1%) were immigrants, among whom a significant overrepresentation was found...... of immigrants from Turkey, Iran, Pakistan, and Lebanon (Observed/Expected-ratios of 1.95, 4.14, 2.67, and 2.45 respectively; p immigrants differed from the Danish-born patients being younger (21 vs 35 years of age; p

Plasma digoxin concentrations and urinary excretion during a 'simpler' regimen of infant digitalization.

Science.gov (United States)

Savage, M O; Hibble, A G; Pickering, D

1975-01-01

We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory. PMID:1103751

Evaluation of Palm Oil-Based Paracetamol Suppositories by ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research January 2014; 13 (1): 23-29. ISSN: 1596-5996 (print); ... Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur-50603, Malaysia .... donated by Hesego Industry (M) Sdn Bhd,. Esterchem (M) ... stainless steel suppository moulds and the paracetamol ...

Comparison of preemptive intravenous paracetamol and caudal block in terms of analgesic and hemodynamic parameters in children

Directory of Open Access Journals (Sweden)

Serbülent Gökhan Beyaz

2012-06-01

Full Text Available Objectives: Paracetamol has a widespread use for feverand symptomatic relief of pain in children. The aim ofthis study was to compare analgesic effects of preemptiveintravenous (i.v. paracetamol, and caudal block withlevobupivacaine.Materials and methods: A total of 60 children with ASAI-II physical status, aged 5-15 years and undergoing inguinalhernia repair, were randomly allocated to threegroups so that each group contained 20 patients. Group Pchildren received i.v. 15mg/kg paracetamol. Group C receivedonly caudal block with levobupivacaine, and GroupPC received both i.v. paracetamol, and caudal block withlevobupivacaine. Pain level assessed by modified EasternOntario Children’s Hospital pain scale (mCHEOPs,sedation status by Ramsey sedation scale at postoperative5, 15, 30 min and 1,3, and 6th hours.Results: No significant differences were found in age,gender distribution, body weight, ASA status, type andduration of surgery between three groups (p>0.05. Althoughsignificant difference were found in mCHEOPsscores within groups by repeated measures, no differenceof pain scores was observed between three groups(p>0.05. There were no significant differences in the hemodynamicparameters (heart rate, blood pressure bothwithin groups and between groups (p>0.05.Conclusions: Preemptive intravenous paracetamol hadsimilar analgesic effects compared with caudal block withlevobupivacaine with regard to postoperative pain scoresin children undergoing inguinal hernia repair. No hemodynamicor other adverse effects were observed withintravenous paracetamol. J Clin Exp Invest 2012; 3(2:202-208

Ibuprofen is superior to paracetamol for pain relief following third molar removal.

Science.gov (United States)

Ferraiolo, Debra M; Veitz-Keenan, Analia

2014-12-01

The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase and the metaRegister of Controlled Trials were searched with no language restrictions. Randomised controlled double-blinded clinical trials using the third molar model were included. Two review authors independently and in duplicate extracted data. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours post-dosing and meta-analysed for comparison. Seven studies involving 2241 patients were included. Two studies were considered to be at low risk of bias, three at high risk and two unclear risk of bias. Ibuprofen was found to be a superior analgesic to paracetamol at several doses, with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. Risk ratio (RR) for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, RR for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials). For combined drug RR for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence). RR not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence). Adverse events were comparable between the treatment groups, but no formal analysis could be undertaken. There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The

Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

NARCIS (Netherlands)

Prins, Sandra A.; van Dijk, Monique; van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

2008-01-01

The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h

The effect of intravenous paracetamol for the prevention of rocuronium injection pain

Directory of Open Access Journals (Sweden)

Sennur Uzun

2014-11-01

Full Text Available Rocuronium is a nondepolarizing neuromuscular blocking agent used in anesthesia induction and is associated with considerable discomfort and burning pain during injection, which is reported to occur in 50–80% of patients. This study was carried out to investigate the effectiveness of intravenous paracetamol pretreatment compared with lidocaine and normal saline to prevent rocuronium injection pain. The study included 150 ASA I–II patients undergoing elective orthopedic, gastrointestinal, and gynecological procedures under general anesthesia. They were allocated into three groups according to pretreatment drugs: lidocaine (40 mg (n = 50, paracetamol (n = 50, and normal saline group (n = 50. Before anesthesia induction with propofol, all patients were pretreated with rocuronium. The pain caused by the injection was evaluated. Local signs were assessed on the arm at the end of the injection, as well as 24 hours after recovery from anesthesia. There were no patients with blurred speech or vision and there was no respiratory depression in any group after pretreatment with the study drug. The level of pain on injection was statistically lower in those who had received paracetamol compared to normal saline (p = 0.009. There were more patients in the saline group with severe pain (p < 0.001. Paracetamol relieved the rocuronium injection pain better than normal saline but lidocaine was the best of the three drugs (p < 0.001.

Kinetics and Mechanism of Paracetamol Oxidation by Chromium(VI in Absence and Presence of Manganese(II and Sodiumdodecyl Sulphate

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Maqsood Ahmad Malik

2007-11-01

Full Text Available The kinetics of paracetamol oxidation are first order each in [paracetamol] and [HClO4]. The kinetic study shows that the oxidation proceeds in two steps. The effects of anionic micelles of sodiumdodecyl sulphate (SDS and complexing agents (ethylenediammine tetraacetic acid (EDTA and 2,2′-bipyridyl (bpy were also studied. Fast kinetic spectrophotometric method has been described for the determination of paracetamol. The method is based on the catalytic effect of manganese(II on the oxidation of paracetamol by chromium(VI in the presence of HClO4 (= 0.23 mol dm−3. Optimum reaction time is 4 to 6 minutes at a temperature of 30∘C. The addition of manganese(II ions largely decreased the absorbance of chromium(VI at 350 nm. This reaction can be utilized for the determination of paracetamol in drugs.

Rat liver microsomal cytochrome P450-dependent oxidation of 3,5-disubstituted analogues of paracetamol

NARCIS (Netherlands)

Bessems, J.G.M.; Koppele, J.M. te; Dijk, P.A. van; Stee, L.L.P. van; Commandeur, J.N.M.; Vermeulen, N.P.E.

1996-01-01

1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -C(H)3, -C2H5, -iC3H7) have been determined with β-naphthoflavone (βNF)-induced rat liver microsomes and produced reverse type I spectral changes. K(s,app) varied

Unexpected paracetamol (acetaminophen) hepatotoxicity at standard dosage in two older patients: time to rethink 1 g four times daily?

Science.gov (United States)

Ging, Patricia; Mikulich, Olga; O'Reilly, Katherine M A

2016-07-01

We present two cases of acute hepatotoxicity associated with elevated paracetamol (acetaminophen) levels in older patients. Both patients were receiving a standard European dose of oral paracetamol (2 × 500 mg QDS) with no risk factors for slowed metabolism (weight paracetamol can be hepatotoxic. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hepatoprotective effect of Aegle marmelos augmented with piperine co-administration in paracetamol model

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Deepti Rathee

Full Text Available ABSTRACT The current study explored hepatoprotective effect of Aegle marmelos (L. Corrêa, Rutaceae, leaves extract. Potentiation of A. marmelos hepatoprotective effect with piperine co-administration was also explored. Wistar rats were randomly divided into seven groups: (i normal control, (ii paracetamol group, (iii silymarin group, (iv extract-25 group (25 mg/kg body, (v extract-50 group: (50 mg/kg, (vi extract-100 group (100 mg/kg and (vii extract-25 + piperine group. Hepatotoxicity was induced by administering paracetamol orally in a dose of 400 mg/kg for seven days. The drugs were administered 30 min prior to paracetamol administration and continued for seven days. Animals were ‘sacrificed’ at the end of treatment and serum was collected for evaluating alkaline phosphatase, bilirubin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase IL-10 and TNF-α levels. Liver homogenates were used for determination of oxidative stress (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione reductase, GSH-S-transferase, glutathione peroxidase and glucose-6-phosphate dehydrogenase. Serum biochemical markers were significantly higher in paracetamol group as compared to normal control group. Significant increase in oxidative stress parameters and inflammatory mediators was also observed. Treatment with A. marmelos curtailed the toxic effects of paracetamol in a dose dependent fashion. 100 mg/kg dose of A. marmelos was found to be most hepatoprotective. The results of extract-100 group were comparable to silymarin group. Low dose of A. marmelos i.e., 25 mg/kg was combined with piperine to evaluate potentiation of hepatoprotective effects of A. marmelos. Piperine co-administration potentiated the hepatoprotective effects, because the combination group results were comparable to high dose A. marmelos group. A. marmelos exerts hepatoprotective activity through its antioxidant and anti

Endostatin concentration in plasma of healthy human volunteers

International Nuclear Information System (INIS)

Shah, I.; Malik, M.O.; Khan, M.J.; Fatima, S.; Habib, S.H.

2017-01-01

Angiogenesis is involved in many cardiovascular and cancerous diseases, including atherosclerosis and is controlled by a fine balance between angiogenic and angiostatic mediators. Endostatin is one of the main angiostatic mediators, and inhibits angiogenesis and prevents progression of atherosclerosis. The available literature shows a broad range of concentrations in relatively small samples of healthy controls and is calculated by using different techniques. This study was aimed to determine the basal endostatin concentration in plasma of healthy volunteers, to fully understand its physiological role. Methods: Fifty healthy adult volunteers were recruited to the study. Participants were advised not to participate in any physical activity on the day before the blood sampling. The volunteers' physical activity, height, weight, heart rate and blood pressure were recorded. The samples were analysed for plasma endostatin concentration, using ELISA. The participants were divided by gender and ethnic groups to calculate any difference. Results: Endostatin and other variables were normally distributed. Most of the participants had a moderate level of physical activity with no gender related difference (p=0.370). The mean value for plasma endostatin in all samples was 105+-12 ng/ml with range of 81-132 ng/ml. For males, it was 107+-13 ng/ml, while for females; 102+-12 ng/ml. There were no significant gender or ethnicity related differences in endostatin concentration. Moreover, endostatin was not significantly related with any anthropometric and physical variable. Conclusion: This study gives endostatin levels in normal healthy people and show no gender and ethnicity related differences in endostatin levels. Endostatin was not related with any anthropometric and physical variable. (author)

Metabolic acidosis caused by concomitant use of paracetamol (acetaminophen) and flucloxacillin? A case report and a retrospective study.

Science.gov (United States)

Berbee, J K; Lammers, L A; Krediet, C T P; Fischer, J C; Kemper, E M

2017-11-01

A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na + , HCO 3 - , Cl - , albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously. In the 2-year study period, approximately 53,000 admissions took place in our hospital. One thousand and fifty-seven patients used paracetamol and flucloxacillin simultaneously, of which 51 patients (4.8%) had a serum pH ≤ 7.35. One patient, the same patient as presented in the case report, had a high anion gap and a toxic level of 5-oxoproline. The prevalence of metabolic acidosis is very low and the only patient identified with the interaction was recognised during normal clinical care. We conclude that automatic alerts based on simultaneous use of paracetamol and flucloxacillin will generate too many signals. To recognise patients earlier and prevent severe outcomes, a warning system (clinical rule) based on paracetamol, flucloxacillin and pH measurement may be helpful. Early calculation of the anion gap can narrow the differential diagnosis of patients with metabolic acidosis and measurement of 5-oxoproline can explain acidosis due the interaction of paracetamol and flucloxacillin.

An Investigation of Safety and Efficacy of Intravenous Paracetamol in Pain Management Following Cardiac Surgery

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Ehsan Mahdavi

2015-09-01

Full Text Available Introduction: Optimum pain management immediately after surgeries can lower the possibility of pain syndrome and its following consequences. Opioids are amongst the analgesics used for postoperative pain control; however, their application can bring about several adverse effects. In this study, all the published articles regarding efficacy of Paracetamol   in post-cardiac surgery pain management were systematically reviewed. Materials and Methods: Pubmed and Scopus were searched for relevant articles. The employed search strategy was as follows: (Paracetamol   OR Acetaminophen OR Propacetamol AND (pain OR analgesia AND coronary. All the English-language articles (with no time restriction, investigating the effectiveness of Acetaminophen in comparison with other analgesics or placebo, were included in the study. All the articles examining the efficacy of Paracetamol   in combination with other analgesics were excluded from the search results. Results: On the whole, our electronic search retrieved 192 articles from PubMed and 365 articles from Scopus. After screening the titles, abstracts, and full texts of the search results, only 5 English-language articles met our inclusion criteria. Conclusion: Although Paracetamol   demonstrated considerable efficacy in minimizing application of post-operative opioids, its strength in soothing post-operative pain is not significantly different from opioids. Further, conducting randomized-controlled-trials with large sample size are necessary to accurately reveal the efficacy of Paracetamol   in curtailing application of opioids in post cardiac surgeries.

Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

Science.gov (United States)

Okkens, A C; Dieleman, S J; Kooistra, H S; Bevers, M M

1997-01-01

The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

Science.gov (United States)

Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

1990-01-01

1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

Structural study of salt forms of amides; paracetamol, benzamide and piperine

Science.gov (United States)

Kennedy, Alan R.; King, Nathan L. C.; Oswald, Iain D. H.; Rollo, David G.; Spiteri, Rebecca; Walls, Aiden

2018-02-01

Single crystal x-ray diffraction has been used to investigate the structures of six complexes containing O-atom protonated cations derived from the pharmaceutically relevant amides benzamide (BEN), paracetamol (PAR) and piperine (PIP). The structures of the salt forms [PAR(H)][SO3C6H4Cl], [BEN(H)][O3SC6H4Cl] and [BEN(H)][Br]·H2O are reported along with those of the hemi-halide salt forms [PAR(H)][I3]. PAR, [PIP(H)][I3]·PIP and [PIP(H)][I3]0·5[I]0.5. PIP. The structure of the cocrystal BEN. HOOCCH2Cl is also presented for comparison. The geometry of the amide group is found to systematically change upon protonation, with the Cdbnd O distance increasing and the Csbnd N distance decreasing. The hemi-halide species all feature strongly hydrogen bonded amide(H)/amide pairs. The amide group Cdbnd O and Csbnd N distances for both elements of each such pair are intermediate between those found for simple neutral amide and protonated amide forms. It was found that crystallising paracetamol from aqueous solutions containing Ba2+ ions gave orthorhombic paracetamol.

Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults.

Science.gov (United States)

Wiffen, Philip J; Knaggs, Roger; Derry, Sheena; Cole, Peter; Phillips, Tudor; Moore, R Andrew

2016-12-27

Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

Conjoint regulation of glucagon concentrations via plasma insulin and glucose in dairy cows.

Science.gov (United States)

Zarrin, M; Wellnitz, O; Bruckmaier, R M

2015-04-01

Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a suppressor of glucagon secretion. We have investigated if and how insulin and glucose contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG, n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin at simultaneously normal glucose concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin, and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area under the curve (AUC)/h in HypoG (41.9 ± 8.1 mU/L) and EuG (57.8 ± 7.8 mU/L) compared with NaCl (13.9 ± 1.1 mU/L; P insulin infusion induces elevated glucagon concentrations during hypoglycemia, although the same insulin infusion reduces glucagon concentrations at simultaneously normal glucose concentrations. Thus, insulin does not generally have an inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is high, glucagon is upregulated to increase glucose availability. Therefore, insulin and glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the plasma glucose status is the key factor to decide if its concentrations are increased or decreased. This regulatory effect can be important for the maintenance of glucose homeostasis if insulin secretion is upregulated by other factors than high

Laser system for measuring small changes in plasma tracer concentrations.

Science.gov (United States)

Klaesner, J W; Pou, N A; Parker, R E; Galloway, R L; Roselli, R J

1996-01-01

The authors developed a laser-diode system that can be used for on-line optical concentration measurements in physiologic systems. Previous optical systems applied to whole blood have been hampered by artifacts introduced by red blood cells (RBCs). The system introduced here uses a commercially available filter cartridge to separate RBCs from plasma before plasma concentration measurements are made at a single wavelength. The filtering characteristics of the Cellco filter cartridge (#4007-10, German-town, MD) were adequate for use in the on-line measurement system. The response time of the filter cartridge was less than 40 seconds, and the sieving characteristics of the filter for macromolecules were excellent, with filtrate-to-plasma albumin ratios of 0.98 +/- 0.11 for studies in sheep and 0.94 +/- 0.15 for studies in dogs. The 635-nm laser diode system developed was shown to be more sensitive than the spectrophotometer used in previous studies (Klaesner et al., Annals of Biomedical Engineering, 1994; 22, 660-73). The new system was used to measure the product of filtration coefficient (Kfc) and reflection coefficient for albumin (delta f) in an isolated canine lung preparation. The delta fKfc values [mL/(cmH2O.min.100 g dry lung weight)] measured with the laser diode system (0.33 +/- 0.22) compared favorably with the delta fKfc obtained using a spectrophotometer (0.27 +/- 0.20) and with the Kfc obtained using the blood-corrected gravimetric method (0.32 +/- 0.23). Thus, this new optical system was shown to accurately measure plasma concentration changes in whole blood for physiologic levels of Kfc. The same system can be used with different optical tracers and different source wavelengths to make optical plasma concentration measurements for other physiologic applications.

[Association between paracetamol exposure and asthma: update and practice guidelines].

Science.gov (United States)

Moral, L; Torres-Borrego, J; Korta Murua, J; Valverde-Molina, J; Pellegrini Belinchón, J; Praena-Crespo, M; Ortega Casanueva, C; Callén-Blecua, M T; Fernández-Llamazares, C M; Calvo Rey, C

2013-09-01

Asthma prevalence has increased over the last few decades, especially in developed countries, and possibly due to different reasons. An association between paracetamol use or exposure at different periods of life, including gestation and childhood, and asthma prevalence has been observed in the last few years. Causality can not be established from observational reports, due to the arguable presence of many confounding factors and biases. Randomised trials are needed to elucidate the nature of this association. The Spanish Paediatric societies subscribing to this paper consider that current evidence is insufficient to discourage the use of paracetamol during gestation or in children with or at risk of asthma. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hepatoprotective effect of Phytosome Curcumin against paracetamol-induced liver toxicity in mice

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Bui Thanh Tung

2017-04-01

Full Text Available Abstract Curcuma longa, which contains curcumin as a major constituent, has been shown many pharmacological effects, but it is limited using in clinical due to low bioavailability. In this study, we developed a phytosome curcumin formulation and evaluated the hepatoprotective effect of phytosome curcumin on paracetamol induced liver damage in mice. Phytosome curcumin (equivalent to curcumin 100 and 200 mg/kg body weight and curcumin (200 mg/kg body weight were given by gastrically and toxicity was induced by paracetamol (500 mg/kg during 7 days. On the final day animals were sacrificed and liver function markers (ALT, AST, hepatic antioxidants (SOD, CAT and GPx and lipid peroxidation in liver homogenate were estimated. Our data showed that phytosome has stronger hepatoprotective effect compared to curcumin-free. Administration of phytosome curcumin effectively suppressed paracetamol-induced liver injury evidenced by a reduction of lipid peroxidation level, and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, glutathione peroxidase in mice liver tissue. Our study suggests that phytosome curcumin has strong antioxidant activity and potential hepatoprotective effects.

Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

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Neil L Spector

Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

the effect of acetaminophen (paracetamol ) on tear production abstract

African Journals Online (AJOL)

LIVINGSTON

cox-1 and cox-2 has long been known to be the mechanism of action ... effects typical of NSAIDS . Chronic excessive alcohol consumption can ... The effect of acetaminophen (paracetamol ) on the tear production of 100 young healthy subjects ...

Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

DEFF Research Database (Denmark)

Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

2014-01-01

OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

Development of concentric equipotential surfaces in bumpy torus plasma

International Nuclear Information System (INIS)

Takasugi, Keiichi; Iguchi, Harukazu; Fujiwara, Masami; Ikegami, Hideo

1983-01-01

Radial profiles of the plasma space potential are measured in Nagoya Bumpy Torus (NBT-1) by the use of a heavy ion beam probe. Asymmetric potential profiles owing to toroidal drift are observed in high pressure operation (C-mode). As the pressure is decreased, toroidal plasma is effectively heated (T-mode), poloidal precessional frequency overcomes the electron collision frequency and the equipotential surfaces becomes concentric inside the hot electron ring. (author)

Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data

International Nuclear Information System (INIS)

Syed, A.A.; Aslam, F.; Hakeem, H.; Siddiqui, F.; Nasir, N.

2017-01-01

To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. Methods: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Results: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. Conclusion: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low. (author)

Intravenous paracetamol versus intramuscular pethidine in relief of ...

African Journals Online (AJOL)

Background: Intramuscular pethidine is one of most common opioids used for labour analgesia. There are a number of concerns in the literature regarding the use of pethidine. The aim of this study is to compare analgesic efficacy of paracetamol with pethidine for labour pain in normal vaginal delivery. Materials and ...

The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance.

OpenAIRE

Mayersohn, M; Conrad, K A; Achari, R

1983-01-01

1 The influence of a meal containing cooked meat (225 g) on creatinine plasma concentration, creatinine urinary excretion and creatinine clearance was determined in six healthy male subjects. 2 The meat meal produced an average 52% increase in creatinine plasma concentration within 1.5 to 3.5 h after ingestion. The 24 h area under the creatinine plasma concentration-time curve increased by about 19%. Urinary creatinine excretion during 24 h increased by an average of 13%. Creatinine clearance...

Use of refractometry for determination of psittacine plasma protein concentration.

Science.gov (United States)

Cray, Carolyn; Rodriguez, Marilyn; Arheart, Kristopher L

2008-12-01

Previous studies have demonstrated both poor and good correlation of total protein concentrations in various avian species using refractometry and biuret methodologies. The purpose of the current study was to compare these 2 techniques of total protein determination using plasma samples from several psittacine species and to determine the effect of cholesterol and other solutes on refractometry results. Total protein concentration in heparinized plasma samples without visible lipemia was analyzed by refractometry and an automated biuret method on a dry reagent analyzer (Ortho 250). Cholesterol, glucose, and uric acid concentrations were measured using the same analyzer. Results were compared using Deming regression analysis, Bland-Altman bias plots, and Spearman's rank correlation. Correlation coefficients (r) for total protein results by refractometry and biuret methods were 0.49 in African grey parrots (n=28), 0.77 in Amazon parrots (20), 0.57 in cockatiels (20), 0.73 in cockatoos (36), 0.86 in conures (20), and 0.93 in macaws (38) (Prefractometry in Amazon parrots, conures, and macaws (n=25 each, PRefractometry can be used to accurately measure total protein concentration in nonlipemic plasma samples from some psittacine species. Method and species-specific reference intervals should be used in the interpretation of total protein values.

[Effects of dietary wheat gluten level on decreasing plasma homocysteine concentration in rats].

Science.gov (United States)

Liu, Yiqun; Han, Feng; Sun, Licui; Lu, Jiaxi; Sugiyama, Kimio; Huang, Zhenwu

2015-05-01

To investigate the effects of different level of casein and wheat gluten on decreasing plasma homocysteine concentration in rats. 48 rats of the Wistar were fed with different level of casein (12.5%, 25% and 50%) and wheat gluten (14.5%, 29% and 58%) diets for 14 days, and they were killed by decapitation to obtain blood and livers was subject to analysis the concentration of homocysteine, cysteine and other amino acids, as well as BHMT and CBS activities. Body weight gain in rats fed wheat gluten dietary was significantly less than casein dietary, but food intake was significantly decreased in wheat gluten group with increasing of the protein content. The plasma homocysteine concentration in rats fed wheat gluten was marketly less than casein, however plasma cysteine concentration in wheat gluten was higher than casein group. The effects of wheat gluten on plasma homocysteine concentration are mainly depends on the low contents of methionine and high cysteine content, but the low contents of lyscine and threonine are not ignored. The mainly mechanism is that the increased cysteine concentration promot enzyme activities of homocystein metabolism, and increase the consumption of homocysteine.

Plasma oxytocin concentrations during late pregnancy and parturition in the dog.

Science.gov (United States)

Klarenbeek, M; Okkens, A C; Kooistra, H S; Mol, J A; M M Bevers; Taverne, M A M

2007-11-01

While oxytocin is widely used in the treatment of dystocia in dogs, there is little information about its secretion before and during normal unassisted whelping. We therefore measured plasma oxytocin concentrations during late pregnancy and the expulsive stage of parturition. Blood samples were collected from eight dogs at 3-min intervals during a 42-min period between the 2nd and 14th day before whelping and during parturition after the birth of 1-3 pups. The litters consisted of 5-15 pups and the progression of the expulsive stage was linear and nearly parallel in the eight bitches. The overall mean (+/-S.D.) plasma oxytocin concentration during late pregnancy was 3.6+/-2.1pg/ml. Mean values in individual dogs ranged from 1.2 to 7.4 pg/ml, but the intra-animal variation was rather small. During the expulsive stage the overall mean (+/-S.D.) plasma oxytocin concentration was 12.9+/-13.9 pg/ml, with mean values in individual dogs ranging from 3.5 to 46 pg/ml. The mean area under the oxytocin curve for parturient dogs was significantly higher (Pdogs. During the expulsive stage, the peak plasma oxytocin level in individual dogs ranged between 10 and 117 pg/ml. In six of the eight dogs a pup was born during blood collection and in five of these animals the plasma oxytocin concentration increased temporarily during periods of abdominal straining and expulsion. However, straining efforts and expulsion were not consistently associated with a rise in the circulating oxytocin level. It is concluded that in the dog plasma oxytocin levels are higher and more variable during the expulsive stage of parturition than during late pregnancy. Interrelationships between the secretion pattern of oxytocin, the level of uterine contractility, and the progress of fetal expulsion in dogs need further exploration.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

Energy Technology Data Exchange (ETDEWEB)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S. [Korea Atomic Emergy Research Institute, Seoul (Korea, Republic of)

1973-03-15

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

International Nuclear Information System (INIS)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S.

1973-01-01

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

NARCIS (Netherlands)

Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

2000-01-01

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain

NARCIS (Netherlands)

Ong, Cliff K. S.; Seymour, Robin A.; Lirk, Phillip; Merry, Alan F.

2010-01-01

BACKGROUND: There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We

Paracetamol versus placebo in treatment of non-severe malaria in children in Guinea-Bissau: a randomized controlled trial

DEFF Research Database (Denmark)

Kofoed, Poul-Erik; Ursing, Johan; Rodrigues, Amabelia

2011-01-01

The current guidelines for treatment of malaria include paracetamol to children with fever. No convincing evidence for the beneficial effects of this practice exists. Studies show that time to parasite clearance is significantly longer in children treated with paracetamol, which questions...

Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with pulmonic stenosis.

Science.gov (United States)

Kobayashi, Keiya; Hori, Yasutomo; Chimura, Syuuichi

2014-06-01

The detailed information between plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and dogs with pulmonic stenosis (PS) is still unknown. The aim of the present study was to investigate the clinical utility of measuring plasma NT-proBNP concentrations in dogs with PS and to determine whether plasma NT-proBNP concentration could be used to assess disease severity. This retrospective study enrolled 30 client-owned, untreated dogs with PS (asymptomatic [n=23] and symptomatic [n=7]) and 11 healthy laboratory beagles. Results of physical examination, thoracic radiography and echocardiography were recorded. Plasma NT-proBNP concentrations were measured using commercial laboratories. Compared to the healthy control dogs, cardiothoracic ratio was significantly increased in dogs with both asymptomatic and symptomatic PS. Similarly, the ratio of the main pulmonary artery to aorta was significantly decreased in dogs with both asymptomatic and symptomatic PS. The pulmonic pressure gradient in the symptomatic PS dogs was significantly higher than that in the asymptomatic PS dogs. Plasma NT-proBNP concentration was significantly elevated in the symptomatic PS dogs compared to the healthy control dogs and the asymptomatic PS dogs. Furthermore, the Doppler-derived pulmonic pressure gradient was significantly correlated with the plasma NT-proBNP concentration (r=0.78, r(2)=0.61, P764 pmol/l to identify severe PS had a sensitivity of 76.2% and specificity of 81.8%. The plasma NT-proBNP concentration increased by spontaneous PS, i.e. right-sided pressure overload and can be used as an additional method to assess the severity of PS in dogs.

Photocatalytic degradation of paracetamol on TiO2 nanoparticles and TiO2/cellulosic fiber under UV and sunlight irradiation

Directory of Open Access Journals (Sweden)

Nabil Jallouli

2017-05-01

Full Text Available In the present study, photocatalytic degradation of acetaminophen ((N-(4-hydroxyphe-nylacetamide, an analgesic drug has been investigated in a batch reactor using TiO2 P25 as a photocatalyst in slurry and under UV light. Using TiO2 P25 nanoparticles, much faster photodegradation of paracetamol and effective mineralization occurred, more than 90% of 2.65 × 10−4 M paracetamol was degraded under UV irradiation. Changes in pH values affected the adsorption and the photodegradation of paracetamol. pH 9.0 is found to be the optimum for the photodegradation of paracetamol. HPLC detected hydroquinone, benzoquinone, p-nitrophenol, and 1,2,4-trihydroxybenzene during the TiO2-assisted photodegradation of paracetamol among which some pathway products are disclosed for the first time. The results showed that TiO2 suspension/UV system is more efficient than the TiO2/cellulosic fiber mode combined to solar light for the photocatalytic degradation of paracetamol. Nerveless the immobilization of TiO2 showed many advantages over slurry system because it can enhance adsorption properties while allowing easy separation of the photocatalyst from the treated solution with improved reusable performance.

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

International Nuclear Information System (INIS)

Afhami, M.R.; Hassanzadeh, J.P.; Panahea, J.R.

2007-01-01

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)

Clinical update on benefit versus risks of oral paracetamol alone or with codeine: still a good option?

Science.gov (United States)

Kress, Hans Georg; Untersteiner, Gerald

2017-02-01

After decades of worldwide use of paracetamol/acetaminophen as a popular and apparently safe prescription and over-the-counter medicine, the future role of this poorly understood analgesic has been seriously questioned by recent concerns about prenatal, cardiovascular (CV) and hepatic safety, and also about its analgesic efficacy. At the same time the usefulness of codeine in combination products has come under debate. Based on a PubMed database literature search on the terms efficacy, safety, paracetamol, acetaminophen, codeine and their combinations up to and including June 2016, this clinical update reviews the current evidence of the benefit and risks of oral paracetamol alone and with codeine for mild-to-moderate pain in adults, and compares the respective efficacy and safety profiles with those of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas there is a clear strong association of NSAID use and gastrointestinal (GI) and CV morbidity and mortality, evidence for paracetamol with and without codeine supports the recommended use even in most vulnerable individuals, such as the elderly, pregnant women, alcoholics, and compromised GI and CV patients. The controversies and widespread misconceptions about the complex hepatic metabolism and potential hepatotoxicity have been corrected by recent reviews, and paracetamol remains the first-line nonopioid analgesic in patients with liver diseases if notes of caution are applied. Due to its safety and tolerability profile paracetamol remained a first-line treatment in many international guidelines. Alone and with codeine it is a safe and effective option in adults, whilst NSAIDs are obviously less safe as alternatives, given the risk of potentially fatal GI and CV adverse effects.

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

OpenAIRE

Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-...

effects of artemether on the plasma and urine concentrations of ...

African Journals Online (AJOL)

Dr Komolafe

2011-05-16

May 16, 2011 ... degeneration of the renal tissue of rats, inability of the damaged kidneys to concentrate urine, which manifested as excessive water loss and electrolyte depletion. Key words: Artemether, electrolytes in plasma, urine concentrations, rats. INTRODUCTION. Artemether, one of the derivatives of artemisinin, is.

Processing-independent proANP measurement for low concentrations in plasma

DEFF Research Database (Denmark)

Mark, Peter D; Hunter, Ingrid; Terzic, Dijana

2018-01-01

BACKGROUND: Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated...

Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

Science.gov (United States)

Hindmarsh, Peter C; Charmandari, Evangelia

2015-04-01

Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

Control of exogenous factors affecting plasma homovanillic acid concentration.

Science.gov (United States)

Davidson, M; Giordani, A B; Mohs, R C; Mykytyn, V V; Platt, S; Aryan, Z S; Davis, K L

1987-04-01

Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.

Paracetamol (Acetaminophen) in stroke 2 (PAIS 2): protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36.5 °C or above.

Science.gov (United States)

de Ridder, Inger R; de Jong, Frank Jan; den Hertog, Heleen M; Lingsma, Hester F; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; Oomes, Peter; van Tuijl, Jordie; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2015-04-01

In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37.0 °C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1.43; 95% confidence interval: 1.02-1.97). This relation was also found in the patients with a body temperature of 36.5 °C or higher (odds ratio 1.31; 95% confidence interval 1.01-1.68). These findings need confirmation. The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36.5 °C or above on functional outcome. The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0.05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36.5 °C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be

Simultaneous determination of caffeine and paracetamol by square wave voltammetry at poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode.

Science.gov (United States)

Tefera, Molla; Geto, Alemnew; Tessema, Merid; Admassie, Shimelis

2016-11-01

Poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode (poly(AHNSA)/GCE) was prepared for simultaneous determination of caffeine and paracetamol using square-wave voltammetry. The method was used to study the effects of pH and scan rate on the voltammetric response of caffeine and paracetamol. Linear calibration curves in the range of 10-125μM were obtained for both caffeine and paracetamol in acetate buffer solution of pH 4.5 with a correlation coefficient of 0.9989 and 0.9986, respectively. The calculated detection limits (S/N=3) were 0.79μM for caffeine and 0.45μM for paracetamol. The effects of some interfering substances in the determination of caffeine and paracetamol were also studied and their interferences were found to be negligible which proved the selectivity of the modified electrode. The method was successfully applied for the quantitative determination of caffeine and paracetamol in Coca-Cola, Pepsi-Cola and tea samples. Copyright © 2016 Elsevier Ltd. All rights reserved.