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The Cochrane Database of Systematic... Jul 2007Paracetamol 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... (Meta-Analysis)
Meta-Analysis Review
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 the drug. This will inform dentists and their patients of the best strategy for pain relief after the surgical removal of wisdom teeth.
OBJECTIVES
To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered postoperatively.
SEARCH STRATEGY
We searched the Cochrane Oral Health Group's Trials Register; the Cochrane Pain, Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE; EMBASE and the Current Controlled Trials Register. Handsearching included several dental journals. We checked the bibliographies of relevant clinical trials and review articles for studies outside the handsearched journals. We wrote to authors of the identified randomised controlled trials (RCTs), to manufacturers of analgesic pharmaceuticals, we searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied. The last electronic search was conducted on 24th August 2006.
SELECTION CRITERIA
Randomised, parallel group, placebo controlled, double blind clinical trials of paracetamol for acute pain, following third molar surgery.
DATA COLLECTION AND ANALYSIS
All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief was calculated for both paracetamol and placebo. The number of patients experiencing adverse events, and/or the total number of adverse events reported were analysed.
MAIN RESULTS
Twenty-one trials met the inclusion criteria. A total of 2048 patients were initially enrolled in the trials (1148 received paracetamol, and 892 the placebo) and of these 1968 (96%) were included in the meta-analysis (1133 received paracetamol, and 835 the placebo). Paracetamol provided a statistically significant benefit when compared with placebo for pain relief and pain intensity at both 4 and 6 hours. Most studies were found to have moderate risk of bias, with poorly reported allocation concealment being the main problem. Risk ratio values for pain relief at 4 hours 2.85 (95% confidence interval (CI) 1.89 to 4.29), and at 6 hours 3.32 (95% CI 1.88 to 5.87). A statistically significant benefit was also found between up to 1000 mg and 1000 mg doses, the higher the dose giving greater benefit for each measure at both time points. There was no statistically significant difference between the number of patients who reported adverse events, overall this being 19% in the paracetamol group and 16% in the placebo group.
AUTHORS' CONCLUSIONS
Paracetamol is a safe, effective drug for the treatment of postoperative pain following the surgical removal of lower wisdom teeth.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Humans; Molar, Third; Outcome Assessment, Health Care; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Tooth Extraction
PubMed: 17636762
DOI: 10.1002/14651858.CD004487.pub2 -
Marine Drugs Nov 2023Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause...
Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-α, IL-1, IL-6, NF-kB, INF-γ, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings.
Topics: Rats; Animals; Antioxidants; Acetaminophen; Liver; Oxidative Stress; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury
PubMed: 37999416
DOI: 10.3390/md21110592 -
Anaesthesia Jan 2009This article is a review of the peri-operative use of paracetamol. It reviews the pharmacology of paracetamol, highlighting new information about the mechanism of... (Review)
Review
This article is a review of the peri-operative use of paracetamol. It reviews the pharmacology of paracetamol, highlighting new information about the mechanism of action, and examines its therapeutic use in the peri-operative period, focusing on efficacy, route of administration, and the use of a loading dose to improve early postoperative analgesia.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Drug Administration Routes; Drug Administration Schedule; Humans; Pain, Postoperative; Postoperative Care
PubMed: 19087009
DOI: 10.1111/j.1365-2044.2008.05674.x -
Anesthesiology Apr 2005Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr.
METHODS
After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing.
RESULTS
One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively.
CONCLUSION
Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.
Topics: Acetaminophen; Aged; Analgesia, Patient-Controlled; Analgesics, Non-Narcotic; Analgesics, Opioid; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Orthopedic Procedures; Pain Measurement; Pain, Postoperative; Prodrugs; Sample Size
PubMed: 15791113
DOI: 10.1097/00000542-200504000-00019 -
CPT: Pharmacometrics & Systems... Jun 2018Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended...
Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury.
Topics: Acetaminophen; Animals; Biomarkers; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Drug Overdose; Humans; Logistic Models; Male; Mice; Models, Statistical; Models, Theoretical
PubMed: 29667370
DOI: 10.1002/psp4.12298 -
British Medical Journal Sep 1968
Topics: Acetaminophen; Female; Humans; Middle Aged; Purpura, Thrombocytopenic
PubMed: 5691822
DOI: 10.1136/bmj.3.5620.743-b -
European Spine Journal : Official... Nov 2008The objective of this study was to assess the efficacy of paracetamol (acetaminophen) in the treatment of pain and disability in patients with non-specific low back... (Meta-Analysis)
Meta-Analysis Review
The objective of this study was to assess the efficacy of paracetamol (acetaminophen) in the treatment of pain and disability in patients with non-specific low back pain. We conducted a systematic review of randomized controlled trials to assess the efficacy of paracetamol in the treatment of pain and disability in patients with non-specific low back pain. A search for randomized controlled trials was conducted using the Medline, Embase and CINAHL databases. Trials were eligible if they were randomized controlled trials comparing paracetamol to no treatment, placebo or another treatment in patients with non-specific low back pain. Two of the authors independently assessed trials for methodological quality on the PEDro Scale and extracted data. Continuous pain and disability data were converted to a common 0-10 scale; ordinal data were dichotomized (e.g., no pain, pain). The data was analyzed using the MIX version 1.61 meta-analysis software. Out of 205 unique articles found in the searches, 7 eligible trials were identified. The trials enrolled a total of 676 participants with 5 investigating acute low back pain, 1 investigating chronic low back pain and 1 investigating both. No trial provided data comparing paracetamol to placebo and only one trial compared paracetamol to no treatment. In general the trials were small (only 1 trial had >25 subjects per group) and of low methodological quality (only 2 had a score above 6 on the quality scale). All but one of the trials provided imprecise estimates of the effects of treatment with confidence intervals spanning clinically important beneficial and also harmful effects of paracetamol. No trial reported a statistically significant difference in favor of paracetamol. There is insufficient evidence to assess the efficacy of paracetamol in patients with low back pain. There is a clear need for large, high quality randomized controlled trials evaluating paracetamol, to provide reliable evidence of paracetamol's effectiveness in patients with low back pain and to establish the validity of the recommendations in clinical guidelines.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Chronic Disease; Data Interpretation, Statistical; Humans; Low Back Pain; Randomized Controlled Trials as Topic; Reproducibility of Results; Sample Size; Treatment Outcome
PubMed: 18797937
DOI: 10.1007/s00586-008-0783-x -
Journal of Internal Medicine Feb 2003
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP2E1; Humans; Liver Diseases; Male; Middle Aged
PubMed: 12542548
DOI: 10.1046/j.1365-2796.2003.01107.x -
Journal of Clinical Laboratory Analysis Feb 2019To evaluate the analytical performance of five commercial acetaminophen assays and select the best method for routine use. (Comparative Study)
Comparative Study
BACKGROUND
To evaluate the analytical performance of five commercial acetaminophen assays and select the best method for routine use.
METHODS
Imprecision, accuracy, linearity, and interferences of three enzymatic assays (Beckman Coulter AU Paracetamol, Abbott MULTIGENT Acetaminophen, and Sekisui Acetaminophen L3K) and two immunoassay-based assays (Beckman Coulter SYNCHRON ACTM (Acetaminophen) Reagent and Siemens SYVA Emit-tox Acetaminophen) were evaluated on a Beckman Coulter AU680 chemistry analyzer. Hook effect for immunoassay-based assays and recovery in ultrafiltrate for enzymatic methods were studied.
RESULTS
Within-run and between-run imprecision of the enzymatic assays ranged 0.26%-0.82% and 0.53%-2.86%, respectively, while that for the immunoassay-based methods ranged 0.96%-6.34% and 1.50%-11.33%, respectively. All assays except the SYNCHRON assay fell within the program analytical performance specifications (±20 µmol/L or 10%) for external quality assurance (EQA) samples, with the highest positive bias (31.7%) observed in the SYNCHRON assay. Icteric interference was demonstrated most significantly in the Abbott assay (up to 88 μmol/L positive bias in blank serum). The lipemic interference on the SYNCHRON was significant (up to 110% positive bias at level of 100 μmol/L). The immunoassay-based methods were less susceptible to hemolytic interference, while the Abbott and AU assays were more susceptible to N-acetylcysteine interference. Both immunoassay-based methods showed no hook effect up to 18 000 μmol/L. Ultrafiltration recoveries for enzymatic methods were satisfactory, ranging from 80.0% ± 5.1% to 89.5% ± 3.0%.
CONCLUSIONS
Proportional bias was observed in the SYNCHRON assay, while the Siemens and Sekisui assays were minimally affected by bilirubin interferences.
Topics: Acetaminophen; Acetylcysteine; Bilirubin; Hemolysis; Humans; Immunoenzyme Techniques; Linear Models; Reproducibility of Results; Sensitivity and Specificity
PubMed: 30288787
DOI: 10.1002/jcla.22683 -
Environmental Science and Pollution... Mar 2023This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in...
The palliative effect of mulberry leaf and olive leaf ethanolic extracts on hepatic CYP2E1 and caspase-3 immunoexpression and oxidative damage induced by paracetamol in male rats.
This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in rats compared to silymarin as a reference drug. Initially, MLE and OLE were characterized using gas chromatography-mass spectrometry (GC/MS). Then, forty male Sprague Dawley rats were divided into five groups: the negative control group orally received distilled water for 35 days, the PTL-treated group (PTG) received 500 mg PTL/kg b. wt. for 7 days, the MLE-treated group (MLTG) received 400 mg MLE/kg b. wt., the OLE-treated group (OLTG) received 400 mg OLE/kg b. wt., and the silymarin-treated group (STG) received 100 mg silymarin/kg b. wt. The last three groups received the treatment for 28 days, then PTL for 7 days. The GC-MS characterization revealed that MLE comprised 19 constituents dominated by ethyl linoleate, phytol, hexadecanoic acid, ethyl ester, and squalene. Moreover, OLE comprised 30 components, and the major components were 11-eicosenoic acid, oleic acid, phytol, and à-tetralone. MLE and OLE significantly corrected the PTL-induced normocytic normochromic anemia, leukocytosis, hypercholesterolemia, and hypoproteinemia. Moreover, the MLE and OLE pretreatment considerably suppressed the PTL-induced increment in serum levels of hepatic enzymes, including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Furthermore, the PTL-induced depletion in antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, and the rise in hepatic malondialdehyde content were significantly reversed by the MLE and OLE pretreatment. Besides, MLE and OLE pretreatment significantly protected the hepatic tissue against PTL-induced DNA damage, pathological perturbations, and increased caspase 3 and CYP2E1 immunoexpression. Of note, OLTG showed better enhancement of most indices rather than MLTG. Conclusively, these findings imply that OLE, with its antioxidant and antiapoptotic capabilities, is superior to MLE in protecting against PTL-induced liver injury.
Topics: Rats; Male; Animals; Antioxidants; Acetaminophen; Morus; Olea; Caspase 3; Cytochrome P-450 CYP2E1; Rats, Sprague-Dawley; Chemical and Drug Induced Liver Injury, Chronic; Oxidative Stress; Liver; Silymarin; Plant Leaves; Plant Extracts; Chemical and Drug Induced Liver Injury
PubMed: 36637651
DOI: 10.1007/s11356-023-25152-z