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British Medical Journal Nov 1978
Topics: Acetaminophen; Chemical and Drug Induced Liver Injury; England; Humans; Wales
PubMed: 719401
DOI: 10.1136/bmj.2.6148.1369-b -
British Medical Journal Jan 1978
Topics: Acetaminophen; Acetylcysteine; Cysteamine; Humans
PubMed: 620179
DOI: No ID Found -
Bulletin of the World Health... 2003Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature... (Review)
Review
Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Child; Clinical Trials as Topic; Drug Costs; Fever; Global Health; Humans; Practice Guidelines as Topic
PubMed: 12856055
DOI: No ID Found -
British Journal of Clinical Pharmacology Feb 2016Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial... (Review)
Review
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.
Topics: Acetaminophen; Chemical and Drug Induced Liver Injury; Chronic Disease; Dose-Response Relationship, Drug; Evidence-Based Medicine; Hepatic Insufficiency; Humans
PubMed: 26460177
DOI: 10.1111/bcp.12802 -
Environmental Science and Pollution... Dec 2022Pharmaceutical products are some of the most serious emergent pollutants in the environment, especially nowadays of the COVID-19 pandemic. In this study,...
Pharmaceutical products are some of the most serious emergent pollutants in the environment, especially nowadays of the COVID-19 pandemic. In this study, nanogold-composite was prepared, and its catalytic activity for paracetamol degradation was investigated. Moreover, for the first time, recycled waste diatomite earth (WDE) from beer filtration was used for reproducible gold nanoparticle (Au NPs) preparation. We studied Au NPs by various psychical-chemical and analytical methods. Transmission and scanning electron microscopy were used for nanogold-composite morphology, size and shape characterization. Total element concentrations were determined using inductively coupled plasma mass and X-ray fluorescence spectrometry. X-ray powder diffraction analysis was used for crystal structure characterization of samples. Fourier transform infrared spectrometer was used to study the chemical changes before and after Au NP formation. The results revealed that the WDE served as both a reducing and a stabilizing agent for crystalline spherical 30 nm Au NPs as well as acting as a direct support matrix. The kinetics of paracetamol degradation was studied by high-performance liquid chromatography with a photodiode array detector. The conversion of paracetamol was 62% and 67% after 72 h in the absence or presence of light irradiation, respectively, with 0.0126 h and 0.0148 h reaction rate constants. The presented study demonstrates the successful use of waste material from the food industry for nanogold-composite preparation and its application as a promising catalyst in paracetamol removal.
Topics: Humans; Gold; Metal Nanoparticles; Acetaminophen; Pandemics; COVID-19
PubMed: 35821312
DOI: 10.1007/s11356-022-21868-6 -
Medicina Oral, Patologia Oral Y Cirugia... Apr 2008For social, cultural and historical motives alcohol (ethanol or isopenthanol) is considered to be just a beverage rather than a liquor. However, from a pharmatherapeutic... (Review)
Review
For social, cultural and historical motives alcohol (ethanol or isopenthanol) is considered to be just a beverage rather than a liquor. However, from a pharmatherapeutic point of view alcohol is a depressor of the central nervous system. The effects of alcohol consumption can range from raised loquacity to drunkenness, loss of consciousness and death as a result of insufficient respiration. Probably the most frequent pharmacological interaction is the combination of alcohol with other depressors of the central nervous system which increases the depression even further. Some medicaments which more frequently produce an interaction are antihistamines, analgesics, antidepressants and medicaments for coughs, common cold and influenza. Paracetamol or acetaminophen is an analgesic medicament similar to acetylsalicylic acid lacking anticoagulatory properties and gastric irritation. However, its major drawback is hepatic toxicity as a result of a toxic metabolite produced in the liver by cytochrome P-450, principally cytochrome CYP2E1, which is detoxified under normal conditions by hepatic glutathione. Ethanol is also detoxified by CYP2E1, which is an inducer of ethanol such that chronic ingestion increases the level of this enzyme. When the ingestion of alcohol is stopped, CYP2E1 is greatly increased and only metabolises the paracetamol giving rise to high quantities of hepatotoxic metabolites so that the hepatic glutathione is unable to detoxify resulting in irreversible hepatic damage. Therefore for odontologists it is important that in chronic alcoholic patients the consumption of alcohol should not be suspended on prescribing paracetamol.
Topics: Acetaminophen; Alcoholism; Analgesics, Non-Narcotic; Drug Interactions; Ethanol; Female; Humans; Male; Mouth Diseases
PubMed: 18379447
DOI: No ID Found -
Minerva Anestesiologica Nov 2009Paracetamol is widely used in the management of acute and chronic pain. The purpose of this review is to give anesthesiologists answers to some of the most common... (Review)
Review
Paracetamol is widely used in the management of acute and chronic pain. The purpose of this review is to give anesthesiologists answers to some of the most common questions about paracetamol, specifically the following questions. What is the mechanism of action of paracetamol? Is paracetamol a NSAID? Which endogenous analgesic systems are influenced by paracetamol? Are the perceived concerns about paracetamol use real? What new research is there into paracetamol-induced liver failure? Is paracetamol safe for use by patients with liver disease or those taking anticoagulants? How effective is paracetamol for the management of postoperative pain? Does paracetamol have any opioid-sparing effects? Which formula has the best analgesic efficacy? Which route of administration has the better pharmacokinetic profile? Is the concentration of paracetamol in blood or cerebrospinal fluid relevant to the analgesic effect? Which starting dose should be administrated in intravenous infusion?
Topics: Acetaminophen; Analgesia; Analgesics, Non-Narcotic; Anesthesiology; Humans; Pain, Postoperative
PubMed: 19881460
DOI: No ID Found -
International Journal of Molecular... Oct 2022The phenolic drug molecules can be metabolized, among others, by the small intestine's enterocytes. The conjugation reactions (glucuronidation and sulfation) show great...
The phenolic drug molecules can be metabolized, among others, by the small intestine's enterocytes. The conjugation reactions (glucuronidation and sulfation) show great importance in these transformations, although the oxidation reactions can be significant. These processes are dependent on the substituents of the phenolic compounds or the reacting functional groups (hydroxyl or carboxyl). Pathologic conditions, e.g., permanent hyperglycemia and diabetes, can alter the activities of the conjugative and possibly the oxidative enzymes, thus forming a change in the metabolic pattern and eventually provoking oxidative stress. A rat intestinal perfusion model was used to investigate the way in which experimental hyperglycemia affects the paracetamol's intestinal elimination and metabolism. Hyperglycemia was induced by the administration of streptozotocin. Two hundred and fifty µM paracetamol was used in the intestinal perfusion solution. For the quantitation of the paracetamol and its major metabolites in the intestinal perfusate, an isocratic high-performance liquid chromatography method with UV-Vis detection was developed. The results revealed that quantities of all of the measured metabolites (glucuronide, sulfate, cysteine, and mercapturic acid conjugates) increased as the effect of the streptozotocin-induced hyperglycemia also did. In the small intestine's homogenate, the glutathione levels showed that there was a decrease in the hyperglycemia levels after the paracetamol administration. In contrast, the tissue levels of the cysteine were lower in the streptozotocin-induced hyperglycemia and increased after the administration of the paracetamol. The changes in the activity of the intestinal CYP 3A4, CYP 2E1, and cyclooxygenase (COX) enzymes were determined in the control and the hyperglycemic cases. Still, there was a significant observable enzyme activity elevation in the intestinal COX enzymes, but there was a decrease in the amount of activity of the intestinal CYP3A4 enzymes, and the CYP2E1 enzyme activity was practically changeless. The results on the cysteine levels in the intestinal homogenate, at least partly, can be explained by the regulation function of the cysteine during the occurrence of oxidative stress.
Topics: Acetaminophen; Acetylcysteine; Animals; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP3A; Glucuronides; Glutathione; Hyperglycemia; Intestinal Absorption; Prostaglandin-Endoperoxide Synthases; Rats; Streptozocin; Sulfates
PubMed: 36233215
DOI: 10.3390/ijms231911913 -
The Cochrane Database of Systematic... Apr 2018In 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... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
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.
OBJECTIVES
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.
SEARCH METHODS
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.
SELECTION CRITERIA
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.
DATA COLLECTION AND ANALYSIS
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; all-cause mortality during initial hospital stay (death); gastrointestinal bleed or stools positive for occult blood; and serum levels of creatinine after treatment (µmol/L).
MAIN RESULTS
We included eight studies that reported on 916 infants. One of these studies compared paracetamol to both ibuprofen and indomethacin. Five studies compared treatment of PDA with paracetamol versus ibuprofen and enrolled 559 infants. There was no significant difference between paracetamol and ibuprofen for failure of ductal closure after the first course of drug administration (typical risk ratio (RR) 0.95, 95% confidence interval (CI) 0.75 to 1.21; typical risk difference (RD) -0.02, 95% CI -0.09 to 0.09); I² = 0% for RR and RD; moderate quality of evidence. Four studies (n = 537) reported on gastrointestinal bleed which was lower in the paracetamol group versus the ibuprofen group (typical RR 0.28, 95% CI 0.12 to 0.69; typical RD -0.06, 95% CI -0.09 to -0.02); I² = 0% for RR and RD; number needed to treat for an additional beneficial outcome (NNTB) 17 (95% CI 11 to 50); moderate quality of evidence. The serum levels of creatinine were lower in the paracetamol group compared with the ibuprofen group in four studies (moderate quality of evidence), as were serum bilirubin levels following treatment in two studies (n = 290). Platelet counts and daily urine output were higher in the paracetamol group compared with the ibuprofen group. One study reported on long-term follow-up to 18 to 24 months of age following treatment with paracetamol versus ibuprofen. There were no significant differences in the neurological outcomes at 18 to 24 months (n = 61); (low quality of evidence).Two studies compared prophylactic administration of paracetamol for a PDA with placebo or no intervention in 80 infants. Paracetamol resulted in a lower rate of failure of ductal closure after 4 to 5 days of treatment compared to placebo or no intervention which was of borderline significance for typical RR 0.49 (95% CI 0.24 to 1.00; P = 0.05); but significant for typical RD -0.21 (95% CI -0.41 to -0.02); I² = 0 % for RR and RD; NNTB 5 (95% CI 2 to 50); (low quality of evidence).Two studies (n = 277) compared paracetamol with indomethacin. There was no significant difference in the failure to close a PDA (typical RR 0.96, 95% CI 0.55 to 1.65; I² = 11%; typical RD -0.01, 95% CI -0.09 to 0.08; I² = 17%) (low quality of evidence). Serum creatinine levels were significantly lower in the paracetamol group compared with the indomethacin group and platelet counts and daily urine output were significantly higher in the paracetamol group.
AUTHORS' CONCLUSIONS
Moderate-quality evidence according to GRADE suggests that paracetamol is as effective as ibuprofen; low-quality evidence suggests paracetamol to be more effective than placebo or no intervention; and low-quality evidence suggests paracetamol as effective as indomethacin in closing a PDA. There was no difference in neurodevelopmental outcome in children exposed to paracetamol compared to ibuprofen; however the quality of evidence is low and comes from only one study. In view of concerns raised regarding neurodevelopmental outcomes following prenatal and postnatal exposure to paracetamol, long-term follow-up to at least 18 to 24 months' postnatal age must be incorporated in any studies of paracetamol in the newborn population. At least 19 ongoing trials have been registered. Such trials are required before any recommendations for the possible routine use of paracetamol in the newborn population can be made.
Topics: Acetaminophen; Administration, Oral; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Injections, Intravenous; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29624206
DOI: 10.1002/14651858.CD010061.pub3 -
British Medical Journal Nov 1968
Topics: Acetaminophen; Adult; Female; Humans; Methemoglobinemia; Postpartum Period; Pregnancy
PubMed: 5683591
DOI: 10.1136/bmj.4.5627.390-a