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Journal of Analytical Toxicology 1981Procedures for rapid screening and quantitation of paracetamol in biological material, including whole blood and liver tissue have been developed. The protein in the...
Procedures for rapid screening and quantitation of paracetamol in biological material, including whole blood and liver tissue have been developed. The protein in the samples was precipitated by dilution with a mixture of ethanol and ethyl acetate. The sample was centrifuged was carried out by HPLC following rapid screening by either HPLC or a colorimetric procedure. The colorimetric procedure may be operated in batches and is recommended for screening large numbers of samples in a forensic laboratory. The HPLC screening procedure is sufficiently quantitative to be recommended for acute emergencies in hospitals.
Topics: Acetaminophen; Chromatography, High Pressure Liquid; Humans; Liver
PubMed: 7265923
DOI: 10.1093/jat/5.3.118 -
American Journal of Therapeutics Mar 2000As a consequence of its consistent safety profile and the low incidence of side effects, paracetamol is one of the most widely used analgesics, both in adults and... (Review)
Review
As a consequence of its consistent safety profile and the low incidence of side effects, paracetamol is one of the most widely used analgesics, both in adults and children. However, paracetamol has the potential for hepatotoxicity, usually as a result of deliberate self-poisoning or, to a much lesser extent, accidental overdose. A variety of factors is thought to influence hepatotoxicity, including dose, concomitant use of microsome-inducing agents and other drugs, underlying disease, malnutrition, fasting, acute and chronic alcohol intake, ethnicity, and age. Unfortunately, none of these factors has been properly studied in humans. From a physiological standpoint, acute paracetamol hepatotoxicity at therapeutic doses is extremely unlikely despite reports of so-called therapeutic misadventure. It is clear that, in many of these cases, grossly excessive doses of paracetamol have been taken. Analyzing the various reports is difficult as the data are often incomplete. In summary, although hepatic toxicity is recognized in patients taking a major paracetamol overdose, the incidence of adverse events with its proper use is very low, particularly when considering with the enormous volume of drug use. Therapeutic misadventure is extremely uncommon and the facts are often misrepresented.
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Child; Drug Overdose; Humans; Liver
PubMed: 11319578
DOI: 10.1097/00045391-200007020-00007 -
Journal of Paediatrics and Child Health Apr 1993
Topics: Acetaminophen; Child; Humans
PubMed: 8489804
DOI: 10.1111/j.1440-1754.1993.tb00454.x -
Acta Pharmaceutica Hungarica Mar 1994Rectal suppositories with a paracetamol content of 300 mg were prepared and the optimal vehicle was searched for experimentally. 9 different kinds of lipophilic,...
Rectal suppositories with a paracetamol content of 300 mg were prepared and the optimal vehicle was searched for experimentally. 9 different kinds of lipophilic, lipohydrophilic and hydrophilic vehicles were used for this purpose. Research was focused on determining the factors influencing in vitro drug liberation. The suppository compositions which proved to be the best by the membrane diffusion method were tested by in vivo animal experiments with respect to their antipyretic effect. The in vitro and in vivo results were evaluated statistically and some of the suppository bases showed significant differences. In the authors' opinion the optimal vehicle for the preparation of paracetamol-containing suppositories is the Witepsol H 15 suppository base containing 10% Miglyol 812 (neutral oil).
Topics: Acetaminophen; Animals; Diffusion; Fever; Male; Rats; Rats, Wistar; Suppositories
PubMed: 8017207
DOI: No ID Found -
Journal of Pharmaceutical Sciences Jan 2006Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS...
Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product.
Topics: Acetaminophen; Administration, Oral; Analgesics, Non-Narcotic; Biological Availability; Chemistry, Pharmaceutical; Dosage Forms; Excipients; Solubility; Therapeutic Equivalency
PubMed: 16307451
DOI: 10.1002/jps.20477 -
Soins; La Revue de Reference Infirmiere Sep 1985
Topics: Acetaminophen; Humans
PubMed: 3853280
DOI: No ID Found -
Deutsche Medizinische Wochenschrift... Jan 1987
Topics: Acetaminophen; Drug Combinations; Humans
PubMed: 3803210
DOI: No ID Found -
Paediatric Drugs Jun 2019Studies in adults have reported frequent episodes of blood pressure drops following intravenous paracetamol administration. We aimed to investigate the hemodynamic... (Review)
Review
AIM
Studies in adults have reported frequent episodes of blood pressure drops following intravenous paracetamol administration. We aimed to investigate the hemodynamic effects of intravenous paracetamol in critically ill children.
METHODS
The charts of 100 pediatric intensive care patients (age range 0.1-18 years) who were treated with intravenous paracetamol between March and September 2017 were retrospectively reviewed. A hemodynamic event was defined as a drop of > 15% in systolic or mean arterial blood pressure within 120 min after drug administration. Hypotension was defined as either a drop in systolic blood pressure (SBP) below the 5th percentile for age or a hemodynamic event associated with tachycardia, increased lactate level, or treatment with a fluid bolus or vasopressors.
RESULTS
A hemodynamic event was observed in 39 patients (39%). In these patients, SBP was in the pre-hypertension or hypertension values in 36/39 patients before paracetamol administration, median (IQR) SBP decreased from the 99th (95-99) percentile for age before to the 50th (50-95) percentile after paracetamol (p < 0.001) and mean heart rate was 137 bpm before treatment and 115 bpm after (p = 0.002). SBP values did not drop below the 5th percentile in any patient. In 15 patients diagnosed with shock on admission, paracetamol treatment did not cause an increase in vasopressor treatment after drug administration.
CONCLUSIONS
In the present study of critically ill pediatric patients, intravenous paracetamol administration was associated with a drop in SBP from high to normal values for age, possibly due to pain relief, with no evidence for a negative hemodynamic event.
Topics: Acetaminophen; Administration, Intravenous; Adolescent; Analgesics, Non-Narcotic; Child; Child, Preschool; Female; Hemodynamics; Humans; Infant; Infant, Newborn; Male; Retrospective Studies
PubMed: 31155693
DOI: 10.1007/s40272-019-00336-8 -
The Journal of Pharmacology and... Oct 2000The mechanism of the analgesic action of one of the world's most widely used drugs-acetaminophen (paracetamol)-remains largely unknown more than 100 years after its...
The mechanism of the analgesic action of one of the world's most widely used drugs-acetaminophen (paracetamol)-remains largely unknown more than 100 years after its original synthesis. Based on the present findings, this elusiveness appears to have resulted from experimental strategies that concentrated on a single target site or mechanism. Here we report on the use of analyses that we previously developed to investigate possible brain/spinal-cord site-site interaction in acetaminophen-induced antinociception. Spinal (intrathecal) administration of acetaminophen to mice produced dose-related, naloxone-insensitive antinociception with an ED(50) value of 137 (S.E. = 23) microgram = 907 (S.E. =153) nmol. In contrast, supraspinal (i.c.v.) acetaminophen administration had no effect. However, combined administration of acetaminophen in fixed ratios to brain and spinal cord produced synergistic antinociception, ED(50) = 57 (S.E. = 9) microgram, that reverted toward additivity, ED(50) = 129 (S.E. = 23) microgram, when the opioid antagonist naloxone was given spinally (3.6 microgram = 10 nmol) or s.c. (3.6 mg/kg). These findings demonstrate for the first time that acetaminophen-induced antinociception involves a "self-synergistic" interaction between spinal and supraspinal sites and, furthermore, that the self-synergy involves an endogenous opioid pathway.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Spinal Cord
PubMed: 10991992
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