-
Journal of Endodontics May 2015The purpose of this review was to discuss new issues related to safety, labeling, dosing, and a better understanding of the analgesic effect of acetaminophen. (Review)
Review
INTRODUCTION
The purpose of this review was to discuss new issues related to safety, labeling, dosing, and a better understanding of the analgesic effect of acetaminophen.
METHODS
The MEDLINE, Embase, Cochrane, and PubMed databases were searched. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Two reviewers independently selected the relevant articles.
RESULTS
Concerns about acetaminophen overdose and related liver failure have led the US Food and Drug Administration to mandate new labeling on acetaminophen packaging. In addition, large-scale epidemiologic studies increasingly report evidence for second-generation adverse effects of acetaminophen. Prenatal exposure to acetaminophen is associated with neurodevelopmental and behavioral disorders. Recent studies also suggest that acetaminophen is a hormone disrupter (ie, it interferes with sex and thyroid hormone function essential for normal brain development) and thus may not be considered a safe drug during pregnancy. Finally, emerging evidence suggests that although the predominant mechanism by which acetaminophen exerts its therapeutic effect is by inhibition of cyclooxygenase, multiple other mechanisms also contribute to its analgesic effect.
CONCLUSIONS
Available evidence suggests that indiscriminate usage of this drug is not warranted. and its administration to a pregnant patient should be considered with great caution.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Drug Labeling; Female; Humans; Pregnancy; United States
PubMed: 25732401
DOI: 10.1016/j.joen.2015.01.024 -
European Journal of Pain (London,... Aug 2015Acetaminophen/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... (Review)
Review
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.
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; History, 19th Century; History, 20th Century; History, 21st Century; Humans
PubMed: 25429980
DOI: 10.1002/ejp.621 -
The Journal of Pediatrics Aug 2021
Review
Topics: Acetaminophen; Bronchopulmonary Dysplasia; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Liver; Lung
PubMed: 33617854
DOI: 10.1016/j.jpeds.2021.02.026 -
Acta Poloniae Pharmaceutica 2014Paracetamol/acetaminophen is one of the most popular and most commonly used analgesic and antipyretic drugs around the world, available without a prescription, both in... (Review)
Review
Paracetamol/acetaminophen is one of the most popular and most commonly used analgesic and antipyretic drugs around the world, available without a prescription, both in mono- and multi-component preparations. It is the drug of choice in patients that cannot be treated with non-steroidal anti-inflammatory drugs (NSAID), such as people with bronchial asthma, peptic ulcer disease, hemophilia, salicylate-sensitized people, children under 12 years of age, pregnant or breastfeeding women. It is recommended as a first-line treatment of pain associated with osteoarthritis. The mechanism of action is complex and includes the effects of both the peripheral (COX inhibition), and central (COX, serotonergic descending neuronal pathway, L-arginine/NO pathway, cannabinoid system) antinociception processes and "redox" mechanism. Paracetamol is well tolerated drug and produces few side effects from the gastrointestinal tract, however, despite that, every year, has seen a steadily increasing number of registered cases of paracetamol-induced liver intoxication all over the world. Given the growing problem of the safety of acetaminophen is questioned the validity of the sale of the drug without a prescription. This work, in conjunction with the latest reports on the mechanism of action of paracetamol, trying to point out that it is not a panacea devoid of side effects, and indeed, especially when is taken regularly and in large doses (> 4 g/day), there is a risk of serious side effects.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Humans
PubMed: 24779190
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1990
Review
Topics: Acetaminophen; Animals; Carcinogens; Dogs; Female; Humans; Mice; Molecular Structure; Mutagens; Pregnancy; Rats; Reproduction
PubMed: 2152767
DOI: No ID Found -
Postgraduate Medical Journal Jul 1980Paracetamol is an analgesic and antipyretic agent which was first marketed for use as a drug in the U.K. in 1956. It has since become popular with the medical profession... (Review)
Review
Paracetamol is an analgesic and antipyretic agent which was first marketed for use as a drug in the U.K. in 1956. It has since become popular with the medical profession and the general public as an alternative to aspirin.
Topics: Acetaminophen; Acetylcysteine; Adult; Animals; Chemical and Drug Induced Liver Injury; Child; Cysteamine; Dextropropoxyphene; Humans; Infant; Kidney Diseases; Methionine
PubMed: 7003571
DOI: 10.1136/pgmj.56.657.459 -
Inflammopharmacology Feb 2014This 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... (Review)
Review
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.).
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Humans; Inflammation
PubMed: 24072615
DOI: 10.1007/s10787-013-0189-1 -
Clinical Pharmacokinetics 1982In therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from... (Review)
Review
In therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from the gastrointestinal tract, its systemic bioavailability being dose-dependent and ranging from 70 to 90%. Its rate of oral absorption is predominantly dependent on the rate of gastric emptying, being delayed by food, propantheline, pethidine and diamorphine and enhanced by metoclopramide. Paracetamol is also well absorbed from the rectum. It distributes rapidly and evenly throughout most tissues and fluids and has a volume of distribution of approximately 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Paracetamol is extensively metabolised (predominantly in the liver), the major metabolites being the sulphate and glucuronide conjugates. A minor fraction of drug is converted to a highly reactive alkylating metabolite which is inactivated with reduced glutathione and excreted in the urine as cysteine and mercapturic acid conjugates. Large doses of paracetamol (overdoses) cause acute hepatic necrosis as a result of depletion of glutathione and of binding of the excess reactive metabolite to vital cell constituents. This damage can be prevented by the early administration of sulfhydryl compounds such as methionine and N-acetylcysteine. In healthy subjects 85 to 95% of a therapeutic dose is excreted in the urine within 24 hours with about 4, 55, 30, 4 and 4% appearing as unchanged paracetamol and its glucuronide, sulphate, mercapturic acid and cysteine conjugates, respectively. The plasma half-life in such subjects ranges from 1.9 to 2.5 hours and the total body clearance from 4.5 to 5.5 ml/kg/min. Age has little effect on the plasma half-life, which is shortened in patients taking anticonvulsants. The plasma half-life is usually normal in patients with mild chronic liver disease, but its prolonged in those with decompensated liver disease.
Topics: Acetaminophen; Administration, Oral; Age Factors; Body Weight; Drug Interactions; Food; Humans; Injections, Intravenous; Intestinal Absorption; Kinetics; Liver Diseases; Protein Binding; Racial Groups; Rectum; Sex Factors
PubMed: 7039926
DOI: 10.2165/00003088-198207020-00001 -
Orvosi Hetilap Jan 1998
-
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