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CNS Drug Reviews 2007The combination of numerous classic drugs with nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety... (Review)
Review
The combination of numerous classic drugs with nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety of situations, including cardiovascular and respiratory systems, ocular pressure, inflammation, and pain. One of the first compounds developed was NCX-701 or nitroparacetamol, resulting from the combination of paracetamol, a classic and popular analgesic used in a great number of over-the-counter medications because of its antipyretic and analgesic properties, and a nitrooxybutyroyl moiety, which releases nitric oxide at a low but steady level. Although paracetamol is devoid of most of the gastrointestinal toxicity associated with aspirin-like drugs, this type of compounds was first designed to take advantage of the cytoprotective properties of nitric oxide when released at low concentrations. However, the combination of these molecules also resulted in an unexpected enhancement of the analgesic activity of paracetamol. In fact, NCX-701 has been shown to be effective in acute nociception as well as in neuropathic pain, situations in which paracetamol and other COX inhibitors are devoid of any effect. In addition, NCX-701 is more potent and, in some circumstances, more effective than its parent compound in different models of inflammatory pain. Furthermore, whereas paracetamol lacks any effective antiinflammatory action, NCX-701 might reduce inflammation. All these results taken together imply that the mechanism of action of NCX-701 is different from that of paracetamol, although it is not yet established for either molecule. NCX-701 appears to be a promising compound in the treatment of different types of pain, with a likely better profile of side effects than its parent molecule, paracetamol. Although recent clinical trials provided data consistent with the preclinical profile of NCX-701, further studies are needed to support its clinical use.
Topics: Acetaminophen; Analgesics; Animals; Humans; Nitrates; Pain
PubMed: 17894645
DOI: 10.1111/j.1527-3458.2007.00016.x -
American Journal of Therapeutics Mar 2000Paracetamol (acetaminophen) has a unique role in children because it is the first-line choice for the treatment of both fever and pain. When used in the recommended... (Review)
Review
Paracetamol (acetaminophen) has a unique role in children because it is the first-line choice for the treatment of both fever and pain. When used in the recommended doses, it has few side effects and is remarkably well tolerated. While fever alone requires no treatment, when associated with discomfort or pain, paracetamol offers relief. Also, for mild to moderate pain, paracetamol, either alone or in combination with another drug, is effective. Even in severe pain, paracetamol offers a significant additive analgesic effect to opiates. Globally, the pediatric dose varies between 10 and 15 mg/kg. In the United Kingdom, 10 mg/kg is given every 4 hours, up to a maximum of four doses per day; in Australia, 15 mg/kg is administered 4-hourly up to a total dose of 60 mg/kg/day. In overdose, paracetamol is hepatotoxic. Single ingestions of more than ten times the recommended dose are potentially toxic. The development of specific antidotes and the universal availability of the Rumack-Matthew Nomogram have made the early treatment of overdose effective without long-term sequelae. There are sporadic case reports of chronic overdosing resulting in liver failure. Although the specific predictors are still being defined, exposures greater than 140 mg/kg/day for several days carry a risk of serious toxicity. In children, aspirin use has almost disappeared with the concurrent decline in Reye Syndrome. Less clinical experience has accumulated with ibuprofen, and it remains the second-line treatment for fever and pain. In conclusion, paracetamol remains the first-choice over-the-counter treatment for analgesia and antipyresis in children.
Topics: Acetaminophen; Child; Fever; Humans; Nonprescription Drugs; Pain
PubMed: 11319581
DOI: 10.1097/00045391-200007020-00010 -
Spectrochimica Acta. Part A, Molecular... Aug 2017This 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...
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 NH and OH groups are correctly reallocated to bands shifted by up to 300cm relatively to previous assignments.
Topics: Acetaminophen; Hydrogen Bonding; Molecular Conformation; Neutrons; Scattering, Radiation; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Vibration
PubMed: 28494395
DOI: 10.1016/j.saa.2017.04.076 -
Tidsskrift For Den Norske Laegeforening... May 1975
Topics: Acetaminophen; Chemical and Drug Induced Liver Injury; Half-Life; Humans
PubMed: 1135828
DOI: No ID Found -
Drugs in R&D Jun 2014Fever is a common symptom of childhood infections that in itself does not require treatment. The UK's National Institute for Health and Care Excellence (NICE) advises... (Review)
Review
Fever is a common symptom of childhood infections that in itself does not require treatment. The UK's National Institute for Health and Care Excellence (NICE) advises home-based antipyretic treatment for low-risk feverish children only if the child appears distressed. The recommended antipyretics are ibuprofen or paracetamol (acetaminophen). They are equally recommended for the distressed, feverish child; therefore, healthcare professionals, parents and caregivers need to decide which of these agents to administer if the child is distressed. This narrative literature review examines recent data on ibuprofen and paracetamol in feverish children to determine any clinically relevant differences between these agents. The data suggest that these agents have similar safety profiles in this setting and in the absence of underlying health issues, ibuprofen seems to be more effective than paracetamol at reducing NICE's treatment criterion, 'distress' (as assessed by discomfort levels, symptom relief, and general behavior).
Topics: Acetaminophen; Child; Fever; Humans; Ibuprofen
PubMed: 24916274
DOI: 10.1007/s40268-014-0052-x -
Acta Paediatrica (Oslo, Norway : 1992) Oct 2023
Topics: Humans; Antipyretics; Acetaminophen; Fever
PubMed: 37471514
DOI: 10.1111/apa.16913 -
The Journal of the Royal Society For... Nov 2008Paracetamol is one of the most commonly used legal drugs in the western world. Its availability is good, cost is low, and its uses include 'over-the-counter' (OTC)...
Paracetamol is one of the most commonly used legal drugs in the western world. Its availability is good, cost is low, and its uses include 'over-the-counter' (OTC) distribution, primary care prescribed therapy, secondary care 'post-operative' application and emergency treatment. Stated benefits of paracetamol include: the drug's analgesic effects, preference to aspirin in avoidance of Reye's syndrome, good patient tolerance, and iatrogenic complications are infrequent and minor. Stated cautions include hepatotoxic effect following minor doses and short duration use and users may incur compromised immune integrity. This paper is concerned with paracetamol's role in fever management. Public concern regarding, in particular, childhood fever and febrile convulsions is largely unwarranted. Despite paracetamol's reputation as a popular fever-reducing agent the drug is poorly effective in the control of febrility and febrile convulsions showing no important advantage compared with placebo. Paracetamol is probably grossly over-prescribed for fever management and its value more perceived than real. Greater efforts are needed to inform patients of the natural benefits of the biological strategy of fever and of the highly limited and in some cases contraindicated use of paracetamol in fever management.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Evidence-Based Medicine; Fever; Humans; Patient Education as Topic; Practice Guidelines as Topic; Seizures, Febrile; Treatment Outcome
PubMed: 19058473
DOI: 10.1177/1466424008092794 -
Ugeskrift For Laeger Feb 1995Administration of paracetamol (acetaminophen) has analgetic and antipyretic effect. After trauma paracetamol has an anti-inflammatory activity. It was presumed that...
Administration of paracetamol (acetaminophen) has analgetic and antipyretic effect. After trauma paracetamol has an anti-inflammatory activity. It was presumed that paracetamol in therapeutic doses had fewer and more acceptable side-effects than other analgetic drugs such as acetylsalicylic acid and NSAID-drugs. However, in toxic concentrations, paracetamol is more life-threatening. The toxic effects of paracetamol most often occur in the liver and kidneys. Phosphate and lactate turn-over can also be impaired. Paracetamol poisoning can induce temporary liver dysfunction or even irreversible liver failure with liver transplantation as the only therapeutic possibility. Chronic alcoholics are especially at risk, as liver damage may occur following paracetamol even in recommended doses. When intoxication with paracetamol is presumed, administration of N-acetylcysteine is vital. N-acetylcysteine therapy should be initiated not later than 15 hours after paracetamol intake. Moreover, the antitoxic effect has been observed even when N-acetylcysteine therapy is initiated 24-36 hours after presumed paracetamol intake. Measures of preventing further absorbtion of paracetamol from the gastrointestinal tract should be taken. Activated charcoal should be given if less than two hours have passed since paracetamol intake. Between two and four hours following paracetamol intake gastric lavage should be performed. During the last 10 years the incidence of paracetamol self-poisoning has increased, but death following paracetamol poisoning is relatively constant at around nine per year in Denmark. It is suggested that the incidence of serious cases of paracetamol poisoning could be reduced by simple measures. Special attention should be paid to the risk-group of chronic alcoholics.
Topics: Acetaminophen; Acetylcysteine; Denmark; Female; Humans; Kidney; Liver; Male; Poisoning
PubMed: 7701645
DOI: No ID Found -
Open Veterinary Journal Jan 2024Paracetamol is one of the most popular drugs; it is used daily by many people especially the elderly, without a limitation on the length of the period allowed for...
BACKGROUND
Paracetamol is one of the most popular drugs; it is used daily by many people especially the elderly, without a limitation on the length of the period allowed for continuous use. Harms from long-term use are less clear, particularly in extrahepatic regions.
AIM
This study aimed to investigate whether using paracetamol at a non-observable adverse effect level dose, known not to cause toxic effects, for a long period can induce toxicity in aged male albino rats.
METHODS
A daily dose of 500 mg per kg body weight of paracetamol was given to adult male albino rats for 12 weeks. During this period, rats were sacrificed at 4, 6, 8, 10, and 12 weeks to evaluate the toxic changes at several time intervals.
RESULTS
Chemical analysis revealed elevated serum alanine transaminase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and declined level of total protein in N-acetyl-p-aminophenol (APAP)-treated group; it also caused oxidative stress, as shown by decreased glutathione, superoxide dismutase, and elevated malondialdehyde in the liver, kidney, and brain. Histopathological examination demonstrated cytoplasmic vacuolation and sinusoidal congestion with the development of single-cell necrosis in the liver. Renal tubular necrosis, glomerular atrophy, and ischemic neuronal injury, especially in the hippocampus were observed. the deleterious effects of APAP were increased in severity with increasing the period of treatment.
CONCLUSION
Our results suggest that acetaminophen in a subtoxic dose for a long period could result in mild toxic effects on the liver but more serious lesions in the kidney and brain.
Topics: Humans; Rats; Male; Animals; Acetaminophen; No-Observed-Adverse-Effect Level; Kidney; Liver; Kidney Diseases; Rodent Diseases
PubMed: 38633179
DOI: 10.5455/OVJ.2024.v14.i1.28 -
Annals of the Rheumatic Diseases Jan 2012Paracetamol is recommended as first-line therapy for pain associated with osteoarthrosis and is one of the most widely used over-the-counter analgesic drugs worldwide.... (Review)
Review
Paracetamol is recommended as first-line therapy for pain associated with osteoarthrosis and is one of the most widely used over-the-counter analgesic drugs worldwide. Despite its extensive use, its mode of action is still unclear. Although it is commonly stated that paracetamol acts centrally, recent data imply an inhibitory effect on the activity of peripheral prostaglandin-synthesising cyclooxygenase enzymes. In this context paracetamol has been suggested to inhibit both isoforms in tissues with low levels of peroxide by reducing the higher oxidation state of cyclooxygenase enzymes. Two recent studies have also demonstrated a preferential cyclooxygenase 2 (COX-2) inhibition by paracetamol under different clinically relevant conditions. This review attempts to relate data on paracetamol's inhibitory action on peripheral cyclooxygenase enzymes to the published literature on its anti-inflammatory action and its hitherto underestimated side-effects elicited by cyclooxygenase inhibition. As a result, a pronounced COX-2 inhibition by paracetamol is expected to occur in the endothelium, possibly explaining its cardiovascular risk in epidemiological studies. A careful analysis of paracetamol's cardiovascular side-effects in randomised studies is therefore strongly advised. On the basis of epidemiological data showing an increased gastrointestinal risk of paracetamol at high doses or when co-administered with classic cyclooxygenase inhibitors, paracetamol's long-term gastrointestinal impact should be investigated in randomised trials. Finally, paracetamol's fast elimination and consequently short-lived COX-2 inhibition, which requires repetitive dosing, should be definitely considered to avoid overdosage leading to hepatotoxicity.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Blood Platelet Disorders; Cardiovascular Diseases; Cyclooxygenase 2 Inhibitors; Gastrointestinal Diseases; Humans
PubMed: 22039164
DOI: 10.1136/ard.2011.200087