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Einstein (Sao Paulo, Brazil) 2022The objective of this study was to answer several questions related to the assessment and treatment of fever, as well as other controversies that exist during its... (Review)
Review
The objective of this study was to answer several questions related to the assessment and treatment of fever, as well as other controversies that exist during its management in pediatric patients. First, an advisory board with medical experts was conducted to discuss the clinical journey of these patients, considering the main challenges and possible solutions. After this discussion, a non-systematic literature review was performed, between November 2019 and January 2020, to collect the most relevant evidence available in the scientific databases MEDLINE, Lilacs, and SciELO. A narrative review was carried out based on scientific evidence and on extensive experience of experts in clinical practice. The experts developed a set of recommendations and clarifications about the assessment of the severity of fever in pediatrics, the need for treatment and the choice of the most appropriate antipyretic. The most common controversies in the management of fever in pediatric patients were also addressed, such as alternating antipyretics, persistent fever, and dose equivalence. In primary management of pediatric patients, fever should be seen as a relevant symptom that requires treatment with antipyretics in potentially more complex or severe cases, when it causes discomfort to children or is associated with infectious diseases.
Topics: Acetaminophen; Antipyretics; Brazil; Child; Fever; Humans; Ibuprofen
PubMed: 35946741
DOI: 10.31744/einstein_journal/2022RW6045 -
Pharmacology 2024Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The... (Review)
Review
BACKGROUND
Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The metabolism and pathogenesis of APAP have been extensively studied in recent years, and many cellular processes such as autophagy, mitochondrial oxidative stress, mitochondrial dysfunction, and liver regeneration have been identified to be involved in the pathogenesis of ALI. Caveolin-1 (CAV-1) as a scaffold protein has also been shown to be involved in the development of various diseases, especially liver disease and tumorigenesis. The role of CAV-1 in the development of liver disease and the association between them remains a challenging and uncharted territory.
SUMMARY
In this review, we briefly explore the potential therapeutic effects of CAV-1 on ALI through autophagy, oxidative stress, and lipid metabolism. Further research to better understand the mechanisms by which CAV-1 regulates liver injury will not only enhance our understanding of this important cellular process, but also help develop new therapies for human disease by targeting CAV-1 targets.
KEY MESSAGES
This review briefly summarizes the potential protective mechanisms of CAV-1 against liver injury caused by APAP.
Topics: Acetaminophen; Caveolin 1; Humans; Animals; Chemical and Drug Induced Liver Injury; Oxidative Stress; Autophagy; Analgesics, Non-Narcotic; Lipid Metabolism
PubMed: 38657589
DOI: 10.1159/000538017 -
The Journal of Pharmacy and Pharmacology Jan 2022Acetaminophen (APAP) (paracetamol) is a widely used non-prescription drug for pain relief and antipyretic effects. The clearance of APAP is mainly through phase-2...
OBJECTIVES
Acetaminophen (APAP) (paracetamol) is a widely used non-prescription drug for pain relief and antipyretic effects. The clearance of APAP is mainly through phase-2 biotransformation catalysed by UDP-glucuronosyl transferases (UGT). Dasabuvir is an anti-hepatitis C drug reported to inhibit several UGT isoforms. The study evaluated the in-vitro inhibitory capacity of dasabuvir versus APAP glucuronidation.
METHODS
Procedures included human liver microsomal incubations with APAP and isoform-selective probe substrates.
KEY FINDINGS
Dasabuvir inhibited APAP metabolism by a reversible, mixed-type (competitive and non-competitive) partial inhibition, with an inhibition constant Ki = 3.4 µM. The index constant 'a' was 6.7, indicating the relative contribution of competitive and non-competitive inhibition. The enzyme-inhibitor complex was still able to catalyse the reaction by 12% of the control capacity. Dasabuvir produced strong partial inhibition effect of UGT1A1 and UGT1A9 and relatively complete inhibition of UGT1A6.
CONCLUSIONS
Consistent with previous reports, dasabuvir inhibits the activity of 3 UGT isoforms associated with APAP metabolism. In-vitro to in-vivo scaling by 2 different approaches showed identical results, predicting an increased AUC of APAP by a factor of 1.3-fold with coadministration of dasabuvir. Until the findings are confirmed in clinical drug interaction studies, APAP dosage should not exceed 3 g per day in dasabuvir-treated patients to avoid potentially hepatotoxic APAP exposures.
Topics: 2-Naphthylamine; Acetaminophen; Antipyretics; Antiviral Agents; Area Under Curve; Drug Interactions; Glucuronosyltransferase; Humans; Isoenzymes; Metabolic Detoxication, Phase II; Microsomes, Liver; Sulfonamides; UDP-Glucuronosyltransferase 1A9; Uracil
PubMed: 34718654
DOI: 10.1093/jpp/rgab144 -
International Journal of Molecular... Oct 2019Implant‑associated infection (IAI), a common condition marked by progressive inflammation and bone destruction, is mentally and financially devastating to those it...
Implant‑associated infection (IAI), a common condition marked by progressive inflammation and bone destruction, is mentally and financially devastating to those it affects, causing severe morbidity, prolonged hospital admissions, significant hospital costs and, in certain cases, mortality. Aspirin, a popular synthetic compound with a history of >100 years, is antipyretic, anti‑inflammatory and analgesic. It is the most active component of non‑steroidal anti‑inflammatory drugs. However, the effects of aspirin on IAI remain unknown. In the present study, an IAI animal model was used, in which a stainless steel pin coated with Staphylococcus aureus was implanted through the left shaft of the tibia in mice. The animals were then randomized into five groups and subjected respectively to IAI, IAI + 15 mg aspirin treatment, IAI + 30 mg aspirin treatment, IAI + 60 mg aspirin treatment and IAI + 120 mg aspirin treatment groups. Aspirin was injected intraperitoneally twice daily for 11 days. Micro‑CT and histological assays were performed to assess the effects of aspirin on IAI. It was found that aspirin reduced osteolysis and periosteal reaction, inhibited the activation of osteoclasts, promoted the activation of osteoblasts and facilitated healing of the infected fracture.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Disease Models, Animal; Female; Humans; Immunohistochemistry; Mice; Osteolysis; Prostheses and Implants; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; X-Ray Microtomography
PubMed: 31432131
DOI: 10.3892/ijmm.2019.4298 -
Biomedicine & Pharmacotherapy =... May 2022Dexketoprofen is an enantiomer of ketoprofen (S+) that belongs to nonsteroidal anti-inflammatory drugs and has analgesic, anti-inflammatory, and antipyretic properties.... (Review)
Review
Dexketoprofen is an enantiomer of ketoprofen (S+) that belongs to nonsteroidal anti-inflammatory drugs and has analgesic, anti-inflammatory, and antipyretic properties. Dexketoprofen has a stronger effect than ketoprofen, which makes it a readily used preparation. The review aims to find in recent original publications data about dexketoprofen and its comparison with other painkilling medications. The systematic literature review was conducted in November 2021 (2018 onwards). We selected 12 articles from PubMed, Google Scholar, Medline Complete databases. In the last 4 years, there have been many publications that shed a new light on dexketoprofen. The article is a comparative analysis of dexketoprofen's action vs other nonsteroidal anti-inflammatory drugs and the combination of dexketoprofen with tramadol vs paracetamol with tramadol. The findings of the review confirm that dexketoprofen is a very good pain reliever more potent than paracetamol. Dexketoprofen produces similar effects to lidocaine and dexmedetomidine. Complex preparations containing dexketoprofen and tramadol are very effective painkilling tandem and are more effective than tramadol and paracetamol therapy in the treatment of acute pain.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Ketoprofen; Tramadol; Tromethamine
PubMed: 35299123
DOI: 10.1016/j.biopha.2022.112819 -
Frontiers in Endocrinology 2020Aspirin is one of the most commonly prescribed drugs worldwide and has been reported to possess anti-cancer properties in addition to antipyretic and analgesic effects.... (Review)
Review
Aspirin is one of the most commonly prescribed drugs worldwide and has been reported to possess anti-cancer properties in addition to antipyretic and analgesic effects. This umbrella review summarizes systematic reviews and meta-analyses that investigate the association between aspirin and cancer risk, aiming to help clinical and public health decision-makers interpret the results of these studies when re-positioning aspirin. An umbrella review of systematic reviews and meta-analyses. The associations that reached statistical significance (17 in total) indicated potential preventive effects of aspirin on certain cancers or precancerous lesions. We found that no association was supported by strong evidence. Only one association (aspirin and overall cancer risk) was supported by highly suggestive evidence. The evidence supporting the association between aspirin and the risk of breast cancer, non-cardia gastric cancer, or prostate cancer was considered to be highly suggestive. The remaining 23 associations were supported by weak (13) or not suggestive evidence (10). The association between aspirin and a reduced risk of esophageal squamous cell carcinoma is supported by strong evidence, researchers and policy makers should pay more attention to the potential merit of repositioning aspirin to prevent esophageal squamous cell carcinoma.
Topics: Aspirin; Chemoprevention; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Meta-Analysis as Topic; Neoplasms; Precancerous Conditions; Systematic Reviews as Topic
PubMed: 32038497
DOI: 10.3389/fendo.2020.00003 -
Current Drug Targets 2021Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition... (Review)
Review
Since its discovery more than 100 years ago, aspirin has been widely used for its antipyretic, analgesic, anti-inflammatory, and anti-rheumatic activities. In addition to these applications, it is increasingly becoming clear that the drug also has great potential in the field of cancer. Here, we briefly review the current insights on aspirin's anti-tumor effects. These are multiple and vary from inhibiting the major cellular mTOR pathways, acting as a calorie-restricted mimetic by inhibition of energy production, suppressing platelet aggregation and granule release, inhibiting the immune escape of tumor cells, to decreasing inflammatory responses. We consider these five mechanisms of action the most significant for aspirin's anti-tumor effects, whereby the anti-tumor effect may ultimately stem from its inhibition of energy metabolism, platelet function, and inflammatory response. As such, aspirin can play an important role to reduce the occurrence, proliferation, and metastasis of various types of tumors. However, most of the collected data are still based on epidemiological investigations. More direct and effective evidence is needed, and the side effects of aspirin intake need to be solved before this drug can be widely applied in cancer treatment.
Topics: Aspirin; Humans; Neoplasms
PubMed: 33050859
DOI: 10.2174/1389450121999201013152931 -
Journal of Ethnopharmacology Oct 2022Houttuynia cordata Thunb. (H. cordata) is a well-known folk traditional Chinese medicine that is renowned for its use in the management of inflammatory respiratory...
ETHNOPHARMACOLOGICAL RELEVANCE
Houttuynia cordata Thunb. (H. cordata) is a well-known folk traditional Chinese medicine that is renowned for its use in the management of inflammatory respiratory diseases and pneumonia. Its essential oils have demonstrated their anti-inflammatory efficacy in vitro, however, their in vivo biological effects via inhalation have not been elucidated.
AIM OF THE STUDY
This study aims to evaluate the anti-inflammation and toxicology of H. cordata essential oil-containing formulation, H16 aerosol in vivo.
MATERIALS AND METHODS
A laser diffraction particle size analyser and a Next Generation Impactor were used to measure the mass median aerodynamic diameter (MMAD) of the H16 aerosol. The anti-inflammatory and antipyretic effects of the H16 aerosol were evaluated in the xylene-evoked ear oedema and Brewer's yeast-induced fever models, respectively. The biological safety of the H16 aerosol was evaluated by acute toxicity and local toxicity tests in animal models.
RESULTS
Our data showed that the MMAD of the bioactive aerosol was 3-5 μm, which implied tracheal and pharyngeal deposits. Significant anti-inflammatory and antipyretic effects were also observed in the animal models treated with H16 aerosol. The maximum tolerable dose of H16 in rats was >2.5 mL/kg. Irritation was not found on respiratory tract mucosa in the local toxicity test.
CONCLUSIONS
Taken together, the present study suggested that H16 could be delivered in the form of aerosol and possessed its antipyretic and anti-inflammatory effects. This study provides a new perspective for the development of a new herbal aerosol therapy and herbal modernization.
Topics: Animals; Anti-Inflammatory Agents; Antipyretics; Houttuynia; Oils, Volatile; Plant Extracts; Rats
PubMed: 35872291
DOI: 10.1016/j.jep.2022.115541 -
Gene Expression Jun 2021Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size... (Review)
Review
Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size from a few nucleotides to hundreds of thousands of nucleotides, which do not encode any protein. Some of these noncoding RNAs (ncRNAs) are directly or indirectly linked to the regulation of expression or functions of 25,000 proteins coded by <2% of the human genome. Among these regulatory RNAs, microRNAs are small (2125 nucleotides) RNAs that are processed from precursor RNAs that have stemloop structure, whereas noncoding RNAs >200 nucleotides are termed long noncoding RNAs (lncRNAs). Circular RNAs (circRNAs) are newly identified lncRNA members that are generated by back-splicing of primary transcripts. The functions of ncRNAs in modulating liver toxicity of xenobiotics are emerging only recently. Acetaminophen (-acetyl--aminophenol, paracetamol or APAP) is a safe analgesic and antipyretic drug at the therapeutic dose. However, it can cause severe liver toxicity that may lead to liver failure if overdosed or combined with alcohol, herbs, or other xenobiotics. This review discusses the role of ncRNAs in acetaminophen metabolism, toxicity, and liver regeneration after APAP-induced liver injury (AILI).
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Chemical and Drug Induced Liver Injury; Cytochrome P450 Family 3; Humans; RNA, Untranslated
PubMed: 33757622
DOI: 10.3727/105221621X16165282414118 -
Pharmacology Research & Perspectives Aug 2021The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX)... (Review)
Review
The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX) inhibition preventing prostaglandin (PG) synthesis. Two COX isoforms (COX1/2) share 60% sequence structure, yet their functions vary. COX variants have been sequenced among various mammalian species including humans. A COX1 splice variant (often termed COX3) is purported by some as the elusive target of ACT's mechanism of action. Yet a physiologically functional COX3 isoform has not been sequenced in humans, refuting these claims. ACT may selectively inhibit COX2, with evidence of a 4.4-fold greater COX2 inhibition than COX1. However, this is markedly lower than other available selective COX2 inhibitors (up to 433-fold) and tempered by proof of potent COX1 inhibition within intact cells when peroxide tone is low. COX isoform inhibition by ACT may depend on subtle in vivo physiological variations specific to ACT. In vivo ACT efficacy is reliant on intact cells and low peroxide tone while the arachidonic acid concentration state can dictate the COX isoform preferred for PG synthesis. ACT is an effective antipyretic (COX2 preference for PG synthesis) and can reduce afebrile core temperature (likely COX1 preference for PG synthesis). Thus, we suggest with specificity to human in vivo physiology that ACT: (i) does not act on a third COX isoform; (ii) is not selective in its COX inhibition; and (iii) inhibition of COX isoforms are determined by subtle and nuanced physiological variations. Robust research designs are required in humans to objectively confirm these hypotheses.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Cyclooxygenase Inhibitors; Humans; Prostaglandin-Endoperoxide Synthases
PubMed: 34278737
DOI: 10.1002/prp2.835