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Biological & Pharmaceutical Bulletin 2020Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared... (Review)
Review
Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N-acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar "dark side" of APAP as an otherwise safe analgesic/antipyretic drug.
Topics: Acetaminophen; Acetylcysteine; Aged; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Chemical and Drug Induced Liver Injury; Endoplasmic Reticulum Stress; Female; Glutathione; Humans; Male; Mitochondria, Liver; Oxidative Stress; Pregnancy
PubMed: 32009106
DOI: 10.1248/bpb.b19-00722 -
Pediatric Rheumatology Online Journal Apr 2020Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable...
Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group.
BACKGROUND
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA.
METHODS
The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement.
RESULTS
The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study.
CONCLUSION
The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease.
Topics: Adrenal Cortex Hormones; Advisory Committees; Antipyretics; Child; Child, Preschool; Cimetidine; Colchicine; Fever; Histamine H2 Antagonists; Humans; Lymphadenitis; Neck; Pharyngitis; Stomatitis, Aphthous; Syndrome; Tonsillectomy; Tubulin Modulators
PubMed: 32293478
DOI: 10.1186/s12969-020-00424-x -
Fever therapy in febrile adults: systematic review with meta-analyses and trial sequential analyses.BMJ (Clinical Research Ed.) Jul 2022To investigate the effects of fever therapy compared with no fever therapy in a wide population of febrile adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the effects of fever therapy compared with no fever therapy in a wide population of febrile adults.
DESIGN
Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
DATA SOURCES
CENTRAL, BIOSIS, CINAHL, MEDLINE, Embase, LILACS, Scopus, and Web of Science Core Collection, searched from their inception to 2 July 2021.
ELIGIBILITY CRITERIA
Randomised clinical trials in adults diagnosed as having fever of any origin. Included experimental interventions were any fever therapy, and the control intervention had to be no fever therapy (with or without placebo/sham).
DATA EXTRACTION AND SYNTHESIS
Two authors independently selected studies, extracted data, and assessed the risk of bias. Primary outcomes were all cause mortality and serious adverse events. Secondary outcomes were quality of life and non-serious adverse events. Aggregate data were synthesised with meta-analyses, subgroup analyses, and trial sequential analyses, and the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Forty two trials assessing 5140 participants were included. Twenty three trials assessed 11 different antipyretic drugs, 11 trials assessed physical cooling, and eight trials assessed a combination of antipyretic drugs and physical cooling. Of the participants, 3007 were critically ill, 1892 were non-critically ill, 3277 had infectious fever, and 1139 had non-infectious fever. All trials were assessed as being at high risk of bias. Meta-analysis and trial sequential analysis showed that the hypothesis that fever therapy reduces the risk of death (risk ratio 1.04, 95% confidence interval 0.90 to 1.19; I=0%; P=0.62; 16 trials; high certainty evidence) and the risk of serious adverse events (risk ratio 1.02, 0.89 to 1.17; I=0%; P=0.78; 16 trials; high certainty evidence) could be rejected. One trial assessing quality of life was included, showing no difference between fever therapy and control. Meta-analysis and trial sequential analysis showed that the hypothesis that fever therapy reduces the risk of non-serious adverse events could be neither confirmed nor rejected (risk ratio 0.92, 0.67 to 1.25; I=66.5%; P=0.58; four trials; very low certainty evidence).
CONCLUSIONS
Fever therapy does not seem to affect the risk of death and serious adverse events.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019134006.
Topics: Adult; Antipyretics; Bias; Critical Illness; Fever; Humans; Quality of Life
PubMed: 35820685
DOI: 10.1136/bmj-2021-069620 -
Cytokine Apr 2019Pyrogens, the fever inducing substances accidently enter into a human body through contamination from medical or pharmaceutical products may create mild to severe... (Review)
Review
Pyrogens, the fever inducing substances accidently enter into a human body through contamination from medical or pharmaceutical products may create mild to severe complications including septicaemia and shocking syndromes. To avoid such drastic situations all the pharmaceuticals and medical devices are analysed for presence of pyrogens prior to their release into market. The entry of exogenous pyrogens like bacterial endotoxins induces the release of endogenous pyrogens or inflammatory cytokines that activate immune system to defend against these pathogens. Generation of heat is considered as one of the important defence mechanism of body achieved through receptor mediated interaction of endogenous pyrogens at the thermoregulatory centre of hypothalamus. However, uncontrolled fever and febrile reaction may cause lethal effects to the subject itself. So a well sophistically functioning antipyretic mechanism is necessary to achieve thermoregulation. The coordinated interaction of antipyretic cytokines and other mediators are active in human immune system which play a crucial role in maintaining thermal homeostasis. The multiple interacting antipyretic signals and their mechanism are the major subjects of this review.
Topics: Antipyretics; Body Temperature Regulation; Cytokines; Fever; Humans; Pyrogens
PubMed: 30711851
DOI: 10.1016/j.cyto.2019.01.008 -
Antimicrobial Agents and Chemotherapy Apr 2017Antipyretics are some of the most commonly used drugs. Since they are often coadministered with antimicrobial therapy, it is important to understand the interactions... (Review)
Review
Antipyretics are some of the most commonly used drugs. Since they are often coadministered with antimicrobial therapy, it is important to understand the interactions between these two classes of drugs. Our review is the first to summarize the antimicrobial effects of antipyretic drugs and the underlying mechanisms involved. Antipyretics can inhibit virus replication, inhibit or promote bacterial or fungal growth, alter the expression of virulence factors, change the surface hydrophobicity of microbes, influence biofilm production, affect the motility, adherence, and metabolism of pathogens, interact with the transport and release of antibiotics by leukocytes, modify the susceptibility of bacteria to antibiotics, and induce or reduce the frequency of mutations leading to antimicrobial resistance. While antipyretics may compromise the efficacy of antimicrobial therapy, they can also be beneficial, for example, in the management of biofilm-associated infections, in reducing virulence factors, in therapy of resistant pathogens, and in inducing synergistic effects. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, targeting virulence factors, enhancing the efficacy of antimicrobial therapy, and reducing resistance may be important strategies.
Topics: Animals; Anti-Infective Agents; Antipyretics; Biofilms; Biological Transport; Communicable Diseases; Drug Interactions; Drug Therapy, Combination; Fever; Humans; Hydrophobic and Hydrophilic Interactions; Mutation; Virulence Factors; Virus Replication
PubMed: 28137805
DOI: 10.1128/AAC.02268-16 -
Scandinavian Journal of Pain Oct 2017Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal... (Review)
Review
Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal acetaminophen was reported to be associated with asthma, lower performance intelligence quotient (IQ), shorter male infant anogenital distance (predicting poor male reproductive potential), autism spectrum disorder, neurodevelopmental problems (gross motor development, communication), attention-deficit/hyperactivity disorder, poorer attention and executive function, and behavioral problems in childhood. Each article has poor power to show risks of acetaminophen, however, the integration of the articles that showed adverse effects of acetaminophen may have power to show them. Acetaminophen use in childhood was associated with autism spectrum disorder, asthma symptoms, wheezing, and allergic disease. Acetaminophen is the safest medicine as analgesics for nociceptive pain and antipyretics in childhood and pregnancy. There is no alternative medication of acetaminophen. Acetaminophen should not be withheld from children or pregnant women for fears it might develop adverse effects. Acetaminophen should be used at the lowest effective dosage and for the shortest time. When we know the possible, rare but serious complications, we should use acetaminophen in pregnancy only when needed and no safer option for pain or fever relief is available. Health care providers should help inform the general lay public about this difficult dilemma.
Topics: Acetaminophen; Adult; Analgesics; Antipyretics; Child; Female; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28986045
DOI: 10.1016/j.sjpain.2017.09.007 -
Handbook of Clinical Neurology 2018Fever depends on a complex physiologic response to infectious agents and other conditions. To alleviate fever, many medicinal agents have been developed over a century... (Review)
Review
Fever depends on a complex physiologic response to infectious agents and other conditions. To alleviate fever, many medicinal agents have been developed over a century of trying to improve upon aspirin, which was determined to work by inhibiting prostaglandin synthesis. We present the process of fever induction through prostaglandin synthesis and discuss the development of pharmaceuticals that target enzymes and receptors involved in prostaglandin-mediated signal transduction, including prostaglandin H synthase (also known as cyclooxygenase), phospholipase A, microsomal prostaglandin E synthase-1, EP receptors, and transient potential cation channel subfamily V member 1. Clinical use of established antipyretics will be discussed as well as medicinal agents under clinical trials and future research.
Topics: Animals; Antipyretics; Fever; Humans; Pharmacology, Clinical; Prostaglandins; Signal Transduction
PubMed: 30459046
DOI: 10.1016/B978-0-444-64074-1.00054-9 -
Primary Care Dec 2015In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and,... (Review)
Review
In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Antiviral Agents; Comorbidity; Diagnosis, Differential; Exanthema; Humans; Immunization; Immunocompromised Host; Primary Health Care; Skin Diseases, Viral
PubMed: 26612372
DOI: 10.1016/j.pop.2015.08.006 -
Current Opinion in Pediatrics Jun 2015The review describes current evidence on the evaluation of febrile seizures in the acute setting, the need for further outpatient assessment, and predictors regarding... (Review)
Review
PURPOSE OF REVIEW
The review describes current evidence on the evaluation of febrile seizures in the acute setting, the need for further outpatient assessment, and predictors regarding long-term outcomes of these patients.
RECENT FINDINGS
New evidence has been added in support of limited assessment and intervention: evidence on low utility of lumbar puncture, emergent neuroimaging, and follow-up electroencephalography, as well as low yield for antipyretic prophylaxis and intermittent use of antiepileptic drugs. Finally, there is growing evidence regarding the genetic basis of both febrile seizures and vaccine-related seizures/febrile seizures.
SUMMARY
Routine diagnostic testing for simple febrile seizures is being discouraged, and clear evidence-based guidelines regarding complex febrile seizures are lacking. Thus, clinical acumen remains the most important tool for identifying children with seizures who are candidates for a more elaborate diagnostic evaluation. Similarly, evidence and guidelines regarding candidates for an emergent out-of-hospital diazepam treatment are lacking.
Topics: Advisory Committees; Anticonvulsants; Antipyretics; Child; Child, Preschool; Electroencephalography; Emergency Medicine; Genetic Predisposition to Disease; Humans; Neuroimaging; Practice Guidelines as Topic; Seizures, Febrile; Spinal Puncture
PubMed: 25944308
DOI: 10.1097/MOP.0000000000000220 -
Minerva Anestesiologica Jan 2021
Topics: Antipyretics; Body Temperature; COVID-19; Fever; Hospitalization; Humans
PubMed: 33231411
DOI: 10.23736/S0375-9393.20.15195-2