Characterization of the Adverse Effects Induced by Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs Based on the Analysis of the Japanese Adverse Drug Event Report Database

Nagai, Junko; Uesawa, Yoshihiro; Shimamura, Ryotaro; Kagaya, Hajime

doi:10.1097/ajp.0000000000000457

Cited by 22 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike most NSAIDs, acetaminophen administration at therapeutic doses has little or no anti-inflammatory or anti-platelet activity (29). Additionally, it does not exhibit the typical side effect profile of NSAIDs, which includes gastrointestinal tract problems and aspirininduced asthma (37,38). Although acetaminophen is among the most popular and widely used analgesics, the mechanism of its analgesic action remain uncertain, though the most suggested mechanism involves inhibition of COX activity (39).…”

Section: Discussionmentioning

confidence: 99%

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Zhuang

et al. 2017

biom rep

View full text Add to dashboard Cite

Abstract. Nefopam, an analgesic drug, effectively elicits antinociception in the majority of noxious and thermal models in rodents. Acetaminophen is among the most commonly used analgesic and antipyretic drugs worldwide, either on prescription or over the counter. The present study aimed to investigate the analgesic activity of nefopam combined with acetaminophen, which was expected to maximize the potency of analgesia and decrease the dose of nefopam required. Three series of experiments, namely acetic acid-induced writhing tests in mice, hot plate tests in mice and tail flick tests in rats, were used to evaluate the analgesic effect. Initially, an optimum proportion of the two drugs, 3.5 mg/kg nefopam (N) + 60 mg/kg acetaminophen (A), was determined by orthogonal array design based on writhing response number. Subsequently, combinations of N and A (1.75 N + 30 A, 3.5 N + 60 A and 7.0 N + 120 A mg/kg) were determined to elicit antinociception in the writhing test (P<0.01 vs. normal saline control) in a dose-dependent manner. In the hot plate test, hot plate latencies up to 60 min after drug treatment were observed. The combination of 7.0 N + 120 A mg/kg exerted a greater cumulative antinociceptive effect throughout the observation period, with an area under the curve value of 1,156.95±199.30 area units (AU), compared with that achieved by 7.0 N mg/kg alone (632.12±62.38 AU). Furthermore, both monotherapy and compound therapy exhibited antinociception dose-dependently in the tail-flick test. However, a combination of 5.0 N + 84 A mg/kg exerted greater analgesic effect compared with 5.0 N mg/kg alone. The data obtained demonstrate that acetaminophen may enhance the antinociceptive activity of nefopam. Thus, coadministration of nefopam with acetaminophen warrants clinical evaluation.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Zhuang

et al. 2017

biom rep

View full text Add to dashboard Cite

show abstract

“…Many studies have investigated the relationship between a drug and adverse drug events using the JADER database. [11][12][13][14] In the SRS database, information on the possibility of a causal relationship between adverse events and drugs that have not been known so far could be detected using signal detection approaches. [15][16][17] In this study, we focused on developing an SCAR classification model using drug structure information from the JADER database.…”

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

In Silico Approach to Predict Severe Cutaneous Adverse Reactions Using the Japanese Adverse Drug Event Report Database

Ambe

Ohya

Takada

et al. 2021

Clinical Translational Sci

View full text Add to dashboard Cite

Severe cutaneous adverse reactions (SCARs), such as Stevens–Johnson syndrome/toxic epidermal necrolysis and drug‐induced hypersensitivity syndrome, are rare and occasionally fatal. However, it is difficult to detect SCARs at the drug development stage, necessitating a new approach for prediction. Therefore, in this study, using the chemical structure information of SCAR‐causative drugs from the Japanese Adverse Drug Event Report (JADER) database, we tried to develop a predictive classification model of SCAR through deep learning. In the JADER database from 2004 to 2017, we defined 185 SCAR‐positive drugs and 195 SCAR‐negative drugs using proportional reporting ratios as the signal detection method, and the total number of reports. These SCAR‐positive and SCAR‐negative drugs were randomly divided into the training dataset for model construction and the test dataset for evaluation. The model performance was evaluated in the independent test dataset inside the applicability domain (AD), which is the chemical space for reliable prediction results. Using the deep learning model with molecular descriptors as the drug structure information, the area under the curve was 0.76 for the 148 drugs of the test dataset inside the AD. The method developed in the present study allows for utilizing the JADER database for SCAR classification, with potential to improve screening efficiency in the development of new drugs. This method may also help to noninvasively identify the causative drug, and help assess the causality between drugs and SCARs in postmarketing surveillance.

show abstract

“…In addition, our previous preclinical study suggests that APAP partly improves renal function in adenine-induced kidney injury model. 25) Although we need to bear in mind the possibility that APAP may cause chronic renal failure due to renal papillary necrosis, [26][27][28][29] the above observations support the renal safety of APAP compared with NSAIDs at the moment.…”

Section: Biographymentioning

confidence: 82%

Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?

Ishitsuka

Kondo

Kadowaki

2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

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.

show abstract

Characterization of the Adverse Effects Induced by Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs Based on the Analysis of the Japanese Adverse Drug Event Report Database

Cited by 22 publications

References 36 publications

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

In Silico Approach to Predict Severe Cutaneous Adverse Reactions Using the Japanese Adverse Drug Event Report Database

Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?

Contact Info

Product

Resources

About