Effects of Aspirin and Acetaminophen in Pregnancy and in the Newborn

Rudolph, Abraham M.

doi:10.1001/archinte.1981.00340030090016

Cited by 46 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) APAP is recommended for pregnant women as an analgesic and antipyretic because it is safe enough during all phases of pregnancy. 2,3) At low dose levels, APAP is mainly detoxified through sulfation and glucuronidation in animals. 4) APAP hepatotoxicity occurs following overdose as a result of metabolism through a cytochrome P450 system that allows toxic products to accumulate and bind to critical intracellular components.…”

mentioning

confidence: 99%

Inhibition of the Antibody Production by Acetaminophen Independent of Liver Injury in Mice.

Yamaura

Ogawa

Yonekawa

et al. 2002

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The causal relationship between the inhibition of antibody production and liver injury induced by single doses of acetaminophen (APAP) was investigated in mice. The liver injury and antibody production were evaluated using the serum transaminase activity and the number of antibody forming cells against sheep red blood cells (SRBC), respectively. The relevance of APAP hepatotoxicity with inhibiting antibody production was elucidated in fasted and fed mice treated with a single oral administration of APAP. In fasted mice, the oral administration of APAP produced serious liver injury, while it was not the case in the fed mice. As the antibody production was measured under these conditions, APAP significantly depressed the antibody production in fed mice as well as in fasted mice. The rate of B220 positive cells in the splenocytes was significantly decreased by APAP administration in both the fasted and fed mice. Splenocytes proliferative responses following mitogenic stimulation with concanavalin A or lipopolysaccharide were inhibited by APAP. Moreover, APAP added directly to the splenocyte culture also inhibited the in vitro antibody-producing response to SRBC. These findings indicate that the APAP-induced depression of antibody production may not be a secondary response to APAP-hepatitis, but may be a primary response to APAP.

show abstract

mentioning

confidence: 99%

Inhibition of the Antibody Production by Acetaminophen Independent of Liver Injury in Mice.

Yamaura

Ogawa

Yonekawa

et al. 2002

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Indomethacin also significantly inhibited 6-keto PGF 1 α, the stable metabolite of PGI 2 or PGE 2 production in freshly isolated term gestation ductus explants compared with APAP. 66) These data suggest that APAP potentially has little effect on ductus arteriosus compared with NSAIDs. Indeed, APAP is widely considered a safer antipyretic and analgesic than NSAIDs during pregnancy.…”

Section: Pharmacological/toxicological Action Of Apap On Ductus Artermentioning

confidence: 96%

“…65) Would APAP, which little affects COX activity in peripheral organs, potentially induce constriction of ductus arteriosus? El-Khuffash et al 66) demonstrated using their ex vivo experimental system that isolated ductus arteriosus from preterm mice or term gestation mice displayed limited response to increasing concentrations of APAP, but showed significant concentration-dependent constriction in response to indomethacin. Indomethacin also significantly inhibited 6-keto PGF 1 α, the stable metabolite of PGI 2 or PGE 2 production in freshly isolated term gestation ductus explants compared with APAP.…”

Section: Pharmacological/toxicological Action Of Apap On Ductus Artermentioning

confidence: 99%

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

“…It has been detected in synovial, spinal, and peritoneal fluids (Soren, 1978); and in saliva (Graham and Rowland, 1972); and breast milk (Levy, 1975). SA crosses the bloodbrain barrier only slowly because of the large fraction of drug in the ionised form and is also actively transported into the placenta (Palmisano and Cassady, 1969;Rudolph, 1981). The volume of distribution (Vj^) of SA increases with increasing plasma concentrations; it usually ranges between 0.1 and 0.35 I/kg at therapeutic concentrations, but can be higher in newborn infants (Levy and Yaffe, 1974).…”

Section: Iharmcokinetics and Metabolism Of Aspirinmentioning

confidence: 99%

Metabolism of Aspirin after Therapeutic and Toxic Doses

et al. 1990

View full text Add to dashboard Cite

1 The urinary recovery of metabolites of aspirin (ASA) was studied in 45 volunteers who took a therapeutic dose (600 mg) of ASA by mouth and in 37 patients who took ASA in overdose. 2 The main metabolite recovered from the volunteers was the glycine conjugate, salicyluric acid (SUA), which accounted for 75.01 ± 1.19% of total urinary metabolites, whereas salicylic acid (SA) accounted for 8.82 ± 0.56%. Recovery of SUA was negatively correlated with that of SA (r = -0.8625, P < 0.001). 3 In 24 patients with admission plasma salicylate concentrations of 240-360 mg 1-1, SUA accounted for 46.66 ± 3.22% and SA for 31.88 ± 4.02%. 4 In 13 patients with admission plasma salicylate concentrations of 715-870 mg 1-1, SUA accounted for 21.57 ± 3.65% and SA for 64.72 ± 4.82%. 5 Reduced excretion of salicylate as SUA was also accompanied by increased elimination as gentisic acid and salicylic acid phenolic glucuronide indicating that the unsaturated processes that lead to the formation of these metabolites contribute significantly (22-23%) to the inactivation of large doses of salicylate. 6 While the Michalis-Menten kinetics of ASA have been well demonstrated at lower doses, our findings illustrate the progressive saturation of SUA formation under conditions of increasing ASA load to toxic amounts and raise issues about the in-vivo glycine pool when ASA is taken in overdose.

show abstract

Effects of Aspirin and Acetaminophen in Pregnancy and in the Newborn

Cited by 46 publications

References 2 publications

Inhibition of the Antibody Production by Acetaminophen Independent of Liver Injury in Mice.

Inhibition of the Antibody Production by Acetaminophen Independent of Liver Injury in Mice.

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

Metabolism of Aspirin after Therapeutic and Toxic Doses

Contact Info

Product

Resources

About