Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs

Hoppmann, Richard

doi:10.1001/archinte.1991.00400070083009

Cited by 111 publications

(29 citation statements)

References 41 publications

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“…NSAIDs have been shown to induce various forms of adverse neurological effects including cognitive dysfunction, confusion, somnolence, behavioral disturbances, seizures and dizziness (Hoppman et al, 1991;Day et al, 2000). In this regard, we found that hOAT3 mRNA was expressed in the brain (Cha et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Although the chemical diversity yields a broad range of pharmacokinetic characteristics (Frust and Munster, 2000), they have some general properties in common. NSAIDs have been shown to induce various forms of adverse drug reactions including adverse gastrointestinal effects (Day et al, 2000), renal dysfunction and nephrotoxicity (Day et al, 2000), liver damage (Zimmerman, 1981;Wood et al, 1985;Purcell et al, 1991;Day et al, 2000), adverse neurological effects (Hoppman et al, 1991;Day et al, 2000), and rhabdomyolysis (Ross and Hoppel, 1987;Leventhal et al, 1989;Delrio et al, 1996).The secretion of numerous organic anions and cations, including endogenous metabolites, drugs, and xenobiotics, is an important physiological function of the renal proximal tubule. The process of secreting organic anions and cations through the proximal tubule cells is achieved via unidirectional transcellular transport involving the uptake of organic anions and cations into the cells from the blood across the basolateral membrane, followed by extrusion across the brush-border membrane into the proximal tubule fluid (Pritchard and Miller, 1993).…”

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confidence: 99%

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Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

Khamdang

Takeda²,

Noshiro³

et al. 2002

J Pharmacol Exp Ther

169

132

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The purpose of this study was to elucidate the interactions of human organic anion transporters (hOATs) and human organic cation transporters (hOCTs) with nonsteroidal anti-inflammatory drugs (NSAIDs) using cells stably expressing hOATs and hOCTs. NSAIDs tested were acetaminophen, acetylsalicylate, salicylate, diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam, phenacetin, and sulindac. These NSAIDs inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4. By comparing the IC 50 values of NSAIDs for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with NSAIDs than did hOAT2 and hOAT4. HOAT1, hOAT2, hOAT3, and hOAT4 mediated the uptake of either ibuprofen, indomethacin, ketoprofen, or salicylate, but not acetylsalicylate. Although organic cation uptake mediated by hOCT1 and hOCT2 was also inhibited by some NSAIDs, hOCT1 and hOCT2 did not mediate the uptake of NSAIDs. In conclusion, hOATs and hOCTs interacted with various NSAIDs, whereas hOATs but not hOCTs mediated the transport of some of these NSAIDs. Considering the localization of hOATs, it was suggested that the interactions of hOATs with NSAIDs are associated with the pharmacokinetics and the induction of adverse reactions of NSAIDs.Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for their anti-inflammatory and analgesic properties. The indications of NSAIDs are broadening from rheumatic diseases and various pain states, such as cancer pain, and biliary and colic pain, to include possibly Alzheimer's disease and colon cancer prevention (Day et al., 2000). Table 1 shows the chemical structures of NSAIDs tested in the current study. Although all of these NSAIDs are weak organic acids, they are grouped in several classes based on their chemical structures. Although the chemical diversity yields a broad range of pharmacokinetic characteristics (Frust and Munster, 2000), they have some general properties in common. NSAIDs have been shown to induce various forms of adverse drug reactions including adverse gastrointestinal effects (Day et al., 2000), renal dysfunction and nephrotoxicity (Day et al., 2000), liver damage (Zimmerman, 1981;Wood et al., 1985;Purcell et al., 1991;Day et al., 2000), adverse neurological effects (Hoppman et al., 1991;Day et al., 2000), and rhabdomyolysis (Ross and Hoppel, 1987;Leventhal et al., 1989;Delrio et al., 1996).The secretion of numerous organic anions and cations, including endogenous metabolites, drugs, and xenobiotics, is an important physiological function of the renal proximal tubule. The process of secreting organic anions and cations through the proximal tubule cells is achieved via unidirectional transcellular transport involving the uptake of organic anions and cations into the cells from the blood across the basolateral membrane, followed by extrusion across the brush-border membrane into the proximal tubule fluid (Pritchard and Miller, 1993). Recently, cDNAs encoding the human organic anion transporter (hOAT) fa...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

Khamdang

Takeda²,

Noshiro³

et al. 2002

J Pharmacol Exp Ther

169

132

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“…Deficient PGD 2 signaling would thus be expected to produce the signs of excessive dopamine activity that are seen in SZ. A role for PGs as endogenous anti-dopaminergic agents is supported by the findings that inhibitors of PG synthesis can cause psychotic symptoms in some people and can worsen psychotic symptoms in SZ patients (Hoppman et al, 1991;Sussman and Magid, 2000). The relationship between SZ and COX products is complex, however, as there are also reports suggesting that COX inhibitors may augment the efficacy of antipsychotic medications (Akhondzadeh et al, 2007;Laan et al, 2010;Müller et al, 2002).…”

Section: Clinical and Physiological Effects Of Aa And Eicosanoidsmentioning

confidence: 99%

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Messamore

Yao

2015

OCL

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-This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.Keywords: Phospholipids / arachidonic acid / eicosanoids / niacin-induced flushing, endophenotype marker / schizophrenia Résumé -Signalisation des phospholipides, de l'arachidonate et de l'écosanoïde dans la schizophrénie. Cet article examine le rôle potentiel de l'acide arachidonique dans la physiopathologie de la schizophrénie. Il est discuté comment des niveaux anormaux d'acide arachidonique peuvent survenir, et comment la dérégulation des molécules de signalisation qui en découle est capable de perturber non seulement la signalisation de la dopamine, mais aussi de nombreux autres processus physiologiques associés avec cette maladie. Des doses pharmacologiques de niacine stimulent la libération d'acide arachidonique ; des molécules dérivées de l'acide arachidonique dilatent à leur tour les vaisseaux sanguins dans la peau. Une brusque rougeur de la peau en réponse à la niacine est observée de manière constante parmi les patients atteints de schizophrénie. La réponse anormale à la niacine peut donc servir de biomarqueur afin d'identifier un sous-type physiologique de la schizophrénie, associé à un système défectueux de signalisation des dérivés de l'acide arachidonique.

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“…Within hours of reintroduction of NSAID comes the onset of fevers, headache, and stiff neck. Ibuprofen is the NSAID most commonly linked to this condition, although cases involving sulindac, naproxen, tolmetin, and diclofenac have been reported 16,17 . To date, there have been no reported cases of aseptic meningitis with ASA use.…”

Section: Rheumatologymentioning

confidence: 99%