Antagonism of thromboxane receptors by diclofenac and lumiracoxib

Selg, E; Buccellati, C; Andersson, M; Rovati, G. Enrico; Ezinga, M; Sala, A; Larsson, A-K; Ambrosio, E; Låstbom, L; Capra, Valérie; Dahlén, B; Ryrfeldt, Å; Folco, G C; Se, Dahlén

doi:10.1038/bjp.2008.106

Cited by 8 publications

(11 citation statements)

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“…Gastrointestinal bleeding is a common adverse event of aspirin and NSAIDs [22] . Spontaneous nongastrointestinal tract bleeding in patients with no history of bleeding disorders treated with NSAIDs is regarded extremely rare, with intracerebral hemorrhage being the most serious bleeding complication [23] .…”

Section: Discussionmentioning

confidence: 99%

Hemoptysis under Diclofenac and Antiplatelet Doses of Aspirin

Yiannakopoulou

2010

Pharmacology

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A previously healthy 60-year-old man receiving aspirin for primary prevention of cardiovascular disease presented with hemoptysis after 1 week of treatment for his back pain with diclofenac. He had not suffered from any bleeding episode in the past and his family history was negative for hemorrhagic disorders. He had been a heavy smoker until his thirties, but had stopped smoking since then. After extensive workup, other pulmonary and nonpulmonary causes of hemoptysis were ruled out. Thus, in this case, because of the temporal relationship between exposure to the drug and the onset of symptoms, diclofenac was considered as the most probable cause of hemoptysis either alone or as a result of its pharmacodynamic interaction with aspirin. The adverse reaction was considered probable according to the Naranjo scale. Diclofenac treatment was discontinued and occasional use of acetaminophen for the back pain was recommended. Regular use of antiplatelet doses of aspirin was also discontinued.

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Section: Discussionmentioning

confidence: 99%

Hemoptysis under Diclofenac and Antiplatelet Doses of Aspirin

Yiannakopoulou

2010

Pharmacology

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“…Nevertheless, it is accepted that some NSAIDs besides to produce in vitro and in vivo inhibition of COX, have additional mechanisms of action [18,19,26,38,[40][41][42]. At this respect, the antinociception observed in the present study would be due to different mechanisms, activation of the nitric oxide-cyclic GMP pathway and ATP-sensitive-, voltage-dependent-, large-and small-conductance Ca 2+ -activated-K + channels [19] or the inhibition of TP receptors [24].…”

Section: Discussionmentioning

confidence: 59%

“…Likewise, it has been demonstrated that the analgesic activity of the combination of lidocaine with opioids (morphine, levorphanol, buprenorphine and endorphin-1) was synergistic in different administration pathways and assays [53][54][55][56]. Lumiracoxib may decrease the excitability of presynaptic neurons by the inhibition of TP receptor [24] and the activation of the nitric oxide-cyclic GMP pathway and K + channels [19]. Lidocaine may synergize with these effects through its ability to inhibit Na + and Ca ++ channels, and 5-HT 3 and NMDA receptors [45][46][47][48][49][50], which would reduce the excitability of presynaptic neurons and postsynaptic dorsal horn neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Our group has demonstrated that lumiracoxib exhibits additional mechanisms of antinociception, particularly the activation of the nitric oxide (NO)-cyclic GMP-potassium channel pathway at the peripheral level on the formalin test [19]. Recently, it was demonstrated that lumiracoxib concentration-dependently and selectively inhibited the contraction responses to TP receptor agonists such as prostaglandin D2 and U-46619 in the tested smooth muscle preparations and the aggregation of human platelets [24].…”

Section: Introductionmentioning

confidence: 99%

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Peripheral Synergistic Interaction Between Lidocaine and Lumiracoxib on the 1% Formalin Test in Rats

Ortiz¹

2011

TOPAINJ

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Abstract:It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and lidocaine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, lidocaine or fixed-dose ratio (1:1) lumiracoxib-lidocaine combinations were administered locally in the formalin-injured paw and the antinociceptive effect was evaluated. All treatments produced a dose-dependent antinociceptive effect. ED 40 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED 40 for the lumiracoxiblidocaine combination was 599.3 ± 58.8 g/paw, being significantly higher than the actually observed experimental ED 40 value, 393.6 ± 39.7 g/paw. This result correspond to a synergistic interaction between lumiracoxib and lidocaine at the local peripheral level, potency being about one and half times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib-lidocaine combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of procedural or inflammatory pain.

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“…The isolated and perfused rat lung (IPL) has been used in our laboratory as a model for studying effects of various pharmacological interventions on lung mechanics and vasoconstriction [11,12]. Recently, the DustGun aerosol technology has been used to expose the IPL, via dry powder inhalation, to aerosols of drugs and toxicants [13][14][15].…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

Vasoconstriction after inhalation of budesonide: A study in the isolated and perfused rat lung

Ewing

Ryrfeldt

Sjöberg

et al. 2010

Pulmonary Pharmacology & Therapeutics

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Abstract:Clinical studies have shown that inhaled corticosteroids can induce rapid vasoconstriction in the airways, leading to decreased mucosal blood flow. The aim of this study was to investigate whether vasoconstriction of the pulmonary circulation after short inhalation of a corticosteroid can be detected in the isolated and perfused rat lung (IPL) -a model which could serve as a substitute or a complement to clinical models.Methods: IPLs were briefly exposed to dry powder aerosol of budesonide. The pulmonary perfusate flow rate was assessed during 100 minutes post exposure. A reduction in perfusion flow rate was interpreted as vasoconstriction.Main Results: Vasoconstriction was more pronounced after brief inhalation of 10 and 50 μg budesonide than 2 μg. The onset of vasoconstriction became statistically significant within 10-40 minutes after inhalation. Co-administration of a selective α 1 -adrenoceptor antagonist (prazosin 50 nM added to the perfusate) reduced vasoconstriction by approximately 50% during 100 minutes of perfusion (p=0.003).Conclusions: Inhaled budesonide rapidly induces pulmonary vasoconstriction suggesting a nongenomic mechanism probably related to disposition of noradrenaline at the neuro-muscular junction. This ex vivo model could serve as a substitute or a complement to clinical models for investigating rapid effects of glucocorticoid receptor agonists on the pulmonary/bronchial circulation. Word count abstract: 202

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Antagonism of thromboxane receptors by diclofenac and lumiracoxib

Abstract: British Journal of Pharmacology (2008) 153, 1763; doi:

Cited by 8 publications

References 0 publications

Hemoptysis under Diclofenac and Antiplatelet Doses of Aspirin

Hemoptysis under Diclofenac and Antiplatelet Doses of Aspirin

Peripheral Synergistic Interaction Between Lidocaine and Lumiracoxib on the 1% Formalin Test in Rats

Vasoconstriction after inhalation of budesonide: A study in the isolated and perfused rat lung

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