Because of its low pKa of 3.5 aspirin is present in a lipidic protonated state in the fasted stomach of humans and other species that are basal acid secretors. Under these conditions aspirin is known ...to induce gastric mucosal injury, and barrier disruption as demonstrated by our lab and those of other investigators. We have also demonstrated that aspirin uptake as determined by HPLC occurs rapidly in the gastric body and antrum of rodents reaching a maximal value by 15 min a time which corresponds with significant reductions in gastric mucosal hydrophobicity and barrier integrity, whereas significantly less aspirin is taken up by the mucosa of the proximal duodenum. We also have evidence that 10 min after intragastric/intraduodenal administration a small but detectable amount of aspirin appears in thoracic duct/mesenteric lymph respectively declining thereafter, whereas salicylic acid in the lymph is present in concentrations fivefold to tenfold greater than aspirin and remains elevated for at least 90 min post-administration. We have also determined that phosphatidylcholine (PC) association tends to increase the concentration of aspirin in the lymph, likely due to increasing the drug's lipophilicity. Conclusion: Aspirin's ability to injury the gastric mucosa is dependent on it being taken up as a lipidic molecule, where it likely associates with phospholipids present in the mucus and surface membrane. This potentially surface injurious action can be attenuated by pre-association with PC, which is the basis of the PC-NSAID technology. We also determined that PC-association may promote the partitioning of aspirin and other NSAIDs into the GI lymphatics, which may explain the enhanced therapeutic efficacy and potency of these novel drugs, which may be due, in part to bypassing hepatic uptake and metabolism. Supported by the NIH grants P30 DK056338 and T-35 DK 07676-21A1.
Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the ...cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining how this therapy provides unique benefit to patients with AERD.
Abstract only Introduction The most common antiplatelet agents administered for neurovascular disease treatment and prevention are aspirin, clopidogrel, and ticagrelor. The utility of monitoring ...various platelet function assays (PFAs) in relation to neurovascular disease is unclear and variability exists in clinical practice. The aim of this study was to evaluate reliability of PFAs as a biomarker of the platelet inhibition in aspirin, clopidogrel, and ticagrelor in patients on antiplatelet agents for a broad range of neurovascular indications. Methods We conducted a retrospective chart review of prospectively collected data on patients who presented to our comprehensive stroke center and had PFAs drawn. PFAs utilized include Aspirin VerifyNow test, measured in aspirin resistance units (ARU) and Plavix VerifyNow test, measured in P2Y12 reaction units (PRU). Values less than 550 ARU are consistent with aspirin‐induced platelet inhibition. Similarly, values less than 197 PRU are indicative of platelet inhibition in clopidogrel or ticagrelor. Compliance and incidence of intracranial hemorrhage (ICH) and other adverse bleeding events were assessed. Social science statistics software was used for data analysis. Results From January to June 2022, a total of 297 patients had platelet function assays drawn for neurovascular indications. Average age was 69.96 (95% CI 68.31, 71.61). One hundred and eighty nine subjects were on aspirin. Mean ARU was 448.73 (95% CI 438.53, 458.93). One hundred twenty three subjects were on clopidogrel. Mean PRU for clopidogrel was 162.84 (95% CI 147.33, 178.35). Fifteen subjects were on ticagrelor. Mean PRU for ticagrelor was 73.27 (95% CI 34.62, 111.91). There was a significant difference in therapeutic platelet inhibition between clopidogrel and ticagrelor in subjects who were compliant (n = 105 clopidogrel complaint; n = 14 ticagrelor complaint) (z‐score 3.63, p‐value 0.00028). Of the patients that were compliant none had a non therapeutic platelet inhibition on aspirin and ticagrelor. Of the 123 patients that were compliant on clopidogrel 76% had non therapeutic PFA (n = 8 clopidogrel and ICH; n = 1 ticagrelor and ICH) (Fisher value = 0.0205). Conclusions Our study suggests that platelet inhibition of aspirin and ticagrelor may be more reliable when compared to that of clopidogrel. Significant limitations include the discrepancy in respective sample sizes. Larger studies are needed to validate our results.
Reply to Dr de Cassai et al Sanders, Rebecca A; Bendel, Markus A; Moeschler, Susan M ...
Regional anesthesia and pain medicine,
07/2018, Letnik:
43, Številka:
5
Journal Article
Background Aspirin-exacerbated respiratory disease (AERD) is manifested by adult-onset asthma, nasal polyposis, chronic rhinosinusitis, and aspirin sensitivity. Previously reported prevalence rates ...have been widely variable based on the population studied, method of diagnosis, and definition of aspirin sensitivity. Objective We sought to determine the prevalence of AERD among asthmatic adults. Methods A systematic review of databases was performed to identify all clinical trials published on or before June 16, 2013, that evaluated the prevalence of AERD. The studies were clustered into 7 different groups based on underlying disease (asthma, nasal polyps or chronic rhinosinusitis, or both), as well as on the methodology of prevalence determination. Results A total of 1770 articles were identified, with 27 considered appropriate for inclusion. Prevalence rates of AERD ranged from 5.5% to 12.4% based on study type. Among all studies in asthmatic patients, regardless of method, the prevalence of AERD was 7.15% (95% CI, 5.26% to 9.03%). The prevalence of AERD was highest among patients with severe asthma (14.89% 95% CI, 6.48% to 23.29%). Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% (95% CI, 2.16% to 17.22%) and 8.7% (95% CI, −1.02% to 18.34%), respectively. Conclusion AERD is a distinct and important subtype of asthma and polypoid sinus disease. The prevalence of AERD is 7% in typical adult asthmatic patients and twice that number in patients with severe asthma, which underscores the importance of recognizing this disorder. Early identification of this syndrome is critical in view of the increased morbidity and costs associated with asthma exacerbations and the option to treat patients with AERD with long-term aspirin treatment after desensitization.
Background Numerous open trials have demonstrated the beneficial clinical effects of aspirin desensitization (AD) in patients with aspirin-induced asthma (AIA). These beneficial effects might be ...attributable to aspirin's potent anti-inflammatory properties, but that supposition requires further corroboration. Objective We sought to compare the clinical and biochemical responses to chronic oral AD in 20 patients with AIA and 14 patients with aspirin-tolerant asthma (ATA). All of the patients had chronic rhinosinusitis and nasal polyposis, and these responses were investigated in a pilot, double-blind, placebo-controlled study. Methods Twelve patients with AIA and 6 patients with ATA were randomly assigned to receive 624 mg of aspirin, and 8 patients with AIA and 8 patients with ATA received placebo. Both aspirin and placebo were administered once daily for 6 months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20) scores, peak nasal inspiratory flows, Asthma Control Questionnaire scores, spirometric parameters, peak expiratory flows, blood eosinophilia, and corticosteroid doses were assessed on a monthly basis. Levels of urinary leukotriene E4 and the stable plasma prostaglandin (PG) D2 metabolite 9α,11β-PGF2 were evaluated at baseline and after 1, 3, 5, and 6 months. Results Only the patients with AIA subjected to AD reported improvements in smell and reductions in sneezing and nasal blockade. The SNOT20 and Asthma Control Questionnaire scores of these patients decreased, and their peak nasal inspiratory flows increased. The dosages of inhaled corticosteroids were reduced. There were no changes in leukotriene E4 or 9α,11β-PGF2 levels after AD. Conclusion The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA.
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