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Potential oxygen radical scavenging properties of the H2-receptor antagonists cimetidine, ranitidine and famotidine were investigated. These drugs, although ineffective against superoxide anion and hydrogen peroxide, can scavenge hydroxyl radical (OH.) with a very high rate constant, which is about tenfold higher than that of the specific scavenger mannitol for famotidine (1.7 x 10(10) mol-1 s-1) and cimetidine (1.6 x 10(10) mol-1 s-1), ranitidine displaying a rate constant of 7.5 x 10(9) mol-1 s-1. These OH. savenging effects are significant beginning from 10, 28 and 100 mumol l-1 concentration for famotidine, cimetidine and ranitidine, respectively, thus suggesting that the drugs may effectively act as OH. scavengers in vivo especially in the gastric lumen. Only cimetidine can apparently bind and inactivate iron, which further emphasizes its antioxidant capacity. Moreover, all drugs, even at 10 mumol l-1 concentration, show powerful scavenging effects on hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. These data suggest that some therapeutical effects of H2-receptor antagonists in peptic ulcer may also be related to their antiradical-antioxidant capacity, and that these drugs could potentially be used in other disease entities characterized by free radical-mediated oxidative stress in vivo.

Objective. To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.Methods. We performed a crossover, open-label study in 9 healthy volunteers. They received for 6 days 3 different treatments separated by 14 days of washout: 1) naproxen 2 hours before aspirin, 2) aspirin 2 hours before naproxen, and 3) aspirin alone. The primary end point was the assessment of serum thromboxane B 2 (TXB 2 ) 24 hours after the administration of naproxen 2 hours before aspirin on day 6 of treatment. In 5 volunteers, the rate of recovery of TXB 2 generation (up to 72 hours after drug discontinuation) was assessed in serum and in platelet-rich plasma stimulated with arachidonic acid (AA) or collagen. Conclusion. Sequential administration of 220 mg naproxen twice a day and low-dose aspirin interferes with the irreversible inhibition of platelet cyclooxygenase 1 afforded by aspirin. The interaction was smaller when giving naproxen 2 hours after aspirin. The clinical consequences of these 2 schedules of administration of aspirin with naproxen remain to be studied in randomized clinical trials. Results. Twenty-four hoursArthritis in general and osteoarthritis in particular are increasingly becoming global problems; however, at this time, there is no known cure for osteoarthritis. Most forms of treatment therefore have dealt with the alleviation and management of chronic pain, which can affect normal functioning and quality of life of patients.

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We studied the influence of cardiovascular (CV) risk factors, previous CV events, and cotreatments with preventive medicines, on residual platelet thromboxane (TX)B production in 182 patients chronically treated with enteric coated (EC)-aspirin (100 mg/day). The response to aspirin was also verified by assessing arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB levels. Residual serum TXB levels exceeded the upper limit value for an adequate aspirin response in 14% of individuals. This phenomenon was detected at 12 hours after dosing with aspirin. The coadministration of statins (mostly atorvastatin) was an independent predictor of residual serum TXB levels, and the percentage of patients with enhanced values was significantly lower in statin users vs. nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB generation by increasing the extent of acetylation of platelet COX-1 by aspirin. In conclusion, the coadministration of statins may counter the mechanisms associated with reduced bioavailability of aspirin detected in some individuals with CV disease.