Naproxen antiplatelet effect

It has been suggested that the increase in thrombotic cardiovascular events in rofecoxib-treated patients probably represents the antiplatelet effect of naproxen (34,45,46). Naproxen has a long pharmacodynamic half-life and inhibits platelet aggregation by 88% for up to 8 hours (47). 

The evidence currently available on the antagonism of antiplatelet effects is insufficient to recommend that ibuprofen is not used with low-dose aspirin. Nevertheless, some have concluded that when patients taking low-dose aspirin for cardioprotection require long-term NSAIDs for inflammatory conditions, the use of diclofenac or naproxen would seem preferable to ibuprofen.A coxib was also suggested as an alternative,but the subsequent suggestion of an increased risk of serious cardiovascular effects with the coxibs (as a class ) probably precludes this. Recently the Commission on Human Medicines (CHM) in the UK has advised that there may be a small increased risk of thrombotic events with the non-selective NSAIDs, particularly when used at high doses and for long-term treatment. ... 

Drug interactions occur with many commonly prescribed medications and are mostly due to naproxen s effects on renal prostaglandins and the associated changes in kidney filtration rate, although many other mechanisms exist. Many drug interactions exist, with examples being ACE inhibitors, beta blockers, methotrexate, lithium, probenecid, antiplatelet agents, diuretics, and vancomycin. 

Preparations from plant materials containing salicylate have been used to treat pain and fever (Stone, 1763) from ancient times into the nineteenth century, when synthetic salicylic acid was synthesized in Germany and used for the same purposes. Acetyl salicylate, aspirin, synthesized as a prodrug for salicylate, was introduced by Bayer in 1899 (Dreser, 1899) and is still widely used to treat pain, fever, and inflammation. In low doses aspirin is also used by many to reduce the incidence of heart attacks by an antithrombotic effect (Antiplatelet Trialists Collaboration, 1994). Eventually, other drugs with therapeutic effects similar to those of aspirin were introduced, including indomethacin, ibuprofen, and naproxen. These... 

Reversible inhibitors of COX 1 and COX 2, with analgesic, antipyretic, and anti-inflammatory actions, include ibuprofen, naproxen, indomethacin, ketorolac, and sulindac. When used as antiinflammatory agents, they are usually no more effective than ASA, but they may be better tolerated. All have antiplatelet actions (reversible) at moderate (not low) doses and cause bleeding tendencies. 

Warfarin reduces the synthesis of prothrombin and several other clotting factors. Carbamazepine and rifampin interfere with this action by increasing the metabolism of warfarin. Cholestyramine decreases the oral absorption of warfarin and other acidic drugs. Vitamin K is the antidote to excessive effects of warfarin. Antiplatelet drugs such as naproxen enhance the anticoagulant effects of warfarin. The answer is (C). 

Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib is at least as effective as naproxen in the symptomatic management of osteoarthritis and at least as effective as naproxen and diclofenac in the symptomatic treatment of rheumatoid arthritis, and it is less likely to cause adverse Gl effects. Celecoxib appears to be effective in the management of pain associated with both of these arthritic conditions, but effectiveness in acute or chronic pain has not been fully demonstrated. Unlike aspirin, celecoxib does not exhibit antiplatelet activity. Concomitant administration of aspirin and celecoxib may increase the incidence of Gl side effects. Another notable potential drug interaction with celecoxib is its ability, like other NSAIDs, to reduce the blood pressure response to angiotensin-converting enzyme inhibitors. A more detailed discussion of the chemical, pharmacological, pharmacokinetic, and clinical aspects of celecoxib is available (81). 

Regular administration of naproxen 500 mg BID can produce an antiplatelet COX-1 effect similar to that of low-dose aspirin... 

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