Effect of Naproxen and of Aspirin on Bleeding Time and Platelet Aggregation

Nadell, Judith; Bruno, John J.; Varady, John; Segre, Eugene J.

doi:10.1002/j.1552-4604.1974.tb01395.x

Cited by 49 publications

(17 citation statements)

References 13 publications

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“…Since available observational studies [18, 45-47] have shown that piroxicam, like naproxen, is not associated with a significant increase in the risk of either acute myocardial infarction or stroke, this NSAID could be considered a suitable alternative to naproxen. It is conceivable that its CV safety be related to its long-lasting antiplatelet activity [192-195], which recalls that of naproxen [196-199]. …”

Section: Discussionmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition t...

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Section: Discussionmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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“…A smaller study of naproxen found abnormal arachidonic acid-induced platelet aggregation in 2 of 3 patients at 2 hours and in 0 of 3 patients at 4 days after the last dose. 6 Recommendations for cessation of antiplatelet therapy, particularly in those with significant cardiovascular risks or need for antiinflammatory medications, should be made in light of data on the length of platelet inhibition after stopping these medications (Table 3).…”

Section: Bleeding Complications Of Drugs Used For Therapeutic Platelementioning

confidence: 99%

Acquired Disorders of Platelet Function

Konkle

2011

Hematology

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Platelet dysfunction is commonly acquired due to medications, procedures, medical conditions, and underlying hematologic disease. These issues are presented, the data reviewed, and recommendations given herein. Many medications and dietary supplements have platelet-inhibitory effects in vitro, although the clinical effects on bleeding risks are unclear for many. Platelet-inhibitory drugs are key in the treatment of vascular disease. Data are available to aid in the management of these medications to prevent hemorrhagic complications. Bleeding in patients with renal failure has decreased with improved dialysis and the use of erythropoietin, but remains a challenge. Platelet dysfunction accompanies cardiac valvular disease and use of cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation. Hematologic disorders including myeloproliferative disorders (MPDs), myelodysplasia, paraproteinemias, and immune thrombocytopenia (ITP) can also be associated with hemorrhagic complications due to platelet dysfunction. Knowledge of which factors affect bleeding risk and how to treat individuals with acquired platelet dysfunction are important in optimizing patient care.

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“…32 The antiplatelet effect of naproxen, also a reversible COX inhibitor, subsides within 4 days. 33 Waiting for platelet function to return to normal is ideal, but what should the clinician do if a patient reports taking aspirin during the SCS trial? Should one wait 14 days to pull the trial leads, running an increased risk of infection?…”

Section: Discussionmentioning

confidence: 99%

Epidural Hematomas After Removal of Percutaneous Spinal Cord Stimulator Trial Leads

Giberson¹,

Barbosa²,

Brooks³

et al. 2014

Regional Anesthesia and Pain Medicine

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Currently, the neuromodulation community ascribes to the American Society of Regional Anesthesia and Pain Medicine guidelines, which state that nonsteroidal anti-inflammatory drugs do not significantly increase the risk for epidural hematoma with neuraxial anesthesia and, therefore, there is no need to discontinue these drugs before epidural or spinal anesthesia. We suggest that these guidelines may not be appropriate for neuromodulatory techniques that likely subject the surrounding vasculature to more trauma than neuraxial anesthesia. We recommend discontinuing nonsteroidal anti-inflammatory drugs, particularly aspirin, before neuromodulation procedures. Further investigation will establish a timeframe for holding these drugs to optimize patient safety.

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Effect of Naproxen and of Aspirin on Bleeding Time and Platelet Aggregation

Cited by 49 publications

References 13 publications

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Acquired Disorders of Platelet Function

Epidural Hematomas After Removal of Percutaneous Spinal Cord Stimulator Trial Leads

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Effect of Naproxen and of Aspirin on Bleeding Time and Platelet Aggregation

Cited by 49 publications

References 13 publications

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Acquired Disorders of Platelet Function

Epidural Hematomas After Removal of Percutaneous Spinal Cord Stimulator Trial Leads

Contact Info

Product

Resources

About

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam