Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a process with inflammatory features and selective cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects by virtue of inhibiting inflammation. However, by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients without coronary artery disease, we performed a MEDLINE search to identify all English-language articles on use of COX-2 inhibitors published between 1998 and February 2001. We also reviewed relevant submissions to the US Food and Drug Administration by pharmaceutical companies. Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials with approximately 1000 patients each. The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95% confidence interval, 1.39-4.00; P =.002). There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were significantly higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials (0.52%): 0.74% with rofecoxib (P =.04 compared with the placebo group of the meta-analysis) and 0.80% with celecoxib (P =.02 compared with the placebo group of the meta-analysis). The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors. Further prospective trial evaluation may characterize and determine the magnitude of the risk.
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PMID:Risk of cardiovascular events associated with selective COX-2 inhibitors. 1244 Oct 30

The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation.
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PMID:COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. 1612 36

Since the discovery of COX-2, a second subtype of cyclooxygenase, selective inhibitors or "coxibs" were developed with the idea that this isoform was inducible at the site of inflammation whereas COX-1 was expressed constitutively in several tissues including gastric epithelium. This new class of non steroidal anti-inflammatory agents was though to be safer for ulcerations of the gastroinstestinal mucosa observed with non selective COX-2 inhibitors. Nevertheless, at the end of September 2004, Merck & Co announced the voluntary withdrawal of rofecoxib (Vioxx) worldwide because of an increased risk of cardiovascular events. This decision raised serious concerns about safety of selective COX-2 inhibitors which are actively marketed today, and the ones currently under development. The mechanism of this cardiovascular toxicity could lie in the inhibition of COX-2 itself, and thus be a class effect. On the other hand, these cardiovascular side effects could be limited on rofecoxib and be dependent on its chemical and/or pharmacological own properties. This hypothesis is undermined by the unexpected findings of one colon cancer study which has shown that celecoxib might also increase the chance of heart attack and stroke in some patients. In this review, we compared the different coxibs marketed to date on the basis of their clinical, pharmacological and chemical properties with the aim of providing some clues in the understanding of their potential or revealed "cardiovascular effects".
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PMID:Coxibs and cardiovascular side-effects: from light to shadow. 1653 64

In order to provide better care to patients, doctors of chiropractic should be informed about adverse affects of certain drugs. Presently, questions are being raised about cardiovascular risks, such as increased deaths due to stroke or myocardial infarction, which may be caused from drugs in the same class as Vioxx(R).(1) Therefore, it is important for doctors of chiropractic to stay apprised of information that may affect the health of their patients, such as COX-2 inhibitor usage.
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PMID:Vioxx(R): What should we tell our patients? 1967 39

Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases owing to the finding that highly specific COX-2 inhibitors (i.e., Vioxx) increased the risk of myocardial infarction and stroke in chronic users. However, the specific impact of COX-2 expression in the intact heart remains to be determined. We report here the development of a transgenic mouse model, using a loxP-Cre approach, which displays robust COX-2 overexpression and subsequent prostaglandin synthesis specifically in ventricular myocytes. Histological, functional, and molecular analyses showed that ventricular myocyte specific COX-2 overexpression led to cardiac hypertrophy and fetal gene marker activation, but with preserved cardiac function. Therefore, specific induction of COX-2 and prostaglandin in vivo is sufficient to induce compensated hypertrophy and molecular remodeling.
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PMID:Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice. 2017 Jun 63

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used agents in clinical practice. They are employed as anti-inflammatory, analgesic, and antipyretic agents for a wide spectrum of clinical conditions. Their anti-inflammatory properties are primarily due to inhibition of prostaglandin synthesis. In this paper we review the neurological effects associated with the use of NSAIDs. Acute CNS toxicity related to NSAID use is pervasive and varied. A prospective study looking at ibuprofen overdose noted that 30% of patients experience CNS effects ranging from drowsiness to coma. Case reports have identified numerous neurologic sequelae including ataxia, vertigo, dizziness, recurrent falls, nystagmus, headache, encephalopathy, and disorientation. Seizures have also been reported, mostly after overdose ingestions, but even therapeutic doses have occasionally been associated with seizures. One of the important neurologic side-effects attributed to the use of NSAIDs is aseptic meningitis. The clinical signs of drug-induced meningitis are similar to those of infectious meningitis and include fever, headache, photophobia, and stiff neck. The laboratory findings are also similar, including cerebrospinal fluid (CSF) pleocytosis of several hundred or thousand cells, mainly neutrophils, elevated levels of protein, normal or low glucose levels and negative cultures. Drug-induced meningitis is a transient disorder with an excellent prognosis. Most or all drugs used for the treatment of headache, including NSAIDs, may cause a condition known as medication overuse headache - a refractory chronic daily headache that tends to resolve following discontinuation of the analgesics. Reye's syndrome is a rare severe illness occurring mainly in children and adolescents and characterized by abnormal liver function, vomiting, and encephalopathy, with a mortality rate approaching 40%. The pathogenesis is currently unknown, but commonly the syndrome is preceded by a viral episode, with an intermediate latent period of 3-5 days. An association with aspirin use is strongly suggested. Aspirin, the classic and most commonly used NSAID, has a well-documented effect in inhibiting intravascular clotting, thus reducing the occurrence of ischemic strokes and other vascular events. NSAIDs, however, have a double impact on coagulation. On the one hand, most agents inhibit the synthesis of thromboxane in the platelets, thereby inhibiting coagulation. On the other hand, they also inhibit the production of prostacyclin by endothelial cells, resulting in a prothrombotic state. Selective inhibition of COX-2 by drugs such as rofecoxib (Vioxx) and valdecoxib (Bextra) results in specific inhibition of synthesis of prostaglandins participating in inflammation and was found to lead to vascular complications including an increased risk for stroke. The connection between inflammation and neuronal degeneration is well established. Most studies, including the prospective Rotterdam study, have found an inverse correlation between the use of NSAIDs and the risk for dementia. Two meta-analyses have found 40% and 25% reduction, respectively, in the risk of Alzheimer's disease among NSAID users. However, some large, well designed studies failed to confirm these results, and some even found that NSAID use is associated with cognitive decline. The clinical impact of NSAIDs on Parkinson's disease (PD) remains unclear. While some studies showed that chronic NSAID use is protective against PD, other studies could not confirm the existence of a significant relationship. A recent meta-analysis indicated that the use of non-aspirin NSAID, particularly ibuprofen, reduces the risk of PD by 15% while the use of aspirin did not show any effect.
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PMID:Nonsteroidal anti-inflammatory drugs exposure and the central nervous system. 2436 21