Article

What have we learnt from Vioxx? BMJ, 334, 120

Department of Medicine, Yale University School of Medicine, 333 Cedar Street, PO Box 208088, New Haven, CT 06520-8088, USA.
BMJ (online) (Impact Factor: 17.45). 02/2007; 334(7585):120-3. DOI: 10.1136/bmj.39024.487720.68
Source: PubMed

ABSTRACT

In October UK patients who had cardiovascular events while taking rofecoxib lost the right to fight Merck in the US for compensation. But researchers and journals can still benefit from this case if they learn from the mistakes, write Harlan Krumholz and colleagues

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Available from: ncbi.nlm.nih.gov
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    • "The intended learning needs are presented in Table 2. The problem triggers that were created15161718to bring out these learning needs are presented in Table 3. Feedback pertaining to various aspects of the problem was collected over a period of 5 years; provided by 57 tutorial groups, each comprising 8–10 students. The pooled results of problem evaluation are presented in Table 4. "
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    ABSTRACT: This paper describes how in a problem-based learning (PBL) medical curriculum, having identified the learning outcomes, problems can be developed from real-life events for teaching-learning clinical pharmacology topics for which PBL cases might be inadequate. Such problems can be very interesting and educational. Using the story of the development and withdrawal of rofecoxib (Vioxx(®)), we developed a problem for undergraduate medical students to address important issues related to clinical pharmacology and therapeutics such as new drug development, preclinical testing, clinical trials, adverse drug reactions, professionalism, and critical appraisal of literature. These topics would otherwise be difficult to address in patient-based problems. The evaluation of the problem based on pooled feedback from 57 tutorial groups, each comprising 8-10 students, collected over 5 years, supported the effectiveness of the problem. A systematic approach described in this paper can be used for the development and validation of educational material for introducing focal topics of pharmacology/clinical pharmacology integrated with other disciplines in innovative medical (and other health profession) curricula.
    Full-text · Article · May 2015 · Indian Journal of Pharmacology
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    • "PGs coordinate secretion of protective mucus, surfactant, and bicarbonate, reduce acid secretion, decrease epithelial permeability, increase mucosal blood flow, and enhance inflammation [9], [10]. Although it was hypothesized that selective inhibition of COX-2 could control pain while preventing adverse effects, COX-2-specific NSAIDs still have GI toxicity [11], [12] and they also increase risk of cardiovascular events [13]–[15]. Studies in COX-1 knockout mice suggest that NSAID-induced damage can be unrelated to COX-1 inhibition and PGE2 levels [16], [17]. "
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    ABSTRACT: Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.
    Preview · Article · Aug 2011 · PLoS ONE
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    • "Like parecoxib, celecoxib and other selective COX-2 inhibitors, it has demonstrated a significant reduction in gastrointestinal toxicity, although its renal adverse effects appear to be similar to those of other NSAIDs. The cardiovascular adverse effects of the selective COX-2 inhibitors like myocardial infarction, hypertension, fluid retention and congestive heart failure, among others, have led to a revoking of Merck’s Vioxx (rofecoxib) and the unavailability of Arcoxia (etoricoxib) in the USA [6, 7]. They are widely prescribed in Europe, South America and Asia for musculoskeletal pain. "
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    ABSTRACT: Drug-induced hyperkalemia is not uncommon and may be life-threatening when presenting acutely in the emergency department. We present a case of severe hyperkalemia precipitated acutely by etoricoxib in a patient who was on telmisartan and a low sodium (potassium chloride-rich) diet. A 75-year-old male with a past medical history of well-controlled diabetes and hypertension was prescribed etoricoxib (90 mg daily) for 3 days for musculoskeletal backache. He had been taking his routine medications including telmisartan and a potassium-rich salt substitute for many years, without any recent change in dosage or quantity. There was evidence of microalbuminurea; however, the renal functions and electrolytes prior to starting etoricoxib were normal. He presented to the emergency department with signs and symptoms of life-threatening hyperkalemia (serum potassium 7.7 mEq/dl), accelerated hypertension, congestive heart failure, pulmonary edema and acute renal failure. Acute medical management and withholding all drugs that could cause hyperkalemia improved his serum potassium levels over 24 h and renal parameters within 5 days. All the other drugs except etoricoxib were restarted under observation over 8 weeks with no recurrence of the acute episode. Non-steroidal analgesics and other COX-2 inhibitors (rofecoxib and celecoxib) have been known to precipitate renal failure and hyperkalemia specially in patients at risk for the same; although not unexpected, this may be the first reported case of life-threatening hyperkalemia precipitated by etoricoxib in a previously stable patient having increased risk of renal failure and hyperkalemia.
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