Vioxx, Rofecoxib, natural pain relief, holistic and arthritis, rheumatoid arthritis natural, natural arthritis treatment, natural remedy for arthritis, natural arthritis cure, natural pain killer, health herb natural medicine pain relief, herb for pain, herb for back pain, drug toxicity, side effects, alternatives

Taking a second look at the so-called "safer" new COX-2 inhibitors: Rofecoxib (Vioxx)

Advertisements on national television and popular magazines seduce people into believing that the new antiinflammatory COX-2 inhibitors will safely reduce pain, and these advertisements encourage patients to make the decision that these drugs are appropriate treatment for their joint pain and inflammation.  Although many people have been mislead to believe that these drugs will alleviate their pain without the risks of side-effects associated with older drugs such as aspirin, the medical research in this area is proving that these newer drugs are associated with severe and sometimes life-threatening toxic side-effects.  

• Increased risk for heart attack and stroke: A recent review published in the Journal of the American Medical Association showed that patients who take Vioxx had their risk of heart attack, stoke, and related events increase by 238%. The authors note that people who take these newer drugs had "significantly higher" rates of heart attack and stroke.
  • "The annualized [heart attack] rates for [the new COX-2 inhibitors] were significantly higher than that in the placebo group..."  JAMA 2001 Aug 22-29; pages 954-9

   

• Increased risk for high blood pressure: Patients taking Vioxx are at increased risk for having their blood pressure get too high. High blood pressure increases the risk for heart attack, stroke, and renal failure.
  • "Systolic blood pressure increased significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated patients..."  Am J Ther 2001 Mar-Apr;8(2):85-95

   

• Increased risk for kidney problems and renal failure: Vioxx can also cause acute kidney failure. Authors in The Lancet describe a patient whose kidneys started to fail after taking Vioxx. The patient's condition improved following discontinuation of the drug, thereby proving that the drug was the cause of the kidney disease.
  • Lancet 2001 Jun 16: pages 1946-7

   

• Lack of effectiveness, despite increased toxicity and increased cost?  These drugs are more toxic, more expensive, and not always more effective than the older drugs, which also have long lists of adverse effects.  A recent article noted that in a comparison study the new drug "was no more effective" than the older, less expensive drugs, and that its pain-relieving effects were "disappointing." 
  • Prescrire Int 2000 Dec;9(50):166-7, 169

 

In contrast to these toxic and ineffective drugs, natural treatments for arthritis and chronic pain actually offer health benefits in addition to their pain-relieving and anti-inflammatory effects.  Many of the natural treatments for pain are also effective for reducing blood pressure, preventing cancer (as proven in animal and human studies), improving memory and preventing dementia and memory loss.

 

Natural treatments for chronic pain are safer, less expensive, and more effective than the "new" pain relievers.

 

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Clin Cornerstone 2001;3(5):50-60

Understanding NSAIDs: from aspirin to COX-2.

Green GA.

Department of Family Practice, UCLA School of Medicine, Los Angeles, California, USA.

Nonsteroidal anti-inflammatory drugs (NSAIDs) annually account for 70 million prescriptions and 30 billion over-the-counter (OTC) medications sold in the United States alone. Despite our familiarity with these drugs, NSAIDs are full of paradoxes that pose significant challenges for the medical community. Although NSAIDs are among the oldest of drugs, new formulations continue to come to market. Some formulas are safe enough to be sold OTC for use in infants with fever, while others are available only as a prescription medication and are a leading cause of iatrogenic reactions, hospitalizations, and death. Physicians face the choice of prescribing lower cost, older NSAIDs versus the more expensive but potentially safer ones. The use of NSAIDs is clearly increasing. Factors contributing to this increase are the availability of OTC preparations and the aging of the population with a concomitant increase in osteoarthritis. One indication of the popularity of NSAIDs is that following the introduction of 2 new cyclooxygenase-2 (COX-2) selective inhibitors in 1999, these drugs immediately became the most frequently prescribed new drugs in the United States. This article will familiarize the practitioner with the various types of NSAIDs, including the newer COX-2 formulations, their mechanism of action, and potential adverse reactions and efficacy. Although most practitioners are aware of the indications for NSAIDs, research is continuing to explore nontraditional applications. A new framework is being created that will allow new additions to the NSAID class of medications.

Lancet 1998 Feb 28;351(9103):643-4

Increase in US medication-error deaths between 1983 and 1993.

Phillips DP, Christenfeld N, Glynn LM.

 

"In 1983, 2876 people died from medication errors. By 1993, this number had risen to 7,391 - a 2.57-fold increase."  

Stat Bull Metrop Insur Co 1992 Jul-Sep;73(3):25-34

Anti-arthritic medication usage: United States, 1991.

In 1991, about 70.3 million prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs) were filled across the United States to treat arthritis and related musculoskeletal problems. The retail costs exceeded $2.2 billion in 1991 and were 6 percent higher than the costs in 1990 despite a 2.2 percent decrease in volume of prescriptions written. Per capita consumption averaged 278.6 prescriptions per 1,000 population with substantial variation by state. Kentucky led with 380.9 per 1,000 population and the District of Columbia had the lowest rate, 177.0. Ibuprofens were the most frequently prescribed class of NSAIDs, with Motrin capturing 20 percent of this generic class. Naproxen (Naprosyn) was the second most frequently prescribed class accounting for 19 percent of the NSAIDs.

Ann Pharmacother 2003 Jan;37(1):80-2

 
Pseudodementia associated with use of ibuprofen.

Bernstein AL, Werlin A.
Memory Disorder Program, Department of Neurology, Kaiser Permanente Medical Center, Santa Rosa, CA 95403-2192, USA.

OBJECTIVE: To report a case of dementing syndrome resulting from ibuprofen use. CASE SUMMARY: A 76-year-old white man with normal mental status became confused, was lost in familiar places, and showed short-term memory loss after beginning a therapeutic regimen of ibuprofen 600 mg 3 times daily for osteoarthritis in anticipation of embarking on a foreign trip. Symptoms of dementia began within 1 week after taking ibuprofen and resolved completely within 1 week after the ibuprofen regimen was stopped. This pattern was repeated 6 months later, when the patient again traveled abroad. Consistently before, during, and after these events, the patient took atenolol, clonidine, lisinopril, aspirin, vitamin C, lecithin, vitamin E, and multivitamins. DISCUSSION: Using the Naranjo probability scale, we reasoned that the patient's dementia-like syndrome could be attributed to the use of ibuprofen because pseudodementia appeared after the suspected drug was administered, improved when the drug was discontinued, reappeared when the drug was readministered, had no apparent alternative cause, manifested similarly after each exposure to ibuprofen, and was confirmed by the family's observation after both episodes. Objective causality assessment revealed that the adverse drug reaction was probable. CONCLUSIONS: Use of ibuprofen must be considered during clinical evaluation of any patient with new onset of dementing illness. The Naranjo probability scale may be clinically useful for evaluating other pharmaceutical agents that may be contributing to development of dementia-like conditions.

 

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Clin Exp Rheumatol 1998 Jan-Feb;16(1):69-71

Sucrose permeability as a marker for NSAID-induced gastroduodenal injury.

Erlacher L, Wyatt J, Pflugbeil S, Koller M, Ullrich R, Vogelsang H, Smolen JS, Graninger W.

Department of Internal Medicine III, University of Vienna, Austria.

OBJECTIVE: To evaluate sucrose permeability as a non-invasive test for the monitoring of upper gastrointestinal mucosal damage (uGMD) in patients treated with NSAIDs. METHODS: 40 patients with non-inflammatory joint pain were enrolled in a prospective study. Before and after 14 days of ibuprofen treatment (3 x 400 mg/day), the rates of urinary sucrose excretion after an oral sucrose load were assessed. Individuals with increased sucrose permeability underwent endoscopy. RESULTS: 8 patients (20%) showed abnormal sucrose permeability before taking any NSAID. In 5/20 patients (25%) who completed 2 weeks of ibuprofen medication, sucrose excretion increased above the normal level. Endoscopic examination and biopsy revealed mild uGMD, but no ulceration in 8/11 (72%) patients with increased permeability to this marker. CONCLUSION: Sucrose permeability testing is a sensitive procedure for research protocols on NSAID-induced gastropathy. Since this test also seems to detect slight and clinically insignificant mucosal damage, however, its use in clinical decision-making regarding gastroprotective medication is limited.

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Aliment Pharmacol Ther 2000 May;14(5):543-9

 
Dose-dependent effects of ketoprofen on the human gastric mucosa in comparison with ibuprofen.

Donnelly MT, Richardson P, Hawkey CJ, Courtauld E, Stack WA.

Division of Gastroenterology, University Hospital Nottingham, Queen's Medical Centre, Nottingham, UK.

BACKGROUND: As non-steroidal anti-inflammatory drugs (NSAIDs) become available for over-the-counter use, it is important to define doses that would not cause undue gastroduodenal damage during the short periods for which self-medication with NSAIDs is licensed. AIM: To establish what dose of ketoprofen most closely resembles the maximum dose of ibuprofen (400 mg t.d.s.) licensed for self-medication. METHODS: We studied healthy volunteers in a double-blind double-dummy randomized crossover study. Each subject took, over four separate 10-day dosing periods, ibuprofen 400 mg t.d.s., ketoprofen 12.5 mg t.d.s., ketoprofen 25 mg t.d.s. or ketoprofen 50 mg t.d.s. Mucosal injury was assessed by endoscopy at baseline and on the 3rd and 10th day of each dosing period. Ex vivo gastric mucosal prostaglandin (PG) E2 evoked by vortex mixing was measured by radioimmunoassay. Serum thromboxane was also measured by radioimmunoassay. RESULTS: Ketoprofen 50 mg t.d.s. suppressed prostaglandin synthesis to a significantly greater extent than ibuprofen and caused significantly more gastroduodenal injury. The profile of prostaglandin synthesis and injury on ketoprofen 12.5 mg t.d.s. most closely resembled that of ibuprofen 400 mg t.d.s. CONCLUSIONS: Ketoprofen 12.5 mg t.d.s. is an appropriate dose for self-medication, which is likely to be similar to ibuprofen 400 mg t. d.s. in its effects on the stomach and duodenum.

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JAMA 2001 Aug 22-29;286(8):954-9

 
Risk of cardiovascular events associated with selective COX-2 inhibitors.

Mukherjee D, Nissen SE, Topol EJ.
Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, F 25, 9500 Euclid Ave, Cleveland, OH 44195, USA.

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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Am J Ther 2001 Mar-Apr;8(2):85-95

Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients.

Whelton A, Fort JG, Puma JA, Normandin D, Bello AE, Verburg KM; SUCCESS VI Study Group.
Universal Clinical Research Center, Inc., Baltimore, MD, USA.

BACKGROUND: Arthritis and hypertension are common comorbid conditions affecting elderly adults. Use of nonsteroidal anti-inflammatory drugs in patients treated with antihypertensive medication can lead to destabilization of blood pressure control and other cardiorenal events. The potential for similar interactions with cyclooxygenase-2-specific inhibitors has not been fully explored. The authors evaluated the cardiorenal safety of two new cyclooxygenase-2-specific inhibitors, celecoxib and rofecoxib.METHODS: This study was a 6-week, randomized, parallel-group, double-blind trial in patients with osteoarthritis who were > or =65 years of age and were taking antihypertensive agents. Patients received once-daily celecoxib 200 mg or rofecoxib 25 mg. The primary endpoints were the development of edema, changes in systolic blood pressure, and changes in diastolic blood pressure as measured at any time point in the study. Measurements occurred at baseline and after 1, 2, and 6 weeks of treatment. FINDINGS: Eight hundred ten patients received study medication (celecoxib, n = 411; rofecoxib, n = 399). Nearly twice as many rofecoxib- compared with celecoxib-treated patients experienced edema (9.5% vs. 4.9%, P = 0.014). Systolic blood pressure increased significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated patients (P = 0.032) at any study time point. Diastolic blood pressure increased in 2.3% of rofecoxib- compared with 1.5% of celecoxib-treated patients (P = 0.44). At week 6, the change from baseline in mean systolic blood pressure was +2.6 mmHg for rofecoxib compared with -0.5 mmHg for celecoxib (P = 0.007). CONCLUSIONS: Patients taking antihypertensive therapy and receiving cyclooxygenase-2-specific inhibitors should be monitored for the development of cardiorenal events. Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib.

 

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Lancet 2001 Jun 16;357(9272):1946-7

Acute tubulointerstitial nephritis associated with the selective COX-2 enzyme inhibitor, rofecoxib.

Rocha JL, Fernandez-Alonso J.

The nephrotoxic effect of COX-2 selective inhibitors has not yet been established. We report a case of reversible acute renal failure due to acute tubulointerstitial nephritis, confirmed by histology of a renal biopsy sample, associated with taking rofecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor.

 

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Int Urol Nephrol 2001;33(4):609-11

Acute renal dysfunction associated with selective COX-2 inhibitor therapy.

Papaioannides D, Bouropoulos C, Sinapides D, Korantzopoulos P, Akritidis N.
Department of Medicine and Urology, Arta General Hospital, Greece.

The recent release of the selective cyclooxygenase-2 (COX-2) enzyme inhibitors for the treatment of various inflammatory disorders and pain syndromes has been associated with a clear-cut decrease in adverse gastrointestinal effects. The nephrotoxic effect of selective COX-2 inhibitors has not yet been firmly established. We report a case of reversible acute renal failure due to rofecoxib treatment in an elderly patient with several risk factors associated with traditional nonselective nonsteroidal anti-inflammatory drug (NSAID)-related nephrotoxicity. It is prudent to approach therapy with selective COX-2 inhibitors cautiously and in a fashion similar to traditional NSAID therapy for patients with risk factors that induce prostaglandin-dependent renal function.

 

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J Rheumatol 2001 Sep;28(9):2133-5

Nephrotoxicity of selective COX-2 inhibitors.

Woywodt A, Schwarz A, Mengel M, Haller H, Zeidler H, Kohler L.
Department of Medicine, University of Hannover School of Medicine, Germany. Woywodt.Alexander@MH-Hannover.de

We describe 2 male patients, a 49-year-old with psoriatic arthritis and impaired renal function and a 43-year-old renal transplant recipient, who both sustained a marked decline in glomerular filtration rate in conjunction with a selective inhibitor of cyclooxygenase-2 (COX-2), rofecoxib. In the second patient, acute renal failure necessitated hemodialysis. Both patients made an uneventful recovery. Our report lends further support to the assumption that COX-2 inhibitors, as a class, can be as nephrotoxic as their nonselective predecessors. Therefore, COX-2 inhibitors should be used with caution in renal transplant recipients and in patients with salt depletion and renal insufficiency.

 

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Pharmacotherapy 2002 Oct;22(10):1317-21

Cyclooxygenase-2 inhibitor-associated acute renal failure: case report with rofecoxib and review of the literature.

Morales E, Mucksavage JJ.
Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway 08854-8020, USA.

Cyclooxygenase (COX)-2 inhibitors are widely prescribed for their antiinflammatory and analgesic effects. The potential for COX-2 inhibitors to exert deleterious effects on renal function similar to those of traditional nonsteroidal antiinflammatory drugs is not well defined. Until recently, COX-1 was considered responsible for the synthesis of renal prostaglandins. However, COX-2 is also constitutively expressed in the human kidney. Clinical studies have reported a significant decrease in glomerular filtration rate in young and elderly sodium-depleted volunteers given COX-2 inhibitors. We describe the case of a 71-year-old woman who developed acute renal failure after receiving a 50-mg dose of the selective COX-2 inhibitor rofecoxib.

 

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Prescrire Int 2000 Dec;9(50):166-7, 169

Rofecoxib: new preparation. A disappointing NSAID analgesic.

(1) Rofecoxib, a nonsteroidal antiinflammatory drug, is licensed in France for symptom relief in osteoarthritis. It is promoted by MSD-Chibret as a "specific inhibitor of type 2 cyclooxygenases (COX-2)". (2) The clinical dossier includes trials versus other antiinflammatory drugs, but the reports available are generally vague. Rofecoxib has not been compared with paracetamol. (3) In these trials rofecoxib 12.5-25 mg/day was no more effective than the comparators (ibuprofen or diclofenac) used at maximal recommended doses. (4) Relative to other nonsteroidal antiinflammatory drugs prescribed at high doses to selected patients in the controlled conditions of clinical trials, rofecoxib only moderately reduces the risk of severe gastrointestinal reactions (1.3% versus 1.8% after a year of treatment) and dyspeptic disorders (23.5% versus 25.5%). (5) Questions persist on other adverse effects, especially those potentially affecting the kidneys and heart. (6) Rofecoxib is subject to the same precautions (pregnancy, interactions, etc.) as other nonsteroidal antiinflammatory drugs.

 

 
The effects of NSAID on the matrix of human articular cartilages.  

Dingle JT.
Addenbrooke's Hospital, UK-Cambridge.

The present paper presents data obtained over a 12 year period, on the matrix synthesis and turnover in some 650 arthritic and 180 non-arthritic (N) human cartilages using a standardised in vitro method. When the relative metabolic (synthetic/repair activity) of these human cartilages was compared, it was demonstrated that in osteoarthritis (OA) and rheumatoid arthritis (RA) cartilages synthetic activity was diminished by approximately 50% as compared with N cartilages. However, the turnover rate of matrix was not significantly different between Non-arthritic and OA, but was very substantially increased in RA cartilages compatible with the activity of inflammatory cells and proteolytic enzymes released from pannus. The action of 13 NSAIDs was compared in terms of their effect on cartilage GAG synthesis. 3 of these NSAIDs were also studied in terms of their effect on cartilage collagen synthesis. Consideration of the results in this study and from published material, led to the suggestion that NSAIDs may be divided into 3 categories in respect of their in vitro action on the extracellular matrix of human arthritic cartilages: 1. Those such as Aceclofenac, Tenidap and Tolmetin which can stimulate matrix synthesis 2. Those such as Piroxicam, Tiaprofenic Acid and Aspirin which appear to be without significant effect on matrix synthesis and, 3. Those like Naproxen, Ibuprofen, Indomethacin, Nimezulide which significantly inhibit matrix synthesis. It is suggested that the stimulatory action of group 1 NSAID is due to inhibition of locally produced IL1 and consequent expression of growth factor activity. Other NSAIDs may also inhibit IL1 synthesis or release, but probably do not have a beneficial effect on chondrocyte synthetic activity as they have toxic effects on cartilage metabolism. These experiments led to the suggestion that NSAIDs such as Aceclofenac would be appropriate for long-term treatment of arthritic conditions provided that one is prepared to extrapolate between in vitro experiments on human cartilage and what may be happening in vivo.

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J Rheumatol 1993 Dec;20(12):2128-33

Effect of sodium salicylate, aspirin, and ibuprofen on enzymes required by the chondrocyte for synthesis of chondroitin sulfate.

Hugenberg ST, Brandt KD, Cole CA.
Department of Medicine, Indiana University School of Medicine, Indianapolis.

OBJECTIVE. To examine the effects of sodium salicylate (Sal), aspirin [acetylsalicylic acid (ASA)] and ibuprofen (Ibu) (as the racemic mixture and the R- and S-enantiomers) on the activities of 2 enzymes involved in the biosynthesis of the hexose components of chondroitin sulfate (CS), i.e., UDP-glucose dehydrogenase (UDP-GD) and glutamine-fructose-6-phosphate-aminotransferase (GFAT), and of glucuronosyltransferase (GT), an enzyme involved in elongation of the nascent CS chain. METHODS. UDP-GD and GT were obtained commercially. A homogenate of bovine articular cartilage chondrocytes was employed as a source of GFAT. In each case, enzymatic activity was measured spectrophotometrically. RESULTS. Neither UDP-GD nor GFAT was inhibited by concentrations of Sal, ASA or Ibu that were achieved clinically in joint tissues (e.g., 1.0 mM Sal and ASA, 170 microM Ibu). In contrast, GT activity was inhibited by Sal and ASA in a concentration dependent fashion; at 1.0 mM, a concentration commonly reached in synovial fluid of patients treated with an antiinflammatory dose of the drug, GT activity in the presence of Sal and ASA was 54% (p = 0.001) and 75% (p = 0.05), respectively, of the control value. In contrast, a clinically relevant concentration of Ibu had no effect on GT activity. CONCLUSION. Salicylates may suppress cartilage proteoglycan synthesis by inhibiting GT.

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Semin Arthritis Rheum 1989 Feb;18(3 Suppl 1):16-8

Effects of nonsteroidal antiinflammatory drugs on collagen biosynthesis of cultured chondrocytes.

Fujii K, Tajiri K, Sai S, Tanaka T, Murota K.
Department of Orthopedic Surgery, Jikei University School of Medicine, Tokyo, Japan.

In conclusion, the data obtained from the present study show that TA has less effect than indomethacin or ASA on cultured chondrocytes in gene expression and synthesis of collagen. These findings cannot be directly interpolated to clinical application, but attention to pharmacologic activities of NSAIDs on chondrocytes may have future applications. Two major NSAIDs, TA, indomethacin, and ASA, were examined for their effects on the biosynthesis and gene expression of articular cartilage collagen. The biosynthesis of type II collagen was suppressed to 70% to 80% of the control by indomethacin and ASA. TA did not suppress collagen synthesis. To know the gene expression of type II collagen, dot blot hybridization was performed using type II collagen cDNA. The effects of NSAIDs on the amount of type II collagen mRNA were consistent with those on collagen biosynthesis. Thus, TA had the least effect on cultured chondrocytes.

 

Acetaminophen, aspirin, and chronic renal failure.

Fored CM, Ejerblad E, Lindblad P, Fryzek JP, Dickman PW, Signorello LB, Lipworth L, Elinder CG, Blot WJ, McLaughlin JK, Zack MM, Nyren O.
Department of Medical Epidemiology, Karolinska Institute, Stockholm , Sweden . 

BACKGROUND: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect METHODS: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics RESULTS: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated CONCLUSIONS: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

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Can J Gastroenterol 1999 Jan-Feb;13(1):31-6

Intestinal permeability before and after ibuprofen in families of children with Crohn's disease.

Zamora SA, Hilsden RJ, Meddings JB, Butzner JD, Scott RB, Sutherland LR.
Department of Pediatrics, Health Science Centre, Calgary, Alberta.

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn's disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid. PURPOSE: To determine intestinal permeability in unaffected first-degree relatives of children with Crohn's disease before and after the administration of an ibuprofen challenge. METHODS: Lactulose-mannitol ratios, a measure of intestinal permeability, were determined in 14 healthy control families (41 subjects) and 14 families with a child with Crohn's disease (36 relatives, 14 probands) before and after ingestion of ibuprofen. An upper reference limit was defined using the control group as mean +/- 2 SD. RESULTS: The proportion of healthy, first-degree relatives with an exaggerated response to ibuprofen (20%, 95% CI 7% to 33%) was significantly higher than controls (P = 0.003). The exaggerated response was more common among siblings than among parents of pediatric probands. CONCLUSIONS: Members of a subset of first-degree relatives of children with Crohn's disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn's disease.

 

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Med Sci Sports Exerc 1996 Jun;28(6):698-705

Gastrointestinal permeability following aspirin intake and prolonged running.

Ryan AJ, Chang RT, Gisolfi CV.
Department of Exercise Science, University of Iowa, Iowa City 52242-1111, USA.

We sought to evaluate the effects of exercise and aspirin on gastroduodenal and intestinal permeability. Seven volunteers (age = 29 +/- 3 yr, VO2max = 56.8 +/- 4.1 ml.kg-1.min-1) rested or performed treadmill exercise (60 min at approximately 68% VO2max), with or without aspirin ingestion. Placebo (glucose) or aspirin (1.3 g) was taken the night before and prior to rest or exercise (total 2.6 g). A permeability test solution (approximately 1300 mOsm.kg-1), containing 10 g lactulose (L), 5 g mannitol (M), and 10 g sucrose (S), was ingested prior to rest or exercise. Urinary excretion rates (6.h-1), expressed as a percentage of ingested dose, were used to quantify intestinal (L/M ratio) or gastroduodenal (S) permeability. Ingestion of aspirin before running increased (P < 0.05) intestinal permeability compared to placebo+running and placebo+rest, but not compared to aspirin+rest; mean (+/-SE) values for the L/M ratio were 0.248 +/- 0.046, 0.029 +/- 0.012, 0.012 +/- 0.004, and 0.104 +/- 0.057, respectively. Gastroduodenal permeability following aspirin+running (3.25 +/- 1.21%) was also elevated (P < 0.05) compared to placebo+running (0.43 +/- 0.15%) and placebo+rest (0.24 +/- 0.11%), but not compared to aspirin+rest (0.66 +/- 0.27%). Neither running nor aspirin ingestion was associated with gastrointestinal (GI) complaints. Thus, GI permeability while running can be markedly elevated by aspirin ingestion.

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J Int Med Res 1977;5(3):155-60

Gastro-intestinal blood loss during administration of indoprofen, aspirin and ibuprofen.

Porro GB, Corvi G, Fuccella LM, Goldaniga GC, Valzelli G.

The acute effect of three non-steroidal anti-inflammatory drugs, ibuprofen, acetylsalicylic acid (ASA) and indoprofen, on faecal blood loss was investigated in 15 subjects by means of 51Cr-labelled erythrocytes. Ibuprofen (900 mg/day for 5 days) and indoprofen capsules and tablets (300 mg and 600 mg/day for 5 days, respectively) slightly increased the amount of blood eliminated in faeces. The increase was of the same order of magnitude for both doses of indoprofen. ASA (1,500 mg/day for 5 days) caused about a 6-fold increase in blood loss. Four days after withdrawal of ASA, faecal blood was still about twice as high as in faeces of subjects given ibuprofen and indoprofen. The method appears sensitive and reliable for comparison of the immediate effect of anti-inflammatory drugs on gastro-intestinal mucosa.

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