Abstract
OBJECTIVE. To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS. The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES. Reduction of complications associated with long-term use of NSAIDs. EVIDENCE. Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES. Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS. Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS. Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION. These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Agmon Y., Brezis M. Effects of nonsteroidal anti-inflammatory drugs upon intrarenal blood flow: selective medullary hypoperfusion. Exp Nephrol. 1993 Nov-Dec;1(6):357–363. [PubMed] [Google Scholar]
- Altman R. D., Perez G. O., Sfakianakis G. N. Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis. Am J Med. 1992 Oct;93(4):396–402. doi: 10.1016/0002-9343(92)90169-c. [DOI] [PubMed] [Google Scholar]
- Armstrong C. P., Blower A. L. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut. 1987 May;28(5):527–532. doi: 10.1136/gut.28.5.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Avorn J. Reporting drug side effects: signals and noise. JAMA. 1990 Apr 4;263(13):1823–1823. [PubMed] [Google Scholar]
- Bakris G. L., Starke U., Heifets M., Polack D., Smith M., Leurgans S. Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects: a double-blind, placebo-controlled, multicenter trial. J Am Soc Nephrol. 1995 Mar;5(9):1684–1688. doi: 10.1681/ASN.V591684. [DOI] [PubMed] [Google Scholar]
- Bianchi Porro G., Caruso I., Petrillo M., Montrone F., Ardizzone S. A double-blind gastroscopic evaluation of the effects of etodolac and naproxen on the gastrointestinal mucosa of rheumatic patients. J Intern Med. 1991 Jan;229(1):5–8. doi: 10.1111/j.1365-2796.1991.tb00298.x. [DOI] [PubMed] [Google Scholar]
- Bjarnason I., Hayllar J., MacPherson A. J., Russell A. S. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology. 1993 Jun;104(6):1832–1847. doi: 10.1016/0016-5085(93)90667-2. [DOI] [PubMed] [Google Scholar]
- Bjarnason I., Hayllar J., Smethurst P., Price A., Gumpel M. J. Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy. Gut. 1992 Sep;33(9):1204–1208. doi: 10.1136/gut.33.9.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjarnason I., Hopkinson N., Zanelli G., Prouse P., Smethurst P., Gumpel J. M., Levi A. J. Treatment of non-steroidal anti-inflammatory drug induced enteropathy. Gut. 1990 Jul;31(7):777–780. doi: 10.1136/gut.31.7.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradley J. D., Brandt K. D., Katz B. P., Kalasinski L. A., Ryan S. I. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med. 1991 Jul 11;325(2):87–91. doi: 10.1056/NEJM199107113250203. [DOI] [PubMed] [Google Scholar]
- Brater D. C. Clinical aspects of renal prostaglandins and NSAID therapy. Semin Arthritis Rheum. 1988 Feb;17(3 Suppl 2):17–22. doi: 10.1016/0049-0172(88)90040-6. [DOI] [PubMed] [Google Scholar]
- Carson J. L., Willett L. R. Toxicity of nonsteroidal anti-inflammatory drugs. An overview of the epidemiological evidence. Drugs. 1993;46 (Suppl 1):243–248. doi: 10.2165/00003495-199300461-00063. [DOI] [PubMed] [Google Scholar]
- Caruso I., Bianchi Porro G. Gastroscopic evaluation of anti-inflammatory agents. Br Med J. 1980 Jan 12;280(6207):75–78. doi: 10.1136/bmj.280.6207.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chien C. P., Townsend E. J., Ross-Townsend A. Substance use and abuse among the community elderly: the medical aspect. Addict Dis. 1978;3(3):357–372. [PubMed] [Google Scholar]
- Ciabattoni G., Cinotti G. A., Pierucci A., Simonetti B. M., Manzi M., Pugliese F., Barsotti P., Pecci G., Taggi F., Patrono C. Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. N Engl J Med. 1984 Feb 2;310(5):279–283. doi: 10.1056/NEJM198402023100502. [DOI] [PubMed] [Google Scholar]
- Clive D. M., Stoff J. S. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1984 Mar 1;310(9):563–572. doi: 10.1056/NEJM198403013100905. [DOI] [PubMed] [Google Scholar]
- Delmas P. D. Non-steroidal anti-inflammatory drugs and renal function. Br J Rheumatol. 1995 Apr;34 (Suppl 1):25–28. doi: 10.1093/rheumatology/xxxiv.suppl_1.25. [DOI] [PubMed] [Google Scholar]
- Dieppe P. A., Frankel S. J., Toth B. Is research into the treatment of osteoarthritis with non-steroidal anti-inflammatory drugs misdirected? Lancet. 1993 Feb 6;341(8841):353–354. doi: 10.1016/0140-6736(93)90147-9. [DOI] [PubMed] [Google Scholar]
- Dunn M. The role of arachidonic acid metabolites in renal homeostasis. Non-steroidal anti-inflammatory drugs renal function and biochemical, histological and clinical effects and drug interactions. Drugs. 1987;33 (Suppl 1):56–66. doi: 10.2165/00003495-198700331-00009. [DOI] [PubMed] [Google Scholar]
- Eberhart C. E., Dubois R. N. Eicosanoids and the gastrointestinal tract. Gastroenterology. 1995 Jul;109(1):285–301. doi: 10.1016/0016-5085(95)90296-1. [DOI] [PubMed] [Google Scholar]
- Elashoff J. D., Grossman M. I. Trends in hospital admissions and death rates for peptic ulcer in the United States from 1970 to 1978. Gastroenterology. 1980 Feb;78(2):280–285. [PubMed] [Google Scholar]
- Elliott S. N., McKnight W., Cirino G., Wallace J. L. A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology. 1995 Aug;109(2):524–530. doi: 10.1016/0016-5085(95)90341-0. [DOI] [PubMed] [Google Scholar]
- Fries J. F., Williams C. A., Bloch D. A. The relative toxicity of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1991 Nov;34(11):1353–1360. doi: 10.1002/art.1780341103. [DOI] [PubMed] [Google Scholar]
- Gabriel S. E., Jaakkimainen L., Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Ann Intern Med. 1991 Nov 15;115(10):787–796. doi: 10.7326/0003-4819-115-10-787. [DOI] [PubMed] [Google Scholar]
- García Rodríguez L. A., Walker A. M., Pérez Gutthann S. Nonsteroidal antiinflammatory drugs and gastrointestinal hospitalizations in Saskatchewan: a cohort study. Epidemiology. 1992 Jul;3(4):337–342. doi: 10.1097/00001648-199207000-00008. [DOI] [PubMed] [Google Scholar]
- Gertner E., Marshall P. S., Filandrinos D., Potek A. S., Smith T. M. Complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs. Arthritis Rheum. 1995 May;38(5):614–617. doi: 10.1002/art.1780380506. [DOI] [PubMed] [Google Scholar]
- Glaser K., Sung M. L., O'Neill K., Belfast M., Hartman D., Carlson R., Kreft A., Kubrak D., Hsiao C. L., Weichman B. Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol. 1995 Jul 25;281(1):107–111. doi: 10.1016/0014-2999(95)00302-2. [DOI] [PubMed] [Google Scholar]
- Goldbloom R., Battista R. N. The periodic health examination: 1. Introduction. CMAJ. 1986 Apr 1;134(7):721–723. [PMC free article] [PubMed] [Google Scholar]
- Graham D. Y., Agrawal N. M., Roth S. H. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet. 1988 Dec 3;2(8623):1277–1280. doi: 10.1016/s0140-6736(88)92892-9. [DOI] [PubMed] [Google Scholar]
- Griffin M. R., Piper J. M., Daugherty J. R., Snowden M., Ray W. A. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med. 1991 Feb 15;114(4):257–263. doi: 10.7326/0003-4819-114-4-257. [DOI] [PubMed] [Google Scholar]
- Grymonpre R. E., Mitenko P. A., Sitar D. S., Aoki F. Y., Montgomery P. R. Drug-associated hospital admissions in older medical patients. J Am Geriatr Soc. 1988 Dec;36(12):1092–1098. doi: 10.1111/j.1532-5415.1988.tb04395.x. [DOI] [PubMed] [Google Scholar]
- Guess H. A., West R., Strand L. M., Helston D., Lydick E. G., Bergman U., Wolski K. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983. J Clin Epidemiol. 1988;41(1):35–45. doi: 10.1016/0895-4356(88)90007-8. [DOI] [PubMed] [Google Scholar]
- Hogan D. B., Campbell N. R., Crutcher R., Jennett P., MacLeod N. Prescription of nonsteroidal anti-inflammatory drugs for elderly people in Alberta. CMAJ. 1994 Aug 1;151(3):315–322. [PMC free article] [PubMed] [Google Scholar]
- Houston M. C. Nonsteroidal anti-inflammatory drugs and antihypertensives. Am J Med. 1991 May 17;90(5A):42S–47S. doi: 10.1016/0002-9343(91)90485-g. [DOI] [PubMed] [Google Scholar]
- Jeremy J. Y., Mikhailidis D. P., Barradas M. A., Kirk R. M., Dandona P. The effect of nabumetone and its principal active metabolite on in vitro human gastric mucosal prostanoid synthesis and platelet function. Br J Rheumatol. 1990 Apr;29(2):116–119. doi: 10.1093/rheumatology/29.2.116. [DOI] [PubMed] [Google Scholar]
- Johnson A. G., Seidemann P., Day R. O. NSAID-related adverse drug interactions with clinical relevance. An update. Int J Clin Pharmacol Ther. 1994 Oct;32(10):509–532. [PubMed] [Google Scholar]
- Kaplan B., Swain R. A. NSAIDs. Are there any differences? Arch Fam Med. 1993 Nov;2(11):1167–1174. doi: 10.1001/archfami.2.11.1167. [DOI] [PubMed] [Google Scholar]
- Kaufmann H. J., Taubin H. L. Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease. Ann Intern Med. 1987 Oct;107(4):513–516. doi: 10.7326/0003-4819-107-4-513. [DOI] [PubMed] [Google Scholar]
- Kim J. G., Graham D. Y. Helicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. The Misoprostol Study Group. Am J Gastroenterol. 1994 Feb;89(2):203–207. [PubMed] [Google Scholar]
- Knight J. R., Campbell A. J., Williams S. M., Clark D. W. Knowledgeable non-compliance with prescribed drugs in elderly subjects--a study with particular reference to non-steroidal anti-inflammatory and antidepressant drugs. J Clin Pharm Ther. 1991 Apr;16(2):131–137. doi: 10.1111/j.1365-2710.1991.tb00294.x. [DOI] [PubMed] [Google Scholar]
- Kremer J. M., Hamilton R. A. The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.5 mg. J Rheumatol. 1995 Nov;22(11):2072–2077. [PubMed] [Google Scholar]
- Laine L., Sloane R., Ferretti M., Cominelli F. A randomized double-blind comparison of placebo, etodolac, and naproxen on gastrointestinal injury and prostaglandin production. Gastrointest Endosc. 1995 Nov;42(5):428–433. doi: 10.1016/s0016-5107(95)70045-5. [DOI] [PubMed] [Google Scholar]
- Lamy P. P. Pharmacotherapeutics in the elderly. Md Med J. 1989 Feb;38(2):144–148. [PubMed] [Google Scholar]
- Lancaster C. Effective nonsteroidal anti-inflammatory drugs devoid of gastrointestinal side effects: do they really exist? Dig Dis. 1995 Jan;13 (Suppl 1):40–47. doi: 10.1159/000171525. [DOI] [PubMed] [Google Scholar]
- Laneuville O., Breuer D. K., Dewitt D. L., Hla T., Funk C. D., Smith W. L. Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 1994 Nov;271(2):927–934. [PubMed] [Google Scholar]
- Lanza F. L., Arnold J. D. Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and endoscopic studies. Clin Rheumatol. 1989 Mar;8 (Suppl 1):5–15. doi: 10.1007/BF02214105. [DOI] [PubMed] [Google Scholar]
- Lanza F. L. Gastrointestinal toxicity of newer NSAIDs. Am J Gastroenterol. 1993 Sep;88(9):1318–1323. [PubMed] [Google Scholar]
- Levy M., Lipshitz M., Eliakim M. Hospital admissions due to adverse drug reactions. Am J Med Sci. 1979 Jan-Feb;277(1):49–56. doi: 10.1097/00000441-197901000-00006. [DOI] [PubMed] [Google Scholar]
- Levy R. A., Smith D. L. Clinical differences among nonsteroidal antiinflammatory drugs: implications for therapeutic substitution in ambulatory patients. DICP. 1989 Jan;23(1):76–85. doi: 10.1177/106002808902300122. [DOI] [PubMed] [Google Scholar]
- Masferrer J. L., Zweifel B. S., Manning P. T., Hauser S. D., Leahy K. M., Smith W. G., Isakson P. C., Seibert K. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3228–3232. doi: 10.1073/pnas.91.8.3228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mené P., Pugliese F., Patrono C. The effects of nonsteroidal anti-inflammatory drugs on human hypertensive vascular disease. Semin Nephrol. 1995 May;15(3):244–252. [PubMed] [Google Scholar]
- Montamat S. C., Cusack B. Overcoming problems with polypharmacy and drug misuse in the elderly. Clin Geriatr Med. 1992 Feb;8(1):143–158. [PubMed] [Google Scholar]
- Moran M., Mozes M. F., Maddux M. S., Veremis S., Bartkus C., Ketel B., Pollak R., Wallemark C., Jonasson O. Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. N Engl J Med. 1990 Apr 26;322(17):1183–1188. doi: 10.1056/NEJM199004263221703. [DOI] [PubMed] [Google Scholar]
- Murray M. D., Black P. K., Kuzmik D. D., Haag K. M., Manatunga A. K., Mullin M. A., Hall S. D., Brater D. C. Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients. Am J Med Sci. 1995 Nov;310(5):188–197. doi: 10.1097/00000441-199511000-00003. [DOI] [PubMed] [Google Scholar]
- Murray M. D., Brater D. C. Nonsteroidal anti-inflammatory drugs. Clin Geriatr Med. 1990 May;6(2):365–397. [PubMed] [Google Scholar]
- Nesher G., Sonnenblick M., Dwolatzky T. Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients. J Rheumatol. 1995 Apr;22(4):713–716. [PubMed] [Google Scholar]
- Nies A. S. Renal effects of nonsteroidal anti-inflammatory drugs. Agents Actions Suppl. 1988;24:95–106. doi: 10.1007/978-3-0348-9160-8_9. [DOI] [PubMed] [Google Scholar]
- Nolan L., O'Malley K. Prescribing for the elderly. Part I: Sensitivity of the elderly to adverse drug reactions. J Am Geriatr Soc. 1988 Feb;36(2):142–149. doi: 10.1111/j.1532-5415.1988.tb01785.x. [DOI] [PubMed] [Google Scholar]
- Patrono C. The role of prostaglandin synthesis inhibition in the renal syndromes associated with non-narcotic analgesics. Med Toxicol. 1986;1 (Suppl 1):23–33. [PubMed] [Google Scholar]
- Piper J. M., Ray W. A., Daugherty J. R., Griffin M. R. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991 May 1;114(9):735–740. doi: 10.7326/0003-4819-114-9-735. [DOI] [PubMed] [Google Scholar]
- Pirson Y., van Ypersele de Strihou C. Renal side effects of nonsteroidal antiinflammatory drugs: clinical relevance. Am J Kidney Dis. 1986 Nov;8(5):338–344. doi: 10.1016/s0272-6386(86)80108-1. [DOI] [PubMed] [Google Scholar]
- Quintero E., Ginés P., Arroyo V., Rimola A., Camps J., Gaya J., Guevara A., Rodamilans M., Rodés J. Sulindac reduces the urinary excretion of prostaglandins and impairs renal function in cirrhosis with ascites. Nephron. 1986;42(4):298–303. doi: 10.1159/000183692. [DOI] [PubMed] [Google Scholar]
- Rampton D. S., McNeil N. I., Sarner M. Analgesic ingestion and other factors preceding relapse in ulcerative colitis. Gut. 1983 Mar;24(3):187–189. doi: 10.1136/gut.24.3.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raskin J. B., White R. H., Jackson J. E., Weaver A. L., Tindall E. A., Lies R. B., Stanton D. S. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995 Sep 1;123(5):344–350. doi: 10.7326/0003-4819-123-5-199509010-00004. [DOI] [PubMed] [Google Scholar]
- Rosen G. D., Birkenmeier T. M., Raz A., Holtzman M. J. Identification of a cyclooxygenase-related gene and its potential role in prostaglandin formation. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1358–1365. doi: 10.1016/0006-291x(89)91819-6. [DOI] [PubMed] [Google Scholar]
- Roth G. J., Stanford N., Majerus P. W. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073–3076. doi: 10.1073/pnas.72.8.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roth S. H. Endoscopy-controlled study of the safety of nabumetone compared with naproxen in arthritis therapy. Am J Med. 1987 Oct 30;83(4B):25–30. doi: 10.1016/0002-9343(87)90589-4. [DOI] [PubMed] [Google Scholar]
- Roth S. H. Nonsteroidal anti-inflammatory drugs: gastropathy, deaths, and medical practice. Ann Intern Med. 1988 Sep 1;109(5):353–354. doi: 10.7326/0003-4819-109-5-353. [DOI] [PubMed] [Google Scholar]
- Roth S. H., Tindall E. A., Jain A. K., McMahon F. G., April P. A., Bockow B. I., Cohen S. B., Fleischmann R. M. A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa. Arch Intern Med. 1993 Nov 22;153(22):2565–2571. [PubMed] [Google Scholar]
- Roth S. H. Upper gastrointestinal safety with nabumetone. J Rheumatol Suppl. 1992 Nov;36:74–79. [PubMed] [Google Scholar]
- Russell R. I. Endoscopic evaluation of etodolac and naproxen, and their relative effects on gastric and duodenal prostaglandins. Rheumatol Int. 1990;10 (Suppl):17–21. doi: 10.1007/BF02274751. [DOI] [PubMed] [Google Scholar]
- Serni U. Global safety of etodolac: reports from worldwide postmarketing surveillance studies. Rheumatol Int. 1990;10 (Suppl):23–27. doi: 10.1007/BF02274752. [DOI] [PubMed] [Google Scholar]
- Shorr R. I., Ray W. A., Daugherty J. R., Griffin M. R. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med. 1993 Jul 26;153(14):1665–1670. [PubMed] [Google Scholar]
- Silverstein F. E., Graham D. Y., Senior J. R., Davies H. W., Struthers B. J., Bittman R. M., Geis G. S. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995 Aug 15;123(4):241–249. doi: 10.7326/0003-4819-123-4-199508150-00001. [DOI] [PubMed] [Google Scholar]
- Smith W. L., DeWitt D. L. Biochemistry of prostaglandin endoperoxide H synthase-1 and synthase-2 and their differential susceptibility to nonsteroidal anti-inflammatory drugs. Semin Nephrol. 1995 May;15(3):179–194. [PubMed] [Google Scholar]
- Tamblyn R. M., McLeod P. J., Abrahamowicz M., Monette J., Gayton D. C., Berkson L., Dauphinee W. D., Grad R. M., Huang A. R., Isaac L. M. Questionable prescribing for elderly patients in Quebec. CMAJ. 1994 Jun 1;150(11):1801–1809. [PMC free article] [PubMed] [Google Scholar]
- Tytgat G. N., Noach L. A., Rauws E. A. Helicobacter pylori infection and duodenal ulcer disease. Gastroenterol Clin North Am. 1993 Mar;22(1):127–139. [PubMed] [Google Scholar]
- Walker A. M., Chan K. W., Yood R. A. Patterns of interchange in the dispensing of non-steroidal anti-inflammatory drugs. J Clin Epidemiol. 1992 Feb;45(2):187–195. doi: 10.1016/0895-4356(92)90015-f. [DOI] [PubMed] [Google Scholar]
- Wallace J. L., Reuter B., Cicala C., McKnight W., Grisham M. B., Cirino G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology. 1994 Jul;107(1):173–179. doi: 10.1016/0016-5085(94)90074-4. [DOI] [PubMed] [Google Scholar]
- Wallace J. L. The 1994 Merck Frosst Award. Mechanisms of nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal damage--potential for development of gastrointestinal tract safe NSAIDs. Can J Physiol Pharmacol. 1994 Dec;72(12):1493–1498. doi: 10.1139/y94-215. [DOI] [PubMed] [Google Scholar]
- Weinblatt M. E., Germain B. F., Kremer J. M., Wall B. A., Weisman M. H., Maier A. L., Coblyn J. S. Lack of a renal-protective effect of misoprostol in rheumatoid arthritis patients receiving cyclosporin A. Results of a randomized, placebo-controlled trial. Arthritis Rheum. 1994 Sep;37(9):1321–1325. doi: 10.1002/art.1780370908. [DOI] [PubMed] [Google Scholar]
- Weir M. R., Klassen D. K., Hall P. S., Schubert C., Voss T. E., Stromatt S. C., Brown J. A. Minimization of indomethacin-induced reduction in renal function by misoprostol. J Clin Pharmacol. 1991 Aug;31(8):729–735. doi: 10.1002/j.1552-4604.1991.tb03768.x. [DOI] [PubMed] [Google Scholar]
- Whelton A., Hamilton C. W. Nonsteroidal anti-inflammatory drugs: effects on kidney function. J Clin Pharmacol. 1991 Jul;31(7):588–598. doi: 10.1002/j.1552-4604.1991.tb03743.x. [DOI] [PubMed] [Google Scholar]
- Whelton A. Renal effects of over-the-counter analgesics. J Clin Pharmacol. 1995 May;35(5):454–463. doi: 10.1002/j.1552-4604.1995.tb04088.x. [DOI] [PubMed] [Google Scholar]
- Wilcox C. M., Shalek K. A., Cotsonis G. Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Arch Intern Med. 1994 Jan 10;154(1):42–46. [PubMed] [Google Scholar]
- Zambraski E. J. The effects of nonsteroidal anti-inflammatory drugs on renal function: experimental studies in animals. Semin Nephrol. 1995 May;15(3):205–213. [PubMed] [Google Scholar]