Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs
New England Journal of MedicinePublished 17 June 1999
M. Michael Wolfe, David R. Lichtenstein, Gurkirpal Singh
Citations1,946
SJR quartileQ1
SJR score19.08
SNIP13.47
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TL;DR
One hundred years have passed since Felix Hoffman reported the successful synthesis of acetylsalicylic acid as the first nonsteroidal antiinflammatory drug (NSAID) and numerous reports have corroborated this observation.
Abstract
One hundred years have passed since Felix Hoffman, working at Bayer Industries, reported the successful synthesis of acetylsalicylic acid as the first nonsteroidal antiinflammatory drug (NSAID).1,2 At the suggestion of Hermann Dreser, Bayer's chief pharmacologist at the time,3 the compound was called “aspirin” and was purported to represent a convenient mechanism for the delivery of salicylic acid in the treatment of rheumatic diseases, menstrual pain, and fever.2 Approximately 40 years elapsed before Douthwaite and Lintott4 provided endoscopic evidence that aspirin could cause gastric mucosal damage. Numerous reports have corroborated this observation,58 and the introduction of more potent agents . . .
Keywords
MedicinePharmacology, Toxicology and Pharmaceutics
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Users of NSAIDs are at approximately three times greater relative risk for developing serious adverse gastrointestinal events than are nonusers.
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The efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs and the presence of fewer than five erosions at each site and not more than mild dyspepsia was compared.
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In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.
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764 Citations1991Marie R. Griffin, Joyce M. Piper +3 more
The data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs and that use of these drugs may be responsible for a large proportion of peptic ulcers among elderly persons.
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High levels of COX-2 mRNA and protein during the acute stages of gastric mucosal lesions may be involved in the repair process of these lesions in mice.
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631 Citations1987C P Armstrong, A L Blower
There appears to be a relationship between the development of a life threatening complication of peptic ulceration and NSAID ingestion and much of the associated mortality and morbidity may be potentially avoidable.
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603 Citations1991Joyce M. Piper, Wayne A. Ray +2 more
The high risk for peptic ulcer disease associated with combined use of NSAIDs and corticosteroids indicates the need to prescribe this drug combination cautiously.
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600 Citations1988David L. DeWitt, William L. Smith
The availability of a full-length cDNA clone coding for prostaglandin G/H synthase should facilitate studies of the regulation of expression of this enzyme and the structural features important for catalysis and for interaction with anti-inflammatory drugs.
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598 Citations1988D.Y. Graham, NaurangM Agrawal +1 more
Results provide the first clear indication that NSAID-induced ulcers are preventable, and Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol.
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573 Citations1997Wallace Jl
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550 Citations1990John L. Wallace, Catherine M. Keenan +1 more
An important role for neutrophils in the pathogenesis of NSAID-induced gastric ulceration is suggested and may be important in the vascular injury that occurs early after administration of these compounds.
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468 Citations1998Gurkirpal Singh
Analysis of prospectively followed patient status and outcomes, drug side effects, and the economic impact of illness for >11,000 arthritis patients at 8 participating institutions in the United States and Canada indicates osteoarthritis and rheumatoid arthritis patients are 2.5-5.5 times more likely than the general population to be hospitalized for NSAID-related GI events.
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463 Citations1992Jaime L. Masferrer, Karen Seibert +2 more
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449 Citations1996J. R. Vane, R M Botting
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440 Citations1996Ali S. Taha, N Hudson +8 more
Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.
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Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers in patients with musculoskeletal pain.
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401 Citations1991Andrew H. Soll, Wilfred M. Weinstein +2 more
Nonsteroidal anti-inflammatory drugs thus appear both to exacerbate an underlying peptic diathesis and to cause de novo ulcers.
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391 Citations1989James F. Fries, Stephen R. Miller +4 more
It is estimated that the syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone.
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382 Citations1989A. Walan, John P. Bader +5 more
A double-blind multicenter study of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole and ranitidine in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up concludes that in the dose used, omepazole is superior to ranitidine in the treatment of benign Gastric ulcers.
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381 Citations1988R. S. B. Ehsanullah, M. C. Page +2 more
Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulcers when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.
The LancetRandomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study
368 Citations1998CJ Hawkey, Zsolt Tulassay +7 more
H. pylori eradication in long-term users of NSAIDs with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs led to impaired healing of gastric ulcers and did not affect the rate ofpeptic ulcers or dyspePSia over 6 months.
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353 Citations1987Edwin Larkai, J L Smith +2 more
It is confirmed that fairly severe gastroduodenal injury occurs in asymptomatic patients with rheumatoid and osteoarthritis, and that symptoms do not predict the presence of damage.
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332 Citations1989Robert T. Schoen, Ronald J. Vender
Current knowledge about the normal function of the gastric mucosal barrier; the role of prostaglandins in cytoprotection and repair; the mechanisms by which aspirin and other weak organic acids are absorbed by the stomach; and the subsequent cascade of events--including ion trapping and back diffusion of hydrogen ions--that leads to gastric erosion and bleeding are examined.
Annals of Internal MedicineIncidence of Gastric Lesions in Patients with Rheumatic Disease on Chronic Aspirin Therapy
321 Citations1979G.R. Silvoso, K. J. IVEY +7 more
Regular aspirin and buffered aspirin users had an ulcer incidence of 23% and 31% respectively, compared with a 6% incidence in enteric-coated aspirin users (P less than 0.05).
Archives of Internal MedicineConcurrent Use of Nonsteroidal Anti-inflammatory Drugs and Oral Anticoagulants Places Elderly Persons at High Risk for Hemorrhagic Peptic Ulcer Disease
319 Citations1993Ronald I. Shorr
The nearly 13-fold increase in the risk of developing hemorrhagic peptic ulcer disease in concurrent users of oral anticoagulants and NSAIDs suggests that NSAIDs should be prescribed with extreme caution in patients undergoing anticoageulation therapy.
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Annals of Internal MedicineDuodenal and Gastric Ulcer Prevention with Misoprostol in Arthritis Patients Taking NSAIDs
297 Citations1993David Y. Graham, Richard H. White +9 more
The efficacy of misoprostol is investigated for the prevention of NSAID-induced duodenal ulcers in arthritis patients receiving long-term NSAID therapy.
GastroenterologyNovel nonsterodial anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat
290 Citations1994John L. Wallace, Brian K. Reuter +4 more
Addition of a nitroxybutyl moiety to two NSAIDs markedly reduced the ability of these agents to induce short-term gastric injury but did not interfere with their ability to suppress inflammatory processes, inhibit prostaglandin synthesis, or inhibit platelet aggregation.
The American Journal of GastroenterologyA guideline for the treatment and prevention of NSAID-induced ulcers
279 Citations1998Frank L. Lanza
Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research and are applicable to all physicians who address the subject without regard to specialty training or interests.
GastroenterologyVariability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs
278 Citations1993David Henry, Annette J. Dobson +1 more
A number of factors can alter the risk of major gastrointestinal complications with NANSAIDs and need to be considered when individual prescribing decisions are made.
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The mechanisms by which the bile salt, sodium taurocholate, potentiates the formation of gastric mucosal erosions induced by indomethacin has been investigated in the rat.
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The toxic effects of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) were endoscopically evaluated in several studies conducted between 1975 and 1983 and involving 843 normal volunteers.
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261 Citations1980Frank L. Lanza, George Royer +1 more
The damaging effect of aspirin on the gastric mucosa has been well documented by endoscopy and studies of fecal blood loss and because of the unquestioned value of aspirin in the treatment of rheumatoid arthritis.
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240 Citations1989Malcolm Robinson, Joseph Griffin +5 more
While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.
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The mammalian stomach is a specialized organ of the digestive tract that serves to store and process food for absorption by the intestine, considered to be the hallmark of gas.
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235 Citations1986David Y. Graham, J. LACEY SMITH
Endoscopic studies linking the extent and degree of acute mucosal injury to various nonsteroidal anti-inflammatory drugs have little or no value in predicting the frequency or severity of chronic gastric ulcer or gastrointestinal bleeding.
American Journal of Physiology-Cell PhysiologyInternalization of fluorescent vasotocin-receptor agonist and antagonist in the toad bladder
232 Citations1990P. Eggena, Mingming Lu +1 more
These experiments suggest that agonists, but not antagonists, form functional complexes with receptors that, via formation of cAMP, trigger not only an increase in membrane permeability to water but also facilitate the clearance of hormone from the cell surface by endocytic uptake.
Archives of Internal MedicineThe Relative Gastrointestinal Toxicity of the Nonsteroidal Anti-inflammatory Drugs
218 Citations1987Jeffrey L. Carson
It is concluded that there are significant and consistent differences in the incidence of UGI tract bleeding associated with the use of NSAIDs in this population of Medicaid patients in the states of Michigan and Minnesota.
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189 Citations1994Luca Santucci, Stefano Fiorucci +4 more
Pentoxifylline prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indometHacin induced release of TNF alpha.
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189 Citations1995Jeffrey B. Raskin, Richard H. White +5 more
The effectiveness and tolerability of three different misoprostol regimens were determined, which were shown to provide significant protection against NSAID-induced gastric and duodenal ulcers and to reduce the incidence of ulcer complications.
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185 Citations1997Neal M. Davies, Arne Røseth +6 more
The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti‐inflammatory properties to the parentNSAID.
American Journal of Physiology-Gastrointestinal and Liver PhysiologyRole of endothelial adhesion molecules in NSAID-induced gastric mucosal injury
181 Citations1993John L. Wallace, W. McKnight +6 more
The hypothesis that interactions at the leukocyte-endothelium interface are critical in the pathogenesis of NSAID-induced mucosal injury, and this interface may represent a rational target for therapies aimed at preventing this form of injury, is supported.
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171 Citations1989M. J. S. Langman
It is uncertain whether individuals with preexisting ulcer are at special risk or whether treatment predisposed equally to ulcer and ulcer complications, and there is no clear evidence that the nature of the disability leading to nonsteroidal antiinflammatory drug treatment influences the risk of gastrointestinal complications.
Annals of Internal MedicineMisoprostol Compared with Sucralfate in the Prevention of Nonsteroidal Anti-inflammatory Drug-induced Gastric Ulcer
170 Citations1991Naurang M. Agrawal, Sanford H. Roth +5 more
PubMedThe acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome.
166 Citations1997J Devlin, Andrew Gough +6 more
Investigating the relationship between change of CRP and Health Assessment Questionnaire over a 24 mo period found elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy.
Lara D. VeekenSafety of Meloxicam: A Global Analysis of Clinical Trials
164 Citations1996M. Distel, Claudia Mueller +2 more
Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutiveCOX-1, and was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen.
Journal of Clinical InvestigationAnti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative.
153 Citations1995John L. Wallace, W. McKnight +3 more
It is demonstrated that NCX 4215 has comparable or enhanced anti-thrombotic activity to that of aspirin, but does not cause gastric damage or alter systemic blood pressure.
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148 Citations1993N Hudson, M Balsitis +2 more
Enhanced gastric mucosal synthesis of LTB4 in patients taking NSAIDs may represent a primary effect of these drugs and could be implicated in the pathogenesis of gastritis and ulceration associated with NSAIDs.
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139 Citations1996G. Bianchi Porro, F. Parente +3 more
H pylori eradication does not confer any significant advantage on the healing of gastric and duodenal ulcers associated with longterm NSAID use and it remains to be established with certainty whether eradication may be helpful in the reduction of recurrence in a specific subset of NSAID associated ulcer.
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139 Citations1899H. Dreser
GastroenterologyDouble-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum
137 Citations1988Frank L. Lanza, Richard L. Aspinall +4 more
It is concluded that misoprostol is highly effective and significantly better than cimetidine in protecting the gastric mucosa from tolmetin-induced injury; however, both agents were highly protective in the duodenum.
Digestive Diseases and SciencesUpper gastrointestinal disease in rheumatoid arthritis
123 Citations1974David C. H. Sun, Sanford H. Roth +2 more
Upper gastrointestinal series were done in 140 consecutive patients with rheumatoid arthritis, irrespective of the presence or absence of symptoms suggesting upper gastrointestinal disease, and a significantly lower mean amplitude of peristaltic contractions was noted in the lower two-thirds of the esophagus.
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113 Citations1986J. Saunders, Robert J. Oliver +1 more
Ranitidine healed most duodenal ulcers and gastric ulcers within four weeks and tolerance to ranitidine was good, and the incidence of complaints was similar on placebo.
Scandinavian Journal of GastroenterologyNonsteroidal Anti-inflammatory Drugs and Upper Gastrointestinal Bleeding, Identifying High-Risk Groups by Excess Risk Estimates
111 Citations1995Jesper Hallas, Jens Lauritsen +2 more
A history of peptic ulcer is associated with adverse outcome of NSAID therapy and should be regarded as a relative contraindication, and the incidence ofNSAID-related UGB can probably be reduced without affecting the overall utilization of NSAIDs.
The American Journal of MedicineSucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage
111 Citations1987Jacques R. Caldwell, Sanford H. Roth +5 more
PubMedHelicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. The Misoprostol Study Group.
110 Citations1994J. G. Kim, David Y. Graham
H. pylori does not confer increased risk of ulceration in arthritics receiving NSAIDs chronically, and stepwise logistic regression analysis indicated none of the variable factors of age, gender, alcohol consumption, type of arthritis, or H.pylori status were significantly associated with development of peptic ulcers.
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109 Citations1997Peter E. Lipsky, Peter C. Isakson
Celecoxib provides significant improvement in patient global assessment, morning stiffness, and the number of painful and tender joints compared with placebo and specific COX-2 inhibition with celecoxib causessignificant improvement in the signs and symptoms of RA.
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108 Citations1990Hiroshi Kitagawa, Fumiyo Takeda +1 more
It is suggested that EDRF plays an important role in the protection of gastric mucosa against HCl, and reduced endothelium-dependent increase in mucosal blood flow may be an etiology of Gastric lesion in rats.
Archives of Internal MedicineA Controlled Study Comparing the Effects of Nabumetone, Ibuprofen, and Ibuprofen Plus Misoprostol on the Upper Gastrointestinal Tract Mucosa
107 Citations1993Sanford H. Roth
Nabumetone is equivalent in ulcerogenicity to concomitant ib uprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.
GastroenterologyIndomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats
101 Citations1995Donna‐Marie McCafferty, D. Neil Granger +1 more
The increased susceptibility of arthritic rats to indomethacin-induced gastric injury may be partly related to elevated levels of ICAM-1-dependent leukocyte adherence.
GastroenterologySilent Peptic Ulceration: Deadly Silence or Golden Silence?
97 Citations1989Roy E. Pounder
Maintenance treatment with H2-receptor antagonists appears to some extent to decrease the frequency of asymptomatic ulcers, but more interestingly to halt the progression of asynchronic ulcers toward symptomatic or complicated ulceration, although more careful studies in comparison with other modalities are needed.
GastroenterologyEndogenous nitric oxide modulates ethanol-induced gastric mucosal injury in rats
97 Citations1995Eiji Masuda, Sunao Kawano +10 more
Endogenous NO modulates ethanol-induced gastric mucosal injury through the regulation of gastricucosal microcirculation through theregulation of endothelium-derived relaxing factor.
Alimentary Pharmacology & TherapeuticsInteraction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production: a controlled double‐blind trial
94 Citations1995Loren Laine, Fabio Cominelli +4 more
The effect of daily NSAIDs ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production are assessed.
Digestive Diseases and SciencesOmeprazole ameliorates aspirin-induced gastroduodenal injury
80 Citations1994James M. Scheiman, Elizabeth M. Behler +2 more
Omeprazole, 40 mg/day eliminates duodenal injury and markedly ameliorates gastric injury due to administration of aspirin 2600 mg/ day, and prophylaxis of NSAID injury deserves further study.
InflammationPharmacological investigation of the role of leukotrienes in the pathogenesis of experimental NSAID gastropathy
78 Citations1992P Väänänen, Catherine M. Keenan +2 more
Data from this study are consistent with the hypothesis that leukotrienes contribute to the epithelial injury and macroscopically visible damage induced by NSAIDs.
Annals of Internal MedicineDose Effects of Aspirin on Gastric Prostaglandins and Stomach Mucosal Injury
78 Citations1994Makau Lee, Byron Cryer +1 more
The goal was to determine the threshold dose for gastroduodenal mucosal prostaglandin inhibition in humans because aspirin doses below this threshold may not damage the gastroduo-mucosal mucosa.
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77 Citations1993Patrick Goggin, D A Collins +5 more
It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy.
Digestive Diseases and SciencesResistance to medical therapy of gastric ulcers in rheumatic disease patients taking aspirin
72 Citations1982Joseph C. O’Laughlin, Gerald K. Silvoso +1 more
In spite of continued aspirin intake, most benign gastric ulcers <0.5 cm in diameter heal medically in two months, and recurrence rate is low with prophylactic therapy even with continuing aspirin intake.
Clinical Pharmacology & TherapeuticsNonsteroidal anti-inflammatory effect of sulindac sulfoxide and sulfide on gastric mucosa
68 Citations1985David Y. Graham, J L Smith +2 more
Both sulindac sulfoxide and sulindAC sulfide are poorly soluble in acid gastric contents and the reduced damage may relate to the inability of high concentrations of the drug to enter gastric mucosal cells.
PubMedGastroduodenal complications of chronic NSAID therapy.
67 Citations1988D.Y. Graham, J L Smith
The current status of nonsteroidal drug therapy can be summarized as follows: new NSAIDs are not safer than the old NSAIDs, as far as major gastrointestinal side effects are concerned, and NSAIDs should be avoided when analgesia is the main goal, and ifNSAIDs are required, the lowest possible dose that achieves pain relief should be used.
Archives of Internal MedicineCost-Conscious Prescribing of Nonsteroidal Anti-inflammatory Drugs for Adults With Arthritis
65 Citations1992J M Greene
The American Journal of MedicineNonsteroidal anti-inflammatory drug-induced gastrointestinal injury
59 Citations1996David J. Bjorkman
In this review, mechanisms of NSAID-induced GI injury are presented, and a clinical approach to diagnosis, treatment, and prevention of these adverse GI effects is provided.
Scandinavian Journal of GastroenterologyA Randomized, Double-Blind, Crossover Comparative Endoscopy Study on the Gastroduodenal Tolerability of a Highly Specific Cyclooxygenase-2 Inhibitor, Flosulide, and Naproxen
59 Citations1997Ingvar Bjarnason, Andrew J. Macpherson +3 more
The results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.
Alimentary Pharmacology & TherapeuticsTreatment of NSAID‐induced gastrointestinal lesions with cimetidine: an international multicentre collaborative study
58 Citations1988J. W. J. Bijlsma
It is suggested that cimetidine 800 mg nocte is effective in healing NSAlD‐induced lesions despite continued NSAID use, and that maintenance treatment with cimetamines can prevent lesions and reduce lesion recurrence during chronic NSAID administration.
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58 Citations1980J R Croker, P B Cotton +2 more
Cimetidine treatment was associated with ulcer healing in 17 out of 21 patients with arthritis even when anti-inflammatory treatment was continued, and Remission was maintained for 1 year by continued cimetidine therapy.
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56 Citations1986Stanisław J. Konturek, N Kwiecień +3 more
It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins.
PubMedAn updated safety profile of etodolac in several thousand patients.
54 Citations1990M Schattenkirchner
It is determined that gastrointestinal disturbances are the most frequently reported side effects, followed by headache, dizziness, rash, and pruritus, and the elderly appear to be no more at risk of experiencing adverse effects than the general population.
Lara D. VeekenTHE INFLUENCE OF CIMETIDINE ON PEPTIC ULCER IN PATIENTS WITH ARTHRITIS TAKING ANTI-INFLAMMATORY DRUGS
54 Citations1986Joan Davies, Amanda Collins +1 more
It was found that the ulceration healed in some patients over a 6-week period even on placebo treatment, and there was no statistical difference found between the healing of these ulcers when compared with the cimetidine-treated group.
The American Journal of MedicineDiabetes in urban african americans. III. Management of type II diabetes in a municipal hospital setting
50 Citations1996David C. Ziemer, Merilyn G. Goldschmid +5 more
In urban African American patients, nonpharmacologic management of type II diabetes substantially improves metabolic control; decreases in HbA1c are comparable in those who do and do not lose weight.
Digestive Diseases and SciencesInterrelationships betweenHelicobacter pylori infection, nonsteroidal antiinflammatory drugs and gastroduodenal disease
50 Citations1994A. V. Thillainayagam, S. Tabaquchali +2 more
H. pylori infection, at least in the short term, neither influences the propensity of nonsteroidal antiinflammatory drugs to produce macroscopic gastroduodenal mucosal injury nor does it effect the occurrence of upper gastrointestinal symptoms.
Archives of Internal MedicineConcurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease
50 Citations1993R. I. Shorr
PubMedWhich patients taking non-aspirin non-steroidal anti-inflammatory drugs bleed? A case-control study.
45 Citations1995Patrick Hochain, I. Berkelmans +5 more
This study identified a group at 'high risk' for GIB which would benefit from the development of a prophylactic therapy.
The American Journal of MedicineFuture trends in the development of safer nonsteroidal anti-inflammatory drugs
43 Citations1998M. Michael Wolfe
As recent observations have implicated COX-2 as an integral component in the maintenance of physiologic homeostasis, careful scrutiny of both the beneficial and the deleterious effects of the selective COx-2 inhibitors is requisite before their approval and widespread use.
Archives of Internal MedicineRanitidine Protects Against Gastroduodenal Mucosal Damage Associated With Chronic Aspirin Therapy
43 Citations1987Jesse M. Berkowitz
The ranitidine/aspirin group had significantly less mucosal damage in the stomach and duodenum than the placebo/aspirationin group, and mean serum salicylate levels were similar between treatment groups after two and four weeks of aspirin therapy.
European Journal of PharmacologyRole of nitric oxide in the gastric cytoprotection induced by central vagal stimulation
39 Citations1993Ágnes Király, Gábor Sütő +1 more
The results suggest that the L-arginine-nitric oxide pathway is involved in the cytoprotective effect of i.c. TRH analog, probably through the modulation of gastric mucosal blood flow.
Clinical RheumatologyThe effect of ranitidine on NSAID related dyspeptic symptoms with and without peptic ulcer disease of patients with rheumatoid arthritis and osteoarthritis
35 Citations1996J.H.L.M. van Groenendael, H. M. Markusse +2 more
The results of this study show that oral ranitidine 150 mg b.i.d. is effective in the treatment of both dyspeptic symptoms and mucosal lesions in RA and OA patient who continue the use of NSAIDs.
Scandinavian Journal of GastroenterologyComparison between Ranitidine and Omeprazole for Protection against Gastroduodenal Damage Caused by Naproxen
35 Citations1992Einar Oddsson, H. Gudjóansson +1 more
It is suggested that acid plays a major role in acute naproxen-induced injury to the duodenal mucosa, and a moderate acid reduction is adequate for protection.
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