Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs

doi:10.1016/0016-5085(93)90952-9

Gastroenterology

Volume 105, Issue 4, October 1993, Pages 1078-1088

https://doi.org/10.1016/0016-5085(93)90952-9 Get rights and content

Abstract

Background: We have assessed the extent to which the risk of serious gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) varies with the age and sex of recipients, use of aspirin or alcohol, administration by the oral or rectal route, and dose and choice of drug. Methods: A case-control study was performed with prospective recruitment of cases of gastrointestinal bleeding or ulcer perforation and age- and sex-matched controls. Information on preadmission drug use obtained by structured interview. Results: Six hundred forty-four patients and 1268 controls were recruited. The odds ratio for upper gastrointestinal complications in users compared with nonusers of NANSAIDs increased with age: ≤ 59 years, odds ratio 2.0; 60–79 years, odds ratio 3.0; ≥ 80 years, odds ratio 4.2; and was higher in women (5.4) than in men (1.9). There was a linear dose-response curve that was steeper in women than in men. Combined exposure suggested additive risks: NANSAIDs and aspirin, odds ratio 6.7; NANSAIDs and alcohol, odds ratio 6.0. NANSAIDs by the oral route were associated with an odds ratio of 2.3, compared with 11.4 with rectal administration. Piroxicam was associated with the highest risk, odds ratio 4.8; and ibuprofen the lowest risk, odds ratio 0.7. Conclusions: 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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In vivo cellular and molecular gastroprotective mechanisms of chrysin; Emphasis on oxidative stress, inflammation and angiogenesis
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Citation Excerpt :
The main aggressive factors include: excessive secretion of gastric acid, alcohol intake, bile salts, abnormal motility, infection with Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs), while the main protective factors include: mucus secretion, gastroprotective prostaglandin synthesis, bicarbonate production and normal tissue microcirculation (Sowndhararajan and Kang, 2013). Amongst the NSAIDs, indomethacin has the highest ulcer-inducing potential to humans (Henry et al., 1993). Few years ago, it was found that indomethacin activates NF-κB and JNK MAPK pathways inducing various pro-inflammatory mediators and also inhibiting the cyclooxygenase (COX)-dependent and angiogenic pathways (Yadav et al., 2012).
Gastric ulcer is one of the major gastrointestinal disorders affecting people worldwide. Despite medical advances, management of gastric ulcer and its complications remains a challenge facing medicine nowadays. In addition, currently available medicines exhibit limited efficacy and several side effects. In the current study, the potential protective effects of chrysin -naturally occurring flavonoid – were tested against indomethacin-induced gastric ulcer model in rats. It was found that chrysin in both doses; 50 and 100 mg/kg were effective in promoting mucus secretion and preventing the rise in ulcer and lesion indices, acid production and histologic changes induced by indomethacin. During investigation of the possible underlying mechanisms, chrysin significantly attenuated indomethacin-induced oxidative injury and inflammatory response. Also, chrysin activated peroxisome proliferator activated receptor-ɣ (PPAR-ɣ) leading to a phenotypic switch from pro-inflammatory M1 macrophages to the anti-inflammatory M2 macrophages that evidenced by the upregulated mRNA expression levels of PPAR-ɣ and M2 marker genes (Arg-1 and CD206) and down regulation of M1 marker genes (IL-6 and CCL3). Furthermore, chrysin promoted angiogenesis via increasing expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and cluster of differentiation-31 (CD31). Collectively, these findings indicate that chrysin possesses a potential protective effect against indomethacin-induced gastric ulcer.
Stomach and Duodenum
2018, Equine Surgery, Fifth Edition
High altitude area – A risk factor for gastric perforation?: A case series
2018, International Journal of Surgery Case Reports
This is an original case series on soldiers evacuated from HAA(High Altitude Area) over last one year(Sept 2017–Aug 2018), of which 100% cases were found to have gastric antrum perforation. This is a deviation from the usual trend that is being noted in Indian subcontinent where duodenal perforations are commonest.
High altitude associated dyspepsia is a common phenomenon and some studies done in high altitude population have recorded high incidence of antral gastritis and mucosal atrophy on histo-pathological evaluation. This is also supported by high incidence of H. pylori infection. The presence of atrophic gastric mucosa associated with antral gastritis, when exposed to hypobaric hypoxemic conditions faced by soldiers posted to heights above 15,000 ft, may leads to increased intra-luminal pressure and ischemia which probably predisposes individuals for gastric antrum perforations.
This is a relatively untouched topic as we have not found studies onhigh altitude related gastric perforations and probably this is the first case series of its kind. The acknowledgement of this phenomenon may pave way for further studies for defining the role of high altitude in gastric perforations.
Safe prescription recommendations for non steroidal anti-inflammatory drugs: Consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG)
2014, Gastroenterologia y Hepatologia
Este artículo señala las recomendaciones claves para una adecuada prescripción de antiinflamatorios no esteroideos a pacientes que presentan indicación de tratamiento con esta medicación, en base a la evidencia científica actual y teniendo en consideración aspectos de seguridad gastrointestinal y cardiovascular. Las recomendaciones se han consensuado por expertos designados por 3 sociedades científicas (Sociedad Española de Reumatología, Asociación Española de Gastroenterología y Sociedad Española de Cardiología), siguiendo una metodología Delphi a 2 rondas. Las áreas que se han tenido en cuenta engloban: eficacia, riesgo cardiovascular, riesgo gastrointestinal, riesgo hepático, riesgo renal, enfermedad inflamatoria intestinal, anemia, dolor postoperatorio y estrategias de prevención. Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones.
This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations
Safe prescription recommendations for non steroidal anti-inflammatory drugs: Consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG)
2014, Reumatologia Clinica
Este artículo señala las recomendaciones claves para una adecuada prescripción de antiinflamatorios no esteroideos a pacientes que presentan indicación de tratamiento con esta medicación, en base a la evidencia científica actual y teniendo en consideración aspectos de seguridad gastrointestinal y cardiovascular. Las recomendaciones se han consensuado por expertos designados por 3 sociedades científicas (Sociedad Española de Reumatología, Asociación Española de Gastroenterología y Sociedad Española de Cardiología), siguiendo una metodología Delphi a 2 rondas. Las áreas que se han tenido en cuenta engloban: eficacia, riesgo cardiovascular, riesgo gastrointestinal, riesgo hepático, riesgo renal, enfermedad inflamatoria intestinal, anemia, dolor postoperatorio y estrategias de prevención. Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones.
This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations
Inhibition of TNF-α, and NF-κB and JNK pathways accounts for the prophylactic action of the natural phenolic, allylpyrocatechol against indomethacin gastropathy
2013, Biochimica et Biophysica Acta - General Subjects
The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically.
Mice were pre-treated with APC for 1 h followed by IND (18 mg kg^− 1) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration.
IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5 mg kg^− 1), trolox (50 mg kg^− 1) and NAC (250 mg kg^− 1) showed similar protection that was better than that by misoprostol (5 μg kg^− 1) and omeprazole (3 mg kg^− 1).
The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis.
Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent.

View all citing articles on Scopus

Supported by grants from the National Health & Medical Research Council of Australia and Pfizer Australia Pty., Ltd.

The preliminary results of this study were published in the form of a letter (Lancet 1991;337:370).

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Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs

Abstract

Lancet

Lancet

J Clin Epidemiol

Gastroenterology

Lancet

Gastroenterology

Gastroenterology

Balliere's Clin Rheumatol

Lancet

Nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding

Arch Intern Med

Peptic ulcer and non-steroidal anti-inflammatory agents

Gut

Non-steroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly

Arch Intern Med

The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding

Arch Intern Med

The relative gastrointestinal toxicity of the nonsteroidal anti-inflammatory drugs

Arch Intern Med

Fatal peptic ulcer complications and the use of non-steroidal anti-inflammatory drugs, aspirin, and corticosteroids

BMJ

Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons

Ann Intern Med

Major upper gastrointestinal tract bleeding

Arch Intern Med

Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside

Q J Med

Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons

Ann Intern Med

Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case control study

Gut

Aspirin and bleeding ulcers in the elderly

BMJ