Long-term Nonsteroidal Anti-inflammatory Drugs Therapy Research Articles

Assessment of liver and kidney function in patients with ankylosing spondylitis on long-term non-steroidal anti-inflammatory drug therapy.

This study aimed to analyze the status of liver [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and kidney (serum creatine) function in ankylosing spondylitis (AS) patients assuming continuously non-steroidal anti-inflammatory drugs (NSAIDs) alone over a long period. Between 2013 and 2022, there were records of 385 AS patients. Of them, 56 were receiving only NSAIDs, and the files of these patients were retrospectively analyzed. Demographic and clinical characteristics were collected. Blood tests, including serum creatinine, AST, and ALT, were assessed at each visit. Of the 56 patients, 39 were male. The mean age was 45.30 years, and the follow-up period was 9.80 years. Of them, 44.6% used indomethacin, 26.8% naproxen, 17.9% diclofenac, 5.4% acemethazine, 3.6% meloxicam, and 1.8% celecoxib. The mean baseline serum creatinine was 0.71 mg/dL. The mean baseline serum AST and ALT were 19.6 u/L and 22.9 u/L, respectively. Baseline creatinine, AST, and ALT were not statistically significantly different between sexes. There was a statistically significant difference between mean creatinine concentrations at baseline and at year 3. One patient on naproxen discontinued treatment due to elevated creatinine. The creatinine level decreased during the patient's follow-up. Liver enzymes above 3 times the normal value were not seen in any patient. Based on real-world data, long-term use of NSAIDs has generally not led to acute liver and kidney injury or progressive impairment of hepatorenal function requiring discontinuation of treatment.

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database.

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.

Gastroprotekcja w trakcie przewlekłej terapii NLPZ – co wiemy po ponad 120 latach obserwacji?

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed classes of medications. The broad spectrum of side effects following long-term NSAID therapy includes mainly, but not only, gastrointestinal complications. Risk stratification of the gastrointestinal complications events is an important element of planning NSAIDs therapy, which allows to determine the indications for the use of proton pump inhibitors. This article presents the criteria for assessment and the method of adequate prevention of gastrointestinal side effects in patients receiving long-term NSAID therapy.

Helicobacter pylori Eradication in Drug-related Peptic Ulcer.

Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin are the most frequently prescribed drugs worldwide, and their long-term use often leads to peptic ulcers (PUs) along with serious complications, such as bleeding and perforation. Helicobacter pylori (H. pylori) infection is a significant risk factor for developing NSAID-related PU and ulcer bleeding during long-term aspirin use. In a revised version of the Clinical Guidelines for Drug-induced Peptic Ulcer, two statements regarding H. pylori eradication are recommended. 1) Patients scheduled for long-term NSAID therapy should be tested and treated for H. pylori infection to prevent PU and its complications. 2) Patients with a history of PU receiving long-term low-dose aspirin (LDA) therapy should undergo treatment for H. pylori infection to prevent PU and its complications. On the other hand, unlike NSAID-naïve patients, the preventive effects of H. pylori eradication in chronic NSAID users are unclear. In addition, anti-ulcer drugs, such as proton pump inhibitors, may be necessary for maintenance therapy after H. pylori eradication in a subset of long-term LDA users, particularly if the patients are taking concomitant antiplatelet agents or anticoagulants.

P1‐376: LONG‐TERM NSAID THERAPY IN OLDER ADULTS: EFFECTS ON AT(N)V IMAGING BIOMARKERS

Observational studies and animal model experiments have suggested that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be protective against Alzheimer's disease (AD). However, randomized controlled trials have not supported this hypothesis. We sought to assess whether long-term use of NSAIDs would be associated with differences in neuroimaging biomarkers of aging and dementia. We analyzed data for adults over 65 years old from the population-based Mayo Clinic Study of Aging. Individuals were classified as NSAID-untreated (n=439) if they reported no regular use of NSAIDs (defined as fewer than 3 days per week) prior to neuroimaging. Individuals who reported taking NSAIDs for 3+ days per week or 5+ years were defined as long-term NSAID-treated (n=519). For these groups, we analyzed the following neuroimaging outcomes based on the A (amyloid)/T (tau)/N (neurodegeneration)/V (cerebrovascular) framework: global amyloid (11C-PiB-PET), global and entorhinal cortex tau (18F-AV-1451-PET), AD-pattern hypometabolism (18F-FDG-PET) and cortical thickness (MRI), and white matter hyperintensities (FLAIR MRI) and fractional anisotropy of the corpus callosum (diffusion tensor imaging MRI). Age and sex were included as covariates in all analyses. Statistical significance was defined as p<0.05. The NSAID-treated group was older (mean age 78.5 vs. 76.1, p<0.001) and more frequently male (61% vs. 46%, p<0.001) than the untreated group. NSAID-treated individuals had a higher burden of late-life cardiovascular and metabolic conditions (p<0.001) but did not differ in APOE ɛ4 allele status, education, or clinical diagnosis (cognitively unimpaired, mild cognitive impairment, dementia) compared to the NSAID-untreated group. Long-term NSAID therapy was not significantly associated with any neuroimaging biomarker analyzed. In this study, we identified no association between long-term NSAID therapy and alterations in AT(N)V neuroimaging biomarkers. Additional work is needed to determine whether aspirin may be associated with differential effects compared to non-aspirin NSAIDs and to assess whether NSAID therapy alters longitudinal biomarker trajectories, particularly in individuals with high burden of cerebrovascular risk factors. As candidates for multi-domain treatment regimens for causes of dementia become available, evaluation of these approaches using AT(N)V biomarkers in the population will allow for rapid and dynamic assessment of potential efficacy and putative mechanism of action.

Demand management of procalcitonin requests in the biochemistry emergency laboratory

Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, which comprise an important compensatory mechanism for maintaining renal blood flow, glomerular filtration, and water and electrolyte homeostasis in the setting of a number of pathophysiologic states including chronic kidney disease (CKD). CKD patients are, therefore, at risk for adverse renal side effects of NSAIDs, including acutely worsened renal function, hyperkalemia, hyponatremia, sodium retention, and exacerbation of hypertension. Although these effects are generally reversible on discontinuation of the drugs, patients with CKD must be monitored closely while taking NSAIDs.Evidence suggests that heavy cumulative NSAID consumption is capable of causing chronic kidney injury with manifestations similar to those seen in classic analgesic nephropathy, including chronic interstitial nephritis and papillary necrosis. The pathogenesis of this disorder is probably renal medullary ischemia resulting from diversion of blood flow to the cortex that occurs with suppression of prostaglandin synthesis. CKD due to NSAIDs is probably rare.Extra caution is indicated when (1) committing patients to high-dose, long-term NSAID therapy or (2) recommending NSAID therapy of any duration to patients with CKD or other risk factors for adverse renal side effects including advanced age, use of diuretics, congestive heart failure, cirrhosis, and hypertension.As with NSAIDs, opioid analgesics must be considered from two standpoints: their ability to cause chronic kidney injury, which appears rare if it occurs at all, and the susceptibility of patients with chronically impaired renal function to the hemodynamic and neurotoxic effects of opioids, a problem commonly confronted in the clinic.

Monitoring side effects of long-term NSAID use in dogs with chronic osteoarthritis

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic medications in human and veterinary medicine. In osteoarthritis they are used for their anti-inflammatory and analgesic actions. A number of...

Risk of upper gastrointestinal adverse events in Malaysian rheumatic patients on long-term non-steroidal antiinflammatory drugs

Background: Non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal (GI) adverse events are well-described in the Western population but data is lacking in Asian patients. This study aims to describe the incidence and predictive factors for NSAID-induced upper GI complications in a cohort of multi-ethnic patients in Malaysia. Methods and Findings: A retrospective cohort study was conducted in adult patients with rheumatoid arthritis (RA) and/or osteoarthritis (OA) from 2010-2013 in four main rheumatology centres in Malaysia with computerized clinical and pharmaceutical records. Clinical, pharmaceutical and demographic data over a 24-months follow-up period were analysed in subjects who were prescribed long-term NSAID therapy (defined as a minimum duration of four weeks). 634 patients were included in the final analysis with the following characteristics: mean age 53.4 ± 12.5 years, 89.9% female, diagnosis: RA 59.5%, OA 10.2% and RA/OA combination 30.3%. 371 (58.5%) patients received non-selective NSAIDs and 263 (41.5%) patients received COX-2 inhibitors. There were a total of 84 GI adverse events during the period of study, giving an incidence rate of 66.2 per 1000 person-years and a risk of 13.2%. The majority of upper GI adverse events was dyspepsia (92.9%), and only 7.1% with peptic ulcer disease/ upper GI bleeding. Multivariate analysis showed that the only independent predictive factor of upper GI adverse event in this cohort was a history of upper GI disease (O.R. 2.073, 95% C.I. 1.029 – 4.176). COX-2 inhibitor showed a trend towards, but not independently predictive of, GI protection in this analysis (OR 0.643; 95% C.I. 0.397 – 1.043). Conclusion: Malaysian rheumatic patients on long-term NSAID therapy, managed at referral centres, have a 13.2% risk of upper GI adverse events, with dyspepsia being the commonest complication. Patients with a history of upper GI disease were twice as likely to develop further upper GI adverse events with the use of long-term NSAIDs.

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

ObjectiveTo assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.DesignA phase 3, 24-week,...

Prescription audit of NSAIDs and gastroprotective strategy in elderly in primary care.

The use of non-steroidal anti-inflammatory drug (NSAIDs) is deemed amajor risk factor for peptic ulcer disease in elderly population that requires concomitant therapy with gastroprotective agents (GPAs). This study evaluated the rational prescribing of NSAIDs and GPAs, and extent of adherence to the guideline recommendations in primary care. Nationwide audit of prescriptions issued to elderly patients (≥65 years) with hypertension or diabetic hypertension in primary care. Among 2090 elderly, 45.9% were on low-dose aspirin, and 13.5% on other NSAIDs. Diclofenac-XR was the most frequently prescribed NSAIDs to three-quarter patients whereas naproxen, the safest NSAID for patients with high cardiovascular (CV) risk, was rarely prescribed. Among those on NSAID, 82.9% were on ascheduled dosing regimen; of these 78.8% received long-term NSAID therapy (3.9±0.9 months). The prescription rate of GPAs was low: 29.2% for aspirin and 33.3% for other NSAIDs. Aquarter of the patients on histamine type-2 receptor antagonists received ranitidine at subtherapeutic single-dose for gastroprotection. Approximately half of the patients on proton pump inhibitors (PPIs) were prescribed supra-therapeutic double-dose regimen: omeprazole and esomeprazole accounted for 63.2% of overall prescribed PPIs. The rational choice of NSAIDs and physicians' adherence to gastroprotective measures was suboptimal in primary care. The choice of NSAIDs and gastroprotective strategy in elderly be guided by the CV and gastrointestinal adverse events likelihood due to the NSAIDs and risk profile of patients for such adverse events.

Elixir for the aging mind: An empirical review of the neuroprotective effect of meditation in elderly

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, which comprise an important compensatory mechanism for maintaining renal blood flow, glomerular filtration, and water and electrolyte homeostasis in the setting of a number of pathophysiologic states including CKD. CKD patients are, therefore, at risk for adverse renal side-effects of NSAIDs, including acutely worsened renal function, hyperkalemia, hyponatremia, sodium retention, and exacerbation of hypertension. Although these effects are generally reversible upon discontinuation of the drugs, CKD patients must be monitored closely while taking NSAIDs.Evidence suggests that heavy cumulative NSAID consumption is capable of causing chronic kidney injury with manifestations similar to those seen in classic analgesic nephropathy, including chronic interstitial nephritis and papillary necrosis. The pathogenesis of this disorder is probably renal medullary ischemia resulting from diversion of blood flow to the cortex that occurs with suppression of prostaglandin synthesis. CKD due to NSAIDs is probably rare.Extra caution is indicated when (1) committing patients to high-dose, long-term NSAID therapy, or (2) recommending NSAID therapy of any duration to patients with CKD or other risk factors for adverse renal side-effects including advanced age, use of diuretics, congestive heart failure, cirrhosis, and hypertension.

Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.MethodsThis was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.ResultsA total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.ConclusionLong-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.Trial registrationClinicalTrials.gov identifier NCT00595517.

Mechanisms Behind the Increased Vulnerability of the Aging Stomach to NSAID-Related Injury: Perhaps Not As Simple As We May Think

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to treat conditions such as arthritis and other musculoskeletal disorders in elderly patients. The usefulness of NSAIDs is, however, often limited by their associated gastrointestinal (GI) toxicity [1, 2]. Elderly patients taking long-term NSAIDs therapy are a particularly high-risk group for NSAIDs-related GI injury [3, 4]. NSAIDs-related GI injury is mainly a consequence of systemic inhibition of GI mucosal cyclooxygenase (COX) activity, which reduces levels of mucosa-protective prostaglandins (PG), for example prostaglandin E2 (PGE2), rather than a result of topical epithelial injury [5–7]. Inhibition of the two isozymes of COX, COX-1 and COX-2, is important in the pathogenesis of NSAIDs-related gastric injury [6]. COX-1 is a constitutive enzyme expressed in most cells of the body, including the stomach [6]. In contrast, COX-2 is an inducible enzyme, with increased expression in response to bacterial polysaccharides and proinflammatory cytokines [6]. Although non-selective NSAIDs (e.g., indomethacin) exert their GI ulcerogenic effects mainly through COX-1 inhibition, the GI ulcerogenic effects of NSAIDs require inhibition of both COX-1 and COX-2 [7, 8]. Mucosa-protective PGs (e.g., PGE2) contribute to gastric mucosal defense by reducing gastric acid secretion and by their nonantisecretory effects referred to as ‘‘cytoprotection’’ (e.g., stimulation of bicarbonate and glycoprotein secretion, increase in mucosal blood flow, among others) [9, 10]. It has been suggested that nitric oxide (NO) is the crucial intermediate in PGE2-mediated cytoprotection [11]. Hence, deficiency in mucosa-protective PGs or NO because of NSAIDs use is associated with compromise of gastric mucosal defense. Mechanisms independent of COX inhibition are also implicated in NSAIDs-related gastric injury. NSAIDs may also produce gastric mucosal injury by interfering with growth factors (e.g., TGF-b, TGF-a) and other mediators responsible for epithelial restitution and adaptive protection (e.g., trefoil family peptides) [12, 13]. Reactive oxygen species and apoptosis are also implicated in indomethacin-induced gastric injury [14]. Why aging stomachs are at greater risk of NSAIDsrelated injury is still poorly understood. Data from outcome studies have identified advanced age as one of the major risk factors for NSAIDs-related upper GI injury [1], possibly because of the finding that the aging gastric mucosa has reduced capacity for repair. A recent study investigating the effect of reactive oxygen species, apoptosis, and angiogenesis on the aging stomach has shown that aging gastric mucosa is gradually replaced by connective tissue, thus impairing gastric mucosal protection [15]. In rats of advanced age, angiogenesis is reduced as a result of reduced expression of VEGF and overexpression of PTEN [16]. Thus, reduction in mucosal defense mechanisms characteristic of the aging stomach may increase susceptibility to NSAIDs-related mucosal injury, although the underlying molecular pathogenesis remains poorly understood. In this issue of Digestive Diseases and Sciences, Hong et al. [17] report investigation of potential molecular mechanisms behind the increased susceptibility of the R. S. Tang (&) Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 94020, 7/F, Clinical Science Building, Shatin, New Territories, Hong Kong e-mail: rtang01@yahoo.com

Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti‐inflammatory drug‐related peptic ulcers in Japanese patients

The use of proton pump inhibitors for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse events is well documented. However, data regarding the efficacy and safety of this approach in Japan are scarce. To evaluate the efficacy and tolerability of esomeprazole in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. Male and female Japanese adult patients (aged ≥ 20 years) with endoscopically confirmed history of peptic ulcers who required long-term oral NSAID therapy for a chronic inflammatory condition were randomised to 24 weeks' treatment with esomeprazole 20 mg once daily or matching placebo. The primary end point was the Kaplan-Meier estimated proportion of ulcer-free patients. Overall, 343 patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168). The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was significantly higher (log-rank P < 0.001) in esomeprazole-treated patients (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9). Esomeprazole was effective at preventing peptic ulcers in both Helicobacter pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free, respectively); however, in the placebo group, the proportion of ulcer-free patients at 24 weeks was markedly lower among H. pylori-positive than -negative patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated ulcer-free rate with esomeprazole. Treatment with esomeprazole was well tolerated. Esomeprazole 20 mg once daily is effective and safe in preventing ulcer recurrence in Japanese patients with a definite history of peptic ulcers who were taking an NSAID (ClinicalTrials.gov identifier: NCT00542789).

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial

BackgroundLow-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain.MethodsThis multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively.ResultsThe cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan–Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400–0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event.ConclusionLansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-012-0541-z) contains supplementary material, which is available to authorized users.

Inhibition of Nuclear Factor κB Activation and Cyclooxygenase-2 Expression by Aqueous Extracts of Hispanic Medicinal Herbs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a primary choice of therapy for diseases with a chronic inflammatory component. Unfortunately, long-term NSAID therapy is often accompanied by severe side effects, including cardiovascular and gastrointestinal complications. Because of this, there is critical need for identification of new and safer treatments for chronic inflammation to circumvent these side effects. Inflammatory diseases have been successfully remedied with natural herbs by many cultures. To better understand the potential of natural herbs in treating chronic inflammation and to identify their mechanism of action, we have evaluated the anti-inflammatory activities of 20 medicinal herbs commonly used in the Hispanic culture. We have established a standardized method for preparing aqueous extracts (teas) from the selected medicinal herbs and screened for inhibition of tumor necrosis factor-alpha-induced activation of nuclear factor kappaB (NF-kappaB), which is the central signaling pathway of the inflammatory response. A number of herbal teas were identified that exhibited significant anti-inflammatory activity. In particular, tea from the herb commonly called laurel was found to be an especially potent inhibitor of NF-kappaB-dependent cyclooxygenase-2 gene expression and prostaglandin E(2) production in cultured murine macrophages. These findings indicate that laurel tea extract contains potent anti-inflammatory compounds that function by inhibiting the major signal transduction pathway responsible for inducing an inflammatory event. Based on these results, laurel may represent a new, safe therapeutic agent for managing chronic inflammation.

Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patients receiving long-term nonsteroidal anti-inflammatory drug therapy and the efficacy of famotidine obtained from the FORCE study

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury, and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.

Geranylgeranylacetone Protects against Diclofenac-Induced Gastric and Small Intestinal Mucosal Injuries in Healthy Subjects: A Prospective Randomized Placebo-Controlled Double-Blind Cross-Over Study

Background and Aims: Little information is available regarding the prevention and treatment of small intestinal mucosal injuries caused by non-steroidal anti-inflammatory drugs (NSAIDs). We planned a pilot study to investigate the protective effects of geranylgeranylacetone (GGA) against NSAID-induced small intestinal injuries using video capsule endoscopy (VCE). Subjects and Methods: Ten healthy male volunteers took oral GGA 300 mg/day (regimen A) or placebo (regimen B) in addition to diclofenac 75 mg/day + rabeprazole 20 mg/day for 7 days. We conducted a cross-over trial of regimens A and B with a 2-week washout period. All subjects underwent VCE before and after each administration period, and were evaluated for NSAID-induced gastric and small intestinal mucosal lesions. Results: The number of mucosal lesions (erosions, ulcers and a red spot with possible bleeding) detected in both stomach and small bowel changed between prior to and immediately after administration period, with significantly fewer lesions for regimen A after administration period (mean ± SD A:B = 2.6 ± 3.2:9.5 ± 8.5; p = 0.027). Conclusions: Combination therapy with GGA and rabeprazole reduced the incidence of gastroenteropathy induced by 1-week administration of diclofenac. Our findings suggest this therapy as a candidate for protecting patients on long-term NSAID therapy.

Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patients receiving long-term nonsteroidal anti-inflammatory drug therapy and the efficacy of famotidine obtained from the FORCE study

The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury,and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.

Helicobacter pylori Eradication in Patients on Long-term Treatment With NSAIDs Reduces the Severity of Gastritis

Maintenance use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often complicated by gastropathy. In non-NSAID users, eradication of Helicobacter pylori is associated with decreased mucosal inflammation, and may halt the progression to atrophy and intestinal metaplasia, but the continuous use of NSAIDs may interfere with these processes. To investigate the effect of H. pylori eradication on gastric mucosal histology during long-term NSAID use, with and without gastroprotective therapy. Patients were eligible for inclusion if they were on long-term NSAIDs and were H. pylori-positive on serologic testing. Patients were randomly assigned to either eradication or placebo. Gastritis was assessed according to the updated Sydney classification for activity, chronic inflammation, gastric glandular atrophy, intestinal metaplasia, and H. pylori density. Biopsy specimens were available for histology of 305 patients. Of these, 48% were on chronic gastroprotective medication. Significant less active gastritis, inflammation, and H. pylori density was found in the eradication group compared with the placebo group in both corpus and antrum (P<0.001). In the corpus, less atrophy was found in the eradication group compared with the placebo group. H. pylori eradication in patients on long-term NSAID therapy leads to healing of gastritis despite ongoing NSAID therapy.