Natural remedies for non‐steroidal anti‐inflammatory drug‐induced toxicity

The liver is an important organ of the body, which has a vital role in metabolic functions. The non‐steroidal anti‐inflammatory drug (NSAID), diclofenac causes hepato‐renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs. Natural products are known for their minimal side effects, low cost and availability. On the other hand, synthetic drugs pose the danger of adverse effects if used frequently or over a long period. Copyright © 2016 John Wiley & Sons, Ltd.     

Eradication of Helicobacter pylori significantly reduced gastric damage in nonsteroidal anti-inflammatory drug-treated Mongolian gerbils

AIM: To examine the effect of eradication of Hellcobacter pylori prior to usage of NSAIDs, by investigating gastric inflammatory activity, myeloperoxidase (MPO) activity, prostaglandin (PG) E_2 synthesis in H Pylori-infected, and H pylori-eradicated gerbils followed by administration of indomethacin and rofecoxib. METHODS: Six-week-old male gerbils were orally inoculated with H pylori. Seven weeks later, anti-H pylori triple therapy and vehicle were given to gerbils respectively and followed by oral indomethacin (2 mg/kg·d) or rofecoxib (10 mg/kg·d) for 2 wk. We examined the area of lesions, gastric inflammatory activity, PGE_2 synthesis and MPO activity in the stomach. RESULTS: In indomethacin and rofecoxib-treated gerbils, the following results were obtained in H pylori-infected group vs H pylori-eradicated group respectively: hyperplasia area of the stomach (mm~2): 82.4±9.2 vs 13.9±3.5 (P＜0.05), 30.5±5.1 vs 1.3±0.6 (P＜0.05); erosion and ulcer area (mm~2): 14.4±4.9 vs 0.86±0.5 (P＜0.05), 1.3±0.6 vs0.4±0.3 (P＜0.05); score of gastritis: 7.0±0.0 vs3.6±0.5 (P＜0.05), 7.0±0.0 vs 2.7±0.5 (P＜0.05); MPO activity (μmol H_2O_2/min/g tissue): 104.7±9.2 vs9.0±2.3(P＜0.05), 133.5±15.0 vs2.9±0.7 (P＜0.05); PGE_2 synthesis (pg/mg wet weight/min): 299.2±81.5 vs102.8±26.2 (P＜0.05), 321.4±30.3 vs 11.9±4.8(P＜0.05). CONCLUSION: Eradication of H pylori reduced gastric damage of NSAID-treated Mongolian gerbils. Rofecoxib caused less severe gastric damage than indomethacin in H pylori-eradicated gerbils.     

Tramadol/acetaminophen combination tablets for the treatment of pain associated with osteoarthritis flare in an elderly patient population

OBJECTIVES: To evaluate the efficacy and safety of adding tramadol 37.5 mg/acetaminophen (APAP) 325 mg combination tablets (tramadol/APAP) to existing therapy for painful osteoarthritis (OA) flare in a subset of elderly patients. DESIGN: Randomized, double-blind, placebo-controlled, 10-day add-on study. SETTING: Thirty outpatient centers. PARTICIPANTS: Of 308 patients with painful OA flare, a subset of 113 patients aged 65 and older. MEASUREMENTS: Average daily pain intensity and pain relief scores for Days 1 through 5 and secondary quality-of-life measures and medication assessments. METHODS: Patients received one or two tramadol/APAP tablets or placebo four times per day for 10 days during ongoing nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drug (NSAID) therapy. RESULTS: Tramadol/APAP (n=69) was significantly superior to placebo (n=44) for average daily pain intensity (P=.034) and pain relief (P=.010) for Days 1 through 5 and Days 1 through 10 (P=.012 and P=.019, respectively). Tramadol/APAP had significantly better investigator (P<.001) and patient (P=.001) overall medication assessments and significantly better scores on three of four Western Ontario and McMaster Universities Osteoarthritis Index measures (P< or =.027). Most common adverse events with tramadol/APAP were nausea (18.8%), vomiting (13.0%), dizziness (11.6%), and constipation (4.3%), with an incidence similar to that of the overall study population. Mean daily dose of tramadol/APAP was 4.5 tablets (168 mg/1,458 mg). CONCLUSION: Tramadol/APAP add-on therapy effectively managed painful OA flare in this elderly subset and was generally well tolerated.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti‐inflammatory drugs or low‐dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti‐inflammatory drugs (NSAIDs) or low‐dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low‐dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long‐term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low‐dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low‐dose aspirin. The apparent protective effect of H. pylori in long‐term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.     

Microcirculatory Changes in Experimental Mesenteric Longitudinal Ulcers of the Small Intestine in Rats

Rats receiving intracolonic administration of indomethacin develop longitudinal ulcers on the mesenteric side of the small intestine that are similar to those seen in the acute phase of Crohn's disease. To investigate the causative role of microcirculatory disturbances and to elucidate the therapeutic effect of antioxidants on this enteropathy in rats, we serially evaluated changes in regional blood flow of the small intestine using laser Doppler perfusion imaging and the colored microsphere injection method. Both methods disclosed stepwise hyperperfusion limited to the mesenteric side of the small intestine following transient ischemia during the initial 30–60 minutes. In addition, both a radical scavenger and a radical production inhibitor significantly ameliorated the mesenteric longitudinal ulcers. We concluded that ischemia–reperfusion on the mesenteric side accompanying excessive production of radicals might be strongly involved in indomethacin-induced longitudinal ulcers of the small intestine in rats.     

Interaction Between NSAIDs and Steroid in Rat Stomach

The relative risk of development of peptic ulcer with the use of nonsteroidal antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs are administered in combination with steroids. We investigated the ulcerogenic potential of a combination of NSAIDs and steroids in rats and the underlying pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the severity of the lesions markedly increased with concomitant administration of prednisolone. However, nimesulide, even in excessive doses, did not produce any gastric lesions, regardless of concomitant administration with prednisolone. Furthermore, we showed that the ulcerogenic potential of indomethacin administered in combination with prednisolone may be related to the induction of physiological changes, such as endogenous prostaglandin deficiency, an increase in neutrophil activation, and gastric hypermotility, by indomethacin and alteration of normal epithelial renewal by the steroid. These results suggest that the ulcerogenic potential of preferential a COX-1 inhibitor increases following concomitant administration with a steroid, whereas, nimesulide, a preferential COX-2 inhibitor, is nonulcerogenic, even when administered concomitantly with a steroid, and is therefore a clinically useful antiinflammatory agent.     

Utility of published guidelines on the use of nonsteroidal anti-inflammatory drugs in the elderly

Canadian Consensus guidelines regarding appropriate use of nonsteroidal anti-inflammatory drugs (NSAID) were recently published. This study was done to evaluate the application of these guidelines on NSAID practice patterns in frail elderly patients referred to a specialist Geriatric Assessment Clinic. A retrospective chart review was undertaken of referrals who were currently prescribed NSAIDs. Data were captured on age, sex, weight, diagnoses, medications and dosages, indication for NSAID treatment, lying BP (as assessed in the clinic) and recent serum creatinine result. Creatinine clearance was subsequently calculated use the Cockcroft-Gault equation. Complete data were available on 107 patients (68% women, average age 80.6 years). Thirty percent were on a traditional NSAID, the remainder were on a Coxib. Concomitant aspirin was prescribed in 37%. Cytoprotection was being used in 38% and did not increase appreciably in patients with additional risk factors for GI toxicity, i.e., concomitant aspirin usage(35%), and history of GI toxicity (48%). Sixty-seven were taking anti-hypertensive medications, although more than two thirds of these patients were uncontrolled. Newly diagnosed hypertension was present in 19.6%. Calculated creatinine clearance revealed moderate to severe renal impairment in 79% of subjects, although serum creatinine was only elevated in 18%. In total, 70% of subjects were found to have relative or absolute risk factors for NSAID therapy. Given the high prevalence of potential contraindications to anti-inflammatory drug usage in this study, we advocate the dissemination and application of these guidelines in geriatric patients in an attempt to reduce potential morbidity and mortality.