Myeloperoxidase as a generator of drug free radicals

1995 ◽  
Vol 61 ◽  
pp. 163-170 ◽  
Author(s):  
Jack P. Uetrecht
Keyword(s):  
Neutrophil Function ◽  
Reactive Metabolites ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions ◽  
Drug Induced ◽  
Nitrenium Ion ◽  
High Incidence ◽  
Inflammatory Bowel

Reactive metabolites are believed to be responsible for many types of toxicity, including idiosyncratic drug reactions. Bone marrow is a frequent target of idiosyncratic reactions, and, since these reactions have characteristics that suggest involvement of the immune system, the formation of reactive metabolites by leucocytes could also play a role in the aetiology of idiosyncratic drug reactions. The major oxidation system in neutrophils and monocytes is a combination of NADPH oxidase and myeloperoxidase. This system oxidizes primary arylamines, such as sulphonamides, to reactive metabolites and these drugs are also associated with a high incidence of agranulocytosis, generalized idiosyncratic reactions and/ or drug-induced lupus. Clozapine is oxidized by this system to a relatively stable nitrenium ion; clozapine is also associated with a high incidence of agranulocytosis. Arylamines that have an oxygen or nitrogen in the para position, such as amodiaquine, vesnarinone and 5-aminosalicylic acid, are oxidized to quinone-like reactive intermediates. Aminopyrine is oxidized to a very reactive dication. Such reactive metabolites could also inhibit neutrophil function and mediate some of the therapeutic effects of these drugs: for example, the use of dapsone for dermatitis herpetiformis and the use of 5-aminosalicylic acid for inflammatory bowel disease.

scholarly journals Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Wunan Zhang ◽  
Cecilia Bohns Michalowski ◽  
Ana Beloqui
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Oral Delivery ◽  
Early Adulthood ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Therapeutic Mechanism ◽  
Inflammatory Bowel ◽  
The Moment

Inflammatory bowel disease (IBD) has been posed as a great worldwide health threat. Having an onset during early adulthood, IBD is a chronic inflammatory disease characterized by remission and relapse. Due to its enigmatic etiology, no cure has been developed at the moment. Conventionally, steroids, 5-aminosalicylic acid, and immunosuppressants have been applied clinically to relieve patients’ syndrome which, unfavorably, causes severe adverse drug reactions including diarrhea, anemia, and glaucoma. Insufficient therapeutic effects also loom, and surgical resection is mandatory in half of the patients within 10 years after diagnosis. Biologics demonstrated unique and differentiative therapeutic mechanism which can alleviate the inflammation more effectively. However, their application in IBD has been hindered considering their stability and toxicity. Scientists have brought up with the concept of nanomedicine to achieve the targeted drug delivery of biologics for IBD. Here, we provide an overview of biologics for IBD treatment and we review existing formulation strategies for different biological categories including antibodies, gene therapy, and peptides. This review highlights the current trends in oral delivery of biologics with an emphasis on the important role of nanomedicine in the development of reliable methods for biologic delivery in IBD treatment.

scholarly journals Lupus-Like Syndrome Caused by 5-Aminosalicylic Acid in Patients with Inflammatory Bowel Disease

1999 ◽  
Vol 13 (2) ◽  
pp. 159-162 ◽  
Author(s):  
Andrew W Kirkpatrick ◽  
Arthur A Bookman ◽  
Flavio Habal
Keyword(s):  
Inflammatory Bowel Disease ◽  
Side Effects ◽  
Bowel Disease ◽  
Acute Inflammation ◽  
Gastrointestinal Disease ◽  
Aminosalicylic Acid ◽  
Drug Induced ◽  
Inflammatory Bowel ◽  
Cessation Of Treatment ◽  
Rule Out

BACKGROUND: Although 5-aminosalicylic acid (5-ASA) preparations used to treat inflammatory bowel disease are reported to have fewer side effects than sulphasalazine, increased clinical use of these compounds has resulted in increased reports of significant side effects.OBJECTIVE: To report four patients with antinuclear antibody-positive migratory arthralgias and acute inflammation unrelated to the underlying inflammatory bowel disease, fulfilling the criteria of a drug-induced lupus-like syndrome.SETTING: A university-affiliated teaching hospital.INTERVENTION: Cessation of treatment with 5-ASA compounds.RESULTS: The cases described constitute a drug-induced lupus-like syndrome. All patients improved rapidly after discontinuation of 5-ASA compounds.CONCLUSIONS: Reversible lupus-like syndrome appears to be a rare but significant side effect of 5-ASA compounds. Patients treated with 5-ASA compounds who experience acute inflammatory symptoms or clinical deterioration not related to their gastrointestinal disease should be screened to rule out a lupus-like reaction.

Drug-Induced Liver Injury

2015 ◽  
Author(s):  
Thanh Tran ◽  
William M. Lee
Keyword(s):  
Liver Injury ◽  
Prescription Drugs ◽  
Clinical Manifestations ◽  
The United States ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Study Results

Drug-induced liver injury (DILI) refers to liver damage caused by over-the-counter and prescription drugs as well as herbal and dietary supplements. Hepatocytes, the main factory cells of the liver, are the primary targets of drug-related injury. During hepatocyte injury, loss of cell integrity results in a leak of liver contents, including a variety of enzymes, into the circulation. Currently, more than 1,000 drugs and herbal products have recognized hepatotoxic properties, with acetaminophen (APAP) being the most common cause of acute liver failure in the United States and amoxicillin-clavulanate the most common cause of severe liver injury worldwide. This review of DILI addresses the epidemiology, classification, pathophysiology, clinical manifestations, diagnosis, common idiosyncratic drug reactions, unusual drug reactions, treatment, and prognosis, with special sections on APAP hepatotoxicity and the approval of prescription drugs by the Food and Drug Administration. Figures show histologic features of DILI, mechanisms of liver injury, genome-wide association study results for lumiracoxib, APAP metabolism, and the Rumack-Matthew nomogram. Tables list classification of DILI, features of idiosyncratic drug reactions, histologic patterns of DILI, haplotypes associated with specific drug-related disorders, and the Roussel-Uclaf causality assessment method. This review contains 5 highly rendered figures, 5 tables, and 54 references.

scholarly journals P453 Comparison of therapeutic effects between groups of thiopurine alone and combination of thiopurine with 5-ASA after remission introduced by oral tacrolimus for patients with severe ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S405-S406
Author(s):  
T Sato ◽  
K Kojima ◽  
R Koshiba ◽  
K Fujimoto ◽  
M Kawai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Rank Test ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Time To Relapse

Abstract Background Although thiopurine is recommended to be used for maintenance after remission, the reliable data of maintenance introduced by tacrolimus is limited for patients with ulcerative colitis (UC). 5-aminosalicylic acid (5-ASA) is reported to induce 6-thioguanine nucleotides (6-TGN) levels higher in patients with inflammatory bowel diseases. However, the data of 5-ASA are few reported among East Asians. Methods A retrospective cohort study was conducted evaluating the 70 patients with severe UC who were primary responders to oral tacrolimus from April 2015 to March 2018. Twenty-seven patients were administered maintenance treatment with thiopurine. We evaluated the efficacy of thiopurines with and without 5-ASA in these patients, using ΔMCV, lowest WBC, highest 6TGN between groups of thiopurine alone and thiopurine+ 5-ASA. Kaplan–Meier analysis was used to assess time to relapse between groups of thiopurine and thiopurine+5-ASA. Results The median follow-up period was 430 days (interquartile range 207–952 days). The statistical significances were not found in patients background between groups of thiopurine and thiopurine+5-ASA. ΔMCV were significantly greater (p < 0.01), lowest WBC were significantly lower (p = 0.02) in the thiopurines+5-ASA group than in thiopurines alone group. The highest 6-TGN levels tended to be higher in thiopurine+5-ASA group than in thiopurine alone group (p = 0.09). The rate of relapse was significantly higher in the thiopurine alone group than in thiopurines+5-ASA group (p = 0.03). Kaplan–Meier curves confirmed that thiopurine+5-ASA group appeared to protect against relapse (log-rank test, p < 0.01). Conclusion Thiopurine+5-ASA induced significantly lower relapse than thiopurine alone after remission introduced by tacrolimus in the patients with severe UC, along with significantly greater the ΔMCV and lower the lowest WBC.

The Effect of Dietary Glutathione and Coenzyme Q10 on the Prevention and Treatment of Inflammatory Bowel Disease in Mice

2004 ◽  
Vol 74 (1) ◽  
pp. 74-85 ◽  
Author(s):  
Liu ◽  
Russell ◽  
Smith ◽  
Bronson ◽  
Milbury ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Coenzyme Q ◽  
Histological Evaluation ◽  
Therapeutic Effects ◽  
Prevention Study ◽  
Prevention And Treatment ◽  
Inflammatory Bowel ◽  
Pre Treatment

Because reactive oxygen species have been implicated as mediators of inflammatory bowel disease (IBD), we evaluated the potential preventive and therapeutic effects of two dietary antioxidants, glutathione (GSH) and coenzyme Q10 (CoQ10) on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty female 8-wk old Swiss-Webster mice were randomly assigned to 4 groups for a pre-treatment 'prevention' study: (1) GSH (1% of diet); (2) CoQ10 (200 mg/kg/d); (3) DSS only (3% of drinking water); (4) control (no treatment). The mice in groups 1 and 2 were fed with GSH or CoQ10 for 21 wks, and the mice in groups 1, 2 and 3 were provided DSS from wk 7 for 4 cycles (1 cycle = 1 wk DSS followed by 2-wk water). Another 50 mice were randomly assigned to 4 groups for a 21-wk 'treatment' study where the mice in groups 1, 2, and 3 were administered DSS for 6 cycles (18 wks) to induce colitis. GSH and CoQ10 were added from wk 7 until the completion of the protocol. Loose stools and hemocult positivity were modestly but significantly reduced with GSH or CoQ10 at several periods during the intervention in both the prevention and treatment studies. In contrast, histological evaluation revealed increases in colonic dysplasia and ulceration with GSH or CoQ10. Thus, in this mouse model, GSH and CoQ10 appear to have a beneficial effect on acute signs of IBD, but may have an adverse impact on the chronic pathophysiology of the disease. Further studies using additional animal models are required to determine whether GSH or CoQ10 provide a favorable or unfavorable benefit:risk ratio in the prevention or treatment of IBD.

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