Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulfasalazine is an important therapeutic agent in the management of chronic inflammatory bowel disease (CIBD). Unfortunately, adverse reactions to this drug have been reported in 5-55% of treated patients. These include dose-related side effects like nausea, malaise, and headache or hypersensitivity reactions such as rash, fever, hives, arthralgia, hepatitis, etc. Studies in adults with successful reintroduction of sulfasalazine after a desensitization program have been reported; however, with regard to children, no such data are available. Fourteen children and adolescents (5-16 yr old) diagnosed to have CIBD manifested hypersensitivity to sulfasalazine within 2 months of onset of treatment. All had pancolitis--secondary to Crohn's disease (CD) in four and to ulcerative colitis (UC) in 10. All of them were on steroids. Sulfasalazine was discontinued in all after symptoms of hypersensitivity developed. Three patients with severe reaction were diagnosed prior to desensitization experience. Desensitization, beginning with 5-50 mg of sulfasalazine/day, was attempted in the other 11 children. The dose was gradually increased by 5-50 mg increments every 3 days. Desensitization was successful in only five children, who were ultimately able to tolerate 1.5-3.0 g of sulfasalazine daily again. In the rest (six of 11 patients), oral 5-ASA (Asacol) was administered, and three could not tolerate it. One of these three with intolerance to Asacol required colectomy. One did not tolerate Asacol or Dipentum. Our findings suggest that sulfasalazine desensitization should be attempted in all patients developing hypersensitivity reactions before trying alternative therapy.
 ...
PMID:Sulfasalazine desensitization in children and adolescents with chronic inflammatory bowel disease. 809 41

There is a growing body of experimental and clinical evidence to suggest that oral or rectal administration of 5-ASA or 5-ASA conjugates is associated with significant adverse side effects including pancreatitis, hepatitis, and renal toxicity. The objective of this study was to assess the ability of 5-ASA to interact with low-molecular-weight iron to yield oxygen-derived free radicals and to determine whether these oxidants could damage model biological compounds. We found that 5-ASA was very effective at chelating ferric iron (Fe3+), and it rapidly reduced Fe3+ to the ferrous form (Fe2+). Addition of the 5-ASA/Fe2+ chelate to solutions containing polyunsaturated fatty acids or deoxyribose resulted in lipid peroxidation and oxidative carbohydrate degradation, respectively. These results are consistent with the formation of the highly reactive (and cytotoxic) hydroxyl radical. Formation of this free radical species was confirmed by the ability of hydroxyl radical scavengers (dimethyl sulfoxide, dimethyl thiourea) to inhibit the 5-ASA/Fe-mediated oxidative reactions. Maximum hydroxyl radical formation was achieved at a 5-ASA-to-Fe3+ ratio of 1.0 (20 microM 5-ASA and 20 microM Fe3+). Increasing this ratio significantly inhibited OH. formation with a concomitant reduction in lipid peroxidation and deoxyribose degradation. Finally, we demonstrated that 5-ASA promotes the reductive release of Fe3+ from ferritin. Data obtained in this study suggest that 5-ASA may, under certain conditions, promote the formation of potentially injurious free radical species. These oxidative reactions may contribute to some of the adverse side effects known to be associated with the newer preparations of 5-ASA.
 ...
PMID:Prooxidant properties of 5-aminosalicylic acid. Possible mechanism for its adverse side effects. 150 90

We report a patient who developed a severe hypersensitivity reaction, including rash, lymph node enlargement, fever, hepatitis, and eosinophilia, after sulphasalazine therapy. Five years later, he developed a similar reaction after exposure to mesalazine, the salicylic compound of sulphasalazine. We conclude that patients with known severe systemic reaction to sulphasalazine therapy are also at risk for such a reaction when treated with a 5-ASA preparation.
 ...
PMID:Kawasaki-like syndrome after treatment with mesalazine. 199 37

Aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) share common pharmacologic effects in the prevention of inflammation, at least in part through inhibition of prostaglandin formation. ASA and NSAIDs have predictable side effects such as gastric pain, ecchymosis, and tinnitus. They also cause anaphylactoid shock, urticaria/angioedema, nephropathy, and hepatitis in individuals who appear to be normal and in whom prediction of such reactions cannot be made. Two selected populations of patients are likely to experience hypersensitivity reactions to both ASA and NSAIDs. Patients with asthma have an 8% to 20% chance of experiencing asthmatic attacks after ingesting ASA and NSAID. If such patients have associated rhinosinusitis (polyps), prevalence increases to 30% to 40%. Patients with chronic urticaria/angioedema have a 21% to 30% chance of experiencing an urticarial flare after ingesting ASA and NSAIDs.
 ...
PMID:Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. 643 54

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
 ...
PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

Oral 5-aminosalicylic acid (5-ASA) has been known as a first-choice drug for ulcerative colitis. However, hypersensitivity reactions, including pancreatitis, hepatitis, and skin rash, have been reported with 5-ASA. Topical formulations of 5-ASA like suppositories have been rarely reported to induce adverse reactions because of their limited absorption rate. We recently experienced a case of acute pancreatitis caused by 5-ASA suppositories in a patient with ulcerative colitis. A 26-year-old male was admitted with abdominal pain and diagnosed as ulcerative colitis. Acute pancreatitis occurred soon after 24 hours of treatment with oral mesalazine. Drug-induced pancreatitis was suspected and administration of mesalazine was discontinued. Then 5-ASA suppositories were started instead of oral mesalazine. Twenty-four hours after taking 5-ASA suppositories, he experienced severe abdominal pain, fever, and elevation of amylase levels. The suppositories were immediately stopped and symptoms resolved over next 48 hours. Herein, we suggest that, in patients treated with 5-ASA suppositories who complain of severe abdominal pain, drug-induced pancreatitis should be suspected.
 ...
PMID:[A case of acute pancreatitis caused by 5-aminosalicylic acid suppositories in a patient with ulcerative colitis]. 1815 75