Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adverse reactions to the drugs employed in the National Cooperative Crohn's Disease Study were sought prospectively at each patient visit and by retrospective review of all patient charts. Prednisone caused evident side effects in over 50% of patients on high-dose suppressive therapy and in approximately one-third of patients on prophylactic dose. Thirty-two percent of patients on high-dose, and 26% on prophylactic-dose prednisone required dose reduction or withdrawal because of side effects. Comparable figures for sulfasalazine were 14% and 12%, and for azathioprine 32% and 20%. The incidence of nausea, vomiting, or anorexia among patients taking sulfasalazine was 46% and 34%, on high and low dose respectively; however, this incidence was no different than that observed among patients taking placebo. These symptoms occasioned withdrawal from the study of only 4% and 3% of patients on high and low doses of sulfasalazine, respectively. Azathioprine produced leukopenia at a dose of 2.5 mg/kg body weight in 15% of patients and the mean white cell count, lymphocyte count, granulocyte count, and hematocrit all fell significantly in patients on this dose. Pancreatitis occurred in 5% of patients taking azathioprine but in no other patients. Sulfasalazine proved to be the safest effective suppressive drug for Crohn's disease. Prednisone toxicity, though substantial, is acceptable in view of its demonstrated suppressive efficacy. Azathioprine was approximately as toxic as prednisone but no more effective than placebo in suppressing active disease. None of the drugs was effective prophylactically, and all showed appreciable long-term toxicity.
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PMID:National Cooperative Crohn's Disease Study: adverse reactions to study drugs. 3 77

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.
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PMID:Sulfasalazine desensitization in children and adolescents with chronic inflammatory bowel disease. 809 41

Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use. Sulfasalazine consists of sulfapyridine linked to mesalazine (5-aminosalicylic acid) via an azobond. Its use is indicated in the treatment of mild to moderately active ulcerative colitis and in the prevention of relapse in patients with quiescent disease. Patients with mild to moderate colonic or ileocolonic Crohn's disease also benefit from this drug, as do a proportion of patients with isolated small bowel disease. Sulfasalazine has not been uniformly effective in preventing relapse in Crohn's disease, although many clinicians continue its use in patients who respond initially. A high incidence of side effects which limit therapy include intolerance, hypersensitivity reactions and impairment of male infertility. The newer aminosalicylates offer targeted delivery of mesalazine to the bowel, with fewer side effects. Topical mesalazine has proved extremely effective in patients with distal ulcerative colitis; oral forms are effective in the treatment of mild to moderately active ulcerative colitis and in relapse. Both types appear to be effective in the treatment of Crohn's disease, and possibly in preventing relapse. There is no current clinical advantage of one mesalazine preparation over another, nor is there an indication for their use in sulfasalazine-treated patients who have satisfactory response without adverse effects. Corticosteroids are indicated for more severe disease activity where the aminosalicylates have limited efficacy-specifically to induce remission in patients with severe or refractory ulcerative colitis or Crohn's disease. They should not be used to maintain disease remission or in the prevention of postoperative recurrence. Topical corticosteroids allow their local use in distal colitis with minimal systemic side effects. Long term use is limited by side effects, many of which are dose related, although alternate-day therapy may lessen the incidence. Immunosuppressive agents are beneficial for the treatment of refractory inflammatory bowel disease unresponsive to other medications, and may also facilitate the withdrawal of steroids in refractory patients. Mercaptopurine has an added benefit in the treatment of Crohn's disease fistulae; the role of cyclosporin in bowel disease has not been established and its use cannot currently be recommended. The potential toxicity of immunosuppressive agents warrants careful consideration of their use by both physician and patient. Metronidazole is indicated for the treatment of mild to moderate Crohn's disease, including perineal disease. Common side effects include peripheral neuropathy and nausea.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease. 167 90

Sulfasalazine has been used for a decade in the United Kingdom for treating rheumatoid arthritis. There is now considerable experience with its adverse reaction profile and the incidence of serious events. In the initial weeks of treatment minor side effects are common, especially upper gastrointestinal problems and nausea. Therapy is thus usually introduced slowly and enteric coated tablets are preferred. In 20-30% of patients treatment is discontinued due to an adverse reaction. Most of such reactions occur within 3 months of starting therapy, are trivial, and are self-limiting after withdrawal of the drug. Potentially more serious adverse reactions include leukopenia, rash, abnormal liver function tests, and dyspnea. These reactions also reverse after treatment is stopped. Side effects leading to drug withdrawal after 1 year of therapy are unusual.
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PMID:Adverse reactions to sulfasalazine: the British experience. 257 30

Sulfasalazine is metabolized by intestinal bacteria, resulting in the release of sulfapyridine and 5-aminosalicylate. The drug is useful in the treatment of active ulcerative colitis as well as in preventing relapses of the disease in remission. Although effective in active Crohn's disease as well, sulfasalazine appears to be of greater benefit to patients with colitis and ileocolitis than those with ileitis alone. 5-Aminosalicylate itself is efficacious when given in enema and suppository form; oral agents capable of delivering 5-aminosalicylate to distal disease sites are now under study. The drug's mechanism of action may relate to its effects on prostaglandin synthesis or interference with arachidonic acid metabolism by the lipoxygenase pathway. Common adverse reactions of sulfasalazine, including nausea, headache, and anorexia, as well as hemolysis, are associated with high serum sulfapyridine levels and often can be avoided by lowering the dose of sulfasalazine. Mild allergic reactions, such as rash and fever, may be overcome by gradual desensitization.
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PMID:Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development. 614 10

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.
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PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

Off-label use of uncoated sulfasalazine tablets (TAB) by rheumatoid arthritis (RA) patients in the United States has resulted in poor gastrointestinal (GI) tolerance and compliance. Two studies have shown that treatment of inflammatory bowel disease with enteric-coated sulfasalazine ([EN] Azulfidine ENtabs) resulted in significantly less frequent and severe GI symptoms, compared with treatment with TAB. The current study was conducted to compare GI tolerance of EN and TAB in rheumatoid arthritis (RA) patients. Fifty adult sulfasalazine-naive patients, who displayed stable RA and no significant GI toxicity with nonsteroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs at baseline, were randomized to receive 2 g EN or TAB, in a prospective, 10-week, investigator-blinded, crossover study. After an initial 3-week dosing period with either EN or TAB and a 2-week washout, patients were crossed over to the alternative sulfasalazine formulation for a 2nd 3-week dosing period and 2-week follow-up. GI tolerance of EN and TAB in patients who completed both arms of the crossover was assessed bv frequency and intensity of reported adverse events (primary endpoints) and responses to health questionnaires (secondary endpoints).Twelve patients dropped out early because of adverse events and the discontinuation rate was similar in E\ and TAB-treated patients. Patients taking EN who completed the study reported significantly fewer (p < 0.001) GI adverse events (abdominal pain, anorexia, flatulence, diarrhea, heartburn, nausea, and vomiting), compared with those patients taking TAB. The intensity of adverse events was predominantly mild in patients treated with either EN or TAB. Responses to questionnaires were similar in patients taking either formulation of sulfasalazine. However, when asked which treatment period was preferred at the end of the study, 849 of patients completing the study (p < 0.001) chose EN. This study suggests that enteric-coating of sulfasalazine improved GI tolerance and RA patient preference.
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PMID:Improved gastrointestinal tolerance and patient preference of enteric-coated sulfasalazine versus uncoated sulfasalazine tablets in patients with rheumatoid arthritis. 1907 85

Abstract To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required.
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PMID:Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets). 2438 62