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

Many idiosyncratic non-steroidal anti-inflammatory drugs (NSAIDs) cause GI, liver and bone marrow toxicity in some patients which results in GI bleeding/ulceration/fulminant hepatic failure/hepatitis or agranulocytosis/aplastic anemia. The toxic mechanisms proposed have been reviewed. Evidence is presented showing that idiosyncratic NSAID drugs form prooxidant radicals when metabolised by peroxidases known to be present in these tissues. Thus GSH, NADH and/or ascorbate were cooxidised by catalytic amounts of NSAIDs and hydrogen peroxide in the presence of peroxidase. During GSH and NADH cooxidation, oxygen uptake and activation occurred. Furthermore the formation of NSAID oxidation products was prevented during the cooxidation indicating that the cooxidation involved redox cycling of the first formed NSAID radical product. The order of prooxidant catalytic effectiveness of fenamate and arylacetic acid NSAIDs was mefenamic acid>tolfenamic acid>flufenamic acid, meclofenamic acid or diclofenac. Diphenylamine, a common moiety to all of these NSAIDs was a more active prooxidant for NADH and ascorbate cooxidation than these NSAIDs which suggests that oxidation of the NSAID diphenylamine moiety to a cation and/or nitroxide radical was responsible for the NSAID prooxidant activity. The order of catalytic effectiveness found for sulfonamide derivatives was sulfaphenazole>sulfisoxazolez.Gt;dapsone>sulfanilic acid>procainamide>sulfamethoxazole>sulfadiazine>sulfadimethoxine whereas sulfanilamide, sulfapyridine or nimesulide had no prooxidant activity. Although indomethacin had little prooxidant activity, its major in vivo metabolite, N-deschlorobenzoyl indomethacin had significant prooxidant activity. Aminoantipyrine the major in vivo metabolite of aminopyrine or dipyrone was also more prooxidant than the parent drugs. It is hypothesized that the NSAID radicals and/or the resulting oxidative stress initiates the cytotoxic processes leading to idiosyncratic toxicity.
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PMID:Idiosyncratic NSAID drug induced oxidative stress. 1239 53

While diagnosing Graves disease in childhood and adolescence does not usually present specific problems, the treatment of hyperthyroidism is still controversial. In particular, with regard to the use of radioiodine therapy, strategies vary between many European and North American pediatric endocrinology centers. After the diagnosis is made, antithyroid drug treatment with methimazole (thiamazole), carbimazole, or propylthiouracil should be performed with caution, in particular, because of severe adverse effects, such as agranulocytosis or hepatitis, that are found in up to 1% of patients. Antithyroid drug treatment should not be continued long-term, particularly since definitive remission cannot be expected in more than 30-40% of patients. In contrast, the risk of severe adverse effects is still present, and the risk of thyroid carcinoma increases with time and appears to be considerably higher than after radioiodine treatment. To a great extent, the success of surgery depends on the skills of a trained surgeon. The question of whether to perform total or subtotal thyroidectomy is yet to be resolved. Surgery should be considered in patients with a large thyroid gland (>80g), severe ophthalmopathy, and a lack of remission on antithyroid drug treatment. Success rates have increased to up to 97%, while severe adverse effects (laryngeal nerve palsy, hypoparathyroidism) occur in approximately 4% of patients. Mortality is below 0.1%. Radioiodine treatment in children >5 years of age does not appear to be associated with an increased risk of thyroid carcinoma; however, long-term data are lacking. Compared with the surgical approach, success rates are lower, particularly if low doses of radioiodine are used. In general, adverse effects are less prevalent than in patients who have undergone surgery.
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PMID:Graves disease in childhood: a review of the options for diagnosis and treatment. 1252 62

Propylthiouracil (PTU) is usually the first choice for the treatment of hyperthyroidism, but it has serious side effects such as hepatitis, cholestatic jaundice, splenomegaly and lupus-like syndrome, in addition to mild and common side effects like granulocytopenia, pruritus, urticaria and maculopapular or papular eruption. Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is another serious side effect. A 14-year-old female receiving PTU treatment for hyperthyroidism was referred to our clinic with fever, cough and dyspnea. The PTU dosage was first decreased but pericardial, dermal and joint involvement ascribed to PTU developed later and the drug was discontinued. ANCA-positive vasculitis due to PTU was considered when tests revealed an ANCA-positive state. We suggest that severe multisystemic vasculitis due to PTU should be considered during PTU usage.
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PMID:Propylthiouracil-induced hypersensitivity syndrome. 1684 20

The purpose of this study was to evaluate certain clinical aspects of hyperthyroidism in Albania, which is an iodine deficient country, as it is known that iodine intake may influence the type of thyroid hyperfunction. The files of sixty-six patients with thyrotoxicosis who were hospitalised for their disease were retrospectively analysed. 59.1% of these patients suffered from toxic multinodular goiter, 27.3% from Grave's disease (toxic diffuse goiter), 10.6% from toxic adenoma, 1.5% from iodide-induced hyperthyroidism and 1.5% from transient hyperthyroidism due to subacute thyroiditis. There was an increased female to male ratio (83.3% vs 16.7%, respectively, p<0.001). 83.9% of all hyperthyroid patients lived in cities, while 16.1% lived in villages. Ophthalmopathy was found in 11.1% of patients with Graves' disease, and thyrotoxic heart disease was found in 14% of patients with thyrotoxicosis. 71.9% of all patients with hyperthyroidism were treated with propylthiouracil (PTU), while 28.1% of them were treated with methimazole; 67.2% of all these patients also received propranolol hydrochloride, while 32.8% were prescribed atenolol. Compliance was lower than that reported in other studies as only 41% of all patients received their treatment regularly. Side effects from treatment with antithyroid drugs were as follows: 4.1% (2/48) of patients treated with propylthiouracil presented leukopenia with agranulocytosis, and 6.1% of them toxic hepatitis, while 11.1% (2/18) of patients treated with methimazole presented agranulocytosis. In conclusion, the mode of presentation and side effects of hyperthyroidism appears to be different in Albania when compared with other countries, probably as a result of iodine deficiency and/or possibly nutritional status. Compliance with treatment is lower than that reported in other series, while antithyroid drug side effects seem to be more frequent. The latter observation may be due to the fact that only hospitalised patients were analysed in this study.
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PMID:Clinical aspects of hyperthyroidism in hospitalised patients in Albania. 1698 78

Cases of fatal, acute, irreversible renal failure and cytopenias, including agranulocytosis and thrombocytopenia, have been disclosed in a postmarketing report on deferasirox, a few months after the European Union authorities and about a year after the FDA proceeded to its accelerated approval. No details on the incidence rate or the cause of these toxicities have yet been reported. Other toxic side effects include skin, gastric, auditory and ocular abnormalities, and hepatitis. Regular serum creatinine, blood counts and other toxicity monitoring as well as withdrawal of deferasirox from the patients affected and those with serum ferritin < 0.5 mg/l was recommended. Toxicity, inability to clear cardiac iron and high cost (60 euros/g) question the future universal role of deferasirox, by comparison with the safety and efficacy records of deferiprone, deferoxamine and their combination in the treatment of transfusional iron overload. Also questioned are the procedures adopted by regulatory authorities and the marketing methods of pharmaceutical companies on orphan drugs, which are of no benefit to thalassaemia patients in developing countries.
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PMID:Deferasirox: uncertain future following renal failure fatalities, agranulocytosis and other toxicities. 1748 Jan 73

Chronic C hepatitis is a global health problem. Its treatment is still unresolved. Pegylated interferon means substantive breakthrough in therapy. The longer effect, the lasting, steady therapeutic blood level are the pharmacokinetic advances. There is no significant difference in the side effects of pegylated interferon and standard interferon. The most frequent side effects leading to dose reduction or cessation of the treatment are depression and hematologic disorders. Neutropenia is induced more frequently by pegylated interferon, than by the standard form according to the literature. Combined antiviral treatment (pegylated interferon alpha-2a and ribavirin) of a 54 years old woman, who suffered from posttransfusion chronic hepatitis C was started. The dose of the pegylated interferon alpha-2a and ribavirin was reduced at the 8th week due to leucopenia and mild anemia. Fever, cough, sore throat and weakness occurred. Agranulocytosis was detected which was accounted as a side effect of pegylated interferon treatment. Antibiotic, antimycotic therapy and filgastrim was given. Leukocyte number increased, fever stopped after 10 days of therapy. The patient returned 17 days later. She had been having high fever, weakness, sore throat for 4 days. Ciprofloxacin was given by GP before her registration because of the suspicion of urinary infection, then she took sulfamethoxazol + trimethoprim without medical advise. Agranulocytosis was detected again, Staphylococcus sepsis developed. No sign of hematologic disease was found in the bone marrow. Agranulocytosis was considered aftermath of sulfamethoxazol + trimethoprim. Antibiotics, antimycotic and antiviral treatment, and filgastrim were given, sepsis healed, leukocyte number became normal. 274 patients suffering from chronic hepatitis C were treated by standard interferon, and 43 were treated by pegylated interferon. Rapid and significant decrease of leukocyte count was observed in the patients treated by pegylated interferon in the first 4 weeks of the treatment then it remained stable. Cessation of the treatment or dose-reduction was not necessary due to neutropenia among patients treated by standard interferon, while dose reduction was reasonable in two more cases in addition to this one, treated by pegylated interferon. The authors stress the importance of the exact follow-up of patients according to the protocol, which renders the early recognition of side effects, the prevention of complications, and their early and adequate treatment possible. Thus, pegylated interferon--inspite of its marked side effects and more serious suppressive effect on bone marrow--is the most effective drug for the treatment of chronic hepatitis C.
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PMID:[Side effect of pegylated-interferon treatment in chronic C hepatitis: agranulocytosis]. 1748 60

Phenytoin, one of the most common antiepileptic drugs, is a major cause of antiepileptic drug hypersensitivity syndrome (AHS), which is a rare but potentially fatal complication. We herein report a 5-year-old boy who developed unexpected agranulocytosis with fever approximately one week after recovering from the typical symptoms of AHS, characterized by fever, rash, lymphadenopathy, and hepatitis, but lacking eosinophilia or lymphocytosis. High-dose steroid therapy for the former symptoms of AHS, and immunoglobulin, granulocyte colony-stimulating factor, and cefepime for the latter agranulocytosis were successfully performed. This unexpected progression from AHS to agranulocytosis shortly after recovering from the former should be recognized as another risk of AHS, possibly leading to a life-threatening condition.
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PMID:Agranulocytosis following phenytoin-induced hypersensitivity syndrome. 1877 64

A 21 year old boy with borderline lepromatous leprosy and normal glucose-6-phosphate-dehydrogenase activity developed haemolytic anaemia, hepatitis and agranulocytosis following 19 weeks of multi-bacillary multi-drug therapy. With early administration of antibiotics and G-CSF our patient recovered without residual complications. All patients taking dapsone should be warned to discontinue the drug immediately in the event of fever, chills and sore throat occurring within the treatment period until further investigations are performed.
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PMID:Dapsone-induced haemolytic anaemia, hepatitis and agranulocytosis in a leprosy patient with normal glucose-6-phosphate-dehydrogenase activity. 1927 91

Proton pump inhibitors (PPIs) are widely used drugs in the treatment or prophylaxis of peptic ulcer and gastro-oesophageal reflux disease. In addition to their well documented efficacy, these drugs are generally well tolerated with only rare serious adverse effects having been reported. Neutropenia and agranulocytosis are rare adverse events associated with PPI treatment. All previously published cases of isolated neutropenia have involved omeprazole, but leukopenia is labelled as a possible adverse effect in the summary of product characteristics of the other PPIs. In this report, we describe a case of omeprazole-induced neutropenia with further recurrence upon pantoprazole treatment. A 60-year-old man with chronic alcoholism and a medical history of pulmonary tuberculosis, untreated chronic C hepatitis, peripheral artery disease, chronic obstructive pulmonary disease and stable stage 3 chronic kidney disease was admitted with dehydration and malnutrition. Omeprazole 20 mg/day and sucralfate 3 g/day were started for diffuse gastritis on gastric endoscopy. While the patient's blood cell count had been within the normal range before this treatment, routine laboratory examination revealed moderate neutropenia (0.9 x 109/L) after 9 days of treatment. His blood cell count returned to the normal range after discontinuation of omeprazole and no further episodes of neutropenia were noted in the following months. One year later, oesophago-gastroscopy revealed a hiatal hernia with an extensive zone of Barrett's oesophagus. As the lesions did not improve with ranitidine and sucralfate therapy, the patient was started on pantoprazole 40 mg/day. His initial white blood cell count was normal, but moderate neutropenia (0.8 x 109/L) was again noted after only 2 days of pantoprazole treatment. Complete and further stable normalization was obtained within 3 days after replacement of pantoprazole with ranitidine. Toxic and immune-mediated mechanisms are the two commonly proposed mechanisms to explain the pathogenesis of drug-induced neutropenia. This report suggests that PPI-induced neutropenia is immune mediated and argues for a possible cross-reactivity between the two PPIs, as has already been described for PPI-induced hypersensitivity reactions. The report also indicates that patients with a history of neutropenia induced by one PPI may be at risk of recurrence of neutropenia if given another member of this drug class. In these patients, close haematological monitoring is proposed.
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PMID:Proton pump inhibitor-induced neutropenia: possible cross-reactivity between omeprazole and pantoprazole. 2058 18

Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well but some may develop life-threatening side effects such as agranulocytosis, aplastic anemia and cholestatic hepatitis. A 45-year-old female was diagnosed with severe hyperthyroidism. Treatment with Carbimazole 30 mg/day was initiated. Within six weeks following the start of therapy, patient developed potentially life-threatening acute cholestatic hepatitis and agranulocytosis as adverse effects to carbimazole. The patient's symptoms and laboratory abnormalities resolved following withdrawal of offending drug. Agranulocytosis and cholestatic hepatitis together is an extremely rare idiosyncratic side effect of Carbimazole treatment and considered to be dose and age-related. Antithyroid drugs are deceptively easy to use, but because of the variability in the response of patients and the potentially serious side effects, all practitioners who prescribe the drugs need to have a working knowledge of their complex pharmacology.
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PMID:Acute cholestatic hepatitis along with agranulocytosis: a rare side effect of carbimazole. 2058 33


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