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)

Ranitidine was first marketed in 1981; since then many patients have been treated such that much experience has been accumulated on the safety of this histamine H2-receptor antagonist in the treatment of gastroduodenal disease. A wide array of ranitidine-associated side effects has been described, but infrequently. As so much information is now available, the aim of this review is to assess the weight of evidence for a causal link between ranitidine and the reported side effects. Overall, ranitidine is well tolerated. The incidence of general side effects at less than 2% is very similar to placebo. Headaches, tiredness, dizziness and mild gastrointestinal disturbance (e.g. diarrhoea, constipation and nausea) are among the most frequent complaints, but have very seldom resulted in stopping treatment. Cardiovascular side effects are extremely rare and unpredictable with the usual doses of oral ranitidine (at most 1 in 1 million patients). They mostly comprise sinusal bradycardia and atrioventricular blockade, especially after rapid intravenous administration, receding after cessation of the drug. Clinical studies, however, have not shown a significant pharmacological effect of ranitidine on the cardiovascular system via H2-receptors, even though individual sensitivities cannot be ruled out in a few isolated reports. Ranitidine is unlikely to be directly hepatotoxic: a transient change in liver function tests has been noted in only 1 in 100 to 1 in 1000 patients. Several cases of mixed hepatitis have been reported, but very few were fully documented. The incidence of ranitidine-associated acute hepatitis has been estimated to be less than 1 in 100,000 patients. Neuropsychiatric complications may be less common and clinically quite similar to those reported with cimetidine, i.e. confusion, disorientation, hallucinations, delirium. These side effects have occurred especially in critically ill and multiple-therapy patients, or patients with chronic renal or hepatic failure, so that the direct causal link with ranitidine treatment was often difficult to ascertain. Even though an H2-receptor-mediated effect is an attractive hypothesis (since similar complications were noted with other H2-receptor antagonists), other mechanisms have been suggested to play a role, e.g. cholinergic or histaminic effects. The overall incidence of neuropsychiatric complications is probably markedly less than 1%. White cell injury (i.e. agranulocytosis) appears to be the most frequent haematological complication, even though case reports are very few and poorly documented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Side effects of ranitidine. 204 87

Treatment of duodenal ulcer with the histamine H2-receptor antagonist, ranitidine, was assessed in a double-blind, randomized, multicenter trial in which patients were treated for two consecutive 4-week periods with ranitidine 150 mg b.i.d. or a placebo. All patients were allowed to take antacids as necessary for symptoms. Three hundred eighty-two patients were entered and 355 completed the first 4-week trial period. Ranitidine significantly improved healing at 2 weeks (37 versus 19%, p less than 0.01) and at 4 weeks (73 versus 45%, p less than 0.01), with better relief of pain and lower use of antacids. In the second 4-week trial period, 124 unhealed patients from the first 4 weeks were re-randomized. Ranitidine treatment resulted in a greater healing rate regardless of previous treatment (p less than 0.05). In this trial, side effects were uncommon and not different between placebo and the tested drug. One case of hepatitis in the ranitidine treated group was presumed on the evidence to be non-A non-B. Ranitidine is effective and appears to be safe in the treatment of duodenal ulcer and its symptoms.
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PMID:A multicenter study of ranitidine treatment of duodenal ulcers in the United States. 353 8

This study was undertaken to determine the effects of two H2-receptor antagonists, cimetidine and ranitidine, on halothane metabolism and hepatotoxicity in the hypoxic Fisher 344 rat model for halothane hepatitis. In this model, liver injury is caused by toxic intermediates formed during metabolism of halothane by a reductive pathway. Administration of cimetidine (120 mg/kg ip) 20 min prior to anesthesia led to inhibition of the reductive pathway, as assessed by measurement of the exhaled metabolites, 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, during anesthesia, and urinary fluoride excretion in the 22-hr postanesthesia period. Oxidative metabolism of halothane, assessed by serum bromide concentrations 22 hr postanesthesia, was unaffected. Cimetidine administration provided partial protection against the hepatotoxic effect of halothane, as indicated by serum alanine aminotransferase activities 22 hr postanesthesia. When ranitidine HCl (120 mg/kg ip) was administered prior to anesthesia, reductive metabolism of halothane was unaffected, but the oxidative pathway was slightly inhibited. Ranitidine did not provide protection against halothane-induced liver injury. These results provide additional evidence that halothane hepatotoxicity in the hypoxic rat model is due to toxic intermediates formed during the reductive metabolism of halothane.
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PMID:Effects of cimetidine and ranitidine on halothane metabolism and hepatotoxicity in an animal model. 614

Liver biopsy specimens of pure autoimmune hepatitis (pAIH), autoimmune forms of chronic hepatitis with positivity for anti-hepatitis C virus (anti-HCV) and negativity for HCV-RNA (cAIH-RNA(-)), autoimmune forms of chronic hepatitis with positivity for anti-HCV and HCV-RNA (cAIH-RNA(+)), and chronic hepatitis C (CHC) were compared histologically and statistically to clarify the histological character of the autoimmune form of chronic hepatitis with HCV infection. The following representative histological features were used to investigate: inflammation, fibrosis, plasma cell infiltration, lymphoid aggregates/follicles, non-suppurative destructive cholangitis, and the shape of the enlarged portal tracts. While a considerable overlap in histological features between the pAIH and cAIH-RNA(-) groups and between the CHC and cAIH-RNA(+) groups was recognized, the overlap between the pAIH and CHC groups was small. Significant differences were found between cAIH-RNA(-) and cAIH-RAN(+) groups, especially in necroinflammatory findings. In conclusion, most cases of cAIH-RNA(-) with histological features similar to those of pAIH were shown to be AIH. The remaining cases might be CHC with subsidence of viral duplication. Conversely, many cases of cAIH-RNA(+) with histological findings similar to those of CHC were shown to be CHC clinically mimicking pAIH. The remaining cases might represent coexistence of pAIH and HCV infection.
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PMID:Autoimmune forms of chronic hepatitis associated with hepatitis C virus (HCV) infection with and without HCV-RNA: histological differences from pure autoimmune hepatitis and chronic hepatitis C. 1079 68

Ranitidine is widely used and well tolerated. Ranitidine-related skin eruption is rare and usually mild. We presented two patients who developed Stevens-Johnson syndrome after ranitidine therapy. Before therapy, both patients had severe liver disease and jaundice. The first was a case of ketoconazole-induced hepatitis, and the second was a case of hepatitis C-related liver cirrhosis with hepatocellular carcinoma. Ranitidine was the most likely drug responsible for causing Stevens-Johnson syndrome in these two patients.
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PMID:Ranitidine-related Stevens-Johnson syndrome in patients with severe liver diseases: a report of two cases. 1135 91

Inflammation of the liver may be caused by a variety of factors that include infectious agents and toxins. Reactive oxygen species (ROS) generated by the NADPH oxidase in Kupffer cells and infiltrating leukocytes play an important role in the pathogenesis of early alcohol-induced hepatitis. Histamine dihydrochloride (histamine) suppresses the generation of ROS through the histamine type-2 receptor (H2 receptor). Histamine was studied as a potential protective treatment against early alcohol-induced liver injury in an experimental hepatitis model. Female Wistar rats were given ethanol (5 g/kg) intragastrically by gavage once daily for 4 weeks, while a control group not receiving ethanol was fed an isocaloric high-fat diet. Animals receiving ethanol had elevated serum levels of alanine and aspartate transaminase (ALT/AST) and developed steatosis, inflammation, and necrosis of the liver. Histamine treatment (0.5 or 5.0 mg/kg, twice daily) protected against this liver injury as evident by normal serum transaminase levels and significantly reduced liver pathology scores. Ranitidine (10 mg/kg), an H2 receptor antagonist, blocked the protective effect of histamine, indicating that the histamine effect is predominantly mediated through the H2 receptor. In conclusion, these results suggest that histamine protects against early alcohol-induced liver injury in rats.
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PMID:Histamine dihydrochloride protects against early alcohol-induced liver injury in a rat model. 1463 89

Ranitidine may cause liver injuries ranging from transient, subclinical serum transaminases increase every 100-1,000 treated patients to cholestatic hepatitis in less than 1/100,000. Other H2-receptor antagonists are more dangerous: 11 toxic hepatitis cases have been reported as adverse effect after 1 year of marketed ebrotidine. A 75-year-old male with ischemic cardiopathy history was started on an 8 days treatment of oral ranitidine due to pirosis, without any other changes of therapy; 48 h after drug withdrawal, light-coloured stools, dark urine and icteric scleras developed. On hospital admission, 10 days later, physical examination showed slight hepatomegaly and severe jaundice with skin excoriations followed by serum mixed bilirubin further increase and aminotransferases activities mild rise. Total bilirubin peaked at 381.33 mmol/l (5.1-17.1) and progressively returned to normal, after discharge home, in 3 months and now, 1 year later, there is no sign of liver disease. Ultrasonographic biliary anomalies and the most frequent causes of liver damage were excluded. Liver biopsy confirmed ranitidine as the most likely cause of liver toxicity since histological and ultramicroscopical study revealed a drug-induced picture. We report a rare case of intrahepatic cholestasis jaundice related to ranitidine, a widely used drug. Diagnosis would need an ethically unacceptable rechallange test.
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PMID:Intrahepatic cholestatic jaundice related to administration of ranitidine. A case report with histologic and ultramicroscopic study. 1578 90