Hepatic effects of drugs used in the treatment of peptic ulcer disease.
Although one member of the H2 blocker family (oxmetidine) proved to be intrinsically hepatotoxic, overt hepatic injury attributable to cimetidine and ranitidine is decidedly rare, given the tens of millions of patients who have received these medications. Even considering the fact that serious adverse reactions may be underreported by as much as a factor of 100, the number of reports submitted to the FDA-DDE of possible hepatic toxicity associated with these agents supports this low incidence. Whether or not a similarly low incidence will be seen with famotidine and the newer H2 receptor antagonists still under investigation must await additional clinical experience. The major effect of cimetidine on the liver is inhibition of the mixed function oxidase system responsible for the metabolism of many drugs and other compounds. Ranitidine and famotidine at usual doses do not appear to share the same drug interaction potential. Although cimetidine may potentiate the action of several medications with a narrow therapeutic range, possibly leading to clinical toxicity, its inhibitory effect on oxidative metabolism also appears to be the basis for its unique, potentially hepatoprotective role against injury due to acetaminophen and certain other hepatotoxins. Whether or not cimetidine will become clinically useful in the setting of acute acetaminophen overdose remains speculative at this time. The investigational drug, omeprazole, a substituted benzimidazole, is also capable of inhibiting the cytochrome P-450 system. Antacids, sucralfate, and other coating agents are devoid of any hepatotoxic potential, as they are essentially nonsystemic compounds. E-type prostaglandins currently under investigation for treatment of peptic ulcer disease do not appear to be intrinsically hepatotoxic, and, in fact, may have important hepatoregulatory and hepatoprotective properties.
D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002927:Cimetidine / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010437:Peptic Ulcer / Q000188:drug therapy*; D011899:Ranitidine / Q000009:adverse effects
D006635:Histamine H2 Antagonists; D002927:Cimetidine; D011899:Ranitidine; D006899:Mixed Function Oxygenases