Adverse hepatic drug reactions: inflammatory episodes as consequence and contributor.
Susceptibility to drug toxicity is influenced by a variety of factors, both genetic and environmental. The focus of this article is the evidence addressing the hypothesis that inflammation is both a result of and a susceptibility factor for drug toxicity, with an emphasis on liver as a target organ. Results of studies suggesting a role for inflammatory mediators in the hepatotoxicity caused by acetaminophen or ethanol are discussed. For several drugs, the evidence from animal models that concurrent inflammation increases injury is presented. In addition, the occurrence of adverse drug reactions in people with preexisting inflammatory diseases is considered. The special case of idiosyncratic drug reactions is discussed and the potential raised for development of animal models for this type of drug toxicity. The conclusion is that inflammatory factors should be considered as determinants of sensitivity to adverse drug reactions.
Ganey
Patricia E
PE
Department of Pharmacology and Toxicology, Center for Integrative Toxicology, 221 Food Safety and Toxicology Building, Michigan State University, East Lansing, MI 48824, USA.
Luyendyk
James P
JP
Maddox
Jane F
JF
Roth
Robert A
RA
D000818:Animals; D002626:Chemistry, Pharmaceutical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D023421:Models, Animal; D014116:Toxicology