Hepatotoxicity of psychotropic drugs

FRANÇAIS :
Les neuroleptiques, les antidépresseurs tricycliques, les anxiolytiques (BZD), les inhibiteurs de l'acétylcholinestérase, les drogues illicites telles que la cocaïne et l'ecstasy ont un potentiel d'hépatotoxicité qui est imprévisible. La plupart de ces drogues psychotropes ont des effets caractéristiques: cholestases pour la chlorpromazine et les tricycliques, actions hépatiques pour les hydrazines et les inhibiteurs de la MAO, la cocaïne et l'ecstasy, qui pourraient mettre en jeu des phénomènes d'hypersensibilité. Ceci pose le problème de l'utilisation de ces drogues chez les patients souffrant de pathologies hépatiques.
ENGLISH :
Psychotropic drugs with hepatotoxic potential can be classified based on their intended use: 1) antipsychotics-neuroleptics including phenothiazines, butyrophenones, an clozapine, 2) antidepressants including tricyclics, serotonin reuptake inhibitors, and monoamine oxidase (MAO) inhibitors; 3) anti-anxiety drugs such as benzodiazepines; 4) acetylcholinesterase inhibitors such as tacrine; and 5) drugs of abuse including cocaine and ecstasy. Antiseizure drugs represent another class of central nervous system (CNS) drugs, but will not be considered here. Hepatotoxicity of psychotropic drugs occurs in a variable but small proportion of users and therefore can be considered unpredictable or idiosyncratic. When these uncommon adverse events occur in association with rash, eosinophilia, and/or a rapid positive rechallenge, sufficient circumstantial evidence exists to ascribe the mechanism to an immune-mediated hypersensitivity reaction. Acute overt reactions to drugs tend to have clinicopathological features of hepatitis (destruction of liver parenchyma), cholestasis (impaired bile secretion), or both. The hepatotoxic reactions to psychotropic drugs conform to these general patterns. Furthermore, as with most hepato toxic drugs, individual psychotropic drugs have a characteristic pattern of injury, i.e., cholestatic for some (e.g., chlorpromazine, haloperidol, tricyclics), hepatitic for others (e.g., hydrazines, MAO inhibitors, cocaine, ecstasy). (Author's abstract.)