ABSTRACT
Acute acetaminophen intoxication was studied in the dog to characterize pathogenesis and in the mouse as a model for antidotal research. In the dog, overt toxicity was manifested principally by cyanosis, facial and paw edema, gastrointestinal disturbance, and coma. Typical laboratory findings were methemoglobinemia, hemoconcentration, leukocytosis, and hepatic centrolobular necrosis. In the mouse, physical signs of acetaminophen overdose appeared to be central in origin; sequelae included anemia, leukopenia, thrombocytopenia, and hepatic centrolobular necrosis. The antidotal profile of acetylcysteine in mice was characterized. When acetylcysteine therapy was instituted early (one hour after acetaminophen overdose), it conferred dose-related protection from lethality coupled with hepatoprotection, as judged from transaminase activity. When acetylcysteine therapy was instituted relatively late (4 1/2 hours after acetaminophen overdose), its beneficial effect on survival persisted but was unaccompanied by distinct hepatoprotection, indicating that SGPT activity was an unreliable prognostic indicator. Acetylcysteine was well tolerated in mice even when administered in the presence of preexisting acetaminophen-induced liver damage.
Subject(s)
Acetaminophen/toxicity , Acetylcysteine/administration & dosage , Acetylcysteine/metabolism , Acetylcysteine/therapeutic use , Animals , Dogs , Dose-Response Relationship, Drug , Edema/etiology , Female , Mice , Transaminases/metabolismABSTRACT
Plasma intact 14C-mixidine levels in rats increased when the drug was administered intraduodenally with 1:3 and 1:5 molar ratios of 2-naphthalenesulfonic acid. Upon histological examination of the duodenums, similar doses of mixidine combined with 2-naphthalenesulfonic acid produced no dose-related lesions. These and previous observations demonstrate that mixidine absorption may be enhanced by ion-pair formation.
