Pediatrics. 1978 Nov;62(5):880-9.

Pathophysiology of acetaminophen overdosage toxicity: implications for management.

Pediatrics

E Piperno, A H Mosher, D A Berssenbruegge, J D Winkler, R B Smith

PMID: 724340

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.

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Substances

• Acetaminophen
• Transaminases
• Acetylcysteine

MeSH terms

• Acetaminophen / toxicity
• Acetylcysteine / administration & dosage
• Acetylcysteine / metabolism
• Acetylcysteine / therapeutic use
• Animals
• Dogs
• Dose-Response Relationship, Drug
• Edema / etiology
• Female
• Mice
• Transaminases / metabolism

Publication Types

• Journal Article

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