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Acetaminophen genera

Tox lecture 6

Absorption 30 – 60 minutes
Half-life: 1-3.5 hours
Metabolism/Excretion Renal unchanged acetaminophen Phase II: (Conjugation) sulfate/glucuronide conjugate Phase I: (CYP 2E1) conjugation with glutathione
Metabolism/Excretion Phase II: (Conjugation) sulfate/glucuronide conjugate
Metabolism/Excretion Renal unchanged acetaminophen
Metabolism/Excretion Phase I (CYP 2E1) conjugation with glutathione
Overdose Risk Factors Dose When history is reliable Increased frequency of APAP dosing Prolonged duration Increased capacity for CYP2E1 activation Decreased glutathione availability Decreased capacity for glucuronidation and/or sulfation
Impact in overdose Delayed absorption Saturation of normal non-toxic metabolic routes
Mechanism of Toxicity (see diagram in book) Normal metabolic pathway Not many drug interactions Note many things metabolized the same way
Mechanism of Toxicity (see diagram in book) Formation of toxic metabolite: A/-acetyl-p-benzoquinoneimine (NAPQI) RoleofCYP2E1 Importance of glutathione Local formation of NAPQI in tissues
Local formation of NAPQI in tissues Liver Kidneys Pancreas, heart, CNS
Other manifestations Early metabolic acidosis/coma Rule out other causes Associated with higher initial [APAP]? Uncommon
Other manifestations Renal function abnormalities -25% with significant hepatotoxicity
Other manifestations Rarely other manifestation Pancreatitis
Created by: pberriochoa