Acetaminophen | Answer |
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 |