Acetaminophen Flashcards
examples of acetaminophen and opioid compounds
Percocet, vicodin
time of absorption of therapeutic dose of acetaminophen
1 hour
time of absorption for overdose of acetaminophen
4 hours
order of kinetics of metabolism of APAP
1st order unless hepatotoxicity is present
elimination half life for therapeutic doses
2.5 hours
mechanism of effects of APAP
poorly understood: weak anti-inflammatory, weak inhibitor of COX, no effect on neutrophils, not a gastric irritant, no effect on bleeding time
acetaminophen plays in important role in px who are contraindicated for..
aspirin and NSAIDs
basis of toxicity of APAP
metabolism by the liver- normal pathways are overwhelmed, build up of NAPQI, glutathione depleted
during overdose/toxicity of APAP, what compounds cause cell death? how are they formed?
ROS, mitochondrial injury, inflammation cytokines due to NAPQI binding to proteins
normally, what compound takes care of NAPQI?
glutathione antioxidant
factors that may be protective for children in toxicity of APAP
increased sulfation, earlier recognition, smaller doses, self-decontamination
if overdose of APAP, what are the outcomes in a px with chronic alcohol abuse vs acute alcohol abuse?
chronic alc: more CYP 1A2 present, predisposed to make more NAPQI (less protected)
acute alc: ethanol competes for CYP2E1 and wins out (more protective)
binge alcohol at time of overdose may decrease/increase NAPQI formation?
decrease; but alcoholics have decreased glutathione stores so they’re less protected
therapeutic index of APAP
low index (ratio of LD/ED)- 3 grams per day for adults
phase 1 of toxicity symptoms/time
nausea, vomiting, elevation of hepatic transaminases, or ASYMPTOMATIC (0.5-24 hrs)
phase 2 of toxicity of symptoms/time
abdominal tenderness, elevated ALT, AST, clotting factors impaired (PPT) - (24-72 hrs)
phase 3 of toxicity of symptoms/time
hepatic injury: jaundice, coagulation defects, hepatic encephalopathy, renal failure, death (72-96 hrs)
phase 4 of toxicity/time
death or resolution of liver failure (4-14 days)
treatment of APAP toxicity
NAC: sulfhydryl tripeptide that acts as a glutathione substitute (increases its synthesis and enhances sulfation of acetaminophen)
dosing of NAC
72 hr protocol - 18 oral doses
risk of toxicity for treatment within 10 hrs of overdose vs 10-24 hrs after overdose
6% — 26% (4 fold elevation (the sooner the NAC is given, the better the outcome)
adverse effects of NAC
vomiting, sulfur smell, anaphylaxis associated with IV
what chart is used to see what px need treatment and which just need to be monitored
RUMACK NOMOGRAM
