Acetaminophen

Question 1

examples of acetaminophen and opioid compounds

Answer 1

Percocet, vicodin

Question 2

time of absorption of therapeutic dose of acetaminophen

Answer 2

1 hour

Question 3

time of absorption for overdose of acetaminophen

Answer 3

4 hours

Question 4

order of kinetics of metabolism of APAP

Answer 4

1st order unless hepatotoxicity is present

Question 5

elimination half life for therapeutic doses

Answer 5

2.5 hours

Question 6

mechanism of effects of APAP

Answer 6

poorly understood: weak anti-inflammatory, weak inhibitor of COX, no effect on neutrophils, not a gastric irritant, no effect on bleeding time

Question 7

acetaminophen plays in important role in px who are contraindicated for..

Answer 7

aspirin and NSAIDs

Question 8

basis of toxicity of APAP

Answer 8

metabolism by the liver- normal pathways are overwhelmed, build up of NAPQI, glutathione depleted

Question 9

during overdose/toxicity of APAP, what compounds cause cell death? how are they formed?

Answer 9

ROS, mitochondrial injury, inflammation cytokines due to NAPQI binding to proteins

Question 10

normally, what compound takes care of NAPQI?

Answer 10

glutathione antioxidant

Question 11

factors that may be protective for children in toxicity of APAP

Answer 11

increased sulfation, earlier recognition, smaller doses, self-decontamination

Question 12

if overdose of APAP, what are the outcomes in a px with chronic alcohol abuse vs acute alcohol abuse?

Answer 12

chronic alc: more CYP 1A2 present, predisposed to make more NAPQI (less protected)

acute alc: ethanol competes for CYP2E1 and wins out (more protective)

Question 13

binge alcohol at time of overdose may decrease/increase NAPQI formation?

Answer 13

decrease; but alcoholics have decreased glutathione stores so they’re less protected

Question 14

therapeutic index of APAP

Answer 14

low index (ratio of LD/ED)- 3 grams per day for adults

Question 15

phase 1 of toxicity symptoms/time

Answer 15

nausea, vomiting, elevation of hepatic transaminases, or ASYMPTOMATIC (0.5-24 hrs)

Question 16

phase 2 of toxicity of symptoms/time

Answer 16

abdominal tenderness, elevated ALT, AST, clotting factors impaired (PPT) - (24-72 hrs)

Question 17

phase 3 of toxicity of symptoms/time

Answer 17

hepatic injury: jaundice, coagulation defects, hepatic encephalopathy, renal failure, death (72-96 hrs)

Question 18

phase 4 of toxicity/time

Answer 18

death or resolution of liver failure (4-14 days)

Question 19

treatment of APAP toxicity

Answer 19

NAC: sulfhydryl tripeptide that acts as a glutathione substitute (increases its synthesis and enhances sulfation of acetaminophen)

Question 20

dosing of NAC

Answer 20

72 hr protocol - 18 oral doses

Question 21

risk of toxicity for treatment within 10 hrs of overdose vs 10-24 hrs after overdose

Answer 21

6% — 26% (4 fold elevation (the sooner the NAC is given, the better the outcome)

Question 22

adverse effects of NAC

Answer 22

vomiting, sulfur smell, anaphylaxis associated with IV

Question 23

what chart is used to see what px need treatment and which just need to be monitored

Answer 23

RUMACK NOMOGRAM