Acetaminophen

Question 1

T/F acetaminophen is an NSAID

Answer 1

false.

Question 2

mechanism of action of acetaminophen

Answer 2

inhibits prostaglandin PG synthesis in CNS. Blocks pain impulse generation peripherally. inhibits hypothalamus heat-regulating centre to reduce fever.

Question 3

hepatic metabolic pathways that Handles drug metabolsim

Answer 3

§ Phase I: Alters the parent molecule
(oxidation/reduction/hydrolysis)

§ Phase II: Conjugates the molecule/metabolite with a water-soluble moiety

§ Phase III: Excretes the molecule/metabolite/conjugate
into bile

Question 4

how Is acetaminophen metabolized in the hepatic system

Answer 4

via Phase 2: conjugation of the molecule with a water soluble moiety, Yiels non-toxic conjugates (glucuronide and sulphate) that are excreted in the urine.

<10% of acetaminophen is metabolized by oxidative process (PHASE1 ) via cytochrome P450, that yields a TOXIC metabolite NAPQI.
Usually, NAPQI is rapidly conjugated with glutathione to form a non-toxic product, buff the system is overwhelmed (ex with alcohol) NAPQI can build up BECAUSE GLUTATHIONE STORES ARE DEPLETED. Alcoholics can OD very quickly even with low doses of Tylenol.

Question 5

how does acetaminophen cause hepatotoxicity

Answer 5

Usually, NAPQI is rapidly conjugated with glutathione to form a non-toxic product, buff the system is overwhelmed (ex with alcohol) NAPQI can build up BECAUSE GLUTATHIONE STORES ARE DEPLETED. Alcoholics can OD very quickly even with low doses of Tylenol.

Overall, NAPQI causes oxidative injury and hepatocellular centrilobular necrosis.

Question 6

outline the stages of acetaminophen toxicity

Answer 6

1. asymptomatic, N/V, diaphoresis,
   lethargy; normal laboratory studies
2. (24-72 hr): initial symptom improvement, then RUQ pain; AST/ALT, INR and bilirubin elevation begins, nephrotoxicity
3. N/V reappears along with jaundice,
   encephalopathy, bleeding diathesis, hypoglycemia, lactic acidosis, renal failure; peak LET/LFT abnormalities; (death)
4. Recovery (typically complete) if they don’t die.

Question 7

Risk factors for acetaminophen-induced hepatotoxicity

Answer 7

age
dose
blood level
chronic excessive alcohol
nutritional fasting
concomitant medication
tine of presentation.

Question 8

Labs to order for acetaminophen toxicity

Answer 8

§ ABCs
§ History (dose, intent, pattern of use
(single/repeated), time of ingestion, co-ingestions,
comorbidities)
§ Serum [acetaminophen]
§ Repeat serum concentration 4 hrs following ingestion or presentation
§ Electrolytes, creatinine, bilirubin, INR, AST/ALT
§ Consider blood and urine toxin screen

Question 9

management for acetaminophen

Answer 9

NAC, may also need to transfer to liver transplant centre. Also should prevent drug absorption via gastric tube or GI decontamination with activated charcoal (within 4 hours)