NSAIDS: nonselective vs selective COX-2 inhibitors, indications and side effects

Which of the following statements is NOT true of acetaminophen when used as part of a multimodal analgesic plan?

A. Acetaminophen has a relatively safe side effect profile when taken at the recommended doses.
B. The use of acetaminophen as part of a multimodal analgesic regimen has reduced the incidence of opioid-related adverse events.
C. Acetaminophen overdose is the leading cause for acute hepatic failure in the United States.
D. N-acetylcysteine, an antidote for acetaminophen-induced hepatoxicity, is effective when given within 8 to 10 hours of acetaminophen ingestion.

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Correct Answer: B

Explanation:

The use of acetaminophen has been linked to at best modest reductions in opioids, but that has not resulted in reductions in opioid-related side effects. Acetaminophen is administered at doses of up to 4 grams per day (up to 15mg/kg/dose every 6 hours in patients less than 50kg) in patients without significant renal/hepatic insufficiency. Acetaminophen overdose is the leading cause for acute hepatic failure in the United States. Unintentional overdose occurs due to the multiple different combination drugs that include acetaminophen such as with hydrocodone (Lortab, Vicodin, Norco), oxycodone (Percocet, Roxicet), butalbital/caffeine (Fioricet), and tramadol (Ultracet). The antidote for acetaminophen overdose is N-acetylcysteine and it is most effective when given within 8 to 10 hours of ingestion.

References:

Jahr JS, Lee VK. “ Intravenous acetaminophen”. Anesthesiol Clin 2010;28(4):619-45

Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. “Acetaminophen-Induced Hepatotoxicity: A Comprehensive Update” J of Clinical and Translational Hepatology 2016;4:131-42

Dahl JB, Nielsen RV, Wetterslev J, Nikolajsen L, Hamunen K, Kontinen VK, et al. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand. 2014 Nov;58(10):1165–81

Pierce CA, Voss B. Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review. Ann Pharmacother. 2010 Mar;44(3):489–506.

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