August 31, 2015 - Acetaminophen Flashcards Preview

COURSE 1 > August 31, 2015 - Acetaminophen > Flashcards

Flashcards in August 31, 2015 - Acetaminophen Deck (10):
1

Dose-Dependent Toxicity

Is a small list of drugs that have a predictable injury.

2

Dose-Independent Toxicity

Are unpredictable and idiosyncratic. There is a long list of drugs that can cause this.

3

Anti-Pyretic

A drug that counteracts a fever. Tylenol is an example of this.

4

Maximum Daily Dose of Acetaminophen

4000mg

 

Doses of 7-10 grams may cause toxicity.

Doses of >12g will likely cause toxicity.

5

Phases of Drug Metabolism

Phase I: Alters the parent molecule through oxidation / reduction / hydrolysis

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

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

 

 

~90% of acetaminophen is metabolized via conjucation (phase II). Specifically glucoronidation and sulfation. 

6

Acetaminophen and Cytochrome P450

Around 10% of acetaminophen is metablozed by oxidative processes (phase I) by using the cytochrome P450 complex. This yields a toxic metabolite No-acetyl-p-benzo-quinone-imine (NAPQI).

NAPQI is rapidly conjugated with glutathione forming non-toxic compounds.

 

 

With toxic doses, more acetaminophen is converted to the toxic NAPQI and the glutathione stores are depleted, allowing NAPQI to cause oxidative injury and hepatocellular necrosis.

7

Clinical Course of Acetaminophen Toxicity

Stage 1 (0.5 - 24 hours): asymptomatic, N/V, diaphoresis, lethargy, normal laboratory studies

Stage 2 (24-72 hours): initial symptom improvement, then RUQ pain, AST/ALT, INR and bilirubin elevation begins, as well as nephrotoxicity.

Stage 3 (72-96 hours): N/V reappears along with jaundice, encephalopathy, bleeding diathesis, hypoglycemia, lactic acidosis, renal failure, and potentially death.

Stage 4 (4-14 days): Recovery, which is typically complete.

8

Chronic Alcohol and Acetaminophen

Cytochrome P450 also metabolizes ethanol. This upregulates the enzymes which causes more acetaminophen to be converted to NAPQI. As a double-whammy, alcohols also have a decreased level of glutathione which causes NAPQI to stick around longer and cause liver injury.

9

Therapeutic Misadventure

An unintentional overdose.

10

Management of Acetaminophen Toxicity

Take a serum [acetaminophen] as well as a good patient history.

Consider administering N-acetylcysteine (NAC). This can seriously reduce the risk of complications. Use the nomogram to determine if NAC administration is required.

 

Acetaminophen is the #1 cause of acute liver failure.

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