Acetaminophen || Questions and 100% Accurate Answers.

Identify the sources of acetaminophen exposure in cats and dogs. correct answers 1. Acetaminophen is present in more than 200 prescription and OTC formulations. 2. Most toxicoses result from well-meaning but ill-informed administration by owners. 3. Accidental ingestion of owner's medications. Why is acetaminophen not commonly used in cats and dogs? correct answers Low therapeutic index What is the level of plasma protein binding of acetaminophen? correct answers 1. Poor protein binding 2. Wide distribution How are dogs and cats exposed to acetaminophen? correct answers 1. Acetaminophen is present in more than 200 prescription and OTC formulations. 2. Most toxicoses result from well-meaning but ill-informed administration by owners. 3. Accidental ingestion of owner's medications. Which is the main organ involved in acetaminophen metabolism? correct answers 1. Liver (glucuronidation, sulfation, CYT P450) 2. Some kidney Identify the pathways of acetaminophen metabolism. correct answers 1. Glucuronidation 2. Sulfation 3. Cytochrome P450 4. Toxic electrophil NAPQI conjugated by reduced GSH Which pathway of acetaminophen metabolism is most toxicologically important and why? correct answers CYP450 metabolizes acetaminophen to NAPQI, a toxic electrophile Toxicity = conjugation pathways and GSH scavenging capacity exceeded Result: NAPQI accumulation Effects of NAPQI - Depletes GSH and decreases GSH production --> oxidative stress - NAPQI covalently binds to sulfhydryl-containing proteins, especially in mitochondria --> decreased ATP --> cell death (esp. in liver) - NAPQI disrupts plasma membrane proteins and therefore calcium homeostasis - NAPQI oxidizes Hgb to MetHgb --> Heinz bodies --> hemolytic anemia, cyanosis What is the role of GSH is acetaminophen toxicity? correct answers GSH conjugates NAPQI