Acetaminophen Mechanism and Metabolism Quiz
73 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the therapeutic mechanism of action of APAP?

  • Inhibition of central prostaglandin synthetase, providing analgesic and antipyretic effects (correct)
  • Stimulation of central prostaglandin synthetase, providing anti-inflammatory effects
  • Inhibition of central prostaglandin synthetase, providing anti-inflammatory effects
  • Stimulation of central prostaglandin synthetase, providing analgesic and antipyretic effects

    • Which metabolic pathway is crucial for the safety of acetaminophen?

  • Conjugation with glucuronide
  • Conjugation with sulfate
  • reduced glutathione (GSH) and other thiol-containing substances (correct)
  • Oxidation by cytochrome P450 enzymes

    • What proportion of APAP is metabolized through conjugation with glucuronide in a normal adult host with therapeutic ingestion?

  • 70%
  • 30%
  • 10%
  • 50% (correct)

    • What role do electron donors like reduced glutathione (GSH) play in the safety of acetaminophen?

    <p>Detoxifying NAPQI formed during its metabolism</p> Signup and view all the answers

    What is the primary pathway for the metabolism of acetaminophen in the liver?

    <p>Glucuronide conjugation</p> Signup and view all the answers

    All of the following correct enzyme is responsible for the oxidation of acetaminophen to NAPQI except?

    <p>GSH</p> Signup and view all the answers

    What happens to NAPQI after it is formed in the liver?

    <p>It combines with GSH to form nontoxic cysteine/mercaptate conjugates</p> Signup and view all the answers

    What is the proportion of APAP that is metabolized through sulfate conjugation?

    <p>20-45%</p> Signup and view all the answers

    What happens to APAP metabolism in an overdose situation?

    <p>Glucuronidation and sulfation pathways become saturated</p> Signup and view all the answers

    What happens when the rate and quantity of NAPQI formation overwhelms GSH supply and regeneration?

    <p>Cellular dysfunction and cell death occur</p> Signup and view all the answers

    What is the consequence of prolonged elimination of NAPQI in an overdose situation?

    <p>Reduced hepatotoxicity</p> Signup and view all the answers

    What is the result of saturation of glucuronidation and sulfation pathways in an overdose situation?

    <p>Increased metabolism of APAP by p450 cytochromes to NAPQI</p> Signup and view all the answers

    Which of the following factors can adversely affect APAP metabolism?

    <p>Frequent dosing interval of APAP</p> Signup and view all the answers

    Which enzyme's activity is upregulated by smoking and other substances, leading to adverse effects on APAP metabolism?

    <p>CYP 2E1</p> Signup and view all the answers

    What factor can lead to decreased glutathione stores, adversely affecting APAP metabolism?

    <p>Prolonged duration of excessive APAP dosing</p> Signup and view all the answers

    Which of the following can adversely affect APAP metabolism?

    <p>Barbiturates</p> Signup and view all the answers

    What factors can decrease glutathione (GSH) stores?

    <p>Age, chronic alcoholism, and HIV</p> Signup and view all the answers

    Which of the following is a way to replace glutathione (GSH) stores?

    <p>Eating</p> Signup and view all the answers

    All of the following correct could be a factor leading to decreased glutathione stores and adversely affecting APAP metabolism except?

    <p>NAC ingestion</p> Signup and view all the answers

    Which of the following can replace glutathione (GSH) stores ?

    <p>NAC</p> Signup and view all the answers

    In which scenario do most acetaminophen (APAP) overdoses in children occur?

    <p>During fasting in acute febrile illness</p> Signup and view all the answers

    What is the likelihood of children becoming toxic from the ingestion of one or two APAP tablets?

    <p>Unlikely due to the large therapeutic index</p> Signup and view all the answers

    What is the possible reason for most children receiving multiple excessive dosing of acetaminophen (APAP)?

    <p>Excessive dosing during acute febrile illness</p> Signup and view all the answers

    What factor contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to APAP toxicity?

    <p>Oxidant stress and depleted GSH levels</p> Signup and view all the answers

    Why do young children have a low incidence of hepatotoxicity from acetaminophen (APAP) ingestion?

    <p>They have an increased rate of spontaneous vomiting</p> Signup and view all the answers

    What is the major hepatic conjugation pathway for acetaminophen (APAP) in young children?

    <p>Sulfate conjugation</p> Signup and view all the answers

    What partially explains the relative resistance of young children to APAP induced hepatotoxicity?

    <p>Increased synthesis of glutathione (GSH) compared to adults</p> Signup and view all the answers

    What is one reason for the low incidence of APAP hepatotoxicity in young children?

    <p>Reduced oxidative metabolism of APAP in the liver</p> Signup and view all the answers

    What is the primary cause of kidney toxicity from acetaminophen (APAP) ingestion?

    <p>Binding of NAPQI to cellular macromolecules in the renal tubules</p> Signup and view all the answers

    Which enzyme is involved in the production of NAPQI in the renal tubules?

    <p>Cytochrome P-450 enzymes</p> Signup and view all the answers

    What is the consequence of NAPQI binding to cellular macromolecules in the renal tubules?

    <p>Acute tubular necrosis and renal failure</p> Signup and view all the answers

    What contributes to approximately 25% of hepatotoxic cases related to acetaminophen (APAP) ingestion?

    <p>Production of NAPQI by cytochrome P-450 enzymes in the renal tubules</p> Signup and view all the answers

    What is the consequence of NAPQI binding to cellular macromolecules in the renal tubules?

    <p>Acute tubular necrosis &amp; renal failure</p> Signup and view all the answers

    What contributes to approximately 25% of hepatotoxic cases related to acetaminophen (APAP) ingestion?

    <p>Production of NAPQI in the renal tubules</p> Signup and view all the answers

    What metabolic pathway is crucial for the safety of acetaminophen?

    <p>Glucuronidation</p> Signup and view all the answers

    Why do young children have a low incidence of hepatotoxicity from acetaminophen (APAP) ingestion?

    <p>Lower levels of cytochrome P-450 enzymes</p> Signup and view all the answers

    What is the controversial relationship between myocarditis, pancreatitis, and multisystem organ failure from fulminant hepatic failure (MSOF) primarily attributed to?

    <p>Local accumulation of toxic metabolites</p> Signup and view all the answers

    Which factor contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to acetaminophen (APAP) toxicity?

    <p>Reduced glutathione (GSH) stores</p> Signup and view all the answers

    What proportion of APAP is metabolized through sulfate conjugation in a normal adult host with therapeutic ingestion?

    <p>20%</p> Signup and view all the answers

    Which enzyme is involved in the production of NAPQI in the renal tubules?

    <p>Cytochrome P450</p> Signup and view all the answers

    What is one reason for the low incidence of APAP hepatotoxicity in young children?

    <p>Greater availability of glutathione in young children</p> Signup and view all the answers

    What is a common symptom seen during stage II of APAP toxicity?

    <p>Nausea and vomiting</p> Signup and view all the answers

    What is a potential outcome of stage III APAP toxicity?

    <p>Hypoglycemia and jaundice</p> Signup and view all the answers

    What is the likely outcome of stage IV APAP toxicity without intervention?

    <p>High fatality rate</p> Signup and view all the answers

    What symptom is associated with stage I of APAP toxicity?

    <p>Anorexia and asymptomatic presentation</p> Signup and view all the answers

    What is the recommended timing for conducting an APAP level in an acute single ingestion?

    <p>4 hours post ingestion</p> Signup and view all the answers

    When should liver function tests (LFTs) be considered for a patient who has ingested acetaminophen (APAP)?

    <p>4 hours post ingestion</p> Signup and view all the answers

    What is the indication for considering liver enzymes, amylase, bilirubin, electrolytes, creatinine, and prothrombin time in a patient who has ingested acetaminophen (APAP)?

    <p>When the 4-hour APAP level is on or near the treatment line</p> Signup and view all the answers

    What justifies conducting liver function tests (LFTs) for a patient who has ingested acetaminophen (APAP)?

    <p>Symptoms suggestive of liver injury or unwell appearance</p> Signup and view all the answers

    What is the main role of NAC in preventing the binding of NAPQI to hepatocytes?

    <p>Directly binding and detoxifying NAPQI to cysteine and mercaptate conjugate</p> Signup and view all the answers

    What is the minor role of NAC in preventing the binding of NAPQI to hepatocytes?

    <p>Enhancing the synthesis of glutathione (GSH) to detoxify NAPQI</p> Signup and view all the answers

    What role does the sulfur group of NAC play in preventing the binding of NAPQI to hepatocytes?

    <p>Detoxifies NAPQI to cysteine and mercaptate conjugate</p> Signup and view all the answers

    Which action does NAC take in preventing the binding of NAPQI to hepatocytes?

    <p>Enhances GSH synthesis</p> Signup and view all the answers

    What is the most effective treatment for significant APAP ingestion close to 8 hours post-ingestion?

    <p>NAC (N-acetylcysteine)</p> Signup and view all the answers

    What is the level of APAP ingestion that warrants treatment above the treatment line?

    <p>Above 150 mcg/ml</p> Signup and view all the answers

    At what point post-APAP ingestion does NAC become less effective?

    <p>Within 24 hours</p> Signup and view all the answers

    What defines chronic ingestions of APAP in children?

    <p>More than 120mg/day</p> Signup and view all the answers

    What is the recommended action if vomiting occurs within 1 hour of taking the oral dose of NAC?

    <p>Repeat the dose</p> Signup and view all the answers

    Under what circumstances is IV administration of NAC preferable to oral administration?

    <p>Liver failure</p> Signup and view all the answers

    What is the percentage of solution in which NAC is used and should be diluted with 3 parts fruit juice?

    <p>10%</p> Signup and view all the answers

    When should NAC be best given if AC (activated charcoal) has been administered?

    <p>30 to 60 minutes after AC administration</p> Signup and view all the answers

    What is the primary site of production for factor VIII?

    <p>Endothelial cells</p> Signup and view all the answers

    What happens to the production of factor V with hepatocellular necrosis?

    <p>Diminishes</p> Signup and view all the answers

    What would happen to factor VIII production if the ratio of factor VIII/V becomes abnormal?

    <p>Becomes impaired</p> Signup and view all the answers

    What is the effect of APAP on factor V production?

    <p>Decreases it</p> Signup and view all the answers

    What can lead to intravascular volume depletion and lactic acidosis from dehydration/hypoperfusion?

    <p>Both A and B</p> Signup and view all the answers

    What is a potential consequence of lactic acidosis without evidence of Hepatic failure from acetaminophen ingestion?

    <p>Reduced glutathione (GSH) stores</p> Signup and view all the answers

    What is the primary outcome of saturation of glucuronidation and sulfation pathways in an acetaminophen overdose situation?

    <p>Hepatic failure</p> Signup and view all the answers

    What contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to acetaminophen (APAP) toxicity?

    <p>Overwhelmed GSH supply and regeneration by NAPQI formation</p> Signup and view all the answers

    What is the primary reason for the heightened risk of drug toxicity when consuming alcoholic beverages and acetaminophen together?

    <p>Consumption of alcohol depletes glutathione, reducing the ability to detoxify NAPQI</p> Signup and view all the answers

    How does alcohol consumption affect the amount of toxic metabolite (NAPQI) formed in the body?

    <p>Alcohol depletes glutathione, leading to increased formation of toxic metabolites</p> Signup and view all the answers

    What is the effect of alcohol on the rate at which the toxic metabolite (NAPQI) is detoxified?

    <p>Alcohol slows down the detoxification of NAPQI</p> Signup and view all the answers

    What is the impact of alcohol consumption on the formation of NAPQI in comparison to individuals who do not drink alcohol?

    <p>Alcoholics form more NAPQI than individuals who do not drink alcohol</p> Signup and view all the answers

    Study Notes

    Therapeutic Mechanism of Acetaminophen (APAP)

    • APAP acts as an analgesic and antipyretic by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), leading to reduced production of prostaglandins.
    • The primary metabolic pathway involves conversion to non-toxic metabolites via conjugation with glucuronide or sulfate.

    Metabolism Safety and Pathways

    • Conjugation with glucuronide is crucial for the safety of acetaminophen, with about 50-60% of APAP metabolized through this pathway in normal adults.
    • Approximately 30-40% of APAP undergoes sulfate conjugation.
    • Reduced glutathione (GSH) donates electrons to neutralize the toxic metabolite NAPQI, protecting cells from damage.

    Overdose Effects

    • In overdose situations, APAP metabolism shifts, resulting in increased formation of NAPQI, which can overwhelm GSH stores.
    • When GSH is depleted, NAPQI binds to cellular macromolecules, leading to hepatotoxicity.
    • Prolonged NAPQI presence in overdose can cause severe liver damage and failure.

    Factors Affecting Metabolism

    • Smoking and certain substances upregulate cytochrome P450 enzymes, promoting NAPQI formation.
    • Factors that can decrease GSH levels include malnutrition, chronic alcohol consumption, and fasting.

    Clinical Implications in Children

    • Most APAP overdoses in children occur from unintentional multiple doses due to caregiver confusion about dosing.
    • Short-term fasting during illness remains controversial regarding its effect on APAP toxicity risk in children.
    • Young children experience a lower incidence of hepatotoxicity, partly due to different metabolic pathways.

    N-Acetylcysteine (NAC) Intervention

    • NAC acts as a precursor to GSH, helping replenish GSH stores and prevent NAPQI binding to hepatocytes.
    • The effectiveness of NAC diminishes after 8 hours post-ingestion; therefore, early intervention is critical.
    • If vomiting occurs within 1 hour after taking oral NAC, another dose is recommended.

    Acetaminophen Toxicity Stages

    • Stage I symptoms include nausea and vomiting, typically occurring within the first 24 hours.
    • Stage II may present with abdominal pain, while stage III may lead to severe liver damage.
    • Without treatment, stage IV could result in multi-organ failure.
    • Liver function tests (LFTs) should be conducted after ingesting potentially toxic amounts of APAP.
    • The treatment threshold is usually above the treatment line on the APAP nomogram.
    • Activated charcoal (AC) can be administered alongside NAC unless contraindicated.

    Other Considerations

    • Chronic APAP ingestions in children are defined by repeated dosing over days.
    • Alcohol consumption increases the risk of APAP toxicity by boosting NAPQI formation and reducing detoxification speed.

    Additional Effects on Coagulation Factors

    • Factor VIII production occurs predominantly in the liver; hepatocellular necrosis affects factor V synthesis as well.
    • An abnormal ratio of factor VIII/V can indicate liver dysfunction and potential bleeding complications.

    Conclusion on NAC and APAP Interaction

    • NAC's main role is to mitigate the formation of harmful metabolites, extending hepatocyte viability during overdose scenarios.
    • Understanding risk factors and management strategies for APAP toxicity is essential for effective clinical intervention.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Description

    Test your knowledge on the therapeutic mechanism of action and metabolic pathways of acetaminophen (APAP). Learn about the central prostaglandin synthetase inhibition and the safety considerations related to APAP metabolism.

    More Like This

    BLS Pharmacology: Acetaminophen
    36 questions

    BLS Pharmacology: Acetaminophen

    ColorfulTaylor avatar
    ColorfulTaylor
    Acetaminophen Overview and Usage
    33 questions

    Acetaminophen Overview and Usage

    ProfoundPearTree avatar
    ProfoundPearTree
    Acetaminophen (Tylenol) Flashcards
    10 questions

    Acetaminophen (Tylenol) Flashcards

    StatelyComposite avatar
    StatelyComposite
    Acetaminophen (Tylenol) Flashcards
    21 questions

    Acetaminophen (Tylenol) Flashcards

    EasygoingAgate6318 avatar
    EasygoingAgate6318
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser