73 Questions
What is the therapeutic mechanism of action of APAP?
Inhibition of central prostaglandin synthetase, providing analgesic and antipyretic effects
Which metabolic pathway is crucial for the safety of acetaminophen?
reduced glutathione (GSH) and other thiol-containing substances
What proportion of APAP is metabolized through conjugation with glucuronide in a normal adult host with therapeutic ingestion?
50%
What role do electron donors like reduced glutathione (GSH) play in the safety of acetaminophen?
Detoxifying NAPQI formed during its metabolism
What is the primary pathway for the metabolism of acetaminophen in the liver?
Glucuronide conjugation
All of the following correct enzyme is responsible for the oxidation of acetaminophen to NAPQI except?
GSH
What happens to NAPQI after it is formed in the liver?
It combines with GSH to form nontoxic cysteine/mercaptate conjugates
What is the proportion of APAP that is metabolized through sulfate conjugation?
20-45%
What happens to APAP metabolism in an overdose situation?
Glucuronidation and sulfation pathways become saturated
What happens when the rate and quantity of NAPQI formation overwhelms GSH supply and regeneration?
Cellular dysfunction and cell death occur
What is the consequence of prolonged elimination of NAPQI in an overdose situation?
Reduced hepatotoxicity
What is the result of saturation of glucuronidation and sulfation pathways in an overdose situation?
Increased metabolism of APAP by p450 cytochromes to NAPQI
Which of the following factors can adversely affect APAP metabolism?
Frequent dosing interval of APAP
Which enzyme's activity is upregulated by smoking and other substances, leading to adverse effects on APAP metabolism?
CYP 2E1
What factor can lead to decreased glutathione stores, adversely affecting APAP metabolism?
Prolonged duration of excessive APAP dosing
Which of the following can adversely affect APAP metabolism?
Barbiturates
What factors can decrease glutathione (GSH) stores?
Age, chronic alcoholism, and HIV
Which of the following is a way to replace glutathione (GSH) stores?
Eating
All of the following correct could be a factor leading to decreased glutathione stores and adversely affecting APAP metabolism except?
NAC ingestion
Which of the following can replace glutathione (GSH) stores ?
NAC
In which scenario do most acetaminophen (APAP) overdoses in children occur?
During fasting in acute febrile illness
What is the likelihood of children becoming toxic from the ingestion of one or two APAP tablets?
Unlikely due to the large therapeutic index
What is the possible reason for most children receiving multiple excessive dosing of acetaminophen (APAP)?
Excessive dosing during acute febrile illness
What factor contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to APAP toxicity?
Oxidant stress and depleted GSH levels
Why do young children have a low incidence of hepatotoxicity from acetaminophen (APAP) ingestion?
They have an increased rate of spontaneous vomiting
What is the major hepatic conjugation pathway for acetaminophen (APAP) in young children?
Sulfate conjugation
What partially explains the relative resistance of young children to APAP induced hepatotoxicity?
Increased synthesis of glutathione (GSH) compared to adults
What is one reason for the low incidence of APAP hepatotoxicity in young children?
Reduced oxidative metabolism of APAP in the liver
What is the primary cause of kidney toxicity from acetaminophen (APAP) ingestion?
Binding of NAPQI to cellular macromolecules in the renal tubules
Which enzyme is involved in the production of NAPQI in the renal tubules?
Cytochrome P-450 enzymes
What is the consequence of NAPQI binding to cellular macromolecules in the renal tubules?
Acute tubular necrosis and renal failure
What contributes to approximately 25% of hepatotoxic cases related to acetaminophen (APAP) ingestion?
Production of NAPQI by cytochrome P-450 enzymes in the renal tubules
What is the consequence of NAPQI binding to cellular macromolecules in the renal tubules?
Acute tubular necrosis & renal failure
What contributes to approximately 25% of hepatotoxic cases related to acetaminophen (APAP) ingestion?
Production of NAPQI in the renal tubules
What metabolic pathway is crucial for the safety of acetaminophen?
Glucuronidation
Why do young children have a low incidence of hepatotoxicity from acetaminophen (APAP) ingestion?
Lower levels of cytochrome P-450 enzymes
What is the controversial relationship between myocarditis, pancreatitis, and multisystem organ failure from fulminant hepatic failure (MSOF) primarily attributed to?
Local accumulation of toxic metabolites
Which factor contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to acetaminophen (APAP) toxicity?
Reduced glutathione (GSH) stores
What proportion of APAP is metabolized through sulfate conjugation in a normal adult host with therapeutic ingestion?
20%
Which enzyme is involved in the production of NAPQI in the renal tubules?
Cytochrome P450
What is one reason for the low incidence of APAP hepatotoxicity in young children?
Greater availability of glutathione in young children
What is a common symptom seen during stage II of APAP toxicity?
Nausea and vomiting
What is a potential outcome of stage III APAP toxicity?
Hypoglycemia and jaundice
What is the likely outcome of stage IV APAP toxicity without intervention?
High fatality rate
What symptom is associated with stage I of APAP toxicity?
Anorexia and asymptomatic presentation
What is the recommended timing for conducting an APAP level in an acute single ingestion?
4 hours post ingestion
When should liver function tests (LFTs) be considered for a patient who has ingested acetaminophen (APAP)?
4 hours post ingestion
What is the indication for considering liver enzymes, amylase, bilirubin, electrolytes, creatinine, and prothrombin time in a patient who has ingested acetaminophen (APAP)?
When the 4-hour APAP level is on or near the treatment line
What justifies conducting liver function tests (LFTs) for a patient who has ingested acetaminophen (APAP)?
Symptoms suggestive of liver injury or unwell appearance
What is the main role of NAC in preventing the binding of NAPQI to hepatocytes?
Directly binding and detoxifying NAPQI to cysteine and mercaptate conjugate
What is the minor role of NAC in preventing the binding of NAPQI to hepatocytes?
Enhancing the synthesis of glutathione (GSH) to detoxify NAPQI
What role does the sulfur group of NAC play in preventing the binding of NAPQI to hepatocytes?
Detoxifies NAPQI to cysteine and mercaptate conjugate
Which action does NAC take in preventing the binding of NAPQI to hepatocytes?
Enhances GSH synthesis
What is the most effective treatment for significant APAP ingestion close to 8 hours post-ingestion?
NAC (N-acetylcysteine)
What is the level of APAP ingestion that warrants treatment above the treatment line?
Above 150 mcg/ml
At what point post-APAP ingestion does NAC become less effective?
Within 24 hours
What defines chronic ingestions of APAP in children?
More than 120mg/day
What is the recommended action if vomiting occurs within 1 hour of taking the oral dose of NAC?
Repeat the dose
Under what circumstances is IV administration of NAC preferable to oral administration?
Liver failure
What is the percentage of solution in which NAC is used and should be diluted with 3 parts fruit juice?
10%
When should NAC be best given if AC (activated charcoal) has been administered?
30 to 60 minutes after AC administration
What is the primary site of production for factor VIII?
Endothelial cells
What happens to the production of factor V with hepatocellular necrosis?
Diminishes
What would happen to factor VIII production if the ratio of factor VIII/V becomes abnormal?
Becomes impaired
What is the effect of APAP on factor V production?
Decreases it
What can lead to intravascular volume depletion and lactic acidosis from dehydration/hypoperfusion?
Both A and B
What is a potential consequence of lactic acidosis without evidence of Hepatic failure from acetaminophen ingestion?
Reduced glutathione (GSH) stores
What is the primary outcome of saturation of glucuronidation and sulfation pathways in an acetaminophen overdose situation?
Hepatic failure
What contributes to uncertainty about whether short-term fasting in acute febrile illness predisposes children to acetaminophen (APAP) toxicity?
Overwhelmed GSH supply and regeneration by NAPQI formation
What is the primary reason for the heightened risk of drug toxicity when consuming alcoholic beverages and acetaminophen together?
Consumption of alcohol depletes glutathione, reducing the ability to detoxify NAPQI
How does alcohol consumption affect the amount of toxic metabolite (NAPQI) formed in the body?
Alcohol depletes glutathione, leading to increased formation of toxic metabolites
What is the effect of alcohol on the rate at which the toxic metabolite (NAPQI) is detoxified?
Alcohol slows down the detoxification of NAPQI
What is the impact of alcohol consumption on the formation of NAPQI in comparison to individuals who do not drink alcohol?
Alcoholics form more NAPQI than individuals who do not drink alcohol
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.
Make Your Own Quizzes and Flashcards
Convert your notes into interactive study material.
Get started for free
