67 Questions
What is the main risk of using acetaminophen (APAP) in alcoholics?
Increased risk for drug toxicity
How does alcohol contribute to the increased risk of drug toxicity when using acetaminophen?
Alcohol depletes glutathione, reducing the ability to detoxify NAPQI
What effect does alcohol have on the toxic metabolite (NAPQI) formed in the body?
Increases the formation of NAPQI
What is the impact of alcohol on the rate at which the toxic metabolite (NAPQI) is detoxified?
Slows down the detoxification of NAPQI
What is the primary reason for synthesizing esters of salicylic acid?
To reduce the irritant effect of salicylic acid when taken orally
Where are the substances converted to salicylate mainly?
In the gastrointestinal mucosa, red cells, and synovial fluid
What is responsible for most of the activity of aspirin and other salicylates?
The salicylic acid moiety
In what way do various derivatives of salicylic acid differ?
In their potency and toxicity
What is the toxic dose of salicylates that may cause serious poisoning?
More than 300 mg/kg
Which of the following is considered a salicylate medicine?
Aspirin
Which form of salicylate is commonly found in liniments and ointments?
Methyl salicylate
What is the potential consequence of consuming over 500 mg/kg of salicylates?
Death
What are the primary types of biochemical abnormalities that appear in salicylate toxicity?
Respiratory and metabolic effects
Which body system is most affected by aspirin overdose?
Respiratory system
What type of acid-base imbalance is associated with salicylate toxicity?
Respiratory alkalosis & metabolic acidosis
What is the primary cause of respiratory alkalosis of salicylate stimulation?
Increased oxygen consumption and breathing rate
How does the bicarbonate buffer system respond to the effect of excessive CO2 loss in respiratory alkalosis?
It decreases hydrogen ion concentration
What is the renal compensation for respiratory alkalosis of salicylate stimulation?
Increased bicarbonate excretion
What is the likely consequence for a patient experiencing delayed renal compensation for respiratory alkalosis caused by salicylate stimulation?
Increased risk of not surviving long enough for intervention
What is the primary impact of salicylates on oxidative phosphorylation?
Prevention of ATP formation during the oxidation of NADH
How does a cell respond to the uncoupling of ATP production from electron transport caused by salicylates?
By increasing the rate of glycolysis
What is the consequence of significant and prolonged obstruction of oxidative phosphorylation by salicylates?
Fatal interference with energy production
What is the major pathway for energy production in a cell affected by salicylates?
Glycolysis
What is the consequence of faster glycolysis due to salicylate overdose?
Metabolic acidosis due to increased production of lactic and pyruvic acids
Which acid is produced in large quantities due to energy depletion by fat oxidation in salicylate overdose?
Acetoacetic acid
What effect does salicylate overdose have on the body's response to energy depletion?
Increased glycolysis and hypoglycemia
What is the end result of the acid load in the blood due to salicylate overdose?
Severe acidosis
What type of acid-base disorder may the patient have?
Metabolic acidosis superimposed on respiratory alkalosis
In which age group does metabolic acidosis develop rapidly ?
Children
What is the presentation often thought to be in children due to brief respiratory alkalosis?
Pure metabolic acidosis
What factor determines the direction of pH change in patients with mixed acid-base disorder?
Age
What mechanism contributes to lactic acidosis in salicylate overdose?
Uncoupling of mitochondrial oxidative phosphorylation
What is the consequence of increased fatty acid metabolism in salicylate overdose?
Ketone formation
What is the primary impact of salicylates on oxidative phosphorylation?
Anaerobic metabolism
Where are substances converted to salicylate mainly?
Liver
What is the primary cause of metabolic acidosis of salicylate overdose?
Renal dysfunction leading to accumulation of sulfuric and phosphoric acids
How does the body respond to the initial respiratory alkalosis caused by salicylate stimulation?
By excreting bicarbonate in the kidneys
What contributes to hypokalemia in the context of salicylate overdose?
Renal bicarbonate diuresis accompanied by sodium and potassium
What is the consequence of renal dysfunction in salicylate overdose?
Accumulation of sulfuric and phosphoric acids
What is the early finding associated with salicylate poisoning?
Nausea, vomiting, hyperpnea, and headache
What contributes to the hypokalemia of salicylate overdose?
Faster glycolysis
What is the primary cause of metabolic acidosis of salicylate overdose?
Blockage of oxidative phosphorylation
Which body system is most affected by aspirin overdose?
Central nervous system
What acid-base abnormality is likely to be present during the initial phase (up to 12 hours) of salicylate overdose?
Alkalosis in blood and urine
What characterizes the phase of salicylate overdose that occurs 12-24 hours post-ingestion?
Shift from alkaline to acid character in blood; presence of coagulation abnormalities
What is the primary effect of salicylate overdose (>24 hours post-ingestion)?
Potassium and hydrogen ion excretion; increase in acidosis
What contributes to the acid-base imbalance during the phase 12-24 hours post-ingestion of salicylates?
Shift from alkaline to acid character in blood; presence of coagulation abnormalities
How is the presence of salicylates in urine tested?
By adding several drops of 10% ferric chloride to 1 mL of urine and observing for a purple color
What does the Done nomogram relate the serum concentration of salicylates to?
Risk and time of ingestion
What serum concentration of salicylate per deciliter is consistent with moderate overdose based on the Done nomogram?
60 mg
What is the relationship between salicylate serum concentration and severity of poisoning?
The serum concentration is closely related to the severity of poisoning
What is the initial step in therapy for aspirin overdose to prevent further absorption of salicylates from the stomach?
Administering ipecac for emesis
In the case of an enteric-coated or sustained-release form of aspirin, what may affect the timeline for performing emesis or lavage?
Decreased absorption in the stomach
What procedure is also helpful in preventing further absorption of salicylates from the stomach in addition to emesis with ipecac and administering activated charcoal?
Administering corticosteroids
What is the primary purpose of gastric lavage in treating aspirin overdose?
To remove salicylates from the stomach
What is the main treatment for dehydration in aspirin overdose?
IV fluids
How is acidosis mainly treated of aspirin overdose?
Bicarbonate
What is the primary purpose of giving enough bicarbonate to maintain the patient’s urine pH above 8?
To enhance elimination of salicylates
What is the central method for controlling seizures in aspirin overdose?
Benzodiazepines
In which type of compartment would salicylic acid be more ionized?
Basic compartment with a relative lack of H+
What happens to salicylic acid in an acidic compartment?
It becomes non-ionized due to its weak acid nature
How is salicylic acid affected by the presence of stronger acids in a compartment?
It becomes more non-ionized due to the presence of stronger acids
Why is salicylic acid described as being 'trapped' in a milieu?
It becomes more non-ionized in an acidic environment
What is the impact of urine pH equal to 8 on the ionization of salicylic acid?
It increases the ionization of salicylic acid
In which condition should hemodialysis be used ?
Liver failure with coagulopathy
What is the impact of ionization on the entry of salicylic acid into the CNS?
It reduces the entry of salicylic acid into the CNS
In what form is almost all salicylic acid present at urine pH equal to 8?
Ionized form
Learn about the heightened risk of drug toxicity when alcoholics consume acetaminophen. Understand how alcohol affects the formation and detoxification of the toxic metabolite NAPQI, leading to a significant decrease in the toxic dose.
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