Risk of Using APAP in Alcoholics 2 +salicylates

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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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