Acetaminophen Toxicity and Food-Drug Interactions

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Questions and Answers

What is the primary way naringin in grapefruit juice affects drug metabolism?

It promotes the elimination of drugs from the body.

It increases the effectiveness of drugs by enhancing their solubility.

It inhibits the enzyme CYP3A4. (correct)

It enhances the absorption of drugs into the bloodstream.

Which type of drugs does naringin notably interact with?

Antihistamines

Antibiotics

Statins (correct)

Antidepressants

What is the consequence of naringin inhibiting CYP3A4 enzyme activity?

Increased drug effectiveness.

Accelerated drug metabolism.

Decreased drug bioavailability. (correct)

Enhanced transport of drugs into cells.

Which of the following is a function of the Organic Anion Transporting Peptide (OATP) family?

Facilitating the transport of drugs from the blood into cells. Signup and view all the answers

What is the specific role of CYP3A4 in the context of drug metabolism?

It is involved in about 50% of all drug metabolism. Signup and view all the answers

What is the primary consequence of increased levels of NAPQI in the liver?

Formation of mercapturic acid conjugates Signup and view all the answers

Which factor is NOT associated with limiting GSH availability during acetaminophen metabolism?

High SAA availability Signup and view all the answers

How does starvation affect acetaminophen metabolism?

Results in higher levels of NAPQI available for liver metabolism Signup and view all the answers

Which mechanism contributes to liver cell death in the presence of NAPQI?

NAPQI attacks protein SH groups Signup and view all the answers

What effect does SAA deficiency have on acetaminophen metabolism?

Limits GSH availability Signup and view all the answers

What condition can result from downstream suppression of aldosterone?

Hyperkalemia Signup and view all the answers

What can a blood potassium level above 6.5 mmol/L potentially cause?

Cardiac complications Signup and view all the answers

How does vitamin K affect the efficacy of anticoagulant drugs like warfarin?

It reduces their effectiveness. Signup and view all the answers

Which antibiotics are known to be affected by calcium in foods?

Tetracycline and fluoroquinolone Signup and view all the answers

What dietary component should be limited when taking anticoagulant medications?

Vitamin K Signup and view all the answers

What is the treatment for severe hyperkalemia?

Dialysis and medications to lower potassium Signup and view all the answers

Which of the following is NOT a symptom of hyperkalemia?

Rash Signup and view all the answers

What is the role of clozapine in the context of food interactions?

It is an anti-psychotic drug. Signup and view all the answers

What is the effect of caffeine on clozapine metabolism?

Caffeine inhibits clozapine metabolism. Signup and view all the answers

What is the bioactive metabolite formed from clozapine metabolism?

N-desmethylclozapine Signup and view all the answers

What can induce CYP1A2 expression and potentially affect clozapine metabolism?

Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) Signup and view all the answers

What percentage of Canadians reportedly misused over-the-counter drugs from 2004 to 2008?

33% Signup and view all the answers

What is a common result of acetaminophen overdose?

Acute liver failure Signup and view all the answers

What is the recommended maximum daily dose of acetaminophen, despite existing controversy?

4.0 g Signup and view all the answers

What percentage of acetaminophen-related hospitalizations in Canada were reported as accidental overdoses?

16% Signup and view all the answers

What type of function is compromised due to neutropenia caused by certain metabolites of clozapine?

Immune function Signup and view all the answers

What is a common behavior that can lead to accidental overdose of acetaminophen?

Using multiple medications containing acetaminophen simultaneously Signup and view all the answers

Which phase of metabolism is NOT typically required for acetaminophen?

Phase I metabolism Signup and view all the answers

What happens to some of the acetaminophen that is metabolized by CYP enzymes?

It forms N-acetyl-p-benzoquinoneimine (NAPQI) Signup and view all the answers

What is the primary consequence of NAPQI reacting with protein sulfhydryl (SH) groups?

Liver cell death Signup and view all the answers

Which CYP enzyme is primarily responsible for high-dose metabolization of acetaminophen?

CYP2E1 Signup and view all the answers

Which of the following conjugation processes is saturated at high doses of acetaminophen?

Both glucuronidation and sulfation Signup and view all the answers

What is a possible outcome when conducting studies on toxic substances?

Old data lacks strong ethical rationale for study Signup and view all the answers

How can glutathione conjugation affect NAPQI?

It can convert NAPQI into a harmless substance Signup and view all the answers

What is the effect of sulfur amino acid (SAA) deficiency on acetaminophen-induced liver damage?

It leads to increased hepatic necrosis at lower acetaminophen doses. Signup and view all the answers

Which pathway becomes more utilized in acetaminophen metabolism when SAA availability is low?

Glucuronidation for excretion. Signup and view all the answers

What happens to GSH levels during high doses of acetaminophen administration?

GSH levels decrease over time. Signup and view all the answers

How does increased activation of CYP2E1 affect acetaminophen metabolism at higher doses?

It increases NAPQI production leading to more liver cell death. Signup and view all the answers

What is the main consequence of low GSH availability during acetaminophen metabolism?

It increases liver cell death due to protein modification. Signup and view all the answers

At what specific dosage does hepatic necrosis occur in 50% of SAA deficient rats compared to those on a complete diet?

280 mg/kg. Signup and view all the answers

What role does ROS play in acetaminophen metabolism related to GSH levels?

ROS is produced during Phase I and is countered by GSH. Signup and view all the answers

What indicates a saturation point in the glucuronidation pathway during high acetaminophen doses?

Increased NAPQI formation. Signup and view all the answers

Study Notes

Acetaminophen Toxicity and Nutritional Status

Acetaminophen is a common medication, but overdose can be fatal
Grapefruit juice can significantly alter the metabolism of many drugs
Naringin, a compound in grapefruit juice, inhibits CYP3A4 activity, a key enzyme in drug metabolism
This can lead to increased drug levels in the body, potentially causing adverse reactions
Medications boosted by grapefruit juice include calcium channel blockers, statins, and immunosuppressants

Food-Drug Interactions

Seafood is rich in iodine
Anti-thyroid medications impair iodine absorption
High dietary iodine intake requires higher anti-thyroid medication doses, potentially increasing drug side effects
Bananas are rich in potassium
ACE inhibitors can cause potassium retention
Combining bananas with ACE inhibitors may cause hyperkalemia (potentially fatal)
Hyperkalemia is a condition of high potassium levels in blood
Symptoms can range from mild to severe cardiac complications

Vitamin K and Anticoagulants

Vitamin K is essential for blood clotting
Phylloquinone and menaquinone are forms of vitamin K
Warfarin is an anticoagulant that inhibits vitamin K-dependent clotting factors
High vitamin K intake can counteract the effects of anticoagulants, increasing clot formation

Calcium and Antibiotics

Calcium can bind some antibiotics, reducing their absorption
This reduces antibiotic bioavailability and may lead to insufficient anti-bacterial effects
Tetracycline and fluoroquinolone antibiotics are affected by calcium
Penicillin is not affected by calcium

Caffeine and Antipsychotics

Caffeine and clozapine are both metabolized by CYP1A2
When taken together, caffeine inhibits clozapine's metabolism
This can reduce clozapine's effectiveness
Other metabolites from clozapine can damage the liver and decrease immune function

Acetaminophen Metabolism

Acetaminophen metabolism typically involves two phases
Phase 1 involves oxidation by enzymes such as CYP 2E1, and possibly others
Phase 2 involves conjugation with glucuronide or sulfate
High doses can overwhelm the conjugation pathways
This leads to the formation of a reactive metabolite (NAPQI)
NAPQI can cause liver damage
Alcohol intake affects liver metabolism, leading to greater toxicity risks to acetaminophen

Chronic Acetaminophen Toxicity

4.0 g maximum daily dose; some controversy around the safety.
325 mg tablets, 5-6g = 20-24 tabs
70 kg adult, 6g = 85 mg acetaminophen/kg body weight
Frequent, chronic ingestion is of concern, especially in combination with other factors.

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Description

This quiz explores the dangers of acetaminophen overdose and highlights significant food-drug interactions, particularly with grapefruit juice, iodine, and potassium. Understanding these interactions is crucial for proper medication management and safety. Test your knowledge on how certain foods affect drug metabolism and side effects.