Acetaminophen (Paracetamol)

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Acetaminophen (Paracetamol)

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Preguntas del estilo USMLE Step 1

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Preguntas del estilo USMLE Step 2

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A 23-year-old woman is brought to the emergency department for evaluation of nausea and vomiting after swallowing several packets of acetaminophen tablets. The patient swallowed the pills 5 hours ago. Past medical history is significant for major depressive disorder which is being treated with fluoxetine. Vitals are within normal limits. Physical examination shows minimal epigastric tenderness. Serum acetaminophen levels are elevated, and the appropriate therapeutic medication is initiated. Which of the following best describes the mechanism of action of this therapy?  

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Acetaminophen p. 494

vs aspirin for pediatric patients p. 494

free radical injury and p. 211

hepatic necrosis from p. 248

for osteoarthritis p. 472

tension headaches p. 532

toxicity effects p. 494

toxicity treatment for p. 247

Glutathione p. 81

acetaminophen and p. 494

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Acetaminophen, also known as paracetamol, is mainly used to treat pain and fever. These conditions are related to an increased production of pro-inflammatory chemicals called prostaglandins.

Now, acetaminophen works by decreasing the production of prostaglandins, thereby relieving pain, and reducing fever.

In order to understand how acetaminophen works, first we need to talk briefly about inflammation, which is the body’s response to a harmful stimulus, such as infection or injury.

So, during inflammation, your immune cells use an enzyme called phospholipase A2 to take membrane phospholipids and make a 20 carbon polyunsaturated fatty acid, called arachidonic acid.

Arachidonic acid is a substrate for an enzyme called cyclooxygenase or COX.

The enzyme cyclooxygenase exists in two different isoforms: COX-1 and COX-2.

COX-1 is a constitutive enzyme, meaning that it’s always active, while on the other hand, COX-2 is an inducible enzyme, meaning that it must be turned on to function. This is usually triggered by immune cells and vascular endothelial cells during inflammation.

Both enzymes produce prostaglandin E2 (PGE2) and prostacyclin (PGI2), which cause vasodilation and attract different immune cells to the area.

They also act on neurons that detect pain, called nociceptors, and make them more sensitive to stimuli by lowering their threshold for activation.

Finally, they stimulate the hypothalamus to increase the body temperature, causing fever.

Prostaglandin E2 also has other effects like causing uterine contractions, decreasing the secretion of acid, and increasing the production of protective mucus in the stomach.

Alright, now let’s focus on acetaminophen. Acetaminophen is administered orally, rectally, or intravenously; and it works by reversibly inhibiting COX in the central nervous system, thereby decreasing production of the prostaglandins that cause fever and pain.

It’s important to note that acetaminophen is not considered a non-steroidal anti-inflammatory drug (NSAID) because it doesn't inhibit COX peripherally; so unlike NSAIDs, it doesn't have anti-inflammatory activity.

Resumen

Acetaminophen (Paracetamol) is a medication used to relieve pain and reduce fever. It is usually taken orally, but can also be given intravenously. Acetaminophen is one of the most common medications used and is generally considered safe when taken as directed. However, acetaminophen can cause serious liver damage if too much is taken or if it is taken with certain other medications such as pexidartinib.

Fuentes

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Kinetics and metabolism of paracetamol and phenacetin." British Journal of Clinical Pharmacology (1980)
  5. "Acetaminophen poisoning and toxicity" Pediatrics (1975)
  6. "Acetaminophen Toxicity" New England Journal of Medicine (1988)
  7. "What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose?" Clin Toxicol (Phila) (2019)
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