History
- First manufactured in 1877 by Harmon Northrop Morse (Johns Hopkins University)
- Clinical trials in 1893 by Joseph von Mering. Mering compared acetaminophen and [[phenacetin]], finding that phenacetin can cause methemoglobinemia; phenacetin was not used until 1949.
- David Lester and Leon Greenberg discovered that the body metabolizes phenacetin into acetaminophen, which has the same effect as phenacetin but does not cause methemoglobinemia or cancer. Since then, acetaminophen has been widely used.
Names
Acetaminophen
Paracetamol
Brand name: Tylenol
Pharmacological Action
The exact mechanism is not currently clear; it is hypothesized to inhibit central cyclooxygenase.
- Antipyretic
- Raises pain threshold (making pain harder to reach)
Weakly inhibits peripheral cyclooxygenase (often classified as an antipyretic analgesic/nonsteroidal anti-inflammatory drug, but its anti-inflammatory effect is very weak and it is not a true NSAID) — not suitable for inflammatory diseases such as arthritis.
Side Effects
Almost no common NSAID side effects such as anticoagulation or gastric irritation, suitable for patients who are intolerant to other NSAIDs (see details in [[aspirin]] side effects).
- Children
- Asthma
High doses cause hepatotoxicity (inflammation of the liver)
- Under normal circumstances, metabolism occurs via conjugation — acetaminophen couples in the liver with other molecules (mainly [[sulfate]] and [[glucuronide]]) to enhance solubility and facilitate clearance.
- In overdose situations, metabolism is diverted to liver enzyme [[cytochrome 3A4 (CYP3A4)]], producing the toxic substance [[NAPQI]], which must bind with glutathione to be excreted. If glutathione is depleted, NAPQI damages other liver proteins, causing liver dysfunction (especially when fasting or dieting causes insufficient glutathione reserves, alcohol intake increases CYP3A4, and glutathione is overconsumed) — at this time, hepatoprotective drugs and injectable glutathione should be used.