化合物信息

Drug Groups

approved

Description

Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.

Indication

For temporary relief of fever and minor aches and pains.

Pharmacology

Acetaminophen (USAN) or Paracetamol (INN) is a widely used analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard doses, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and unlike opioid analgesics, acetaminophen does not cause euphoria or alter mood in any way. Acetaminophen and NSAIDs have the benefit of being completely free of problems with addiction, dependence, tolerance and withdrawal. Acetaminophen is used on its own or in combination with pseudoephedrine, dextromethorphan, chlorpheniramine, diphenhydramine, doxylamine, codeine, hydrocodone, or oxycodone.

Toxicity

Oral, mouse: LD50 = 338 mg/kg; Oral, rat: LD50 = 1944 mg/kg. Acetaminophen is metabolized primarily in the liver, where most of it is converted to inactive compounds by conjugation with glucuronic acid and, to a lesser extent, sulfuric acid. Conjugates are then excreted by the kidneys. Only a small portion is excreted in unchanged in urine or oxidized via the hepatic cytochrome P450 enzyme system (CYP2E1). Metabolism via CYP2E1 produces a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). The toxic effects of acetaminophen are due to NAPQI, not acetaminophen itself nor any of the major metabolites. At therapeutic doses, NAPQI reacts with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is excreted by the kidneys. High doses of acetaminophen may cause glutathione depletion, accumulation of NAPQI and hepatic necrosis. The maximum daily dose of acetaminophen is 4 g. Liver failure has been observed at doses as low as 6 g per day. As such, the maximum daily and single dose of acetaminophen is currently being reviewed in some countries. N-acetyl-cysteine, a precursor of glutathione, may be administered in the event of acetaminophen toxicity.

Affected Organisms

Biotransformation

Approximately 90 to 95% of a dose is conjugated in the liver with glucuronic acid and sulfuric acid. A small percentage of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI), a toxic metabolite which is then conjugated to glutathione and excreted renally. Accumulation of NAPQI may occur if primary metabolic pathways are saturated.

Absorption

Rapid and almost complete

Half Life

1 to 4 hours

Protein Binding

25%

Elimination

Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged.

References

External Links