Intravenous Acetaminophen Use in Infants and Children

Marcia L. Buck, Pharm.D., FCCP, FPPAG


Pediatr Pharm. 2011;17(4) 

In This Article

Mechanism of Action

The exact mechanism by which acetaminophen produces its analgesic and antipyretic effects remains undefined. The primary mechanism of action is believed to be inhibition of cyclooxygenase (COX), with a predominant effect on COX-2. Inhibition of COX enzymes prevents the metabolism of arachidonic acid to prostaglandin H2, an unstable intermediate byproduct which is converted to pro-inflammatory compounds. In the central nervous system, inhibition of COX enzymes reduces concentrations of prostaglandin E2, which lowers the hypothalamic set-point to reduce fever, and activation of descending inhibitory serotonergic pathways to produce analgesia.[1–4]

While acetaminophen shares the analgesic and antipyretic properties of other COX inhibitors such as aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs), it does not possess significant anti-inflammatory properties. Unlike aspirin, acetaminophen does not inhibit thromboxane and, as a result, does not alter platelet aggregation.[1–4]

Recent studies have suggested that acetaminophen may work through additional mechanisms, including modulation of the body's endogenous cannabinoid system. One of the metabolites of acetaminophen (N-arachidonoylphenolamine or AM404) inhibits the uptake of anandamide, increasing concentrations of endogenous cannabinoids. These substances can both modulate serotonergic descending pain pathways and lower body temperature. Other investigators have suggested that acetaminophen produces direct inhibition of N-methyl-D-aspartate (NMDA) receptors, blocking substance P-dependent synthesis of nitric oxide through the L-arginine-nitric oxide pathway and reducing nociception. These proposed mechanisms are not likely exclusive; in fact, they may all be components of an interwoven series of responses to acetaminophen administration.[1–4]


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