Acetaminophen is both an analgesic and antipyretic. It is thought to act centrally byinhibiting activation of COX. It does not actually bind the COX enzyme but instead prevents the activation of COX by reducing heme at its peroxidase site. Acetaminophen also may modulate descending inhibitory serotonergic pathways. Acetaminophen is opioid-sparing and frequently comprises part of a multimodal analgesic regimen. Lipoxygenase is part of the pathway of arachidonic acid metabolism to
leukotrienes. It is not involved in analgesia. Central a2 receptors are activated by clonidine and tizanidine. Both of these drugs have sedative, anxiolytic, and analgesic properties, but tizanidine has a shorter duration of action than clonidine and is also thought to have less effect on heart rate and blood pressure. This leads to decreased release of norepinephrine at both central and peripheral sites, which in part explains the roles these drugs play in a multimodal regimen. Both of these medications can cause hypotension. GABA receptors are activated by many anesthetic agents, such as benzodiazepines, but not acetaminophen.