Browsing Pathways

Acetaminophen (also named paracetamol or APAP) is not a Nonsteroidal anti-inflammatory drugs (NSAIDs). However, it still can be used to treat pain and fever. Acetaminophen can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of acetaminophen.

Acetaminophen is an oral/IV antipyretic and analgesic drug used to treat fevers and mild to moderate pain. Its exact mechanism is unknown but it is thought to target the cyclooxygenase pathway in the CNS (brain). It does not inhibit the cyclooxygenase pathway in peripheral tissues, an therefore, does not have any peripheral anti-inflammatory effect. The cyclooxygenase (COX) pathway begins in the cytosol with arachidonic acid being formed from membrane phospholipids via phospholipase A2. On the endoplasmic reticulum membrane, arachidonic acid is converted to prostaglandin G2 then to prostaglandin H2 using the enzymes prostaglandin G/H synthase 1 & 2 (COX-1 & COX-2). Prostaglandin H2 leads to the formation of thromboxane A2 (via thromboxane-A synthase), prostacyclin (via prostacyclin synthase) and prostaglandin E2 (via prostaglandin E synthase). Prostaglandin E2 (PGE2) is responsible for mediating pain and fever. Acetaminophen enters the cell through the solute carrier family 22-member 6 transporter and inhibits the COX-1 & COX-2 enzymes on the endoplasmic reticulum membrane. This prevents the production of prostaglandin H2 from arachidonic acid, thereby lowering the concentration of prostaglandin E2 in the cell. Since PGE2 causes pain and fever, reduction of PGE2 would lessen fevers and increase threshold for pain sensation. There are very few side effects associated with acetaminophen, but some people may have allergic reactions which may include itching, rash, difficulty breathing and swelling of face, hands, throat or mouth.

Acetaminophen (APAP) is metabolized primarily in the liver. Glucuronidation is the main route, accounting for 45-55% of APAP metabolism, and is mediatied by UGT1A1, UGT1A6, UGT1A9, UGT2B15 in the liver and UGT1A10 in the gut. APAP can also by metabolized via sulfation, accounting for 30-35% of the metabolism. In the liver, this step is catalyzed by the sulfotransferases SULT1A1, SULT1A3, SULT1A4, SULT1E1 and SULT2A1. Moreover, APAP can also be activated to form the toxic N-acetyl-p-benzoquinone imine (NAPQI) under the mediation of CYP3A4, CYP2E1, CYP2D6 CYP1A2, CYP2E1 and CYP2A6.

Acetarsol is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Acetarsol passes through the liver and is then excreted from the body mainly through the kidney.