Cocaine is a local anaesthetic used for diagnostic procedures or surgery on or through the nasal cavity. It is administered as a spray in the nose where it enters the blood vessels of the nose and travels through the body. When taken illicitly it is snorted through the nose and enters through the same blood vessels. Cocaine is metabolized in hepatic liver cells. Cocaine diffuses through the liver membrane. On the endoplasmic reticulum membrane it is metabolized by cytochrome P450 3A4 into norcocaine. It is also predicted by biotransformer to metabolize by cytochrome P450 1A2 into benzoylecgonine. Both of these metabolites are inactive and the main metabolite when cocaine is taken on its own. When cocaine is taken with alcohol however, it metabolizes into the active metabolite cocaethylene by the hepatic enzyme carboxylesterase in the endoplasmic reticulum lumen. Norcocaine, benzoylecogonine, and cocaethylene all diffuse through the hepatic cell membrane into the blood where they travel to the kidney and are excreted renally. However, cocaethylene is an active metabolite that is much more toxic than cocaine and has a higher affinity for dopamine re-uptake receptors, and therefore will activate similar pathways to cocaine. It takes much longer for it to be excreted renally than cocaine. Cocaethylene is often fatal.

Cocaine metabolism References