ROLE OF LIVER IN DRUG DETOXIFICATION

Liver is the gateway to body and plays very important role in drug detoxification.

• Filtering blood to remove large toxins.
• Enzymatically breaking down unwanted chemicals. It usually occurs in two steps: phase 1- modifying the chemicals to make them on easier target for phase 2 enzyme system.
• Synthesizing and secreting bile for excretion of fat soluble toxins and cholesterol.

PHASE 1 :

It consist of oxidation reduction and hydrolysis. It is catalyzed by 50-100 enzyme referred as cytochrome P450 enzyme group or mixed function oxidase MFO. They reside in hepatocytes or liver cells. They detoxify both exogenous and endogenous compounds, as well as play an important central role in the synthesis of steroids hormones and bile acids. The wide effect of this metabolic activity is the production of free radicals. The most important antioxidant for neutralizing those free radicals is glutathione, which is needed for both phases. 

Human liver cell possess the genetic code for many isozymes P450 whose synthesis can be induced upon exposure to some drugs.

PHASE 2:

It is called conjugation pathway whereby the liver cells and another substances (cysteine glycine or a Sulphur molecule ) to a toxic chemical or drug to render it less harmful.It makes drug water soluble so it can be excreted from body via watery fluids such as bile, urine. Besides glutathione conjugation, the other pathways are amino acid conjugation, methylation,  sulfation,  sulfoxidation, acetylation and glucuronidation. These enzyme system need nutrients and metabolic energy to function. If liver cells do not function properly, phase 2 detoxification slows down and increases the load of toxic intermediates. 

FOR EXAMPLE : Barbiturate, such as phenobarbital, is a drug that acts as a central nervous system depressant, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia.