Question

The liver is a key site for drug and hormone metabolism.

a. Describe how drugs and hormones are metabolized in the liver, in addition to other locations in the body (be sure to state where this may occur, the main types of proteins involved and the action).

b. Explain how drug-induced liver disease occurs, and outline the basic types of drug induced liver disease.

c. Choose one specific drug/drug type associated with cholestatic reactions, and describe that drug’s mechanism of action. Explain how this drug may cause a cholestatic drug reaction.

Answer 1

Liver is the largest organ in human body that involves in metabolism. Drugs given to treat various diseases are metabolised in different organs like gastrointestinal system, lungs, kidneys. But majority of drugs metabolised in the liver. Hepatocytes of the liver cells consists of metabolites that helps in drug metabolism. Oxidation,reduction and hydrolysis are the first phase in drug metabolism. Conjugation is the second phase in drug metabolism. In liver the concentration of drug metabolites are more. Hence the inactive form of drugs are activated by the phase 1 activation and latter the toxic metabolites are removed and the active form of drug is transformed to inactive component and excreted in the urine and stools.

Drug induced liver disease results from the usage of illicit drugs, over the counter drugs, physician prescribed drugs, intake of vitamins, herbal supplements that causes marked impairment in the liver. The two types of drug induced liver diseases are intrinsic and idiosyncratic. Intrinsic occurs as a result of drug dosage and the idiosyncratic is not related to the dosage of the drugs and is caused due to hypersensitivity or allergic reaction to the drug.

Cholestatic reaction refers to the inability of the bile flow from the liver to the duodenum. The common drug that causes cholestatic reactions are ibuprofen.