Information of Drug induced liver damage


 Drug induced liver damage

Disease condition

Many chemicals that are inhaled or swallowed can damage the liver. Among these are drugs, industrial solvents and pollutants. Almost every known drug has at one time or another been implicated as a cause of liver damage.

Chemicals which damage the liver fall onto two groups:

http://www.nlfindia.com/images/bullet.gif Predictable liver toxins - These damage the liver regularly following exposure to a certain amount of the substance.

http://www.nlfindia.com/images/bullet.gif Unpredictable liver toxins - These cause damage in only a small percentage of people exposed to them.

Type and example

Pathogenesis

Acute hepatocellular injury

 

Toxic necrosis (e.g., CCl4,acetaminophen)

Membrane damage, some via toxic metabolite; dose-related, predictable

Hepatitis-like (e.g.,isoniazid, methyldopa)

Idiosyncrasy; ? immune, ? metabolic; unpredictable, not dose-related

 

 

Cholestasis

 

Inflammatory (e.g.,chlorpromazine)

Unknown; unpredictable; periportal inflammation and cholestasis

Pure (e.g., oral contraceptives)

Exaggeration of normal hormonal effect on bile transport; ?genetic idiosyncrasy; pure cholestasis, no inflammation

Miscellaneous acute/subacute

Variable, usually unknown

 

 

Chronic liver disease

 

Chronic hepatitis (e.g., isoniazid, methyldopa)

Idiosyncrasy; ? immune, ? metabolic

Chronic cholestasis (e.g., chlorpromazine)

Unknown; rare

Fibrosis/cirrhosis (e.g., methotrexate)

Dose-related, insidious toxic metabolic damage

Tumor: adenomas (oral contraceptives)

Unknown; rare

Disease Etiology:

Why is the Liver susceptible to injury by chemicals and drugs?

The reason seems to be linked to the liver's unique function of processing the chemicals and drugs which enter the blood stream. Many of these chemicals are difficult for the kidneys to excrete out of the body. The liver helps by removing these chemicals from the blood stream and changing them into products that can be readily removed through the bile or urine. In this process, unstable toxic products are sometimes produced. These can attack and injure the liver.

Analgesics (pain killers) and antipyretics (fever reducers) that contain acetaminophen are a common cause of liver inflammation. If over-the-counter medications are used, never increase the dose beyond what is recommended on the bottle / packaging. 

These medications can damage the liver when taken in doses that are not much greater than the recommended therapeutic dose. If patient drinks heavily or regularly, he/she should completely avoid these medications or discuss safe doses with the treating physician. 

Other problem drugs for the liver include the general anesthetic halothane, methyldopa, isoniazid (used for the treatment of tuberculosis), methotrexate, amiodarone, and HMG CoA reductase inhibitors, which are also called statins. 

Some medications can interfere with the flow of bile, which can also lead to liver inflammation. These include erythromycin, oral contraceptives, chlorpromazine, and anabolic steroids. Usually, drug-related hepatitis subsides within days or weeks after the offending drug is stopped. 

NSAID medications such as ibuprofen and naproxen may also cause drug-induced hepatitis. 

Symptoms

The symptoms are similar to those of viral hepatitis, and include a yellowish skin tone (jaundice), nausea, vomiting, and white or clay-colored stools. Some patients may have no symptoms.

Diagnosis

Diagnosis requires first and foremost a careful history of drug ingestion, including over-the-counter and illicit agents as well as prescribed medications. 

http://www.nlfindia.com/images/bullet.gif Elevated liver enzymes 

http://www.nlfindia.com/images/bullet.gif Enlarged liver 

http://www.nlfindia.com/images/bullet.gif Abdominal tenderness - right upper quadrant

Treatment – Medical, Surgical

Acute damage usually resolves when the offending agent is withdrawn, but cases of severe acute necrosis can be fatal or result in postnecrotic scarring..

Life expectancy and Quality of Life

In cases of chronic injury, further hepatocellular damage and inflammation will generally cease when the drug is stopped, but any concomitant fibrosis will be irreversible.