Drug Induced Liver Disease (cont.)
What are the symptoms of liver disease?
Patients with mild liver disease may have few or no symptoms or signs.
Patients with more serious disease develop symptoms and signs that may be
nonspecific or specific.
Nonspecific symptoms, that is, symptoms that don't suggest that the liver is
their cause, include:
Symptoms and signs that are specific for liver disease include:
- yellowing of the skin (jaundice) due to the
accumulation of bilirubin in the blood,
- itching, and
- easy bruising due to decreased production of blood clotting factors by the
diseased liver.
Severe, advanced liver disease with cirrhosis can produce symptoms and signs
related to cirrhosis; these symptoms include:
How do drugs cause liver disease?
Drugs can cause liver disease in several ways. Some drugs are directly
injurious to the liver; others are transformed by the liver into chemicals that
can be injurious to the liver directly or indirectly. (This may seem strange in
light of the liver's important role in transforming toxic chemicals into
nontoxic chemicals, but it happens.) There are three types of liver toxicity;
dose-dependent toxicity, idiosyncratic toxicity, and drug allergy.
Drugs that cause dose-dependent toxicity can cause liver
disease in most people if enough of the drug is taken. The most important
example of dose-dependent toxicity is acetaminophen (Tylenol) overdose (discussed later in
this article.).
Drugs that cause idiosyncratic toxicity cause disease in
only those few patients who have inherited specific genes that control the
chemical transformation of that specific drug, causing accumulation of the drug
or products of their transformation (metabolites) that are injurious to the
liver. These inherited idiosyncratic toxicities usually are rare, and depending
on the drug, typically occur in less than 1 to10 per 100,000 patients who are
taking that drug; however, with some drugs the prevalence of toxicity is much higher.
Even though the risk of developing drug-induced idiosyncratic liver disease is
low, idiosyncratic liver disease is the most common form of drug-induced liver
disease because tens of millions of patients are using drugs, and many of them
are using several drugs.
Idiosyncratic drug toxicity is difficult to detect in early clinical trials that
usually involve, at most, only a few thousand patients. Idiosyncratic toxicity
will surface only after millions of patients begin to receive the drug after the
drug is approved by the FDA.
Drug allergy also may cause liver disease, though it is uncommon. In drug
allergy, the liver is injured by the inflammation that occurs when the body's
immune system attacks the drugs with antibodies and immune cells.
Next: What types of liver disease do drugs cause? »
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