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Effects of Liver Disease on Drug Metabolism

By

Danielle Tholey

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Apr 2021
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Liver disease may have complex effects on drug clearance, biotransformation, and pharmacokinetics Overview of Pharmacokinetics Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution... read more . Pathogenetic factors include alterations in intestinal absorption, plasma protein binding, hepatic extraction ratio, liver blood flow, portal-systemic shunting, biliary excretion, enterohepatic circulation, and renal clearance. Sometimes alterations increase levels of bioavailable drug, causing normal drug doses to have toxic effects. However, levels and effects for an individual drug are unpredictable and do not correlate well with the type of liver injury, its severity, or liver test Laboratory Tests of the Liver and Gallbladder Laboratory tests are generally effective for the following: Detecting hepatic dysfunction Assessing the severity of liver injury Monitoring the course of liver diseases and the response to treatment... read more results. Thus, no general rules are available for modifying drug dosage in patients with liver disease.

Clinical effects can vary independent of drug bioavailability, especially in chronic liver disease; eg, cerebral sensitivity to opioids and sedatives is often enhanced in patients with chronic liver disease. Thus, seemingly small doses of these drugs given to cirrhotic patients may precipitate encephalopathy. The mechanism of this effect probably involves alterations in cerebral drug receptors.

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