The pharmacokinetics of several drugs have been shown to be influenced by concurrent disease processes.16 The clearance of many drugs decreases in those individuals with chronic hepatic disease such as cirrhosis. In contrast, in acute reversible liver conditions, such as acute viral hepatitis, the clearance of some drugs is decreased or the half-life increased and for others, no change is detected. The volumes of distribution of some drugs are unaltered in hepatic disease while an increase is observed for other drugs, especially those bound to albumin in individuals with cirrhosis. This phenomenon is due to the decreased synthesis of albumin and other proteins. The influence of liver disease on drug absorption is unclear. It is probable though that the oral bioavailability of drugs highly extracted from the liver is increased in cirrhosis. The reasons are decreased first pass hepatic metabolism and the development of portal bypass in which blood enters the superior vena cava directly via esophageal varices.
Renal diseases such as uremia may result in decreased renal clearance of certain drugs.16 Gastrointestinal diseases, such as Crohn's disease, result in increased plasma protein binding of several drugs due to increased levels of binding proteins. Further, respiratory diseases such as cystic fibrosis increase the renal clearance of some drugs.
Patients commonly receive two or more drugs concurrently and most individuals who abuse drugs are poly-drug users. Multiple drug use may result in drug interactions. This occurs when the pharmacokinetics or pharmacodynamics of one drug is altered by another. This concept is important to consider because interaction may result in decreased therapeutic efficacy or an increased risk of toxicity. The degree of drug interaction depends on the relative concentrations and therefore dose and time.16 Changes in absorption rate, competition for binding sites on plasma proteins, oral bioavailability, volume of distribution, and hepatic and renal clearance have been demonstrated for therapeutic drugs. Few studies have systematically documented pharmacokinetic interactions between illicit drugs.
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