Mechanisms of Drug Toxicity or Intolerance

Classically, adverse drug reactions had been considered as type A reactions which are related to the main pharmacological action of the drug and therefore are predictable. Such reactions are predictable, reversible, and usually can be managed by lowering the dose of the offending drug. However, other adverse effects of drugs can occur which are unrelated to the main pharmacological action of the drug type B reactions. Such adverse effects are termed idiosyncratic and are often initiated by metabolites of the parent drug or by other indirect mechanisms. The detailed understanding of adverse drug events has become a major focus of the regulatory agencies throughout the world. The pharmacotherapy of gastrointestinal and liver disorders is becoming increasingly complex. In recent years, with the advent of novel therapeutic agents to treat a host of disorders, including viral hepatitis, gastrointestinal motility disorders, inflammatory bowel disease and others, the potential for serious clinically relevant drug reactions has increased. In the pharmacotherapy of gastrointestinal and liver diseases, a significant number of adverse events that occur can be explained by drug interactions. Some pharmacokinetic drug interactions are based on the competitive inhibition of the rate of drug metabolism of one of the drugs, leading to an increased concentration of the drug which was not intended. In other examples, the interaction can be mechanistic in which one or more drugs when co-administered potentiate each other's actions without any change in drug levels, termed pharmacodynamic interactions. Copyright (C) 2011 S. Karger AG, Basel