Two principal aspects of drug metabolism are addressed in this chapter, namely drug-drug interactions and adverse reactions. Since drug-drug interactions can occur at various stages following drug administration, these are systematically subdivided into interactions associated with the pharmacodynamic phase, pharmacokinetic interactions, and interactions occurring during the biotransformation phase. Known interactions between drugs and food, alcohol and tobacco smoke are treated separately. A special feature of the present chapter is an extensive tabulation of drug-drug interactions which serves as a useful reference to those occurring most frequently, together with their biological consequences. In the treatment of adverse reactions that follows, these are first defined and an attempt to classify them according to various criteria is presented. A significant emphasis is given to allergic reactions and associated toxicity in the extensive discussion that follows. The latter is supported by a wide range of examples. Finally, a brief outline of some of the modern approaches to predicting drug metabolism is presented.

Today, with the increasing complexity of therapeutic agents available, and widespread polypharmacy (a particular problem especially in the elderly, who receive more medications than younger individuals), the potential for drug interactions is enormous. Drugs can interact to alter the absorption, distribution, metabolism or excretion of a drug, or interact in a synergistic or antagonistic fashion altering their pharmacodynamics. Generally, the outcome of an interaction can be harmful, beneficial or clinically insignificant. Although clinically often unrecognized, many of the drug interactions are responsible for increased morbidity. Drug interactions are of utmost importance in clinical practice, since they account for 6-30% of all adverse reactions (ADRs). In some cases, drug interactions can be useful, and it is already a relatively current practice for prescribers to use known interactions to enhance efficacy in the treatment of several conditions such as epilepsy, hypertension or cancer. An example illustrating beneficial effects rather than ADRs, involves the coadministration of carbidopa (an extracerebral dopadecarboxylase inhibitor), together with levodopa to prevent its peripheral degradation to dopamine. On the other hand, association of theophylline with ciprofloxacin, for instance, causes a two- to threefold increase in theophylline serum level, resulting in theophylline toxicity.

It should be stressed that usually the term ‘drug interactions’ refers to drug-drug interactions, although it can be taken to include interactions between drugs and food constituents, alcohol, or environmental factors. In addition, the term may include even interferences by drugs in clinical laboratory tests, with important consequences for diagnoses. Drugs may also interact with diseases, potentially worsening their symptoms. A definition with important implications was given a decade ago by Thomas, according to which a drug interaction is “considered to occur when the effects of giving two or more drugs are qualitatively and quantitatively different from the simple sum of the observed effects when the same doses of the same drugs are given separately”. The implications mentioned above may involve different aspects: either increased or decreased activity of two drugs given concurrently (in a purely quantitative manner.

Best Regards,
Nancy Ella
Associate Managing Editor
Drug Designing: Open Access