Nonanaphylactic Drug Disorders

In this chapter, the authors review the classification of Adverse drug reactions (ADRs), as well as general concepts of drug metabolism, drug presentation to the immune system, and types of drug hypersensitivity reactions. In contrast, unpredictable reactions are usually dose-independent, they are not related to the pharmacological actions of the drug, and they occur only in susceptible individuals. In most instances, reactive drug intermediates are promptly detoxified (or “bioinactivated”) to nonreactive products. In certain circumstances, however, reactive metabolites are able to cause injury by either direct toxicity or by immune-mediated hypersensitivity. Maculopapular or morbilliform rashes are the most common cutaneous adverse drug reactions, and they may occur with the administration of any drug. Most frequently, they are associated with the use of p-lactams, sulfonamides, anticonvulsants, allopurinol, and NSAIDs. The generation of drug-specific T-cell clones from allergic patients has led to an improved ability to study and to characterize these cells in vitro.