Chapter 15 Drug allergy and Hymenoptera sensitivity

Abstract

Adverse reactions to drugs (ADRs) represent the majority of illnesses due to physician intervention. Surveys of hospitalized (medical) patients yield an ADR prevalence of 6% to 15%. ADRs are complicated by the frequent use of nonprescription drugs and by multiple drug prescribing. Allergic drug reactions probably account for only 6% to 10% of all ADRs. Allergy to drugs may affect 5% of the population; 15% categorize themselves as drug allergic. ADR may be characterized as predictable (80%) or unpredictable. Predictable reactions include (1) overdose or toxicity, (2) side effect, (3) secondary or indirect effects, and (4) drug interactions. The most serious ADRs are toxic. Side effects represent the most frequent ADR and may be unavoidable at pharmacologic doses. Delayed side effects include carcinogenicity and teratogenicity. Secondary/indirect effects include consequences of the pharmacologic action of the drug that are not universal. Drug interactions are common due to frequent prescribing of multiple drugs. Unpredictable ADRs include (1) intolerance (lowered threshold to normal pharmacologic actions), (2) idiosyncrasy (a qualitatively unusual, nonimmunologic reaction to normal pharmacologic doses in susceptible individuals; these may be genetically determined defects, such as hemolytic anemia associated with G6PD/primaquine), (3) pseudoallergic reactions (similar clinical manifestations and often similar pathogenic mechanisms to allergic reactions), and (4) allergic reactions (reaction between a drug and antibodies or sensitized T cells). For a drug to be immunogenic, it must either be a complete antigen (insulin or foreign antiserum) or, more commonly, a hapten-protein complex. All usual immunologic mechanisms may be seen in ADRs. Drugs may produce pseudoallergic reactions that often use a nonimmunologic mechanism to activate common inflammatory pathways.