Key Points
ÎWhat has often been referred to as drug desensitization is more appropriately described as induction of drug tolerance. Induction of drug tolerance can involve immunoglobulin E (IgE) immune mechanisms, non-IgE immune mechanisms, pharmacologic mechanisms, and mixed or unknown mechanisms. All involve administration of incremental doses of the drug.
ÎAdverse drug reactions (ADRs) are commonly encountered in both inpatient and outpatient settings and result in major health problems in the United States. (C)
Definitions
ÎADRs are broadly categorized into predictable and unpredictable reactions. (D)
ÎUnpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions. (D)
> Drug intolerance is an undesirable pharmacologic effect that occurs at low and sometimes subtherapeutic doses of the drug without underlying abnormalities of metabolism, excretion, or bioavailability of the drug. (D)
> Drug idiosyncrasy is an abnormal and unexpected effect that is unrelated to the intended pharmacologic action of a drug. (D)
> Drug allergy reactions are immunologically mediated responses that result in the production of drug-specific antibodies, T cells, or both. (B)
> Manifestations of pseudoallergic (anaphylactoid) reactions mimic IgE-mediated allergic reactions, but they are due to direct release of mediators from mast cells and basophils and do not require a preceding period of sensitization. (B)
Classifications of Immunologically Mediated Drug Hypersensitivity Reactions
ÎSome drug allergic reactions may be classified by the Gell-Coombs classification paradigm of hypersensitivity (type I: IgE mediated; type II: cytotoxic; type III: immune complex; type IV: cell mediated), whereas others cannot be classified because of lack of knowledge of their immunopathogenesis or a mixed mechanism. (C)
ÎAllergic drug reactions may also be classified according to the predominant organ system involved (eg, cutaneous, hepatic, renal) or according to the temporal relationship to onset of symptoms (immediate, accelerated, delayed). (D)
ÎTo some extent, the structural characteristics of drugs may permit predictions about the type of hypersensitivity reactions they are likely to cause. (C)
