Immunological and non-immunological mechanisms involved in adverse reactions to drugs

This communication reviews the mechanisms involved in anaphylactic and anaphylactoid reactions to intravenous drugs used in anaesthesia. Although the mechanisms involved are pertinent to other drugs and substances used in clinical practice, the use of the intravenous route makes this a particularly worrying problem in anaesthetic practice. Despite the similarity of the clinical manifestations to those expected from immediate immunological hypersensitivity (anaphylaxis), relatively few reactions involve antibodies. Instead, a variety of mechanisms occur where activation of the blood inflammatory response systems, particularly complement, may be either primary or secondary to activation of the coagulation or fibrinolytic cascades of the blood clotting mechanisms. Immediate anaphylactoid reactions, manifest in the release of vasoactive substances such as histamine, may therefore pose very minor problems compared with coagulation problems arising in the peri- and post-operative period. It is important to discover the mechanism of all adverse reactions not only if these are to be avoided in the reactants in the future but also because of the necessity for devising suitable prophylactic and therapeutic measures for general use. The practical problems of such investigations are explored with particular reference to the laboratory investigation of subclinical reactions in terms of plasma histamine release and changes in blood leucocyte distribution.