Chemical and Pharmaceutical Aspects of Drug Allergy

Bundgaard, Hans

doi:10.1007/978-3-642-69088-4_2

Cited by 6 publications

(2 citation statements)

References 106 publications

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“…Of all the drugs studied so far that elicit immediate allergic reactions [19–21], the NMBDs demonstrate a number of intriguing departures from the currently accepted explanations of the mechanisms underlying the allergic immune response to ‘small’ molecules such as drugs and simple chemicals [22–25]. The most striking and obvious of these differences are summarized.…”

Section: Neuromuscular Blocking Drugs Allergy and Immunological Dogmamentioning

confidence: 99%

On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective

Baldo

Fisher

Pham

2009

Clin Experimental Allergy

118

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Following the demonstration 25 years ago that substituted ammonium groups on neuromuscular blocking drugs (NMBDs) are the main allergenic structures recognized by IgE antibodies in the sera of some patients who experience anaphylaxis during anaesthesia, immunoassays for these drugs were quickly applied to supplement skin tests in the diagnostic assessment of suspected adverse reactions to anaesthetic agents. Many subjects who react to an NMBD do so on first exposure and this led to the speculation that the origin of allergic sensitization is an environmental agent(s) or another drug containing an ammonium ion. Direct antibody binding and hapten inhibition studies revealed that morphine, which contains a tertiary amino group, was strongly recognized by IgE in sera from anaphylactic patients and a morphine-solid phase immunoassay was found to be superior to NMBD-based assays for the detection of NMBD-reactive IgE antibodies. Extensive inhibition experiments indicate the likelihood of antibody combining site heterogeneity with recognition at the fine structural level of features additional, and adjacent to, ammonium ions. Further quantitative investigations are needed to identify these neighbouring groups on different NMBDs. Recent work has implicated the morphine analogue pholcodine as the sensitizing agent in Norway where, unlike Sweden, anaphylactic reactions to NMBDs are not uncommon and the medicament is available over-the-counter. This has led to the suggestion that allergenic sensitization to the ammonium group of pholcodine may account for the different incidences of anaphylaxis during anaesthesia in the two countries. This work is subjected to critical review and some alternative speculations on the nature and origin of the sensitizing agent(s) are presented.

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Section: Neuromuscular Blocking Drugs Allergy and Immunological Dogmamentioning

confidence: 99%

On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective

Baldo

Fisher

Pham

2009

Clin Experimental Allergy

118

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“…From the time of some of the earliest immunochemical studies on antigenicity (12) it has been assumed that a nonantigenic substance such as a chemical of "small" molecular mass (500-1000 Da) can only prime for antibody formation and stimulate synthesis of antibodies after combination with a macromolecular carrier, usually protein. For drugs, the formation of such hapten-protein complexes may occur directly in vivo between the unmodified drug and an endogenous protein or cell membrane (12)(13)(14) or after metabolic or degradative changes to the drug (15,16) (Figure 1). Despite long acceptance of this dogma, it is often not possible to demonstrate protein binding or, from the structure of the chemical, envisage how protein binding could occur even when all possible metabolites or degradation products are considered (16,17).…”

Section: Introduction To Drug Allergymentioning

confidence: 99%

Structure-Activity Studies on Drug-Induced Anaphylactic Reactions

Baldo

Pham²

1994

Chem. Res. Toxicol.

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As a result of recent research and development, an expanding range of in vitro assays for the detection of drug-reactive IgE antibodies is now available for the diagnosis of individual drug allergies. Continuing immunochemical studies on drugs implicated in allergic reactions via further development of specific immunoassays and production of drug-protein conjugates will allow us to build up a picture of the repertoire of drug and drug-derived B-cell allergenic determinant structures and to identify and predict cross-reactivities. Although we have made good progress in identifying some drug B-cell determinants, we remain ignorant of drug T-cell determinants and, indeed, of the nature of T-cell recognition of all nonpeptide molecules. Demonstration that drugs specifically recognize T-cells from drug-allergic patients may reveal associations with HLA phenotypes, the nature and location of interaction between drug and MHC molecules, and the nature and identity of drug or drug-derived T-cell antigens. A knowledge of the molecular nature of T-cell determinants inducing allergic responses is fundamental to therapeutic attempts to modulate these deleterious reactions. The possibility now exists for the allergenic screening of drugs as part of their toxicological evaluation, and identification of allergenic structures on drugs also has implications for the testing of allergenic activity and sensitizing potential of other chemicals in our environment. Obvious and important areas for the application of our methods and findings are the pharmaceutical and cosmetic industries.

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Techniques d'exploration en allergie médicamenteuse

Weck¹

1996

Revue Française d'Allergologie et d'Immunologie Clinique

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Chemical and Pharmaceutical Aspects of Drug Allergy

Cited by 6 publications

References 106 publications

On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective

On the origin and specificity of antibodies to neuromuscular blocking (muscle relaxant) drugs: an immunochemical perspective

Structure-Activity Studies on Drug-Induced Anaphylactic Reactions

Techniques d'exploration en allergie médicamenteuse

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