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Review
. 2014 Jul;78(1):14-23.
doi: 10.1111/bcp.12290.

Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis

Anna M Brusch  1 , Russell C Clarke, Peter R Platt, Elizabeth J Phillips
Affiliations
Review

Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis

Anna M Brusch et al. Br J Clin Pharmacol. 2014 Jul.

Abstract

Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions.

Keywords: anaphylaxis; drug hypersensitivity; neuromuscular blocking agent; pholcodine; substituted ammonium ions.

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Figures

Figure 1
Figure 1
Chemical structure of a selection of neuromuscular blocking agents (NMBAs). (A) Aminosteroid NMBAs. (B) Benzylisoquinoline NMBAs
Figure 2
Figure 2
Chemical structure of pholcodine, morphine and suxamethonium
See this image and copyright information in PMC

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