National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.

Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Allergy (Impact Factor: 6). 10/2009; 65(4):498-502. DOI: 10.1111/j.1398-9995.2009.02193.x
Source: PubMed

ABSTRACT The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased.
National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop test (>0.35 kU(A)/l), collected in nine countries representing high and low PHO-consuming nations.
There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization.
This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to peri-operative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs (table 1), 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 NMBA drugs 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, 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 non-prescription 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 sensitise 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.
    British Journal of Clinical Pharmacology 11/2013; · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Perioperative anaphylaxis is a life-threatening condition with an estimated prevalence of 1:3,500 to 1:20,000 procedures and a mortality rate of up to 9 %. Clinical presentation involves signs such as skin rash, urticaria, angioedema, bronchospasm, tachycardia, bradycardia, and hypotension. Prompt recognition and treatment is of utmost importance to the patient's prognosis, since clinical deterioration can develop rapidly. Epinephrine is the main treatment drug, and its use should not be postponed, since delayed administration is associated with increased mortality. Elevated levels of serum tryptase help to confirm the diagnosis. The main agents involved in IgE-mediated perioperative anaphylaxis are neuromuscular blocking agents, latex, antibiotics, hypnotics, opioids, and colloids. Specific investigation should be conducted 4 to 6 weeks after the reaction and relies on skin tests, serum-specific IgE, and challenge procedures. This review aims to discuss the main aspects of perioperative anaphylaxis: risk factors, diagnosis, treatment, culprit agents, specific investigation, and preventive measures.
    Current Allergy and Asthma Reports 08/2014; 14(8):452. · 2.75 Impact Factor
  • British Journal of Clinical Pharmacology 03/2014; · 3.69 Impact Factor

Full-text (2 Sources)

Available from
May 30, 2014