Chemistry of drug allergenicity

Abstract

Of the very large number and variety of drugs used in medicine, those that are frequently implicated in immediate allergic reactions are relatively small in number and include neuromuscular blocking drugs used in anaesthesia, beta-lactam antibiotics, some other antibacterial agents including broad-spectrum antibiotics and quinolones and, less often, some narcotics. Structure-activity and immunochemical investigations have been most numerous and detailed for neuromuscular blocking drugs and beta-lactams, particularly penicillins. For the former group of drugs, morphine is proving to be a useful agent for the in-vitro detection of clinically relevant neuromuscular blocking drug-- as well as morphine- and fentanyl-reactive IgE antibodies. The employment of so-called 'major' and 'minor' determinants for a range of different penicillins and cephalosporins has revealed previously unsuspected heterogeneity in patient recognition responses, and has reinforced findings on the allergenic importance of side-chain groups. Many reports have been published on anaphylaxis to chlorhexidine, and progress in identifying allergenic determinants is reviewed together with the still inadequately understood subject of IgE antibody recognition of quinolone antibacterial agents.

Influence of the type of anaesthesia used, the diet and the consumption of sugar and alcohol on the intradermal skin test to morphine

“…[23] IgE specific for morphine and codeine has been also identified. [25] Taken together, the results from the present study suggest that the link between certain quantities of sugar, vegetables or alcohol and positive intradermal skin test to morphine could lead to the introduction of these parameters at least in patients that are expected to use morphine treatment. Further studies with a larger cohort of patients would be needed to establish a clear link between diet and optimal drug therapy that can be applied to patients.…”

Anaphylaxis during anaesthesia: diagnostic approach

“…Skin tests start with SPT, which are, if negative, followed by IDT. Skin testing should not be limited to the classical and commercial reagents benzylpenicilloyl poly-l-lysine (PPL) and so-called minor determinants mixture (MDM), but should include amoxicillin (AX) and ampicillin (AMP), as well as the culprit compound(s) (87,88)). Maximum concentrations for SPT and IDT for PPL, MDM, AX, AMP and other penicillins and for most cephalosporins are summarized in Table 3.…”

“…Therefore, historically, the recommendation has been to switch to a different subclass with a distinct chemical structure in order to avoid antibody recognition (127). However, the observation that codeine, meperidine and methadone, representatives of the different opioid subclasses react with morphine antibodies put into question this practice (87,123). In the absence of validated drug specific diagnostic tools, correct diagnosis of opiate allergy remains a clinical challenge.…”

“…In some patients, anaphylaxis to chlorhexidine, was preceded, sometimes by years, by chlorhexidineinduced contact dermatitis (168). Evidence for an IgEmediated hypersensitivity to chlorhexidine was first provided in 1984 (169) and hapten inhibition studies have shown the entire chlorhexidine molecule to be complementary to the IgE antibody binding sites and the 4-chlorophenol, bisguanide and hexamethylene structures together constitute the allergenic determinant (87,170). Symptoms of chlorhexidine anaphylaxis have been attributed to cutaneous, percutaneous, mucosal, and parenteral application.…”

Quaternary ammonium compounds – new occupational hazards

“…Działanie alergizujące QACs, podobnie jak w przypadku innych czynników o małej masie cząstecz-kowej, może wynikać z ich zachowywania się w ustroju jak hapteny, czyli cząstkowe antygeny zdolne do immunizacji po koniugacji z nośnikiem białkowym (27). Nie wyklucza się jednak możliwości rozwoju uczulenia na QACs w mechanizmie IgE-zależnym (28,29).…”