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To the allergologist, hypersensitivity to drugs means immunological drug reactions as classified in the Gell and Coombs system. To others, it may also include non-dose related adverse drug reactions including the non-immune mediated idiosyncratic drug reactions (type B). In the following discussion the broad definition of idiosyncrasy including all type B reactions and a clinical approach rather than a mechanistic one will be used.
Pyrazolones are veteran drugs. Antipyrine was synthesised for clinical use in 1883. The methylated nitrogen derivative aminopyrine was introduced in 1897 and taken off the market in the 1970s because of its propensity to form nitrosamines. Dipyrone has been in clinical use since 1922. In some countries it was banned because of the risk of agranulocytosis. In others it is the leading analgesic/antipyretic drug. Annual sales figures of pyrazolones amount to kilotons, mainly dipyrone and propyphenazone.
Unlike the acidic non-steroidal anti-inflammatory drugs (NSAIDs) which are known to act on inflamed tissue by the inhibition of prostaglandin synthesis, pyrazolones produce analgesic/antipyretic effects associated with a much less potent anti-inflammatory effect on peripheral tissues. As shown in several animal species and also in humans, dipyrone acts on the central nervous system by the inhibition of prostanoids.1 2 Dipyrone has more than 20 known metabolites.3 A central hypothesis of immune mediated (hypersensitivity) drug reactions has been that drugs are metabolised to a reactive metabolite which can act as an hapten.4There are limited reports concerning the immunogenic potential of pyrazolone and pyrazolidine metabolites.5 6 Genetic heterogeneity could also predispose patients to adverse drug reactions by the formation or inability to detoxify a reactive metabolite.
In 1977 Szczeklik et al 7 put forward the hypothesis that, in sensitive patients, induction of asthmatic attacks by aspirin-like drugs is due to inhibition of tissue prostaglandin biosynthesis. In about …
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