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HYPERSENSITIVITY TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS:
FROM PATHOGENESIS TO CLINICAL PRACTICE / ARTIGO DE REVISÃO

CLINICAL MANIFESTATIONS and fifty percent of them have corticosteroid -dependent
asthma 16,17 .
Hypersensitivity reactions to NSAIDs can display a
wide spectrum of symptoms, from rhinitis, conjunctivitis, PATHOGENESIS
bronchospasm, urticaria, angioedema and anaphylaxis. The underlying pathophysiological mechanisms of
The reactions occur generally within 30 to 60 minutes NSAIDs hypersensitivity are usually non -immunological,
after drug administration but can be delayed up to 4 related to pharmacological properties and/or to dose
hours. Beyond these immediate reactions, late reactions amount of NSAID. NSAIDs act in the arachidonic acid
2
may occur and delay up to 48 hours . (AA) metabolic pathway, reducing prostaglandin synthe-
The overall incidence is greater after the third decade sis through inhibition of cyclooxygenase (COX) -1 with
of life, with predominance of respiratory symptoms in increased release of cysteinyl leukotrienes (LTs). These
adults and cutaneous symptoms in children. In adults, mediators induce inflammation, bronchoconstriction
greater incidence is found in females, whereas in pediat- (LTC4, LTD4, LTE4) and have a chemiotactic action
ric age males are more frequently affected (2:1) 17,18 . (LTB4, LTE4). Concomitant decrease in prostaglandin
There are different clinical patterns, with respiratory synthesis (PGE , PGI ) amplifies bronchoconstriction 17,19 .
2 2
or cutaneous predominance, according to the last clinical Two cyclooxygenase isozymes (COX -1 and -2) were
classification (NERD, NECD, NIUA). identified: COX -1 (constitutive; involved in prostaglandin
In NERD, rhinorrhea and nasal obstruction used to synthesis) and COX -2 (inducible in pathologic circum-
appear first, in the fourth decade of life. Therapy -resistant stances, such as inflammation). The AA metabolites pro-
rhinosinusitis and recurrent nasal polyps combined with duced by COX -1 protect the gastric mucosa, regulate
asthma appear typically some years before. These pa- renal blood flow and induce platelet aggregation . Anti-
20
tients suffer from severe asthma with near -fatal outcome, -inflammatory effects of NSAIDs results from COX -2

Figure 1. Relation between the profile of enzymatic inhibition and the pharmacological effect

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REVIST A POR TUGUESA DE IMUNO ALERGOLOGIA