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

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twice daily . In the last decade, several studies have dem- NSAIDs. Promising formulations including a vasodilating
onstrated clinical efficacy with lower dosage (300 to 975mg agent naproxcinod as the prototypical COX -inhibiting
daily) 55, 57 . Available data have demonstrated that this in- nitric oxide has the potential to improve the gastroin-
tervention is beneficial in reducing both nasal and bron- testinal safety profile and protect against to the vaso-
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chial symptoms with subsequent reduction of systemic constrictive and prothrombotic effects . Hydrogen
corticosteroids, decreasing the rate of polyp formation sulfide (HS) -releasing compounds seem to protect gas-
and as a result, lesser number of surgeries, and addition- trointestinal mucosa. Some of these compounds are
ally improving the quality of life of these patients 52,58 . currently being developed in preclinical studies including
diclofenac, naproxen, indomethacin, ketorolac, and as-
pirin . For instance, HS -diclofenac caused 90% less
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UNMET NEEDS / FUTURE PERSPECTIVES gastric damage compared with traditional diclofenac .
New reliable injectable formulations for perioperative
Currently, the NSAIDs are the pharmacological group and inpatient use as ibuprofen, parecoxib and tenoxicam
most frequently responsible for hypersensitivity reac- are currently available . Innovative products including
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tions. Most of these reactions result from activation of glycopolymers have been used to produce intra -articular
the leukotriene pathway without specific immunological extended -release NSAIDs combined with hyaluronic
recognition and potential cross -intolerance. However, acid . Nano -formulations of submicron NSAIDs, allow-
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there are a growing number of selective reactions, in- ing to deliver lower doses with similar efficacy, have
duced by immunological mechanisms (mediated by IgE been tested in diclofenac, indomethacin, naproxen, and
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antibodies or by T cells). Considering the heterogeneity meloxicam .
of clinical patterns, the underlying mechanisms need to Further research in NSAIDs is required to develop
be better clarified. Neither skin testing nor in vitro tests enhanced formulations and delivery vehicles that can im-
may be used as diagnostic tools for all NSAIDs. Most of prove their safety profile.
these patients undertake multiple drug challenges to con-
firm diagnosis or, considering the severity of the clinical
history are exclusively challenged with safer alternative CONCLUSIONS
drugs. Further research to develop both in vivo and in
vitro tests is required in order to perform an accurate The prevalence of NSAIDs hypersensitivity can reach
diagnosis. Eventually genetic studies will enable to explore 6% of the general population, increasing up to 20% in
individual predispositions and improve our understanding asthmatic patients and up to 40% in chronic urticaria.
of selective reactors. Clinical manifestations range from rhinoconjunctivitis,
Despite the promising emergence of coxibs as alterna- asthma and urticaria to anaphylaxis. The leading patho-
tive drugs, safety concerns mainly due to its cardiovas- genic mechanism results from COX -1 inhibition with
cular effects remain under suspicion. Cardiovascular ef- increasing release of inflammatory mediators, which are
fects are more related to the individual agent rather than responsible for the occurrence of respiratory and cutane-
the COX -2 selectivity of every drug. The underlying ous symptoms in susceptible patients. NSAIDs cross-
mechanisms are not fully explained by prothrombotic -reactivity is a common feature, considering the mecha-
state and requires further investigation. nism of enzymatic inhibition. Nevertheless, up to one
Several novel pharmaceutical manipulations are un- third of patients might react to a single NSAID, tolerating
der development, to improve safety and efficacy of the remaining groups of NSAIDs.

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