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Inês Mota, Ângela Gaspar, Mário Morais-Almeida

There are other routes of challenge tests: inhaled, or less. Different results, around 30%, were found with

intranasal, conjunctival, and intravenous (the usefulness doses from 1000mg to 1500mg. It seems to occur a rela-
of the last two has not been sufficiently documented). tion between reactivity with low dose of ASA and the
Bronchial challenge with inhaled lysine acetylsalicylate is possibility of cross -reactivity with acetaminophen.
useful in patients with bronchial symptoms after drug At therapeutic doses, acetaminophen is a preferential
27
intake and history of asthma . Intranasal challenge with COX -3 inhibitor, and a weak COX -1 and COX -2 inhibi-
30
lysine acetylsalicylate can be employed in patients with tor . Considering this dose -dependent mechanism and
nasal symptoms or bronchial symptoms in whom other the possibility for a COX -1 inhibition, patients should be
2
routes are not recommended due to asthma severity . advised to avoid acetaminophen’s daily consumption
higher than 1500mg.

ALTERNATIVE DRUGS 2. Preferential COX -2 inhibitors

NSAIDs that are weak COX inhibitors, including ace- 2.1. Nimesulide
taminophen and non -acetylated salicylates, like magne- Nimesulide belongs to sulphonanilides and have anti-
sium choline salicylate, sodium salicylate, and salicylsalicy- -inflammatory, antipyretic, and analgesic properties.
late, are usually well tolerated, but less effective as Seve ral mechanisms of its action have been proposed:
anti -inflammatory or analgesic drugs. Furthermore, sa- preferential COX -2 inhibition; inhibition of neutrophilic
licylates are not available in the Portuguese market, ex- oxidative metabolism; recruitment of reactive oxygen
cept for topical use and, although rare, reactions with species; prevention of alpha -1 -antitripsine inactivation;
acetaminophen have been described. Considering these inhibition of leukotrienes and platelet -activating factor
constraints, selective (coxibs) and preferential (meloxi- (PAF) synthesis; inhibition of histamine release from mast
cam and nimesulide) COX -2 inhibitors are suitable alter- cells and basophils. Preferential COX -2 inhibition explains
natives in case of hypersensitivity reactions to classical its anti -inflammatory activity and slighter incidence of
NSAIDs, with a satisfactory tolerance profile in most gastrointestinal effects.
patients. Published studies have shown that nimesulide is well
During investigation of an alternative drug, concomi- tolerated from 80 to 90% of patients with hypersensitiv-
tant intake of leukotriene antagonists in atopic patients ity to classical NSAIDs 31 -33 . Asthmatic patients with ASA
and under specialized surveillance, can enable to achieve intolerance rarely react to nimesulide, compared to pa-
28
tolerance in case of mandatory drug consumption . tients with cutaneous reactions (8.6 -21.3%) . A Portu-
33
guese study reported tolerance in 72% of ASA -susceptible
34
1. Acetaminophen patients .
Acetaminophen (paracetamol), which is widely used In 2007, reports of nimesulide -associated hepatotox-
in clinical practice for all ages, is associated to a limited icity led to the temporary withdrawal of this drug from
number of adverse reactions. Despite being the first al- several European countries and thereafter safety data
ternative in case of NSAIDs hypersensitivity, in some have been revised. Restrictions were introduced, after
patients (ASA -susceptible), there is a potential cross- considering the confirmed risk of hepatotoxicity. Nime-
-reactivity when acetaminophen is taken in higher doses sulide should be used as a second -line therapy and with
(dose -dependent effect) . Low frequency of cross- the lowest possible effective dose. In patients with hy-
29
-reactivity (up to 6%) was described with doses of 650mg persensitivity to NSAIDs, it is recommended to prescribe

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REVIST A POR TUGUESA DE IMUNO ALERGOLOGIA