1.
Background: Non-steroidal anti-inflammatory drugs (NSAID) belong to a variety of chemical classes with no common features except the absence of a steroid structure. Their primary effect is pain relief, but also with anti-pyretic and anti-inflammatory effects. Basically prescribed for symptomatic relief, they do not have a curative effect on chronic disease processes. 2. INFLAMMATORY EFFECTS OF PROSTANOIDS (THROMBOXANE A2 AND PROSTAGLANDINS): Inflammation basically results from the pro-algogenic and vascular effects of prostanoids. Their pro-algogenic effects are explained by sensitization of nociceptive nerve endings to the stimulating effect (algogenic) of kinins (bradykinin), serotonin and histamine. In addition, production of prostanoids in the brain has a thermoregulatory effect. 3.
Mode of action: NSAID have a common effect, inhibiting the production of prostanoids via reduced activity of two cyclo-oxygenases (COX-1 and COX-2). COX-2 is an isoform predominantly expressed during the inflammatory process. Excepting two compounds recently marketed (celecoxib, rofecoxib) selective for COX-2, all other NSAID have few or no selective properties. COX-1 is implicated in the regulation of many physiological functions. Inhibition of COX-1 explains most of the classical side effects of non-selective NSAID. 4.
Comparison: It is classical to emphasize the interindividual variable anti-inflammatory and antalgesic effects of the different NSAID without developing a coherent explanation. In addition, it is very difficult to make objective comparisons between different NSAID because of the different sizes of the study populations, indications and dosages. There is no evidence favoring a given NSAID on the basis of its anti-inflammatory or antalgesic effect in a given indication; no hierarchy in terms of efficacy can be established. For acute pain, it is preferable to use oral NSAID absorbed rapidly to achieve rapid relief. 5.
Paracetamol: This antalgesic, antipyretic drug has no anti-inflammatory action. Its mechanism of action remains to be fully elucidated. It is not a member of the NSAID class and is a poor inhibitor of COX, particularly COX-2 (30% maximal inhibition). For identical dose (1-3 g/d), the antalgesic activity of paracetamol is comparable to that of aspirin for pain in general. There does not appear to be any difference in the anti-pyretic efficacy between NSAID and paracetamol. 6.
Official indications: In general, NSAID are not indicated for anti-inflammatory action in the ENT conditions discussed here. It this light, the official indications in France published on November 14, 1988 concerning ENT disease in children and adults without risk factors is most noteworthy. It is stipulated that there is no need to institute NSAID treatment at an anti-inflammatory dose in combination with general antibiotic therapy, except when there is an important inflammatory component. This guideline does not concern NSAID at antalgesic and antipyretic doses used for ENT conditions with or without an infectious component. 7. SELECTIVE INHIBITORS OF COX-2: Selective inhibitors are only indicated in two chronic inflammatory diseases: osteoarthritis and rheumatoid arthritis. There is no indication for these inhibitors in ENT disease. The only beneficial effect that has been demonstrated to date for the use of selective inhibitors of COX-2 is better digestive tract tolerance. 8.
Role of prostanoids in the clinical expression of allergic rhinitis: It is insufficient to warrant use of NSAID in this disease, particularly due to the efficacy of anti-H1 and local corticosteroids. NSAID are not indicated in nasal polyposis and are even contraindicated in case of intolerance to NSAID, observed in about 15-20% of all patients with nasal polyposis. However, local application of lysine acetylsalicylate at progressive doses from 20 micrograms to 4 mg can reduce relapse by half after polypectomy. There is no proof of the efficacy of NSAID in chronic sinusitis and their efficacy has not been studied in laryngitis. Finally, there is no sufficient evidence, either from experimental data or clinical trials, to recommend NSAID for otitis, with the exception for an antalgesic and/or antipyretic effect. 9. CHOOSING AN ANTI-INFLAMMATORY OR ANTALGESIC NSAID: The choice is generally guided by the frequency and severity of undesirable effects. These undesirable effects often appear during the first weeks of treatment. 10.
Different adverse effects: Digestive tract effects appear in 20 to 40% of the patients after a few weeks of treatment using anti-inflammatory doses. Symptomatic gastroduodenal ulcers, digestive bleeding, and perforations are the most serious adverse effects of NSAID. Nevertheless, the risk of such complications, compared with the number of prescriptions, is very low. At high dose (anti-inflammatory dose), age over 60 years and history of severe gastrointestinal complications are factors increasing the risk of severe gastrointestinal adverse effects of NSAID. Minor adverse effects, and more importantly severe adverse effects, are significantly reduced with selective COX-2 inhibitors compared with classical NSAID. It is important to note that these beneficial effects in terms of tolerance are not better than with NSAID treatments except for treatments at anti-inflammatory doses for more than one week. Selective COX-2 inhibitors would have the same adverse effect on the kidney as classical NSAID, as pointed out by the precautions for use published by the manufacturers. COX-2 is not expressed by platelets. Specific inhibitors do not inhibit platelet aggregation and do not lengthen bleeding time. Specific inhibitors, like classical NSAID, are not recommended for women desiring pregnancy, especially because the risk of a teratogenic effect has not been excluded. Conversely, for patients with asthma triggered by classical NSAID, selective COX-2 inhibitors do not trigger acute asthma. Finally, selective COX-2 inhibitors are not currently indicated for children and not for ENT disease.