Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update
Abstract
:1. Introduction
Selectivity | Drugs |
---|---|
Weak COX inhibitors | Acetaminophen,Salsalate |
Inhibitors of COX-1 and COX-2 | Acetylsalicylic acid, Piroxicam, Indomethacin, Sulindac, Tolmetin, Ibuprofen, Naproxen, Fenoprofen, Meclofenamate, Mefenamic acid Diflunisal, Ketoprofen, Diclofenac, Ketorolac, Etodolac, Nabumetone, Oxaprozin, Flurbiprofen |
Preferential COX-2 inhibitors | Nimesulide, Meloxicam |
Selective COX-2 inhibitors | Celecoxib, Rofecoxib,Valdecoxib, Etoricoxib, Parecoxib, Lumiracoxib |
2. Hypersensitivity Reactions to NSAIDs
3. Clinical Picture
- (1)
- Respiratory reactions: Observed in patients with Aspirin Exacerbated Respiratory Disease (AERD), also called aspirin triad, Samter’s disease, or aspirin intolerant asthma. These individuals experience a chronic disease characterized by chronic rhinosinusitis, severe persistent and steroid-dependent asthma, with or without nasal polyposis. Acute asthma exacerbations occur when they receive aspirin or classic NSAIDs. These asthma attacks are severe and may be life-threatening. Various genetic polymorphisms have been associated with this condition [10].
- (2)
- Cross reacting urticaria and angioedema: Exacerbations of urticaria and/or angioedema induced by COX-1 inhibitors are observed in up to one third of patients with chronic urticaria, more often with drugs of the heteroaryl group (naproxen, diclofenac, ibuprofen) [11]. Various genetic polymorphisms, including genes coding for HLA antigens, LTC4 synthase, 5-lipooxygenase, and the high affinity receptor for IgE have been observed in these patients [10].
- (3)
- Urticaria, angioedema and anaphylaxis induced by multiple NSAIDs: In patients who do not suffer other morbid conditions NSAIDs can precipitate acute urticaria, angioedema or systemic reactions. This variant of hypersensitivity is more prevalent in atopic individuals [8,12] and facial angioedema is the most frequent clinical manifestation [13]. It has been associated with A444-C allele of LTC4 synthase [14].
- (4)
- Urticaria, angioedema and anaphylaxis induced by a single NSAID: More frequently triggered by pyrazolones, but also reported for aspirin, paracetamol, ibuprofen, diclofenac and naproxen. These reactions constitute about 30% of adverse reactions to NSAIDs and are observed with increased frequency in patients with previous history of atopic disease, food or drug allergy. The clinical manifestations include urticaria, angioedema, laryngeal edema, anaphylaxis, generalized pruritus, rhinitis or bronchospasm.
4. Pathogenesis
5. Diagnosis
Patients with respiratory symptoms (AERD) | |||
---|---|---|---|
Hour | Day 1 | Day 2 | Day 3 |
08:00 | Placebo | ASA 3 or 30 mg | ASA 150 mg |
11:00 | Placebo | ASA 60 mg | ASA 325 mg |
14:00 | Placebo | ASA 100 mg | ASA 650 mg |
Monitor pulmonary function, naso-ocular symptoms/signs | |||
Test positive if a decrease of FEV1 ° 20 % is observed | |||
Patients with urticaria and/or angioedema | |||
08:00 | Placebo | ASA 100 mg | ASA 325 mg |
10:00 | Placebo | ASA 200 mg | ASA 650 mg |
Skin scores recorded every 2 hours |
6. Patient Management
Group | Drugs |
---|---|
Salicylic acid derivatives | Aspirin, sodium salicylate, choline magnesium trysalicylate, salsalate, diflunisal, salicilsalicylic acid, sulfasalazine, olsalazine |
Para-aminophenol derivatives | Acetaminophen |
Indol and indene acetic acids | Indomethacin, sulindac, etodolac |
Heteroaryl acetic acid | Tolmetin, diclofenac, ketorolac |
Arilpropionic acid | Ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, oxaprozin |
Antranilic acid (fenamates) | Mefenamic acid, meclofenamic acid |
Enolic acid | Oxicams (piroxicam, tenoxicam), pyrazoledinediones (fenilbutazone, oxyfentathrazone) |
Alkanones | Nabumetone |
Pyrazolic derivatives | Antipyrin, aminopyrin, dipyrone |
7. Conclusions
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Sánchez-Borges, M.; Caballero-Fonseca, F.; Capriles-Hulett, A.; González-Aveledo, L. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update. Pharmaceuticals 2010, 3, 10-18. https://doi.org/10.3390/ph3010010
Sánchez-Borges M, Caballero-Fonseca F, Capriles-Hulett A, González-Aveledo L. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update. Pharmaceuticals. 2010; 3(1):10-18. https://doi.org/10.3390/ph3010010
Chicago/Turabian StyleSánchez-Borges, Mario, Fernan Caballero-Fonseca, Arnaldo Capriles-Hulett, and Luis González-Aveledo. 2010. "Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update" Pharmaceuticals 3, no. 1: 10-18. https://doi.org/10.3390/ph3010010