Aspirin and NSAIDs

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

Cross-reactions with aspirin and NSAIDs are of practical importance. Typically, AIA patients are sensitive to all NSAIDs that preferentially inhibit COX-1 (table 2). Acetaminophen (paracetamol), a weak inhibitor of COX-1, is regarded as a relatively safe therapeutic alternative for almost all patients with AIA. High doses of the drug (>1,000 mg) have been reported to provoke mild, easily reversed bronchos-pasm in some AIA patients [13]. Some rare, well-documented cases of coexistence of aspirin and paracetamol sensitivity have been described. However, according to a recent meta-analysis, less that 2% of asthmatics are sensitive to both aspirin and paracetamol [14]. 

Aspirin and NSAIDs can induce allergic and pseudoallergic reactions. Because these drugs are used so widely, with much over-the-counter use, the health care professional must have a basic understanding of the types of reactions that can occur and how to prevent them. Three types of reactions occur bron-chospasm with rhinoconjunctivitis, urticaria/angioedema, and anaphylaxis. Remember that patients with gastric discomfort... 

IgE -mediated urticarial/angioedema reactions and anaphylaxis are associated with aspirin and NSAIDs. Urticaria is the most common form of IgE-mediated reaction. This class is second only to fi-lactams in causing anaphylaxis. The potential for cross-reactivity between agents in IgE-mediated reactions appears small, but caution is advised. Because aspirin therapy is highly beneficial in primary and secondary prevention in... 

Do not take other medications, including OTC drugs (especially aspirin and NSAIDs), without physician approval... 

Patients with aspirin sensitivity should avoid aspirin and NSAIDs while taking mon-telukast... 

Stevenson DD. Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am. 2004 24 491-505. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS ASPIRIN t risk of renal impairment. 1 efficacy of captopril and enalapril with high-dose (>100mg/day) aspirin Aspirin and NSAIDs can cause elevation of BP. Prostaglandin inhibition leads to sodium and water retention and poor renal function in those with impaired renal blood flow Monitor renal function every 3-6 months watch for poor response to ACE inhibitors when >100mg/day aspirin is given... 

Despite the high prevalence of the use of minor analgesics (aspirin and paracetamol) there is little information available on the association between the use of these analgesics and the risk of hypertension. A prospective cohort study in 80 020 women aged 31-50 years has provided some useful information (5). The women had participated in the Nurses Health Study II and had no previous history of hypertension. The frequency of use of paracetamol, aspirin, and NSAIDs was collected by mailed questionnaires and cases of physician-diagnosed hypertension were identified by self-report. During 164 000 person-years of follow-up, 1650 incident cases of hypertension were identified. Overall, 73% of the cohort had used paracetamol at least 1-4 days/month, 51% had used aspirin, and 77% had used an NS AID. Compared with non-users of paracetamol the age-adjusted relative risk... 

The mechanism by which cyclooxygenase inhibition produces bronchospasm in susceptible individuals is unknown. Arachidonic acid metabolism through the 5-lipoxygenase pathway may lead to the excess production of leukotrienes C4 and D4. Leukotrienes C4, D4, and E4 produce bronchospasm and promote histamine release from mast cells, whereas the administration of leukotriene receptor antagonists and 5-lipoxygenase inhibitors ablate the pulmonary and nonpuhnonary responses to aspirin in aspirin-sensitive asthmatics. The precise mechanism by which augmented leukotriene production occurs is unknown, and available hypotheses do not explain why only a small number of asthmatic patients react to aspirin and NSAIDs. 

Aspirin and NSAID suppress prostaglandin production by inhibiting cyclooxygenase enzymes. Renal blood flow, particularly within the renal medulla, is highly dependent upon systemic and local production of vasodilatory prostaglandins. 

Thus, this region, in the setting of combined aspirin and NSAID use, is more prone to ischemic damage. Loss of proteoglycans and glycosaminoglycans, essential constituents of medullary matrix may occur. 

Aspirin and NSAIDs inhibit the COX enzymes and prostaglandin production they do not inhibit the lipoxygenase pathways of AA metabolism and hence do not suppress LT formation (see Chapter 25). Table 26-1 provides a classification of NSAIDs and other analgesic and antipyretic agents based on their chemical structures. 

Certain individuals display hypersensitivity to aspirin and NSAIDs, as manifested by symptoms that range from vasomotor rhinitis with profuse watery secretions, angioedema, generalized urticaria, and bronchial asthma to laryngeal edema, bronchoconstriction, flushing, hypotension, and shock. Aspirin intolerance is a contraindication to therapy with any other NSAID because cross-sensitivity can provoke a life-threatening reaction. 

An established but sparsely documented interaction. The potential problems arising from this interaction should be recognised in any patient given aspirin and phenylbutazone. The concurrent use of aspirin and NSAIDs increases the risk of gastrointestinal damage and is not recommended. Al-... 

The combined use of aspirin and NSAIDs increases the risk of gastrointestinal damage. There is no clinical rationale for the combined use of anti-inflammatoiy/analgesic doses of aspirin and NSAIDs, and such use should be avoided. There are numerous early pharmacokinetic studies of aspirin and NSAIDs, many of which showed that aspirin reduced the levels of NSAIDs. 

In a case-control study of data from 1993 to 1998 in the UK General Practice Research Database the risk of upper gastrointestinal bleeding or perforation was increased by slightly more than an additive effect in patients taking both aspirin and NSAIDs (8.2-fold), when compared with aspirin alone (2.4-fold), or NSAIDs alone (3.6-fold). The specifrc NSAIDs were not mentioned. Another study provided similar findings, as have studies... 

The damaging effects of aspirin and NSAIDs on the gut appear to be additive. The mechanisms behind the pharmacokinetic changes have not been resolved. Changes in the rates of absorption and renal clearance and competition for plasma protein binding have been proposed. 

The additive risk of gastrointestinal damage from combining aspirin and NSAIDs is established. Because of this, and the lack of clear benefit from the combination, the use of anti-inflammatory/analgesic doses of aspirin with NSAIDs should be avoided. For information on low-dose aspirin and NSAIDs see NSAIDs + Aspirin Antiplatelet dose , p.l44. Consider also NSAIDs + NSAIDs , p. 151. 

It is well known that aspirin and NSAIDs have additive gastrointestinal adverse effects (see NSAIDs + Aspirin Anti-inflammatory dose , p.l42). This occurs even at the low doses of aspirin used for antiplatelet effects (doses as low as 75 mg daily). ... 

The risk of serious upper gastrointestinal bleeding was inereased by the use of more than one NSAID in a meta-analysis of data from three ease-eontrolled studies (odds ratio 4.9 with one NSAID and 10.7 with two). Another study provided similar findings the odds ratio was 7.1 with one NSAID and 12.3 with two or more NSAIDs. Similar findings have been reported with aspirin and NSAIDs, see NSAIDs + Aspirin Anti-inflammatory dose , p.l42. Analysis of yellow eard reports to the CSM in the UK, of gastrointestinal perforation, obstruetion, uleeration or bleeding with diclofenac, naproxen, and ibuprofen, revealed that 6% of the patients were reeeiving another non-aspirin NSAID. ... 

Data from animal studies suggest that the absorption and thus the effects of aspirin and NSAIDs can be reduced by omeprazole and H2-receptor antagonists via a pH dependent meehanism."> However, note that clinical studies have not found H2-receptor antagonists to have any important effect on the pharmacokinetics of aspirin or NSAIDs, see NSAIDs or Aspirin + H2-receptor antagonists , p.l49. It has been suggested that reducing gastric acidity with omeprazole results in the earlier disruption of enteric-coated tablets, and an increased absorption rate. ... 

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