Aspirin and Other NSAIDs

In this bromoaspirin-inactivated structure, Ser , which lies along the wall of the tunnel, is bromoacetylated, and a molecule of salicylate is also bound in the tunnel. Deep in the tunnel, at the far end, lies Tyr, a catalytically important residue. Heme-dependent peroxidase activity is implicated in the formation of a proposed Tyr radical, which is required for cyclooxygenase activity. Aspirin and other NSAIDs block the synthesis of prostaglandins by filling and blocking the tunnel, preventing the migration of arachidonic acid to Tyr in the active site at the back of the tunnel. 

Aspirin and other NSAIDs function by blocking the cyclooxygenase (COX) enzymes that carry out the body s synthesis of prostaglandins (Sections 7.11 and 27.4). There are two forms of the enzyme, COX-1, which carries out the normal physiological production of prostaglandins, and COX-2, which mediates the body s response to arthritis and other inflammatory conditions. Unfortunately, both COX-1 and COX-2 enzymes are blocked by aspirin, ibuprofen, and other NSAIDs, thereby shutting down not only tire response to inflammation but also various protective functions, including the control mechanism for production of acid in the stomach. 

The term refers to a distinct clinical syndrome characterized by aggressive and continuous inflammatory disease of the airways with chronic eosinophilic rhinosinus-itis, asthma and often nasal polyposis [6-8]. Aspirin and other NSAIDs that inhibit COX-1 exacerbate the condition, precipitating violent asthmatics attacks. This is a hallmark of the syndrome. The prevalence of aspirin hypersensitivity in the general population ranges from 0.6 to 2.5%, but is much more frequent in adult asthmatic subjects where it reaches 10-15%, although it is often underdiagnosed. 

Dietary and pharmacologic agents influence the risk of colon cancer. Diets high in fat and low in fiber are associated with increased colon cancer risk, whereas the regular use of aspirin (and other NSAIDs) and calcium supplementation may decrease the risk of colon cancer. 

Hypersensitivity to salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs). Use extreme caution in patients with history of adverse reactions to salicylates. Cross-sensitivity may exist between aspirin and other NSAIDs that inhibit prostaglandin synthesis, and aspirin, and tartrazine. Aspirin cross-sensitivity does not appear to occur with sodium salicylate, salicylamide, or choline salicylate. Aspirin hypersensitivity is more prevalent in those with asthma, nasal polyposis, chronic urticaria. 

Preexisting asthma About 10% of patients with asthma may have aspirin-sensitive asthma. Because cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, do not administer... 

The best representative of an NSAID is aspirin (acetylsalicylic acid Fig. 15-1). Newer NSAIDs are usually compared to aspirin in terms of efficacy and safety. Acetaminophen is another agent that is similar to aspirin and other NSAIDs in its ability to decrease pain and fever. Acetaminophen, however, is not considered an NSAID because it lacks anti-inflammatory and anticoagulant properties. For a discussion of the comparative effects of aspirin, newer NSAIDs, and acetaminophen, see Comparison of Aspirin with Other NSAIDs. ... 

Aspirin and other NSAIDs are effective in treating mild-to-moderate pain of various origins, including headache, toothache, and diffuse muscular aches and soreness. Aspirin appears to be especially useful in treating pain and inflammation in musculoskeletal and joint disorders.71,87,89 The safe and effective use of aspirin in both rheumatoid arthritis and osteoarthritis is well documented (see Chapter 16).53,66,84 Aspirin is also recommended for treating the pain and cramping associated with primary dysmenorrhea.70... 

Meclofenamate Meclomen No apparent advantages or disadvantages compared to aspirin and other NSAIDs. 

Mefanamic acid Ponstel No advantages often less effective and more toxic than aspirin and other NSAIDs. 

The primary difference between aspirin and other NSAIDs is cost. Most of the NSAIDs still require a physician s prescription. The cost of prescription NSAIDs can be anywhere from 10 to 20 times more expensive than an equivalent supply of aspirin. NSAIDs that are available in nonprescription form (e.g., ibuprofen) can still cost up to five times as much as aspirin. 

Aspirin is employed for mild to moderate pain of varied origin but is not effective for severe visceral pain. Aspirin and other NSAIDs have been combined with opioid analgesics for treatment of cancer pain, where their anti-inflammatory effects act synergistically with the opioids to enhance analgesia. High-dose salicylates are effective for treatment of rheumatic fever, rheumatoid arthritis, and other inflammatory joint conditions. 

The efficacy of flurbiprofen at dosages of 200-400 mg/d is comparable to that of aspirin and other NSAIDs in clinical trials for patients with rheumatoid arthritis, ankylosing spondylitis, gout, and osteoarthritis. It is also available in a topical ophthalmic formulation for inhibition of intraoperative miosis. Flurbiprofen intravenously has been found to be effective for perioperative analgesia in minor ear, neck, and nose surgery and in lozenge form for sore throat. 

Analgesics. Opiates can precipitate hepatic encephalopathy in patients with decompensated liver disease. If required to control postoperative pain, doses should be reduced to 25-50% of normal. Constant intravenous infusions should be avoided if the patient is not to be insidiously overdosed. Codeine can precipitate hepatic encephalopathy by its constipating effect alone. Aspirin and other NSAIDs may exacerbate impaired renal function and fluid retention by inhibiting prostaglandin synthesis and may also precipitate gastrointestinal bleeding. 

Drugs that are an irritant to the gastric mucosa and cause unpleasant side effects such as nausea and vomiting. Examples include aspirin and other NSAIDS (e.g., naproxen). 

A study of the risk factors for gastrointestinal perforation, a much less frequent event than bleeding, has confirmed that aspirin and other NSAIDs increase the risk of both upper and lower gastrointestinal perforation (OR 6.7, Cl 3.1-14.5 for NSAIDs) (53). Gastrointestinal perforation has been associated with other factors, such as coffee consumption, a history of peptic ulcer, and smoking. The combination of NSAIDs, smoking, and alcohol increased the risk of gastrointestinal perforation (OR 10.7, Cl 3.8-30) (SEDA-21, 97). 

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