Aspirin with Other NSAIDs

Generic Name Aspirin Trade Name(s) Many trade names Specific Comments—Comparison to Other NSAIDs Most widely used NSAID for analgesic and anti-inflammatory effects also used frequently for antipyretic and anticoagulant effects. 

Diclofenac Voltaren Substantially more potent than naproxen and several other NSAIDs adverse side effects occur in 20°/o of patients. 

Diflunisal Dolobid Has potency 3-4 times greater than aspirin in terms of analgesic and anti-inflammatory effects but lacks antipyretic activity. 

Etodolac Lodine Effective as analgesic/anti-inflammatory agent with fewer side effects than most NSAIDs may have gastric-sparing properties. 

Fenoprofen Nalfon Gl side effects fairly common but usually less intense than those occurring with similar doses of aspirin. 

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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 is the oldest and most widely used NSAID, and other NSAIDs are compared with aspirin in terms of efficacy and safety. Hence, this discussion focuses primarily on the clinical applications of aspirin and the problems typically associated with aspirin. For the most part, clinical use and problems can also be applied to most nonaspirin NSAIDs. The major similarities and differences between aspirin and the other NSAIDs are discussed in Comparison of Aspirin with Other NSAIDs. ... 

Retrospective cohort Discharge after CVD Mortality Aspirin alone (6285) Aspirin with Ibuprofen (187) Aspirin with Diclofenac (206) Aspirin with other NSAID (429) Increased all-cause mortality and cardiovascular mortality in those taking aspirin with ibuprofen compared with the other groups. 1... 

Retrospective cohort Discharge after Ml and on aspirin Death in first year Aspirin alone (66739) Aspirin with Ibuprofen (844) Aspirin with other NSAID (2733) Risk of death comparable between the 3 groups. 5... 

Willow bark (weidenrinde, white willow, purple osier willow, crack willow) S lixalba, purpurea, fragilis Analgesic Adverse reactions are those associated with the salicylates Do not use with aspirin or other NSAIDs. Do not use in patients with peptic ulcers and other medical conditions in which the salicylates are contraindicated. 

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. 

Concomitant use with NSAiDs - Ketorolac is contraindicated in patients currently receiving aspirin or other NSAIDs ketorolac also is contraindicated with the concomitant use of probenecid. 

Anaphylactoid reactions have occurred in patients without known exposure to NSAiDs, but they typically occur in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAiDs. 

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... 

Consider for patients with GI intolerance to aspirin or patients in whom interference with normal platelet function by aspirin or other NSAIDs is undesirable... 

The drugs like ibuprofen, flurbiprofen, ketoprofen etc. possess antiinflammatory property similar to aspirin but toxicity and adverse effects are fewer and of lesser intensity. These preparations alone and in combination with other NSAIDs are used for treatment of inflammatory disorders. 

A topical 3% gel formulation of the nonsteroidal anti-inflammatory drug diclofenac (Solaraze) has shown moderate effectiveness in the treatment of actinic keratoses. The mechanism of action is unknown. As with other NSAIDs, anaphylactoid reactions may occur with diclofenac, and it should be given with caution to patients with known aspirin hypersensitivity (see Chapter 36). 

For patients with ulcers caused by aspirin or other NSAIDs, either H2 antagonists or proton pump inhibitors provide rapid ulcer healing so long as the NSAID is discontinued however continued use of the NSAID impairs ulcer healing. In patients with NSAID-induced ulcers who require continued NSAID therapy, treatment with a once- or twice-daily proton pump inhibitor more reliably promotes ulcer healing. 

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... 

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. 

Contraindications fc>r nonsalicylate NSAID therapy are the same as those for aspirin (see Box 7-I).The formation of a gastric ulcer or erosion that may bleed profusely is a serious potential problem with NSAIDs. Consequently, the nonsalicylate NSAIDs should be avoided or used with great caution in patients with active peptic ulcer disease. NSAIDs may increase the risk of GI complications even when used in conjunction with low-dose aspirin for cardioprotection. In addition, because of potential crosssensitivity to other NSAIDs, the nonsalicylate NSAIDs should not be given to patients in whom aspirin or other NSAIDs have caused symptoms of asthma, rhinitis, urticaria, angioedema, hypotension, bronchospasm, or of symptoms of hypersensitivity reactions. Opioids, tramadol, or acetaminophen may be suitable alternatives for patients with known or suspected susceptibility. 

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. 

One case-control study showed no increased risk of intracerebral hemorrhage in patients using aspirin or other NSAIDs in low dosages as prophylaxis against thrombosis (21). However, intracerebral hemorrhage has been reported with aspirin, even in low doses, and in the SALT study (22) and the Physicians Health Study of 1989 (23) hemorrhagic stroke and associated deaths occurred with aspirin. 

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). 

There is considerable cross-reactivity with other NSAIDs and the now widely banned food colorant tar-trazine (78). Cross-sensitization between aspirin and tar-trazine is common for example, in one series 24% of aspirin-sensitive patients also reacted to tartrazine (SEDA-9, 76). 

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