Anti-Inflammatory Effects of Aspirin

The anti-inflammatory effect of aspirin appears to be due to the acetylation of a serine residue at the active site of the cyclooxygenase, which irreversibly inactivates the enzyme (fig. 19.18). Aspirin has no effect on the peroxidase activity of the enzyme. 

Aspirin has some beneficial effects when mixed with caffeine, because caffeine increases the pain-relieving and anti-inflammatory effects of aspirin. Brand names of pain relievers that combine aspirin and caffeine include Alka-Seltzer , Anacin , and Cope Analgesic Pain Reliever. 

Acetaminophen is a potent analgesic drug, but it lacks the anti-inflammatory effects of aspirin. It also is less likely to cause stomach irritation. 

Yamashita reported anti-inflammatory effect of astaxanthin when administered with aspirin. An oral preparation has been developed by Alejung and Wadstroem for the treatment of Helicobacter infections of the mammalian gastrointestinal tract. Strong evidence suggested that astaxanthin modulated the humoral and non-humoral immune systems. It enhanced the release of interleukin-1 and tumor necrosis factor-... 

Q88 Anti-inflammatory doses of aspirin may cause tinnitus and deafness. These side-effects are symptoms of salicylate intoxication. 

Mechanism of action The antipyretic and anti-inflammatory effects of the salicylates are due primarily to the blockade of prostaglandin synthesis at the thermoregulatory centers in the hypothalamus and at peripheral target sites. Furthermore, by decreasing prostaglandin synthesis, the salicylates also prevent the sensitization of pain receptors to both mechanical and chemical stimuli. Aspirin may also depress pain stimuli at subcortical sites (that is, the thalamus and hypothalamus). 

Aspirin is often given in a buffered form. The addition of small amounts of antacids decreases GI irritation and increases the dissolution and absorption rate of the aspirin. Nonacetylated salicylates, including salsalate, sodium salicylate, choline salicylate, magnesium salicylate, and various salicylate combinations, are usually more expensive but can be effective. Although these aspirin substitutes provide less anti-inflammatory effects than aspirin, they exhibit minimal antiplatelet properties and have fewer GI side effects.They can therefore be useful for patients who cannot tolerate aspirin or other NSAIDs. 

Ibuprofen was developed by researchers at the Boots Company, a British drug manufacturer, in the early 1960s. Those researchers had found that the anti-inflammatory property of aspirin was due to the presence of a carboxylic acid (-COOH) group in the compound. They searched for other carboxylic acids that might have similar properties and, after testing more than 600 compounds, discovered that ibuprofen met that criterion. It was twice as effective as... 

Early studies evaluating non-aspirin NSAIDs in rheumatoid arthritis commonly permitted the concurrent use of aspirin, which was then in wide use for this condition. The unexpected finding that indometacin was no more effective than placebo in patients taking aspirin in one study led to a number of pharmacokinetic studies with this combination (see Indometacin, below), and subsequently other NSAID/aspirin combinations. These studies generally have little clinical relevance to current clinical practice where anti-inflammatory doses of aspirin should not be used in combination with NSAIDs because of the increased risk of gastrointestinal bleeding (see above) and lack of proven additional benefit. However, the pharmacokinetic studies are briefly summarised below. 

The antihypertensive effects of spironolactone in patients with hypertension were unaffected by anti-inflammatory doses of aspirin in one small study, although there is evidence that these doses of aspirin reduce the spironolactone-induced loss of sodium in the... 

An adequately but not extensively documented interaction. Despite the results of the studies showing a reduced natriuretic effect, the small study in hypertensive patients shows that the blood pressure-lowering effects of spironolactone might not be affected by anti-inflammatory doses of aspirin. In general, concurrent use need not be avoided, but if the diuretic response to spironolactone is less than expected consider this interaction as a cause. 

Aspirin is acetylsalicylic acid and is used as an antiplatelet agent and for pain relief. Its use for anti-inflammatory effects is limited by the occurrence of side-effects, which include tinnitus and deafness, both features of salicylate poisoning. 

Reduction of inflammation with nonsteroidal anti-inflammatory drugs (NSAIDs) often results in relief of pain for significant periods. Furthermore, most of the nonopioid analgesics (aspirin, etc) have anti-inflammatory effects, so they are appropriate for the treatment of both acute and chronic inflammatory conditions. 

Ibuprofen is a simple derivative of phenylpropionic acid (Figure 36-1). In doses of about 2400 mg daily, ibuprofen is equivalent to 4 g of aspirin in anti-inflammatory effect. Pharmacokinetic characteristics are given in Table 36-1. 

The eicosanoids have been implicated as mediators of tissue inflammation since aspirin s anti-inflammatory effect was shown to be the result of its inactivation of cyclooxygenase. How eicosanoids cause tissue inflammation is the focus of much current research. 

Chang M. L., Klaidman L. K., and Adams J. D., Jr. (1997). The effects of oxidative stress on in vivo brain GSH turnover in young and mature mice. Mol. Chem. Neuropathol. 30 187-197. Chiang N., Arita M., and Serhan C. N. (2005). Anti-inflammatory circuitry Lipoxin, aspirin-triggered lipoxins and their receptor ALX. Prostaglandins Leukot. Essent. Fatty Acids 73 163-177. 

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. ... 

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