Action of Aspirin

These actions of aspirin are thought to result from its abiHty to reduce the production of prostaglandin formed by platelet cells without appreciably... 

The understanding of these actions of aspirin started in 1971 (45) and resulted in the recommendations of the medical community that small doses of aspirin, used under the care of the doctor, may be a prevention measure for heart attack, and stroke for those considered at risk in the population. Further reported work may expand health benefits to prevention of certain kinds of cancer (46). 

In view of the well-known pharmacological action of aspirin, it was thought that the fluorine analogue, O (fluoroacetyl) salicylic acid, might be of considerable interest. The compound was readily made by acylation of salicylic acid by fluoroacetyl chloride in the presence of pyridine. The l.d. 50 for subcutaneous injection into mice was approximately 15 mg./kg. After injection the mice went into a drugged sleep, and died overnight. 

The antipyretic and analgesic actions of aspirin are believed to occur in a certain area of the brain. It is also thought by some that the salicylates exert their analgesia by their effect on water balance. Aspirin is anti-inflammatory because it inhibits the biosynthesis of chemicals called prostaglandins. The irritation of the stomach lining caused by aspirin can be alleviated with the use of mild bases such as sodium bicarbonate, aluminum glycinate, sodium citrate, aluminum hydroxide, or magnesium trisilicate (a common trademark for this type of aspirin is Bufferin ). 

The antiplatelet action of aspirin contraindicates its use by patients with hemophilia. Although previously not recommended during pregnancy, aspirin may be valuable in treating preeclampsia-edampsia. 

Abramson, S., et al. Modes of Action of Aspirin Like Drugs, Proceedings, National Academy of Sciences 82(21) 7227 (November 1985). 

Weissmann, G., Aspirin. Sci. Am. 264 84-90, 1991. An interesting article that discusses the mechanism of action of aspirin in connection with eicosanoid metabolism. 

FIGURE 25.2 Sites of action of aspirin, colchicine, and parthenolide. 

Pharmacodynamic alcohol interactions are also of great clinical significance. Additive central nervous system depression with other sedative-hypnotics is most important. Alcohol also potentiates the pharmacologic effects of many nonsedative drugs, including vasodilators and oral hypoglycemic agents. There is some evidence that alcohol also enhances the antiplatelet action of aspirin. 

Mechanism of action of aspirin and laboratory evaluation of aspirin responsiveness. (Seep. 141.)... 

The mechanism of action of aspirin may be more involved than is indicated above. Aspirin also induces the formation of NO-radicals in the body, which in mice have been shown to have an independent mechanism of reducing inflammation salicylic acid and its derivatives can modulate signalling through NF-kB, a transcription factor complex that plays a central role in many processes, including inflammation. 

Abramson SB, Korchak H, Ludewig R, Edelson H, Haines K, Levin RI, Hennan R, Rider L, Kinunel S, Weissman G Modes of action of aspirin-like drugs. Proc. Natl. Acad. Sd USA 7227,1983... 

The anti-inflammatory, analgesic and antipyretic actions of aspirin are those of NSAIDs in general... 

Aspirin can also play a role in esophageal bleeding, ulceration, or benign stricture, and it should be considered as a possible cause in patients, particularly the elderly, who present with any of these features. There have also been reports of rectal stricture in the elderly, associated with the use of aspirin suppositories. Effects on both these strictures emphasize the significance of a direct local action of aspirin as well as a systemic action and underlines the relevance of the involvement of oxygen-derived free radicals in the pathogenesis of mucosal lesions in the gastrointestinal tract (54-56). 

Moncada S, Vane JR. Mode of action of aspirin-like drugs. Adv Intern Med 1979 24 1-22. 

Cambridge H, Lees P, Hooke R E et al 1991 Antithrombotic actions of aspirin in the horse. Equine Veterinary Journal 23 123-127... 

The mucosa of the stomach is also damaged by the action of aspirin, the chemical name of which is acetylsalicylic acid. Aspirin is itself a moderately weak acid ... 

A relatively nonpolar molecule, acetylsalicylic acid has the ability to penetrate membrane barriers that are also made up of nonpolar molecules. However, inside the membrane are many small water pockets, and when an acetylsalicylic acid molecule enters such a pocket, it ionizes into and acetylsalicylate ions. These ionic species become trapped in the interior regions of the membrane. The continued buildup of ions in this fashion weakens the structure of the membrane and eventually causes bleeding. Approximately 2 ml of blood are usually lost for every aspirin tablet taken, an amount not generally considered harmful. However, the action of aspirin can result in severe bleeding in some individuals. It is interesting to note that the presence of alcohol makes acetylsalicylic acid even more soluble in the membrane, and so further promotes the bleeding. 

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