Aspirin dose-dependent actions

All agonists in this therapeutic group decrease the sensation of painful stimuli, which is their main clinical application. They tend to subdue dull, persistent pain rather than sharp pain, but this difference is to some extent dose dependent. The major difference between the non-opioid analgesics such as aspirin and the opiates is that the former reduce the perception of peripherally mediated pain, by reducing the synthesis of local hormones that activate the pain fibres, whereas the latter attenuate the affective reaction to pain without affecting the perception of pain. This clearly suggests that the site of action of the opiate analgesics is in the central nervous system. 

Aspirin is the only NSAID that causes irreversible inhibition of COX, It forms a covalent bond via acetylation of a serine hydroxyl group near the active site. Its actions are dose dependent. 

Aspirin is a well-established antiplatelet drug In the treatment of atherothrombotic vascular disease (87,88,89). As stated earlier, aspirin works by its ability to acetylate and irreversibly deactivate platelet COX (COX-1), and Its antithrombotic effect remains for the life span of the platelet (7-10 days). Aspirin also has been shown to have other antithrombotic effects that are unrelated to its action on COX-1 (87). These effects include the dose-dependent inhibition of platelet function, the enhancement of fibrinolysis, and the suppression of blood coagulation. 

Aspirin covalently modifies COX-1 and COX-2, irreversibly inhibiting COX activity. This is an important distinction from all the NSAIDs because the duration of aspirin s effects is related to the turnover rate of COX in different target tissues. The duration of effect of nonaspirin NSAIDs, which competitively inhibit the active sites of the COX enzymes, relates more directly to the time course of drug disposition. The importance of enzyme turnover in relief from aspirin action is most notable in platelets, which, being anucleate, have a markedly limited capacity for protein synthesis. Thus, the consequences of inhibition of platelet COX (COX-1) last for the lifetime of the platelet. Inhibition of platelet COX-1-dependent TXA formation, therefore, is cumulative with repeated doses of aspirin (at least as low as 30 mg/day) and takes roughly 8-12 days (the platelet turnover time) to recover once therapy has been stopped. 

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