Aspirin cyclooxygenase affected

In the presence of aspirin, cyclooxygenase is irreversibly inactivated by ) acetylation. New cyclooxygenase molecules are not produced in platelets, because these cells have no nuclei and, therefore, cannot synthesize new mRNA. Thus, the inhibition of cyclooxygenase by aspirin persists for the lifespan of the platelet (7-10 days). When aspirin is taken daily at doses between 81 and 325 mg, new platelets are affected as they are generated. Higher doses do not improve efficacy but do increase side effects, such as gastrointestinal bleeding and easy bruisability. 

Aspirin sensitive asthma, affecting about 10% of all asthmatics, is a nonallergic response to aspirin and other agents that inhibit cyclooxygenase-1. Mechanistically, the most likely reasons are lack of bronchoprotective prostaglandin E2 and shunting of arachidonic acid into the leukotriene pathway. 

Unlike aspirin and other cyclooxygenase inhibitors that work on the COX-1 and COX-2 enzymes, acetaminophen works on the COX-3 enzyme, which is present in the spinal column and brain. This helps it to avoid shutting down prostaglandin function elsewhere in the body, which is why it has no anti-inflammatory effects and does not affect blood platelets or the stomach lining. 

In Box 7.13 we saw that the widely used analgesic aspirin exerted its action by acetylating the enzyme cyclooxygenase (COX) which is involved in the production of prostaglandins. Prostaglandins are modified C20 fatty acids synthesized in animal tissues and they affect a wide variety of physiological processes, such as... 

Acetaminophen [a seat a MIN oh fen] and phenacetin [fe NASS e tin] act by inhibiting prostaglandin synthesis in the CNS. This explains their antipyretic and analgesic properties. They have less effect on cyclooxygenase in peripheral tissues, which accounts for their weak anti-inflammatory activity. Acetaminophen and phenacetin do not affect platelet function or increase blood clotting time, and they lack many of the side-effects of aspirin. [Note Phenacetin can no longer be prescribed in the United States because of its potential for renal toxicity. However, it is present in some proprietary preparations.]... 

Aspirin inhibits cyclooxygenase, thus impairing platelet aggregation, This may be additive to other drugs with a similar effect and to those which affect other aspects of blood clotting. The risk of interactions and adverse effects is reduced by using a lower dose (e.g. 75mg) fortunately, a full antiplatelet effect is seen at this dose,... 

It was established that PG synthetase is inhibited by aspirin and other acidic NSAIDs. It was determined somewhat later that actual inhibition occurs at the active site of the cyclooxygenase component probably by competing with the polyunsaturated acid substrates such as AA. As will be seen, the PG-mediated effects of inflammation, pain, platelet aggregation, and vasoconstriction are all affected by this enzyme inhibition. 

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