对乙酰氨基酚APAP阿片及非阿片机制阿片镇痛效应.PPTVIP

* Arachidonic acid is a polyunsaturated fatty acid, one of the essential fatty acids required by most mammals. It is present in the membranes of the bodys cells, and is a precursor in the production of eicosanoids: the prostaglandins, thromboxanes, prostacyclin and the leukotrienes. A prostaglandin is any member of a group of lipid compounds that are derived from fatty acids and have important functions in the animal body. They are mediators and have a variety of strong physiological effects; although they are technically hormones they are rarely classified as such. There are two pathways for metabolism of arachidonic acid to prostaglandins, mediated by COX-1 and COX-2. COX-1 is constitutive and is responsible for the production of prostaglandins that protect the GI tract and maintain normal platelet function. COX-2 controls the production of prostaglandins that mediate inflammation and pain.1,2 NSAIDs inhibit both COX-1 and COX-2 and are non-specific in their mode of action, controlling pain and inflammation but also causing characteristic adverse effects.3 New strategies have focused on the development of therapeutic agents with pharmacological activity based on specific inhibition of COX-2.3 The rationale is that the therapeutic effects of NSAIDs are achieved by COX-2 inhibition, but that many of the toxic effects, most commonly gastroduodenal injury, result from COX-1 inhibition.4 COX-2 is also found as a normal constituent of certain tissues such as the brain, kidney and reproductive tract.1 --------------------------------------------------------------------------------- Cyclooxygenase in Platelets COX 1 is the only isoform of COX present in platelets and is responsible for the synthesis of thromboxane A2 (TxA2) which in turn is responsible for promoting platelet aggregation. Non-specific COX inhibitors such as ASA and NSAIDs inhibit the production of TxA2 via their effect on COX 1 resulting in a decrease in platelet aggregation and a mild bleedin