Prostaglandin myocardial infarction

NS AIDs Cyclooxygenases (COX-1, COX-2) l Prostaglandins l Thromboxanes l Sensitization of sensory neurons f Inhibition of spinal neurons Nonselective gastrointestinal ulcers, perforation, bleeding, renal impairment COX-2 thrombosis, myocardial infarction, stroke... 

Sulfinpyrazone is a uricosuric and also inhibits platelet functions, probably mainly as a result of some inhibition of prostaglandin synthesis. However clinical efficacy in secondary prevention of myocardial infarction is inconsistent at the most. 

The salicylates are also potent antipyretic agents, with the exception of diflunisal, which is only weakly active. Aspirin acts at two distinct but related sites. It decreases prostaglandin-induced fever in response to pyrogens and induces a decrease in interleukin-1 modulation of the hypothalamic control of body temperature. Thus, the hypothalamic control of body temperature returns, vasodilation occurs, heat dissipates, and fever decreases. Other uses of aspirin include inhibition of platelet aggregation via inhibition of thromboxanes, which has been shown to decrease the incidence of blood clots, myocardial infarction, and transient ischemic attacks. 

Fliers E, Duren DR, van Zwieten PA. A prostaglandin analogue as a probable cause of myocardial infarction in a young woman. BMJ 1991 302(6773) 416. 

Meyer WJ, Benton SL, Hoon TJ, Gauthier DW, Whiteman VE. Acute myocardial infarction associated with prostaglandin E2. Am J Obstet Gynecol 1991 165(2) 359-60. 

Antagonistic effects of cyclo-oxygenase inhibitors (indo-metacin or aspirin) have been repeatedly reported both in hypertension and in heart failure, strongly suggesting that there may be prostaglandin participation in the clinical response to ACE inhibitors (103,104). In animals, although not in all experimental models, aspirin can attenuate the beneficial effects of ACE inhibitors on ventricular remodelling after myocardial infarction. 

Cardiovascular effects of prostaglandins are more complex. The coagulation system is clearly modulated by platelet-derived thromboxanes, which have procoagulation effects and the anticoagulative effects of endothelial cell-derived prostacyclin. Thromboxanes are clearly COX-1 derived because platelets do not express COX-2. The source of endothelial cell prostacyclin production is less clear with both enzymes expressed and mixed opinions on the relative contribution of the two enzymes. Recent results with Vioxx, a selective COX-2 inhibitor, imply a modest effect on myocardial infarction rate in patients taking the compound but do not define whether this is caused by a change in ratio simply by a lack of platelet effect or that inhibition of endothelial cell prostacyclin also skews the pro- and anticoagulant ratio. 

Aspirin Irreversibly inhibits cyclooxygenase. Thus prevents formation of thromboxane A2 and prostaglandins (which induce platelet aggregation). Reduce risk of recurrent transient ischemic attacks or stroke. Reduces risk of myocardial infarction in patients with unstable angina or prior infarction. Also used for antiinflammatory and analgesic purposes. Gl ulceration, bleeding, hemorrhage, salicylism. 

Figure 6.8 Urinary, 2,3-dinor-thromboxane (Tx) B2 (normal < 350 pg/mg creatinine) and 2,3-dinor-6-keto-prostaglandin (PG) (normal < 220 pg/mg creatinine) in 6h urine aliquots over 2 days in a patient admitted with unstable angina who subsequently developed an acute myocardial infarction...

In addition to their effects on coronary thrombosis, prostaglandins may play a role in modulating the degree of tissue injury in acute myocardial infarction. Infusion of prostacyclin in the isolated perfused heart limits hypoxic injury independent of its effects on tissue perfusion or platelet function, suggesting that prostacyclin exerts a direct myoprotective effect . Prostacyclin biosynthesis increases markedly following acute myocardial infarction in... 

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