抄録
An area of great focus for the medical/scientific community over the last several years has been that of the cardiovascular (CV) and renal safety profile of non-steroidal anti-inflammatory drugs commonly referred to as NSAIDs. The analgesic and anti-inflammatory attributes of these drugs are linked to the inhibition of cyclooxygenase-2 (COX-2) while many of the side-effects including CV and renal have variably been linked to COX-1 and/or COX-2 inhibition and in some cases directly to the secondary pharmacologic properties of the select drugs. The major CV related adverse effects in humans included thrombo-embolic events and hypertension with marked drug-specific differences in their occurrence and severity. The exact mechanism of these CV effects has been under intense discussion and scrutiny. Conventional nonclinical safety studies of up to 2 year in duration have shown that chronic inhibition of cyclooxygenases in normal animals is not associated with an increased risk of cardiovascular toxicity or prothrombotic potential. Non-clinical studies in disease animal models (e.g., hypertension and thrombosis) have produced very variable results. It is anticipated that on-going research in this area will be able to answer many of the outstanding questions in understanding the potential mechanisms of toxicity. This presentation will focus on the expression and function of COX enzymes in the kidney and the cardiovascular system and discuss the pathophysiologic effects associated with COX inhibition.
