Healthy Clinical Trial
Official title:
Effect of Opioids and NSAIDs on Sympathetic Nervous System and Vascular Function in Healthy Subjects and Patients With Osteoarthritis
Evaluation of the effect of different analgesic treatments (Tramadol, Paracetamol, Diclofenac) on sympathetic nerve activity, blood pressure, heart rate, heart rate, and vascular function in osteoarthritis patients and healthy subjects.
Hundreds of millions of patients worldwide require pain-relieving therapy to maintain an acceptable quality of life. Pain relievers, including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, however, exert unwanted potent adverse systemic off-target effects and their use is associated with a well-documented excess of cerebrovascular and cardiovascular events. This of particular concern for the one fourth of the world's population aged over 35 years suffering from chronic pain, particularly with arthritis of whom half also present with established or at high risk of cardiovascular disease. This uncertainty around the cardiovascular safety of pain relieving drugs leaves practitioners and their patients with difficult management decisions and underscores the need to investigate potential differential cardiovascular effects of NSAIDs and opioids and to better delineate the underlying mechanisms involved. Indeed, currently available NSAIDs invariably disrupt the balance between prostacyclin and thromboxane, but may also exert multiple and opposing cardiovascular effects on endothelial factors, including nitric oxide and reactive oxygen species, the sympathetic nervous system and vascular inflammation. Intriguingly, the net effect of pain relieving drugs on vascular function and sympathetic nerve activity and its resulting deterioration of blood pressure control is increasingly recognized as a major possible determinant in explaining the cardiovascular side effects of NSAIDs. As a result of the ongoing concerns around the cardiovascular safety of NSAIDs and coxibs many patients are being withheld effective pain relieve or switched to opioids and/or paracetamol under the assumption of their yet unproven greater cardiovascular safety. The absence of evidence about the cardiovascular safety of these drugs presents a major dilemma for patients and physicians, who have been warned about the toxicity of NSAIDs. ;
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