請慎用止痛藥!腎臟科名醫沉痛告白 發稿時間:2017/02/08「親愛的醫生:
止痛藥破壞腎臟保護機制 非類固醇消炎止痛藥(Nonsteroidal anti-inflammatory drugs,NSAIDs)
Analgesic nephropathy: Proper kidney function depends upon adequate blood flow to the kidney. Kidney blood flow is a complex, tightly regulated process that relies on a number of hormones and other small molecules, such as prostaglandins. Under normal circumstances, prostaglandin E2 (PGE2) produced by the kidney is necessary to support adequate blood flow to the kidney. Like all prostaglandins, PGE2 synthesis depends upon the cyclooxygenases. Aspirin and other NSAIDs are inhibitors of the cyclooxygenases. In the kidney, this inhibition results in decreased PGE2 concentration causing a reduction in blood flow. Because blood flow to the kidney first reaches the renal cortex (outside) and then the renal medulla (inside), the deeper structures of the kidney are most sensitive to decreased blood flow. Thus the innermost structures of the kidney, known as the renal papillae, are especially dependent on prostaglandin synthesis to maintain adequate blood flow. Inhibition of cyclooxygenases therefore rather selectively damages the renal papillae, increasing the risk of renal papillary necrosis. NSAIDs caused no adverse effects on renal function in healthy dogs subjected to anesthesia. Most healthy kidneys contain enough physiologic reserve to compensate for this NSAID-induced decrease in blood flow. However, those subjected to additional injury from phenacetin or paracetamol may progress to analgesic nephropathy.
Chronic kidney disease: targeting prostaglandin E2 receptors. Am J Physiol Renal Physiol. 2014 Aug 1;307(3) Chronic kidney disease is a leading cause of morbidity and mortality in the world. A better understanding of disease mechanisms has been gained in recent years, but the current management strategies are ineffective at preventing disease progression. A widespread focus of research is placed on elucidating the specific processes implicated to find more effective therapeutic options. PGE2, acting on its four EP receptors, regulates many renal disease processes; thus EP receptors could prove to be important targets for kidney disease intervention strategies. This review summarizes the major pathogenic mechanisms contributing to initiation and progression of chronic kidney disease, emphasizing the role of hyperglycemia, hypertension, inflammation, and oxidative stress. We have long recognized the multifaceted role of PGs in both the initiation and progression of chronic kidney disease, yet studies are only now seriously contemplating specific EP receptors as targets for therapy. Given the plethora of renal complications attributed to PG involvement in the kidney, this review highlights these pathogenic events and emphasizes the PGE2 receptor targets as options available to complement current therapeutic strategies.
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