林中生洪弘昌Hung-chung Hung醫學研究所2026-10-282003-08-012003https://handle.ncl.edu.tw/11296/6hkn39https://scholars.csmu.edu.tw/handle/123456789/34998全身性搔癢是一種常見於膽汁鬱積性肝病患者之不舒服的肝外表徵。其治療效果常不盡理想。膽汁鬱積性搔癢不只干擾日常作息，嚴重時甚至剝奪睡眠或造成自殺傾向。近年來發現，以serotonin type 3(5-HT3)接受器之拮抗劑，可用來紓解對傳統止癢療法(如cholestyramine, antihistamine)無反應之膽汁鬱積性搔癢。 目的：針對有膽汁鬱積性搔癢之肝硬化病患，評估對其靜脈投予ondansetron之治療效果。 方法：此為控制對照研究，在12例有膽汁鬱積性搔癢但對於傳統止癢療法無反應之肝硬化患者(年齡由46至74歲不等，其中 男/女:8/4。生化檢查各項平均值─總膽紅素T.B.: 3.85 ± 1.17mg/dl；麩氨基轉化脢 g-GT: 334.78 ± 116.05u/l；鹼性磷酸脢ALK-P: 573 ± 373.59u/l)，在接受治療前五天起停止使用所有止癢藥物。每位病人分別依序由前臂靜脈投予8毫克的ondansetron、對照組(即生理食鹽水)、4毫克的ondansetron；注射時間間隔為48小時，藉此以評估各組不同之短期療效。 如果在靜脈投予後2小時內，病人的搔癢程度能減少百分之五十以上，便視為成功療效。搔癢程度由visual rating scale(VRS) 從0(無搔癢)到10(病人所能想像最難以忍受的搔癢)逐級區分，且分別於注射後15、30、60及120分鐘時作成記錄。注射後病人所產生之副作用亦予以記錄。在注射24小時內，患者須評估搔癢回復到治療前之強度時的時距。 結果：由靜脈注射ondansetron 8毫克與4毫克均可於60分鐘內將搔癢強度減少百分之五十。產生成功療效所需時間以注射8毫克組為短(30分鐘內產生成功療效，8毫克組:4毫克組:對照組 為100%:75%:0%)。注射4毫克及8毫克的ondansetron之成功療效與對照組相比在第30到120分鐘時，都具有統計學上明顯的差異(p<0.001)。成功療效在8毫克組可持續較長的時間 ( 8毫克組: 4毫克組為8.33±1.30小時:4.00 ±0.95小時，p<0.01)。此外，治療過程中並無副作用產生。 結論：Ondansetron能有效地緩解膽汁鬱積性搔癢，可能與降低膽汁鬱積性患者對搔癢的感受度有關。Serotonin則被認為經由5-HT3接受器與搔癢形成或感度有關。因此，5-HT3接受器之拮抗劑可能是治療膽汁鬱積性搔癢之重要原則。然而，受限於價格及靜脈注射之不方便性，5-HT3接受器之拮抗劑宜用於接受傳統止癢治療失敗之持續搔癢病例。Generalized pruritus as an extrahepatic manifestation of cholestatic liver disease is a well-known, uncomfortable symptom. Its treatment is often unsatisfactory. Cholestatic pruritus may not only interfere with normal activity but may lead to sleep deprivation and suicidal attempt. The pruritus may have a severe impact on a patient’s quality of life and may be an indication for liver transplantation Because the pathogenesis and etiology of cholestatic pruritus is only not well understood and several hypothesis have been proposed Treatments of cholestatic pruritus consist mainly of bile acids chelating agents (e.g., cholestyramine), antihistamine, hepatic enzyme inducers (phenobarbitone, rifampin), propofol, anabolic steroids, and Heroic measures (for example, charcoal hemoperfusion, partial external diversion of bile) have also been tried. But all these conventional antipruritic treatment are not consistent efficacious. Treatment of patients with cholestatic pruritus with opiate receptor antagonist (e.g., naloxone, nalmefene) lead to a relief of pruritus but can induce an opioid withdrawal syndrome, suggesting the participation of endogenous opioids in the generation and/ or sensation of pruritus But no signs of withdrawal syndrome or known side effects could be observed under treatment with ondansetron a specific serotonin type 3 receptor antagonist (5-HT3). In conclusion, ondansetron administration is associated with amelioration of the perception of pruritus in cholestatic patients. It is suggested that serotonin, acting via the 5-HT3 receptor antagonist is involved in the generation or sensation of pruritus. Furthermore, the 5-HT3 receptor antagonist may be a novel therapeutic principle for the treatment of cholestatic pruritus.5-HT3接受器之拮抗劑thesis