SIADH ( ) ( ) mannitol [Na] [H 2O] [Na] [H 2O] >20 mmol/l / <20 mmol/l (glucocorticoid deficiency) >20 mmol/l (mineralocorticoid deficiency) (cerebral

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1 臨床藥物治療學 Therapeutics of Clinical Drugs 疑似藥品引起 SIADH 不良反應 阮綜合醫院藥劑科藥師鍾雅筑 商蕙如 溫雅妃 陳秀雅 胡淑寶 摘要 (syndrome of inappropriate antidiuretic hormone secretion SIADH) SIADH diuretics oxcarbazepine SIADH SIADH SIADH indapamide oxcarbazepine 壹 前言 (hyponatremia) 15% (extracellular fluid volume ECF) (hypervolemia) (normovolemia) (hypovolemia) 60% (syndrome of inappropriate antidiuretic hormone secretion SIADH) ( ) 貳 案例報告 C (9 19 ) Na meq/ 102 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep

2 SIADH ( ) ( ) mannitol [Na] [H 2O] [Na] [H 2O] >20 mmol/l / <20 mmol/l (glucocorticoid deficiency) >20 mmol/l (mineralocorticoid deficiency) (cerebral salt wasting) <20 mmol/l ( ) 1 圖一低血鈉症之鑑別診斷 L K meq/l Osm ( ) 249 mosm/kg U-osmolarity 326 mosm/kg Cre ( ) 0.5 mg/ dl ( ) indapamide () 1000 ml/day indapamide (1.5 mg) ( 9/14-9/19) furosemide (40 mg) 1 # bid spironolactone (25 mg) 1 # tid slow-k (600 mg) 1 # tid K (3.5 meq/l) Na (119 meq/l) oxcarbazepine (150 mg) 1.5 # bid oxcarbazepine 9 27 clopidogrel aspirin etodolac omeprazole (K meq/l Na meq/l) 28 3 Sep 藥學雜誌第 112 冊 103

3 臨床藥物治療學 Therapeutics of Clinical Drugs 10 1 參 討論 2,3 一 抗利尿激素不適當分泌症候群 ( 一 ) 臨床症狀 2% 280 mosm/kg ADH (8-10%) ADH ADH SIADH Na meq/l meq/l SIADH ( thiazide diuretics) ( 二 ) 診斷 SIADH 1. (hypotonic hyponatremia) ( 270 mosm/ kg Na 135 meq/l) ( 30 meq/l) ( ) 6. 二 SIADH 治療 SIADH SIADH ( 一 ) 限水 Na 120 meq/ L ( ml/24h) Na ( 二 ) 去除病因 SIADH ( ) ( ) ( 三 ) 補充鈉 4-8 g/day ( ) Na 115 meq/l 3% NaCl ( 513 meq/l) 3% NaCl (central pontine myelinolysis) 1-2 meq/l/hr 8-12 meq/l/24h 48 Na 18 meq/l 140 meq/l ( ) 104 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep

4 SIADH 3 表一可能引起低血鈉的藥品 Drugs affecting sodium and water homeostasis Diuretics Increased hypothalamic production of ADH Antidepressants Antipsychotic drugs Antiepileptic drugs Anticancer agents Potentiation of ADH effect Antiepileptic drugs Antidiabetic drugs Anticancer agents NSAIDs Reset osmostat Antidepressants Antiepileptic drugs thiazides, indapamide, amiloride, loop diuretics (rare) Tricyclic antidepressants amitryptiline, protriptyline, desipramine Phenothiazines thioridazine, trifluoperazine carbamazepine, oxcarbazepine, sodium valproate Platinum compounds cisplatin, carboplatin Alkylating agents intravenous cyclophosphamide, melphalan, ifosfamide carbamazepine, lamotrigine chlorpropamide, tolbutamide Alkylating agents, intravenous cyclophosphamide venlafaxine carbamazepine Selective serotonin reuptake inhibitors Monoamine oxidase inhibitors Butyrophenones haloperidol Vinca alkaloids vincristine, vinblastine Miscellaneous methotrexate, levamisole, pentostatin, monoclonal antibodies, interferone α and γ Opiates furosemide mg iv q4-6h prn KCl 表二根據病人血清 Na 計算 3%NaCl 的輸注速率 (3% NaCl ) Na+ Na + 1 ( ) ( 四 ) 藥品 fludrocortisone ( mg bid) demeclocycline ( mg tid-qid) lithium carbonate (300 mg bid-qid) vasopressin V2 antagonists tolvaptan (15-60 mg qd) 三 案例討論 2009 Na ( meq/ L) ( meq/l) ( ) 28 3 Sep 藥學雜誌第 112 冊 105

5 臨床藥物治療學 Therapeutics of Clinical Drugs 表三病人用藥紀錄 prednisolone 5 mg 6 # qd ticlopidine 100 mg 1 # bid clopidogrel 75 mg interferon β-1a 44 mcg 1's tiw oxcarbazepine 300 mg 1.5 # bid rosuvastatin 10 mg 0.5 # qod 0.5 # qd 0.5 # qod baclofen 5 mg 1 # qid 2 # tid 2 # qid 3 # qid trazodone 50 mg atenolol 100 mg Amtrel 2 # qd 1 # bid Sevikar 1 # bid Brinerdin 0.5 # qd nifedipine 30 mg labetalol 200 mg 1 # bid furosemide 40 mg 0.5 # qd gliclazide MR 30 mg metformin 500 mg 1 # tid 1 # bid sennosides 20 mg 2 # hs tamsulosin 0.2 mg clonazepam 0.5 mg clonazepam 2 mg slow-k 600 mg 1 # tid Luckyhepa 70 mg 1 # tid ursodeoxycholic acid 300 mg 1 # bid Na meq/l ( ) K meq/l ( ) Osm ( ) 249 HbA1c 7.6 ( 一 )Indapamide-induced hyponatremia ( / mmhg) Brinerdin (reserpine 0.1 mg, clopamide 5 mg, dihydroergocristine 0.5 mg) clopamide thiazide-type diuretic chlorothiazide 7 25 Na 127 meq/l K 2.6 meq/ L8 24 Brinerdin 9 14 indapamide (1.5 mg) Coaprovel ( hydrochlorothiazide 12.5 mg ) 106 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep

6 SIADH Indapamide-induced hyponatremia 5% micromedex 1.25 mg indapamide 1.5 mg ( 二 )Carbamazepine or oxcarbazepine-induced hyponatremia 4 oxcarbazepine 450 mg bid carbamazepine oxcarbazepine ( carbamazepine ) Carbamazepine SIADH 4%-21.7% oxcarbazepine 1%-23% carbamazepine carbamazepine oxcarbazepine thiazide-type diuretics Na 肆 結論 SIADH 3% NaCl 參考資料 : UpToDate: Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3. George Liamis, MD, Haralampos Milionis, MD, and Moses Elisaf, MD: A Review of Drug-Induced Hyponatremia. American Journal of Kidney Diseases, Vol 52, No 1 (July), 2008: MICROMEDEX Suspected Drug-Induced SIADH Ya-Chu Chung, Huei-Ru Shang, Ya-Fei Wen, Hsiu-Ya Chen, Shu-Bauh Hu Department of Pharmacy, Yuan s General Hospital Abstract Hyponatremia is a common symptom of electrolyte disorder in inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is often the main cause. This case is an elderly female patient with a history of multiple sclerosis, hypertension, hyperlipidemia, type 2 diabetes, with a long term condition of hyponatremia and hypokalemia. Here we discuss drugs which can cause or worsen SIADH, and introduce the symptom, diagnosis and treatment of hyponatremia due to SIADH Sep 藥學雜誌第 112 冊 107