1. 門診處方討論 Fludrocortisone (Florinef) 用於 Orthostatic hypotension 報告者 : 黃玉鈴 94.11

2. Fludrocortisone 之 Clinical Applications A potent oral mineralocorticoid FDA Approved Indications  Addison’s disease-Adrenal insufficency  Adrenogenital disorder Effective in treating orthostatic hypotension

4. Orthostatic hypotension 發生之原因 神經性 — 中樞或週邊神經病變所致 1. 原發性 2. 次發性 — 腫瘤. 中風. 感染. 糖尿病. 酒精神 經性病變 非神經性 — 心衰竭. 血管內容積不足. 血液滯留靜脈. 藥 物

5. Orthostatic hypotension 發生之原因 血容量不足, 減少 1. 貧血 2. 電解質失衡 3. 長期臥床 4. 藥物 Diuretics, ACEI ; Vasodilators: NTG, Isosorbide dinitrate; Calcium channel blockers

6. Orthostatic hypotension 之症狀 坐 / 站立之間血壓過度下降 ( 典型者 >20/10mmHg ) 血壓明顯改變, 躺臥的時候即恢復 頭暈.. 軟弱無力.. 眩暈.. 視力模糊

7. 臨床證據 1 Fludrocortisone has been effective in the treatment of hypotension, achieving clinical improvement in 84.3% of patients with doses as high as 2mg/d (Frick, 1966). The initial dose is usually 0.1 mg daily, increased by 0.1 mg every 5 to 7 days as needed. The usual maintenance dose ranges from 0.1 to 1.0 mg/day because treatment limit it’s side effect (Van Lieshout et al, 2000; Watt et al, 1981a; Chobanian, 1979a); (Holh et al, 1965).

8. 臨床證據 2 Stroke volume (SV), cardiac output (CO), and standing blood pressure improved significantly following treatment of neurogenic orthostatic hypotension (NOH) with fludrocortisone and elevated-head sleep positioning, in an open label, controlled clinical study

9. F ludrocortisone 於 Orthostatic hypotension 治療之機轉 ↑ the resorption of Na + and increase the urinary excretion of K + and H + at the distal tubule in the kidney ↑ plasma volume ( a increases in blood pressure due to Na + retaining-effects ) ↑ the sympathetic response to norepinephrine ↑ increased peripheral resistance

10. Fludrocortisone 於 Orthostatic hypotension 之 Pharmacokinerics Absorbed from the GI: 100% Peak blood levels : 1.7 hours after P.O. Protein bounding: 42% Metabolized: liver, primary site Half-life: 3.5 hours

11. Fludrocortisone 於 Orthostatic hypotension 之治療劑量 In severe orthostatic hypotension : 0.1 mg P.O. bid to tid Higher dose: 0.4 to 2 mg daily P.O. Low doses and long-term fludrocortisone was shown to be poorly tolerated in elderly patients being treated for hypotensive disorders (Hussain et al, 1996)

12. Fludrocortisone 之 Adverse Reactions Hypernaltremia, hypokalemia High doses may cause suppression of hypophyseal corticotropin secretuon Significant fluid retention (edema, dyspnea, weight gain, and CHF)

13. Fludrocortisone 之注意事項 Serum electrolytes Blood glucose Blood pressure, standing and recumbent Muscle strength

14. Fludrocortisone 治療 Orthostatic hypotension 之結論 FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence is inconclusive Recommendation: Adult, Class IIb Strength of Evidence: Adult, Category B See Drug Consult reference:See Drug Consult reference: "RECOMMENDATION AND EVIDENCE RATINGS"

15. References  MICROMEDEX  NEJM, 352(10):1004-1010, 2005