膀 胱 過 動 症 之 藥 治 療 新 進 展 藥 嘉 義 基 督 教 醫 院 藥 劑 藥 師 陳 佳 南 賴 輝 雄 林 慧 娟 摘 要 AUA/SUFU 2015 β 3- overactive bladder antimuscarinics β 3- adrenoceptor agonists botulinum toxin 壹 前 言 (overactive bladder, OAB) 1 2008 4.55 20185.46 22.1% 10.9% (11.9%) (9.8%) 2 (American Urological Association, AUA) (Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, SUFU) (antimuscarinics) β 3 - (β 3 -adrenergic receptor agonists) 3,4 5 貳 膀 胱 排 尿 和 儲 尿 生 理 機 制 ( 功 能 ) 322 Jun. 30 2016 藥 雜 誌 127 45
藥 Pharmaceutical Sciences () 6 M 3 M 2 M 3 7 M 2 M 3 G phospholipase C (inositol triphosphate) M 2 (adenylate cyclase) (camp) 7 β 3 - β 3 - camp 8 β 3-7 β 3-8 6 參 治 療 藥 藥 理 分 類 β 3 - ( ) 4 β 3 - () 表 一 膀 胱 過 動 症 和 急 迫 性 尿 失 禁 治 療 藥 之 4-9 證 據 等 級 和 建 議 強 度 / Antimuscarinic drugs Tolterodine 1 A Trospium 1 A Solifenacin 1 A Darifenacin 1 A Oxybutynin 1 A Propiverine 1 A Antidepressants Imipramine 3 C Duloxetine 2 C a-adrenoreceptor antagonists Alfuzosin 3 C Doxazosin 3 C Prazosin 3 C Tamsulosin 3 C Terazosin 3 C β-adrenoreceptor agonists Mirabegron (b3) 2 B Albuterol (b2) 3 C Terbutaline (b2) 3 C Toxins Botulinum toxin 3 B Other drugs Baclofen, intrathecal 3 C Estrogen (for women) 2 C 一 抗 毒 蕈 鹼 藥 (M 1-5 ) M 2 M 3 M 3 ( ) 9 6 ( 46 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016
藥 ) 7,9 amine CYP-450 7 7,9 表 二 抗 毒 蕈 鹼 藥 的 藥 動 力 和 建 議 劑 量 Oxybutynin IR/ER Tolterodine IR/ER Darifenacin Solifenacin Trospium IR/ER Propiverine 393.9 475.6 507.5 480.55 427.97 403.95 N- Tertiary Tertiary Tertiary Tertiary Quaternary NA High Low-moderate Moderate Low-moderate Very low NA FDA/ 1999 2001 2005 2005 2004 2006 CYP2D6, N-desethyloxybutynin 5-hydroxymethyltolterodine CYP2D6, Ester hydrolysis, CYP450 CYP2D6, Propiverine N-oxide 2/13 hr. 2/8 hr. 12 hr. 45-68 hr. 20/35 hr. 15 hr. IR: 5 mg bid-qid ER: 5-30 mg qd IR: 1-2 mg bid ER: 2-4 mg qd 7.5-15 mg qd 5-10 mg qd IR: 20 mg qd-bid ER: 60 mg qd 15 mg qd-tid IR, immediate release; ER, extended release; NA, not available; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily M 3 M 3 6 2012 Buser 40,000 10 oxybutynin propiverine trospium 40 mg 60 mg 3 β 3-4 322 Jun. 30 2016 藥 雜 誌 127 47
藥 Pharmaceutical Sciences 二 β 3- 腎 上 腺 接 受 體 作 用 劑 β- β 1 β 2 β 3 β 3-6 β 3-8 6 2015 AUA/SUFU β 3-4 mirabegron solabegron ritobegron 9 Mirabegron β 3 - FDA 2011 20122013 9,11 Mirabegron (Tmax) 3.5 CYP2D6 20% 40 71670L70% α-1 acid glycoprotein 12 25 mg 50 mg 9 50 mg 100 mg 4,13 24 13 4,13 β 3-12 mirabegron 11,12 ( 180 mmhg / 110m) 6 三 肉 毒 桿 菌 毒 素 (Botulinum toxin, BTX-A) BTX-A (Clostridium botulinum) 7 (botulinum toxin A-G) A (botulinum toxin A) FDA 2011 BTX-A (neurogenic bladder)2013 (idiopathic overactive bladder) 4,11 BTX-A 25 (SNAP-25) 2 (synaptic vesicle protein 2, SV2) 14 BTX-A 9 (12.2%) (5.4%) (5.0%) 6 OnabotulinumtoxinA 100 U 121.5 100 U 10 ml 2-815 20 3-4 BTX-A 14 BTX-A β 3 - onabotulinumtoxina 11 48 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016
藥 四 其 他 治 療 藥 β 3 - duloxetine () 9 6,9 β 3 - α- 9 肆 非 藥 治 療 4 8 BTX-A 骶 (SNS) (PTNS) 4 伍 結 論 β 3 - New Drug Therapy in Advance for Overactive Bladder Chia-Nan Chen, Hui-Hsiung Lai, Hui-Chuan Lin Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital Abstract Overactive bladder (OAB) is the presence of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a 322 Jun. 30 2016 藥 雜 誌 127 49
藥 Pharmaceutical Sciences urinary tract infection or other obvious pathology. Antimuscarinics have been up to date, the mainstay of OAB treatment. Recently, AUA/SUFU guideline amendment published in 2015 introduced oral b3-adrenoceptor agonists and intravesical administration of botulinim toxin as second-line and third-line treatment respectively. This article focused on the development status and discussions of new drugs for OAB to provide physician choices of the appropriate selection agents. Further to establish treatment goals that maximize symptom control and patient quality of life while minimizing adverse events and patient burden. 參 考 資 料 : 1. Haylen BT, de Ridder D, Freeman RM, et al: An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. 2. Irwin DE, Kopp ZS, Agatep B, et al: Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011;108(7):1132-8. 3. Gormley EA, Lightner DJ, Burgio KL et al: Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455-63. 4. Gormley EA, Lightner DJ, Faraday M, et al: Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015;193(5):1572-80. 5. Aballéa S, Maman K, Thokagevistk K, et al: Cost Effectiveness of Mirabegron Compared with Tolterodine Extended Release for the Treatment of Adults with Overactive Bladder in the United Kingdom. Clin Drug Investig. 2015;35(2):83-93. 6. Jayarajan J, Radomski SB: Pharmacotherapy of overactive bladder in adults: a review of efficacy, tolerability, and quality of life. Res Rep Urol. 2013;6:1-16. 7. Abrams P, Andersson KE: Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007;100(5):987-1006. 8. Ouslander JG: Management of overactive bladder. N Engl J Med. 2004;350(8):786-99. 9. Cipullo LM, Cosimato C, Filippelli A, et al: Pharmacological approach to overactive bladder and urge urinary incontinence in women: an overview. Eur J Obstet Gynecol Reprod Biol. 2014;174:27-34. 10. Buser N, Ivic S, Kessler TM, et al: Efficacy and adverse events of antimuscarinics for treating overactive bladder: network meta-analyses. Eur Urol. 2012;62(6):1040-60. 11. Andersson KE: New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxina. Ther Clin Risk Manag. 2013;9:161-70. 12. Bridgeman MB, Friia NJ, Taft C, et al: Mirabegron: 3- adrenergic receptor agonist for the treatment of overactive bladder. Ann Pharmacother. 2013;47(7-8):1029-38. 13. Wu T, Duan X, Cao CX, et al: The role of mirabegron in overactive bladder: a systematic review and meta-analysis. Urol Int. 2014;93(3):326-37. 14. Jambusaria LH, Dmochowski RR: Intradetrusor onabotulinumtoxina for overactive bladder. Expert Opin Biol Ther. 2014;14(5):721-7. 50 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016