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Τα αντιχολινεργικά ΔΕΝ είναι όλα τα ίδια. Α. Αθανασόπουλος Ουρολόγος Επίκουρος Καθηγητής Νευροουρολογίας & Ουροδυναμικής Επιστημονικός Υπεύθυνος Μονάδας Ουροδυναμικής Ουρολογίας Πανεπιστημίου Πατρών. ΠΑΝΕΠΙΣΤΗΜΙΟ ΠΑΤΡΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΥΓΕΙΑΣ ΤΜΗΜΑ ΙΑΤΡΙΚΗΣ. Αντιμουσκαρινικά Φάρμακα. - PowerPoint PPT Presentation

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  • : Yarker YE et al. Drugs & Aging. 1995;6:243-262.

  • A ( Oxford A )OXYBUTININ (IR,ER,TSD,S) +TOLDERODINE (IR,ER)SOLIFENACINDARIFENACINTROSPIUM CLORIDEPROPIVERINE +

  • OxybutyninE 1 3. . .

  • Oxybutynin ( ), in vitro 500 1. . . , 2,3, 4,5 6.

    1.Andersson K-E 19992.Collas D & Malone-Lee JG,19973.Winkler HA & Sand PK,19984.Brendler CB et al,19895.OFlynn KJ &Thomas DG, 19936.Davila GW et al,2001

  • Tolterodine ( ). , .

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    placebo

    1. Abrams P et al. Br J Urol. 1998;81:801-810. 2. Messelink EJ. Br J Urol. 1999;83(suppl 2):48-52.

  • Trospium Cloride . . .

  • Propiverine . . ( ) , . .

  • DarifenacinE 3 . .

    placebo1,2.

    1.Chapple C et al, BJU Int.2005;95:993-10012.Lipton RB et al, J Urol.2005;173:493-498

  • Solifenacin ( ). . ( ) 1. . .

    1. C. R Chapple et al: BJU International 2004; 93, 303-310

  • OBJECT & OPERA TRIALS

  • Oxybutynin TDS (MATRIX)1 OAB OXY-TDS,

    OAB OXY-TDS , ,

    , OXY-TDS , (

  • Tolderodine ER vs. Oxybutynin ERAbrams P et al. Br J Urol. 1998; 81:801-810. /24h ( )0-0.5-1-1.5-2-2.5-3Placebo (n = 57) 2 mg bid (n = 118) 5 mg tid (n = 118)P = 0.0022 vs placeboP = 0.068 vs placebo

  • Tolderodine ER vs. Oxybutynin ERAbrams P et al. Br J Urol. 1998; 81:801-810. /24h ( )0-0.5-1-1.5-2-2.5Placebo (n = 57) 2 mg bid (n = 118) 5 mg tid (n = 118)P = 0.22 vs placebo

    P = 0.023 vs placebo

  • Propiverine vs. Oxybutynin

  • Trospium vs. Oxybutynin: 1,2

    1.Halaska M, et al. World J Urol. 2003;20:392-3992.Madersbacher H, et al. Expert Opi Pharmacother. 2006;7:1373-1380

  • Darifenacin vs. Oxybutynin IR:Oxybutynin>Darifenacin>Placebo 1 15 mg 2

    1.Ziner N, et al. World J Urol. 2005;23:248-2522.Sreers W,et al. BJ Urol Int.2005;95:580-586

  • Solifenacin vs. Tolderodine ERSTAR 1: Solifenacin > Tolderodine

    : Solifenacin > Tolderodine :Solifenacin > Tolderodine

    :Solifenacin > Tolderodine

    1. Chapple CR,et al. Eur Urol. 2005;48:464-470

  • Solifenacin 12 52 . / (%)N = 1580Kelleher BJU;95: 81-85

  • 9 SolifenacinHaab EU 47; (2005):376-384

  • STAR - % Solifenacin ER 50%

  • ; Oxybutynin Propiverine . Propiverine Oxybutynin 1,2,3.

    1.Marschall-Kehrel et al.J Urol. 20042.Madersbacher et al. Eur Urol. 20063.Alloussi et al. Eur Urol. 2006

  • (DD01) , Nilvebrant L et al. Life Sci. 1997;60:1129-1136.

  • Adapted from Nilvebrant L et al. Eur J Pharmacol. 1997;327:195-207. , . Tolterodine 0.0110.10.0110.1 (mg/kg)1007550250-251007550250-25TolterodineOxybutynin (mg/kg) (%) (%)

  • 1Othake A, Eur J Pharmacol 2004; 492: 243-250

    Chart4

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    1.Siami et al (2002) in STAT .2.Haab F et all Eur. Urol, (2005):47:376-384

  • () . VENUS1 Solifenacin 5mg Placebo.

    1.Toglia M, et al. Neurourol Urodyn.2006;25:655.Abstract 123

  • : Oxybutynin > Tolterodine1

    : Solifenacin = Tolterodine2

    1.Diokno AC,et al. Mayo Cli Proc. 2003;78:687-6952. Chaple CR,et al. Eur Urol. 2005;48:464-470

  • vs. Placebo (n = 57) 2 mg bid (n = 118) 5 mg tid (n = 118) (%) 9080706050403020100**Abrams P et al. Br J Urol. 1998;81:801-810.*P < 0.001 vs placebo.

  • - -

  • 30 ; DD01 350 - vs.

  • oxybutynin tolderodine 1 darifenacin 3 2,3,4.

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    Solifenacin 3 Darifenacin. Oxybutynin TDS (MATRIX)5

    1.Chu FM, et al. Am J Obstet Gyn. 2005;192:1849-18552.Lipton Rb,et al. J Urol. 2005;173:493-4983.Rovner EW. Drugs.2004;64:2433-24464.Kay G,et al.Eur Urol.2006;50:317-3265.Sand P,et al.BJU Intren.2007;99:1-9

  • ( )1.

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    1.Kay G,et al.Eur Urol.2006;50:317-3262.Diefenbach et al.Br J U Internat. 2005;95:3-6

  • QT 1.

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    1.J.Cardiovasc Pharmacol. 2006;48:199-206

  • 5mg 1 .

    1.Ko Y et al. Pharmacotherapy,2006;26:1694-1702.

  • 1,2. : Darifenacin (7.5 15 mg QD) Oxybutynin ( 5-30mg TID)

    : Solifenacin ( 5 10mg QD)

    1.Staskin DR,et al.Am J Med.2006;119(suppl 3A):9S-15S.2.Staskin DR,et al.Am J Med.2006;119(suppl 3A):24S-28S.

  • STAR solifenacin 5mgtolterodine 4mg ERsolifenacin 10mgtolterodine 4mg ER + placebo51% tolterodine ER %

  • . - .

  • C. Chapple (Eur. Urol.; 48:2005) - .

  • C. Chapple 1 2 Solifenacin Tolderodine IR Oxybutynin ER Tolderodine ER.

  • C. Chapple Oxybutynin ER > Tolderodine ER > placebo Oxybutynin IR, Oxybutynin TDS , Oxybutynin ER

  • C. Chaple Tolderodine ER . Oxybutynin IR . Darifenasin Solifenacin placebo. Oxybutynin TDS 6 Tolderodine ER

  • 11.Staskin RS.Drug Aging.2005;22:1013-1028

  • . - .

  • Effective treatment should provide an optimal balance of maximum achievable improvement in clinical symptoms coupled with acceptable tolerability and thereby an identifiable and worthwhile improvement in QoL. ( Chapple et all, 2005).

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    Slide 11: Antimuscarinic PharmacotherapyAntimuscarinic drugs are generally regarded as standard therapy for overactive bladder. Antimuscarinics decrease detrusor muscle activity, allowing the bladder to fill normally. This improved bladder capacity delays the initial urge to void with a resulting decrease in micturition frequency. However, the impact on frequency and incontinence episodes is not usually seen for several weeks, as modification of voiding habits is a gradual process.9 The utility of previously available antimuscarinic drugs was diminished by a lack of organ selectivity and a propensity to cause unwanted side effects such as dry mouth, blurred vision, somnolence (drowsiness), and constipation.9 With oxybutynin, for example, dry mouth occurs in at least 50% of patients and may result in up to 25% of patients discontinuing treatment.10Slide 20: TolterodineTolterodine is a potent antimuscarinic agent that is selective for the bladder over the salivary glands. Tolterodine has been shown to be equivalent to oxybutynin in reducing the symptoms of overactive bladder. Tolterodine significantly reduces the number of incontinent episodes, significantly increases bladder capacity, and reduces frequency of micturition.10 These effects are sustained during long-term therapy.18

    OAB OXY-TDS, OAB OXY-TDS , , , OXY-TDS , (