排尿障礙治療中心版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien.

排尿障礙治療中心版權所有 Innervation of Lower Urinary Tract Bladder- cholinergic parasympathetic- contraction; beta-adrenergic & NO– relaxation Bladder neck – alpha-adrenergic- contration Urethral muscles- cholinergic parasympathetic, NO, cholinergic somatic nerves

排尿障礙治療中心版權所有 Treatment Goals of Voiding Dysfunction To increase bladder capacity – Bladder Hypersensitivity To reduce detrusor overactivity – Detrusor overactivity To increase urethral resistance – Urethral incompetence To reduce urethral resistance -- Bladder outlet obstruction To increase bladder contractility – Detrusor underactivity or acontractility To improve bladder compliance – Low bladder compliance

排尿障礙治療中心版權所有 Improved Voiding Efficiency Increase detrusor contractility – increase detrusor muscle tone or contractility Reduce urethral resistance – bladder neck, urethral sphincter, prostatic urethra Improved bladder capacity and compliance Combination of all of the above

排尿障礙治療中心版權所有 Storage of Urine Stable bladder Good compliance Competent urethra- mucosa, submucosa, smooth muscles, striated skeletal muscles (external sphincter) Good pressure transmission and hammock effect during stress

排尿障礙治療中心版權所有 Storage Problems Bladder hypersensitivity Low bladder compliance Detrusor overactivity – neurogenic or idiopathic Low urethral resistance Bladder outlet obstruction Combination of the above

排尿障礙治療中心版權所有 Empty of Urine Sustained detrusor contraction- cholinergic parasympathetic fibers Relaxation of bladder neck – alpha- adrenergic sympathetic nerves Relaxation of external sphincter- cholinergic pudendal nerves Patent non-obstructive urethra

排尿障礙治療中心版權所有 Empty Problems Bladder outlet obstruction – Bladder neck dysfunction, BPH, Urethral stricture, Dysfunctional voiding, DESD Bladder hypersensitivity Detrusor underactivity or areflexia Poor urethral sphincter relaxation Combination of the above

排尿障礙治療中心版權所有 Pharmacology of Micturition- Increase storage efficiency Reduce detrusor overactivity Anticholinergic agents- oxybutynine, flavoxate, imipramine Ganglion blocker- bentyl Beta-adrenergic agents Botulinum toxin Vanilloid receptor blockers- capsaicin, resiniferatoxin

排尿障礙治療中心版權所有 Pharmacology of Micturition- Increase outlet resistance Increase smooth muscle tone – Imipramine, methylephedrine Increase striated muscle tone – Nitric oxide synthase inhibitor Pelvic floor muscle training

排尿障礙治療中心版權所有 Pharmacology of Micturition- Decrease outlet resistance Decrease bladder neck & urethral resistance Alpha-adrenergic blockers- dibenyline, terazosin, tamsulosin, doxazosin Nitric oxide donors Botulinum toxin Polysynaptic blocker – baclofen, diazepam

排尿障礙治療中心版權所有 Combined Medication- Improved Storage Efficiency Detrusor Overactivity- anticholinergics, sympathomimetics, imipramine Intrinsic sphincter deficiency- imipramine, sympathomimetics DHIC- depends on voiding efficiency and grades of incontinence

排尿障礙治療中心版權所有 Combination of Medication- Improve Voiding Efficiency Increased bladder sensation- intravesical capsaicin, RTX Detrusor overactivity- anticholinergic, intravesical RTX, botulinum toxin Detrusor underactivity – parasympathomimetics, alpha-blocker, NO donors, striated muscle relaxant, periurethral botulinum toxin injection

排尿障礙治療中心版權所有 Combined Medication – Improved Voiding Efficiency Urethral sphincter hypertonicity- alpha- blocker, NO donors, striated skeletal muscle relaxant Urethral sphincter overactivity- alpha- blocker, striated muscle relaxant, NO donors, botulinum toxin Bladder neck dysfunction- alpha-adrenergic blocker

排尿障礙治療中心版權所有 Medication for Detrusor hyperreflexia Oxybutynin & anticholinergics Imipramine Intravesical capsaicin & resiniferatoxin Intra- detrusor botulinum toxin Multiple medication increases adverse effect especially in elderly with inadequate detrusor contractility (DHIC)

排尿障礙治療中心版權所有 Anticholinergics Treatment Oxybutynin – the most effective and safe drug currently available Detrusitol – M3 antagonist, less salivary and GI side effects than Ditropan Flavoxate – mild effect on detrusor Imipramine – central and anticholinergics

排尿障礙治療中心版權所有 Tolterodine vs Oxybutynin A secondary amine with competitive muscarinic receptor blocking property As potent as oxybutynin in inhibiting detrusor contractions 8 times less potent in inhibiting salivation than oxybutynin 2mg bid tolterodine in comparison to 5mg tid of oxybutynin Titration doses from 1-2 mg bid to 4mg bid

排尿障礙治療中心版權所有 Side effects of Anticholinergic Post-synaptic receptors M1 and M2 are widespread in CNS, anticholinergics may have cognitive dysfunction, especially in elderly Dry mouth, constipation, blurred vision Darifenacin has 11-fold higher affinity to M3 than M2 receptors and a 5-fold lower affinity for M receptors in parotid gland

排尿障礙治療中心版權所有 Intravesical Therapy for Detrusor overactivity Blocking efferent cholinergic fibers – intravesical oxybutynin, atropine Blocking neuromuscular junction – intravesical botulinum A toxin injection Blocking afferent fibers that mediate detrusor reflex – intravesical lidocaine Blocking C-fiber mediated detrusor contractions – intravesical capsaicin, resiniferatoxin

排尿障礙治療中心版權所有 Intravesical Capsaicin Therapy Patients who are refractory to conventional treatment Capsaicin 10 -5 M in 30ml N/S instilled to bladder for 30 minutes Resiniferatoxin 10 -8 M in 30ml N/S A burning sensation or urge at instillation Relief of pain and urge in the later days

排尿障礙治療中心版權所有 Therapeutic Effects of Resiniferatoxin on Detrusor Overactivity 10 -5 to 10 -7 M RTX is effective for DH of SCI and DH of CNS origin 10 -8 M RTX can significantly improve voiding pattern and pain score in hypersensitive disorders and bladder pain RTX is safe for application in humans Less initial irritative response in RTX treatment than capsaicin

排尿障礙治療中心版權所有 Urodynamic Changes after RTX in Chronic SCI with DESD BaselinePost-RTXStastistics Cystometric capacity(ml) 102.1±31236.6±88.6P<0.001 Bladder compliance (ml/cmH 2 O) 23.7±12.125.9±15.3P>0.05 Voiding pressure (Pdet, cmH 2 O) 55.9±23.247.5±28.1P>0.05 Presence of DESD (n=20) 100%

排尿障礙治療中心版權所有 Intravesical RTX in treatment of Neurogenic Detrusor Overactivity C-fiber mediated detrusor reflex does not predominate neurogenic detrusor overactivity in lesion above pons Resiniferatoxin in 10 -6~-7 M can activate initial excitatory responses Therapeutic results are not as satisfactory as that in SCI patients An alternative for patients who cannot tolerate or refractory to anticholinergic agents

排尿障礙治療中心版權所有 Therapeutic Results of RTX in Neurogenic v Non-neurogenic Voiding Dysfunction 22/41 patients (53.6%) with detrusor overactivity improved after RTX 10 -7 M instillation (initial concentration) 6/10 (60%) Neurogenic DH, 4/13 (31%) Idiopathic DI, 12/18 (67%) BOO related DI improved 6/7 (86%) type I, 1/3 (33%) type II, 7/16 (44%) type III, 8/15 (53%) type IV

排尿障礙治療中心版權所有 Urodynamic Changes after RTX in Detrusor Overactivity BaselinePost-RTXStatistics Cystometric capacity(ml) (n=41) 216±106302±133P=0.000 Qmax (ml/sec)12.7±7.621.8±28.9P=0.224 Voiding pressure (Pdet, cmH 2 O) 33.6±11.734.1±19.5P=0.923 Residual urine (ml)41.1+52.749.4+98.9P=0.725

排尿障礙治療中心版權所有 Botulinum A toxin Injection Inhibition of acetylcholine (Ach) release from presynaptic cholinergic fiber Induce paralysis of muscle fibers Intravesical injection can inhibit detrusor overactivity Urethral injection can reduce urethral resistance and sphincter spasticity Duration of effect about 3-6 months

排尿障礙治療中心版權所有 Table 1.The Urodynamic Parameters at Baseline and after Botulinum Toxin in Effective Patients BaselinePost-BotoxStatistics* Capacity (n=53)331.4±148.8333.2±155.40.922 Qmax (n=53)6.7± 6.79.4± 5.70.003 Voiding pressure (n=53)62.0± 43.145.9±37.80.000 MUCP (n=21)97.1±31.751.1±23.20.027 FPL (n=21)3.35±0.593.30±0.330.773 PVR (n=53)225.4±174.4110.1±137.60.000 MUCP=maximal urethral closure pressure, FPL=functional profile length, PVR= postvoid residual volume *Comparison between baseline and 4weeks after treatment

排尿障礙治療中心版權所有 Therapeutic Results after Botox Urethral Injection for Voiding Dysfunction GoodImprovedFailed Detrusor underactivity (n=27) 13 (48.2%) 8 (29.6%) 6 (22.2%) DESD (n=18) 3 (16.7%) 10 (55.6%) 5 (27.8%) Dysfunctional voiding (n=18) 6 (33.3%) 10 (55.6%) 2 (11%) Poor relaxation of urethral sphincter (n=12) 3 (25%) 7 (58.3%) 2 (16.6%) TOTAL (n=75) 25 (33.3%) 35 (43.7%) 15 (20%) DESD=Detrusor external sphincter dyssynergia

排尿障礙治療中心版權所有 Initial Results of BotulinumToxin Detrusor Injection for Incontinence NoSex / AgeDiseaseDESECapacityDysuriaIncontinence 1M / 35DESD250 UImproved －＋ 2F / 10DI100 U No Change －＋＋＋ 3F / 45DI200 UImproved －－ 4M / 48DHIC200 UImproved －＋ 5F / 56DH200 UImproved －－

排尿障礙治療中心版權所有 Medication for Bladder outlet obstruction Bladder neck – alpha-adrenergic blocker Smooth muscle – Nitric oxide donors (nitroglycerine, isosorbid mononitrate), anticholinergics Striated muscle – baclofen, diazepam, dantrolene, calcium channel blocker, NO donors, botulinum A toxin Enlarged Prostate – finasteride (Proscar)

排尿障礙治療中心版權所有 Medical Treatment for Female BOO Skeletal muscle relaxant – diazepam, baclofen, dantrolene, calcium blocker Alpha-adrenergic blocker – dibenylene, terazosin, doxazosin, tamsulosin Nitric oxide donor- nitroglycerine, isosorbid mononitrate Estrogen Botulinum A toxin

排尿障礙治療中心版權所有 Medical Therapy for BPH Prostatic smooth muscle tension was mediated by alpha 1-adrenoreceptors Smooth muscle contractions contribute 40% of outflow obstruction Alpha 1- blockers can rapidly improve Qmax and relieve LUTS Phenoxybenzamine, terazosin, doxazosin have side effect of dizziness and hypotension

排尿障礙治療中心版權所有 Prostatic specific alpha- adrenoreceptor Alpha 1A- AR subtype comprises 70% of all alpha-1 receptors Alpha 1A-AR agonist – tamslosin has 13 x more affinity to prostatic smooth muscle than urethral muscle, 10 x than vascular smooth muscle Side effects are still reported Long-acting (once daily) dose

排尿障礙治療中心版權所有 Hormone based medical therapy 5-alpha-reductase catalyzes conversion of testosterone to dihydrotestosterone Inhibition of 5-alpha-reductase can arrest prostatic growth and relieve obstruction Finasteride can improve symptom score, Qmax, QOL score Effective especially in prostatic weight of >40 gm and effective in prostatic hematuria

排尿障礙治療中心版權所有 Combination therapy with alpha-blocker and finasteride Terazosin is effective therapy, finasteride was not, combination was no more effective than terazosin alone (Lepor, N Engl J Med 1996; 335: 533) Combined dibenyline and finasteride has an additive effect than dibenyline or finasteride alone in improvement of Qmax and prostatic size

排尿障礙治療中心版權所有 Desmopressin The circardian rhythm of vasopressin was lost in the elderly with nocturnal polyuria Atrial natriureteric peptide in the elderly was higher during night time Use of arginine vasopressin analogue patients with nocturnal enuresis and nocturnal polyuria become dry

排尿障礙治療中心版權所有 Therapeutic Effects of Desmopressin in Nocturnal Polyuria BaselinePosttreatment P Value (Paired t Test) Nocturnal frequency (time/night) 5.20 ± 1.162.24 ± 1.12<0.0001 Nocturnal urine volume (mL) 955.6 ± 255.9255.8 ± 210.5<0.0001 Quality of life 4.47 ± 1.071.05 ± 0.91<0.0001 Urine specific gravity 1.012 ± 0.0071.016 ± 0.0050.011 Serum Sodiun (mEq/L) 139.5 ± 4.34139.7 ± 3.840.761 Serum Potassium (mEq/L) 4.46 ± 0.354.31 ± 0.440.022

排尿障礙治療中心版權所有 Combination therapy for geriatric Nocturnal polyuria Combined anticholinergics and DDAVP for detrusor overactivity and nocturnal polyuria for DI & NP Combined alpha-blocker and DDAVP for BOO and NP Combined alpha-blocker and anticholinergics and DDAVP for BOO & DI & NP

排尿障礙治療中心版權所有 Treatment of spastic urethral sphincter Behavioral therapy: hydration, laxatives, time voiding, changing voiding posture Physiotherapy: pelvic floor muscle exercises Electric stimulation : interferential current stimulation Biofeedback: visual or Uroflowmetry & EMG Medication: baclofen, alpha-adrenergic blockers, estrogen, combination therapy Urethral injection of botulinum A toxin

排尿障礙治療中心版權所有 Therapeutic results of baclofen and terazosin in treatment of spastic urethral sphincter IPSSQmaxResidual urine BaselineTratedBaselineTreatedBaselineTreated Baclofen (n=73) 15.2±6.710.4±5.714.3±9.716.7±8.165.7±33.937.5±21.7 % of change 31.6±21.516.87±12.742.9±34.1 Baclofen plus 12.7±7.96.1.±4.514.8±11.022.677.558.1±21.831.01±31.2 Terazosin (n=64) % of change 51.7±27.452.7±31.146.5±29.3 Statistics* P<0.05 NS

排尿障礙治療中心版權所有 Medication for Dysfunctional voiding Oxybutynin – effective in reducing detrusor overactivity, side effects of mucosal dryness & constipation Ditropan XL – elimination of peak drug effect and reduce adverse effects Tolterodine – M3 anticholinergic Alpha-adrenergic blocker to reduce urethral resistance Phenylpropanolamine, pseudoephedrine – in ISD with incontinence ready for CIC

排尿障礙治療中心版權所有 Treatment of Nocturnal Enuresis Conditioning therapy: Alarm system or dry- bed training,effective in about 30-80% Medcal therapy: (1) Tricyclic antidepressant (TCA), imipramine, amitriptyline effective in 10-50% (author 24%) (2) anti-cholinergics (3) desmopressin (DDAVP) Side effect in combination medical therapy

排尿障礙治療中心版權所有 DDAVP Therapy in Nocturnal Enuresis in Children DDAVP in dose of 10-20 ug intranasally is effective in 70% of children with PNE After discontinuing DDAVP for 3months, 21% remained dry without medication 20 ug is adequate in treating PNE, in children not responded to 20ug, 40ug did not effective No serious adverse effect

排尿障礙治療中心版權所有 Treatment of Adult Nocturnal Enuresis DDAVP in patients proven to have nocturnal polyuria (nocturnal urine volume > 35% daily urine volume, or >900ml/N) Oxybutynine in patients proven to have DI Imipramine or methylephedrine in patients suspicious to have urethral incompetence Pelvic floor muscle exercises or functional electrostimulation might be helpful

排尿障礙治療中心版權所有 Medical treatment of Interstitial Cystitis Cyclosporine Methotrexate Tice strain BCG– 60% response rate vs 27% in placebo Elmiron (PPS 100mg tid) – 6.2% to 18.7% response rate Electromotive administration of intravesical lidocaine & dexamethasone – 62% effective

排尿障礙治療中心版權所有 Inravesical Heparin therapy Patients with urgency frequency and a positive potassium test Intravesical Heparin 25000u/10ml saline and holding for 2 hours 2x or 3x per week for 12 weeks 67% patients have improvement in symptoms and increase in bladder capacity

排尿障礙治療中心版權所有 The changes of urodynamic parameters before and after heparin treatment Baseline3 monthsStatistics P value FSF(ml)96.5±46.4146.1±55.40.001 US(ml)225.4±96.2264.9±84.20.009 Cystometric capacity(ml)262.0±89.8304.3±84.80.002 PdetQmax(cmH 2 O)25.7±9.128.3±9.30.07 Qmax (ml/sec)12.9±5.715.1±7.70.063 Residual urine(ml)29.4±38.414.5±25.70.096 IPSS (points)19.5±4.69.0±4.00 Nocturia (times/night)5.7±2.02.3±1.10 Pain scale of KCl (points) 3.2±0.50.7±0.70

Detrusor Overactivity and Contracted Bladder

排尿障礙治療中心版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien.

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排尿障礙治療中心 版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien.

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Presentation on theme: "排尿障礙治療中心 版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien."— Presentation transcript:

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排尿障礙治療中心版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien.

Presentation on theme: "排尿障礙治療中心版權所有 Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien."— Presentation transcript: