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Medical Treatment for Lower Urinary Tract Dysfunction

Medical Treatment for Lower Urinary Tract Dysfunction. Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien. Innervation of Lower Urinary Tract. Bladder- cholinergic parasympathetic- contraction; beta-adrenergic & NO– relaxation

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Medical Treatment for Lower Urinary Tract Dysfunction

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  1. Medical Treatment for Lower Urinary Tract Dysfunction Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien

  2. 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

  3. Neuroanatomy of Lower Urinary Tract

  4. 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

  5. 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

  6. 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

  7. Storage Problems • Bladder hypersensitivity • Low bladder compliance • Detrusor overactivity – neurogenic or idiopathic • Low urethral resistance • Bladder outlet obstruction • Combination of the above

  8. Detrusor overactivity during Bladder filling phase

  9. Detrusor Overactivity followed by Valsalva maneuver

  10. 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

  11. Normal Micturition – relaxation of urethral sphincter

  12. 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

  13. Dysfunctional Voiding in a girl with Bilateral Hydronephrosis

  14. Low Detrusor Contractility

  15. 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

  16. Pharmacology of Micturition- Increase empty efficiency • Parasympathomimetic agent- Urecholine • Adrenergic blockers- inhibition of detrusor relaxation (?)

  17. Pharmacology of Micturition- Increase outlet resistance • Increase smooth muscle tone – Imipramine, methylephedrine • Increase striated muscle tone – Nitric oxide synthase inhibitor Pelvic floor muscle training

  18. SUI & Urethral Incompetence induced Detrusor Overactivity

  19. 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

  20. Decreased MUCP after Botulinum Toxin Injection

  21. Reduction of MUCP after Nitric Oxide Donors (NTG)

  22. Combined Medication- Improved Storage Efficiency • Detrusor Overactivity- anticholinergics, sympathomimetics, imipramine • Intrinsic sphincter deficiency- imipramine, sympathomimetics • DHIC- depends on voiding efficiency and grades of incontinence

  23. 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

  24. 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

  25. Dysfunctional voiding in A woman with Multiple Stroke

  26. 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)

  27. 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

  28. 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

  29. 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

  30. Pharmacology of Detrusor Overactivity

  31. Extended-release system for oxybutynin & tolterodine

  32. 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

  33. 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

  34. 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

  35. Urodynamic Result after RTX Therapy in a SCI patient

  36. Urodynamic Changes after RTX in Chronic SCI with DESD

  37. 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

  38. Therapeutic Results of RTX in Neurogenic v Non-neurogenic Voiding Dysfunction • 22/41 patients (53.6%) with detrusor overactivity improved after RTX 10-7M 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

  39. Urodynamic Changes after RTX in Detrusor Overactivity

  40. 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

  41. Mechanism of Botulinum A Toxin in Neuromuscular Junction

  42. Botulinum A Toxin Urethral Injection in Woman

  43. Cystoscopic Urethral Injection in Men * * * *

  44. Table 1.The Urodynamic Parameters at Baseline and after Botulinum Toxin in Effective Patients MUCP=maximal urethral closure pressure, FPL=functional profile length, PVR= postvoid residual volume *Comparison between baseline and 4weeks after treatment

  45. Therapeutic Results after Botox Urethral Injection for Voiding Dysfunction DESD=Detrusor external sphincter dyssynergia

  46. Botulinum Toxin Detrusor Injection for Detrusor Hyperreflexia

  47. Btulinum A Toxin Detrusor Injection for DH

  48. Initial Results of BotulinumToxin Detrusor Injection for Incontinence

  49. 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)

  50. Bladder neck dysfunction in woman

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