Over active bladder drug treatment Mark Weatherall University of Otago Wellington

2 Detrusor over activity Urodynamic detrusor over activity is spontaneous or provoked bladder contraction during the filling phase of urodynamics Normal bladder filling 1ml/min Bladder stretch promotes relaxation This persists until pontine micturition centre is released from inhibition for higher centres University of Otago Wellington

3 Overactive Bladder Lower urinary tract symptoms associated with detrusor over activity are frequency, urgency, nocturia, urge incontinence Activation of micturition cycle at lower bladder volumes, higher pressure and sustained contractions, exceed duration of external urethral sphincter function University of Otago Wellington

4 Outcome measures Voided volume records Patient completed outcome such as ICIQ-OAB and ICIQ- OABqol Day frequency Night frequency Episodes of incontinence Pad weighing Urodynamic University of Otago Wellington

5 Receptors and smooth muscle Detrusor is smooth muscle (involuntary) Parasympathetic nerves from sacral nerve roots S2 to S4 Activated by acetylcholine at muscarinic M3 receptors Similar receptors on salivary glands, muscle of lens accommodation, gut muscle, and central nervous system University of Otago Wellington

6 Acetylcholine Chemical acting like a key in a lock to activate cells Two broad type of receptors: Nicotinic on skeletal voluntary muscle and Muscarinic on smooth muscle and other tissues Nicotinic means responds to nicotine, muscarinic to muscarine Broken down after release from nerve ends by the enzyme acetylcholinesterase University of Otago Wellington

7 Anticholinergics versus Placebo Randomised controlled trials show that there is an effect compared to nothing resulting in an average of four less episodes of leakage and five less episodes of voiding: per week About one third of placebo ‘respond’ to treatment University of Otago Wellington

8 Anticholinergics versus each other Randomised controlled trials of only some of all possible combinations and there is no evidence of efficacy difference Possibly the drug company funded trials of extended release preparations show less dry mouth University of Otago Wellington

9 Study duration and adherence Most of the controlled trials are only of weeks duration, a couple of trials of 52 week duration In the trials persistence with treatment not much different between placebo or between different agents In non-experimental studies long term persistence with treatment is low University of Otago Wellington

10 Agents in NZ Funded agents are oxybutynin and solifenacin but possibly tolterodine may be funded There are other registered agents University of Otago Wellington

11 Adverse Events Dry mouth is an inevitable result of blocking salivary gland production Blurred vision from lens problems Constipation Delirium in those vulnerable, especially older adults and dementia University of Otago Wellington

12 Issues with older adults Often have reduced salivary production anyway and dentures High prevalence of visual impairment, constipation, and cognitive impairment In men urinary outflow obstruction may require generation of high bladder pressures so urinary retention In those with inadequate detrusor function and detrusor overactivity can get retention (diabetes, idiopathic) University of Otago Wellington

13 Other therapies Bladder retraining, scheduled toileting, catching strategies Tricyclic anti-depressants (Imipramine), other side effects of sedation and orthostatic hypotension Reduce outflow obstruction (alpha blockers, finasteride) TURP Botulinum toxin Sacral nerve root stimulation Clam cystoplasty University of Otago Wellington