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 12-24 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