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