This document discusses treatments for detrusor overactivity (OAB), including anticholinergic/antimuscarinic drugs and mirabegron. It provides statistics on the prevalence and projected increase of OAB worldwide. Anticholinergics work by blocking muscarinic receptors in the bladder to reduce contractions. Mirabegron is a beta-3 adrenergic agonist that works differently by activating beta-3 receptors to relax the detrusor muscle. The document reviews the mechanisms and side effect profiles of various anticholinergic drugs and mirabegron as alternatives or additions for treating OAB.
2. World Wide
• In the 2013 dataset, the prevalence of OAB was 7.2%
(Male: 7.7%; Female: 6.7%).
• Prevalence was the highest among those aged more
than 74 years (9.3%), identifying as White (7.4%), and
residing in urban areas (7.5%).
• By 2027, OAB is projected to increase by 48.1%
8. Muscarinic receptors are
distributed to most of the
organs in the body.
Antimuscarinics have
important sites of action
outside the bladder that
cause effects limiting
their clinical use.
10. Mirabegron: clinical considerations in OAB*
First b3-adrenoceptor agonist approved for OAB
Once-daily oral administration
Reduces the frequency of micturition, incontinence
and urgency and improves HR-QOL
Sustains these improvements over 52 weeks’ therapy
Generally well tolerated
Beta-3 adrenergic drug for the treatment of OAB -
11. • Sympathetic nerve activity triggers
the release of noradrenaline
(NA),which relaxes the
detrusormuscle and promotes
contraction of the urethra, thereby
promoting the storage of urine.
• Like noradrenaline, mirabegron
acts on the β3-adrenoreceptor,
triggering detrusor muscle
relaxation and improved urine
storage
* Br J Clin Pharmacol-2015,80:4; 762–764
Beta-3 adrenergic drug MOA* The β3-
adrenergic receptor agonist mirabegron
-
13. Sites of action and mechanisms of therapeutic agents used for the treatment of neurogenic overactive bladder
- Mov Disord. 2018 Mar; 33(3): 372–390.
Cholinergic pelvic nerves release acetylcholine
(ACh), which, via activation of muscarinic M3
receptors, induce contraction of the detrusor
muscle and emptying of the bladder.
Anti-muscarinic agents (e.g., solifenacin)
block the muscarinic receptor and reduce
detrusor muscle contractions.
adrenergic nerves release norepinephrine (NE), causes
urinary retention by activating β3-adrenergic receptors in
the detrusor muscle and alpha-adrenergic receptors in the
internal sphincter of the urethra.
Mirabegron, a β3-adrenergic
receptor agonist, reduces bladder
contractions in patients with
neurogenic detrusor overactivity.
14. Treatment Recommended dosing regimen Adverse events Receptor selectivity CNS penetration
Anticholinergic agents
Darifenacin 7.5 or 15 mg/day Constipation, dry mouth, urinary retention M3 selective Low
Trospium
20 mg twice a day
60 mg/day (extended release form)
Constipation, dry mouth, dry eyes, headache, urinary
retention
Non-selective Low
Solifenacin 5 or 10 mg/day
Constipation, dry mouth, blurred vision, nausea,
dyspepsia, urinary retention
M3 and M1 selective Moderate
Oxybutinin
5 mg up to 4 times/day
5-30 mg/day (extended release form)
3 pumps once a day (gel)
1 patch every 3-4 days (patch)
Constipation, dry mouth, blurred vision, nausea,
dyspepsia, urinary retention
M3 and M1 selective Moderate
Tolterodine
2 mg twice a day
2 or 4 mg/day (long acting form)
Constipation, dry mouth, dyspepsia, dizziness, blurry
vision, urinary retention
Non-selective Moderate
Fesoterodine 4 or 8 mg
Constipation, dry mouth, dyspepsia, dizziness, blurry
vision, urinary retention
Non-selective Moderate
β3-adrenergic agonists
Mirabegron 25 or 50 mg/day
Hypertension, irregular heart rate, abdominal or pelvic
pain, worsening dyskinesias in PD (one case report)
β3-selective Low
Pharmacological treatments for neurogenic detrusor overactivity
Mov Disord. 2018 Mar; 33(3): 372–390.
15. β3-adrenergic agonists-
β3-adrenergic receptors contribute to detrusor muscle relaxation.
Mirabegron, a selective β3-adrenergic receptor, elicits relaxation of the
detrusor muscle during the storage phase, thereby improving bladder
capacity without impeding bladder voiding.
Oral mirabegron administered once daily (25-50 mg) is effective to
improve urinary frequency,urgency, and incontinence in patients with
overactive bladder.
Mirabegron is devoid of anticholinergic adverse events but can
cause urinary retention, pelvic/abdominal pain, and
hypertension
