Overactive Bladder Medications

Antimuscarinics/Anticholinergics

oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, trospium

Beta-3 receptors agonist

Mirabegron (Myrbetriq), vibegron (gemtesa)

Medication for neurogenic and spastic bladder

Bethanechol (Urecholine)

Which sensory receptors are located in the bladder to detect level of fullness?

Cholinergic receptors, alpha-adrenergic receptors, and beta-adrenergic receptors

Anticholinergic Medications Use / MOA

Used initially

Antimuscarinic / Inhibits involuntary contractions

Act on cholinergic receptors / oppose parasympathetic stimulation → relax bladder smooth muscle

Beta-3 receptor agonist Use / MOA

Used for those with contraindications, intolerance, or lack of response to anticholinergics

Increases relaxation of bladder

Act on adrenergic receptors

Onabotulinumtoxin A Use / MOA

Used for those with contraindications, intolerance, or lack of response to anticholinergics

Blocks acetylcholine release at the NMJ

Antimuscarinics Contraindications

Angle-closure glaucoma, obstructive uropathy, urinary retention

Antimuscarinics ADE

DRY AND DROWSY : dry mouth, urinary retention, constipation, dry eyes, HA, tachycardia, cognitive impairment, confusion

Antimuscarinics Drug Interactions

Cholinesterase inhibitors and anticholinergics

Antimuscarinic Clinical Pearls

ER formulation may be associated with less dry mouth and other muscarinic effects

What counseling points is/are important to discuss with the pt when prescribing an antimuscarinic agent?

Anticholinergics can cause urinary retention and cognitive impairment

Oxybutynin Clinical Pearls

No dose adjustment needed for renal or hepatic impairment

Oxybutynin (Oxytrol) Transdermal Product Info

Avoids first pass metabolism and as effective

ADE: pruritus; less dry mouth, constipation, somnolence, blurry vision

Oxybutynin (Oxytrol for WOMEN) transdermal

ADE: fewer systemic but high incidence of pruritus at application site

Dry Mouth → limiting ADE

Oxybutynin Topical Gel (Gelnique) product info

Gel and transdermal similar plasma concentrations

ADE: dry mouth, application site reactions, constipation

Apply once daily to dry skin, do not shower for 1 hour after application, do not use same application site

Tolterodine (detrol, detrol LA) product info

Renal Impairment

Clinical Pearls: lower incidence of dry mouth, take with food

Fesoterodine (Toviaz) ER product info

Active metabolite of tolterodine

Renal adjustment

Trospium (Sactura, Sanctura XR) product info

10% of dose is absorbed after oral administration

TAKE ON EMPTY STOMACH

Renal adjustment

Solifenacin (Vesicare) product info

Higher affinity for bladder smooth muscle

solifenacin 5 mg less dry mouth

ADE: serious GI toxicity such as intestinal obstruction

Renal and hepatic dose adjustment

Darifenacin (Enablex) product info

greater affinity for M3 muscarinic receptors which mediate effects on bladder, GIT, salivary gland, and iris sphincter than M1 receptors that mediate CNS effects

Dry mouth

No renal adjustment needed, avoid in severe hepatic impairment

Less negative impact on cognitive

Rank tolerability of selected agents from least to most tolerable

Oxybutynin IR/PO > Oxybutynin ER PO/tolterodine IR PO > fesoterodine ER PO > tolterodine ER PO > oxybutynin TDS or gel

What would you advise a patient prior to starting solifenacin (vesicare)?

It has been assocaited with bowel obstruction

Beta-3 adrenergic agonists Indication

Overactive bladder - monotherapy or in combo with antimuscarinic agent

Neurogenic detrusor overactivity - only mirabegron

Beta-3 adrenergic agonists MOA

Relaxes the detrusor muscle

Beta-3 adrenergic agonists ADE

Leading to discontinuation: N/D/C, dizziness, tachy, HA; urinary retention

Increases BP - not recommended for use in patients with severe uncontrolled HTN

Beta-3 adrenergic agonists Drug Interactions

Mirabegron is a moderate inhibitor of CYP2D6

When taken with an anticholinergic (solifenacin), can increase risk of urinary retention

Beta-3 adrenergic agonists Clinical Pearls

May be better tolerated than anticholinergics but urinary retention can occur, drug interactions may be problematic, long-term safety is unknown

What is the mechanism of action of mirabegron?

Enhance beta-3 adrenoceptor effects to relax the detrusor muscle

Onabotulinumtoxin A MOA

blocks acetylcholine release at the neuromusclar junction

Onabotulinumtoxin A ADE

Urinary retention may occur requiring catheterization

UTI

Onabotulinumtoxin A Drug Interactions

Muscle relaxants could potentiate the effect of the toxin

Onabotulinumtoxin A Patient Counseling

pts must be willing to perform self-cath

Wait at least 12 weeks before re-treating

Injected into detrusor muscle

Onabotulinumtoxin A Clinical Pearls

For patients that cannot tolerate or have an inadequate response to anticholinergic therapy

Not interchangable with other botox preparations

Bethanechol (Urecholine) Indications

Treat urinary retention due to neurogenic bladder

Bethanechol (Urecholine) MOA

Cholinergic agonist / stimulates parasympathetic nervous system to cause contractions which initiate urination

Bethanechol (Urecholine) contraindications

mechanical obstruction of the GI or GU tract

Drug Induced OAB / Urinary Incontinence

Physiologic and structural disorders or urinary system

Increased urinary output

Urinary retention

Difficulties in reacting to the urge to urinate/getting to the toilet

What effect do antihistamines and tricyclic antidepressants have on the bladder?

urinary retention in overflow incontinence (BPH)

What effect do opiates have on the bladder?

urinary retention, sedation

What effect do terazosin, doxazosin have on the bladder?

Urethral relaxation, may cause or exacerbate stress incontinence in females

What effect do nasal decongestants have on the bladder?

Urinary retention in males with overflow incontinence (BPH)

What effect do dihydropyridines (CCB) have on the bladder?

urinary retention, nocturnal diuresis d/t fluid retention

What effect do long-acting benzos have on the bladder?

sedation, delirium, immobility

What effect do loop diuretics and thiazide diuretics have on the bladder?

polyuria, frequency urgency