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Wednesday, July 30, 2025

Urinary antispasmodics


Definition and Pharmacological Purpose
Urinary antispasmodics are a class of medications used primarily to relieve smooth muscle spasms in the urinary tract. These drugs are especially effective in managing symptoms of overactive bladder (OAB), urinary urgency, frequency, urge incontinence, and nocturia. They are also utilized to manage neurogenic bladder dysfunction, bladder spasms post-surgery or catheterization, and discomfort associated with urinary tract infections (UTIs).

These agents exert their effects primarily through anticholinergic (antimuscarinic) or beta-3 adrenergic agonist activity. By modulating bladder muscle tone and suppressing involuntary contractions of the detrusor muscle (the smooth muscle of the bladder wall), urinary antispasmodics improve bladder storage capacity and reduce episodes of incontinence.

Mechanism of Action

Urinary antispasmodics operate mainly through one or more of the following pathways:

  1. Muscarinic receptor antagonism (anticholinergic action)

    • Blocks M2 and M3 receptors in the bladder detrusor muscle.

    • Reduces parasympathetic stimulation leading to decreased involuntary bladder contractions.

    • Increases bladder capacity and delays urgency sensation.

  2. Beta-3 adrenergic receptor agonism

    • Activates β3 receptors in the bladder wall.

    • Promotes relaxation of detrusor smooth muscle during the filling phase.

    • Increases bladder storage without reducing contraction strength during voiding.

  3. Direct smooth muscle relaxants

    • Some agents work by directly inhibiting muscle spasm without anticholinergic effects.

Clinical Indications

  • Overactive bladder (OAB) with symptoms of urge incontinence, frequency, urgency

  • Neurogenic detrusor overactivity (e.g., in spinal cord injury or multiple sclerosis)

  • Detrusor instability due to bladder outlet obstruction or idiopathic causes

  • Nocturnal enuresis (off-label)

  • Bladder spasms after surgery or catheter use

  • Irritable bladder syndrome

Commonly Used Generic Drugs in Urinary Antispasmodics

Generic NamePharmacological Class
OxybutyninAnticholinergic
TolterodineAnticholinergic
TrospiumAnticholinergic
SolifenacinAnticholinergic (M3 selective)
DarifenacinAnticholinergic (M3 selective)
FesoterodineAnticholinergic (prodrug of 5-HMT)
FlavoxateDirect smooth muscle relaxant
PropanthelineAnticholinergic
MirabegronBeta-3 adrenergic agonist
VibegronBeta-3 adrenergic agonist
HyoscyamineAnticholinergic (alkaloid)
Belladonna alkaloidsAnticholinergic


Detailed Pharmacological Profiles

1. Oxybutynin

  • Mechanism: Non-selective antimuscarinic; also exhibits direct muscle-relaxant and local anesthetic properties.

  • Forms: Oral (IR, ER), transdermal patch (Oxytrol), gel (Gelnique)

  • Typical Dose: 2.5–5 mg 2–4 times/day (IR); 5–30 mg once/day (ER)

  • Adverse Effects: Dry mouth, constipation, blurred vision, cognitive impairment (especially in elderly)

  • Notes: Widely used, but high side effect burden due to non-selectivity

2. Tolterodine

  • Mechanism: Antimuscarinic, slightly more bladder-selective

  • Forms: IR and ER oral tablets

  • Typical Dose: 1–2 mg BID (IR), 4 mg once/day (ER)

  • Advantages: Better tolerated than oxybutynin in some patients

3. Solifenacin

  • Mechanism: M3 receptor selective antagonist

  • Dose: 5–10 mg once daily

  • Advantages: More bladder-specific; fewer CNS side effects

  • Common Brands: Vesicare®

4. Darifenacin

  • Mechanism: Highly selective M3 receptor blocker

  • Dose: 7.5–15 mg once daily

  • Notes: Lower incidence of cognitive side effects due to minimal CNS penetration

5. Trospium Chloride

  • Mechanism: Non-selective antimuscarinic; quaternary ammonium compound (less CNS penetration)

  • Dose: 20 mg BID or 60 mg ER once daily

  • Notes: Safer for elderly due to low CNS penetration

6. Fesoterodine

  • Mechanism: Prodrug of active metabolite of tolterodine (5-HMT)

  • Dose: 4–8 mg once daily

  • Advantages: Consistent response due to bypassing of CYP2D6 metabolism

7. Mirabegron

  • Mechanism: Beta-3 adrenergic receptor agonist → detrusor muscle relaxation

  • Form: Extended-release tablets

  • Dose: 25–50 mg once daily

  • Adverse Effects: Hypertension, headache, nasopharyngitis

  • Advantages: No anticholinergic side effects; alternative for patients intolerant to antimuscarinics

8. Vibegron

  • Mechanism: Selective β3 agonist

  • Dose: 75 mg once daily

  • FDA Approved: 2020

  • Advantages: Similar to mirabegron but without CYP interactions

9. Flavoxate

  • Mechanism: Direct smooth muscle relaxant, possibly with weak anticholinergic activity

  • Dose: 100–200 mg three to four times daily

  • Use: Painful urination, bladder spasms, dysuria

  • Notes: Less effective for urge incontinence; adjunct use

10. Propantheline Bromide

  • Mechanism: Anticholinergic, non-selective

  • Dose: 15 mg 3–4 times/day before meals

  • Use: Older agent, also used for peptic ulcer and hyperhidrosis

  • Caution: High anticholinergic burden

11. Hyoscyamine

  • Mechanism: Belladonna alkaloid; antimuscarinic effects

  • Forms: Sublingual, oral, extended-release

  • Use: Bladder spasms, irritable bowel syndrome

  • Notes: Used more in GI spasms but sometimes applied to urinary conditions

Adverse Effects of Antispasmodics

SystemCommon Effects
Central NervousDrowsiness, dizziness, confusion (especially elderly), hallucinations
GastrointestinalDry mouth, constipation, nausea, bloating
OphthalmicBlurred vision, dry eyes
UrinaryUrinary retention
CardiovascularTachycardia, palpitations, QT prolongation (rare)
GenitourinarySexual dysfunction (anticholinergics)
Allergic reactionsRare, mostly with plant-derived products (e.g., belladonna)



Contraindications and Precautions

  • Urinary retention or gastric retention

  • Uncontrolled narrow-angle glaucoma

  • Severe liver or renal impairment (depending on drug)

  • Use in elderly (risk of CNS effects)

  • Pregnancy and breastfeeding: caution advised, risk-benefit analysis required

Drug Interactions

AntispasmodicInteraction
AnticholinergicsAdditive effects with other anticholinergic drugs (e.g., TCAs, antihistamines)
MirabegronMay increase levels of CYP2D6 substrates (e.g., metoprolol, desipramine)
Beta-3 agonistsPotential to elevate BP when used with MAO inhibitors or sympathomimetics
QT-prolonging agentsRisk increases when used with antiarrhythmics or fluoroquinolones


Monitoring Parameters

  • Efficacy: Reduction in urgency, frequency, and incontinence episodes

  • Adherence: High discontinuation rates due to side effects

  • Cognition: In elderly, monitor for anticholinergic cognitive burden

  • Blood pressure: For beta-3 agonists like mirabegron

  • Liver and renal function: Especially with drugs metabolized hepatically

Special Populations

  • Elderly: Prefer beta-3 agonists or CNS-sparing anticholinergics (trospium)

  • Pediatric: Used off-label in neurogenic bladder; specialist care required

  • Pregnancy: Avoid unless clearly indicated

  • Renal Impairment: Dose adjustments for trospium, tolterodine, fesoterodine

Clinical Notes and Guidelines

  • First-line treatment for OAB: Behavioral therapy (bladder training, fluid management)

  • Pharmacologic treatment: Begins when conservative measures fail

  • Combination therapy: Anticholinergic + beta-3 agonist may be used in resistant cases

  • Long-term use: Evaluate periodically; may not be necessary lifelong




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