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Bladder Antispasmodic

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Bladder Antispasmodic, Urinary Tract Antispasmodic, Urinary Antispasmodic, Bladder Relaxant, Bladder Antimuscarinic, Muscarinic Antagonists for Urge Incontinence, Oxybutynin, Oxybutynin XR, Oxytrol for Women, Ditropan, Flavoxate, Urispas, Hyoscyamine sulfate, Cystospaz, Tolterodine, Detrol, Vesicare, Solifenacin, Enablex, Darifenacin, Beta-3 Adrenergic Agonist, Mirabegron, Myrbetriq, Vibegron, Gemtesa

  • Indications
  1. Urge Incontinence
  2. Urinary Catheter leakage
  • Mechanism
  1. Anticholinergic Medications
  2. Inhibit involuntary detrusor contractions
  • Efficacy
  1. First-line management for Urge Incontinence are non-pharmacologic measures
    1. Decrease Caffeine intake
    2. Schedule voiding times
    3. Bladder TrainingExercises
  2. All Bladder Relaxants are only modestly effective
    1. Reduce Urinary Frequency and Incontinence by approximately 1 episode daily
    2. Expect 1 in 7 patients to benefit
    3. Expect 1 in 5 patients to have significant side effects (typically Anticholinergic)
  3. References
    1. Shamliyan (2012) Ann Intern Med 156(12):861-74 [PubMed]
  • Adverse Effects
  1. Anticholinergic side effects (antimuscarinic agents, no beta-3 Agonists)
    1. Anticholinergic symptom examples: Dry Mouth, confusion, Tachycardia, Blurred Vision
    2. See Medication Use in the Elderly (Beers List, STOPP)
    3. Seen less with Tolterodine then with Oxybutynin
    4. Seen less with long acting agents and transdermal agents
  • Preparations
  • Non-selective Agents (M1/M2/M3 antimuscarinics)
  1. Long-acting Oral agents: (preferred of the non-selective agents)
    1. Detrol LA (Tolterodine LA) 2 to 4 mg daily
      1. Similar efficacy compared to Oxybutinin XR
      2. Tolterodine causes less Dry Mouth
      3. Diokno (2003) Mayo Clin Proc 78:687-95 [PubMed]
    2. Ditropan XL or Oxytrol XR (Oxybutynin XR) 5 to 10 to 30 mg daily
      1. Ditropan XL is now generic
      2. Reduces Urge Incontinence 28%
      3. Dry Mouth is more common
      4. Least likely to cause Constipation
      5. CNS effects such as Dizziness and sedation are more common
    3. Sanctura XR (trospium XR)
      1. No Drug Interactions with CYP3A4 metabolized agents
      2. Renal Clearance
      3. Less CNS effects (does not cross BBB)
      4. Dry Mouth is less common
    4. Toviaz XR (Fesoterodine XR)
      1. Risk of high drug levels in decreased metabolism of Cytochrome P450 2D6
  2. Transdermal agents
    1. Tolterodine transdermal patch
    2. Oxybutynin transdermal patch (Oxytrol) apply 2x/week
      1. As effective as oral agent
      2. Less Anticholinergic side effects
      3. Frequently causes skin reaction
      4. Dmochowski (2003) Urology 62:237-42 [PubMed]
    3. Oxytrol for Women (OTC, Oxybutynin patch)
      1. Indicated for women over age 18 years with at least 3 months of urinary urgency with frequency or Urinary Incontinence
      2. Cost is $30 per month (OTC out-of-pocket cost) versus $270 for prescription
      3. Contraindicated in men (due to Overflow Incontinence risk due to BPH related urinary obstruction)
      4. (2013) Presc Lett 20(9):51
  3. Short acting oral agents (avoid now that Ditropan XL is now generic)
    1. Increased Anticholinergic side effects (Dry Mouth, Constipation)
    2. Tolterodine (Detrol) 1 to 2 mg PO bid
    3. Oxybutynin (Ditropan) 2.5 to 5 mg PO qid
  • Preparations
  • M3 Selective Antimuscarinics
  1. Indications
    1. Urge Incontinence (preferred agents due to less cognitive effects)
  2. Mechanism
    1. Selective for M3 Muscarinic Receptor blockade
    2. Less drowsiness and Dizziness than agents above
    3. Higher rate of Constipation, Dry Mouth, Vision change
  3. Agents
    1. Solifenacin (Vesicare) 5 to 10 mg PO daily
    2. Darifenacin (Enablex) 7.5 to 15 mg PO daily
  • Preparations
  • Beta-3 Adrenergic Agonist
  1. Agents
    1. Mirabegron (Myrbetriq)
    2. Vibegron (Gemtessa)
      1. Does not appear to have Blood Pressure, Heart Rate effects or CYP450 2D6 interactions
        1. Contrast with Mirabegron
  2. Indications
    1. Consider in patients intolerant to the Anticholinergic effects of the anti-muscarinic agents
    2. Examples: Cognitive Impairment, Glaucoma
  3. Mechanism: Beta-3 Agonist
    1. Relaxes Smooth Muscle including the Bladder
    2. Secondary increase in Bladder storage capacity
  4. Efficacy
    1. Similar to effectiveness to antimuscarinics (e.g. Oxybutynin)
    2. However, substantially more expensive than antimuscarinics (>$400 per month)
  5. Adverse effects (Mirabegron)
    1. No Anticholinergic side effects
    2. Hypertension
    3. Tachycardia
    4. Headache
    5. Dizziness
    6. Gastrointestinal Upset
  6. Drug Interactions (Mirabegron)
    1. Inhibits CYP450 2D6
    2. Raises levels of Metoprolol, Desipramine, Digoxin
  • Preparations
  • Older agents now replaced by those above
  1. Flavoxate (Urispas) 100 to 200 mg PO qid
  2. Hyoscyamine (Cystospaz) 0.125 to 0.5 mg PO qid
  3. Dicyclomine (Bentyl) 10 to 20 mg PO qid
  • References
  1. (2021) Presc Lett 28(3): 17
  2. (2012) Presc Lett 19(10): 57-8
  3. Appell (2001) Mayo Clin Proc 76:358-63 [PubMed]