Autonomic Drugs in Urological Disorders

LUT Innervation - The Plumbing Pilots

• Storage Phase (Filling): Sympathetic Dominance
  • Bladder (Detrusor): Relaxed via $\beta_3$ adrenergic receptors.
  • Bladder Neck & Proximal Urethra: Contracted via $\alpha_1$ adrenergic receptors.
  • Somatic (Pudendal n.): External urethral sphincter contracted.
• Voiding Phase (Micturition): Parasympathetic Dominance
  • Bladder (Detrusor): Contracts via $M_3$ muscarinic receptors.
  • Bladder Neck & Proximal Urethra: Relaxed (inhibition of $\alpha_1$ tone).
  • Somatic: External urethral sphincter relaxes.

⭐ The predominant muscarinic receptor subtype in the human detrusor muscle is $M_3$, with $M_2$ being more numerous but $M_3$ mediating contraction primarily. (NEET PG Favourite)

📌 Storage = Sympathetic; Peeing = Parasympathetic

Overactive Bladder Tx - Urge Under Arrest

Manages urgency, frequency, urge incontinence. 📌 "Urge Under Arrest"

• 1st Line: Behavioral (bladder training, Kegels).

• 2nd Line: Pharmacotherapy

  • Antimuscarinics (M3 blockers): Relax detrusor.
    • Oxybutynin (⚠️ caution elderly: cognitive SEs), Tolterodine.
    • M3 Selective: Solifenacin, Darifenacin (↓ SEs).
    • Trospium (quaternary: ↓ CNS SEs).
    • Common SEs: Dry mouth, constipation, blurred vision.
  • Beta-3 Agonists: Relax detrusor, ↑ capacity.
    • Mirabegron (monitor BP: can ↑ HTN).
    • Vibegron (newer, potentially fewer BP effects).
    • Fewer anticholinergic SEs vs. antimuscarinics.

• 3rd Line: Botox, PTNS, Sacral Neuromodulation.

⭐ Mirabegron is a preferred option for OAB patients intolerant to antimuscarinic side effects or where cognitive impairment is a concern.

BPH & Retention Tx - Go With the Flow

• BPH (Lower Urinary Tract Symptoms - LUTS):
  • α1-Blockers (Dynamic Relief): Rapid action. Relax prostatic & bladder neck smooth muscle.
    • Prazosin, Terazosin, Doxazosin (α1-selective): Risk of first-dose hypotension, postural dizziness.
    • Tamsulosin, Silodosin (α1A/α1D uroselective): Fewer systemic BP effects; risk of ejaculatory dysfunction.
    • 📌 Mnemonic: "Sins" of the prostate (Tamsulosin, Silodosin, Doxazosin, Prazosin).
  • 5α-Reductase Inhibitors (Static Relief): Reduce prostate size by blocking Testosterone → Dihydrotestosterone (DHT).
    • Finasteride, Dutasteride.
    • Slow onset (3-6 months). Side effects: ↓ libido, erectile dysfunction.
  • Combination therapy (α1-blocker + 5ARI) for significant LUTS & enlarged prostate.
• Urinary Retention (Non-Obstructive Atonic Bladder):
  • Cholinomimetics (Muscarinic Agonists):
    • Bethanechol: Stimulates M3 receptors on detrusor muscle, promoting bladder contraction.
    • Uses: Post-operative, post-partum urinary retention; neurogenic bladder.
    • ⚠️ Contraindications: Mechanical obstruction, asthma, peptic ulcer disease, bradycardia.

⭐ Uroselective α1A-blockers like Tamsulosin are preferred for BPH in normotensive patients; Silodosin has highest ejaculatory dysfunction risk.

Other Uses & Cautions - Tricky Waters

• Stress Urinary Incontinence (SUI):
  • Alpha-agonists (Midodrine): ↑ urethral tone.
  • Duloxetine (SNRI): ↑ pudendal nerve activity.
• Neurogenic Bladder:
  • Anticholinergics for overactivity.
  • Alpha-blockers for outlet obstruction.
• Nocturnal Enuresis: Imipramine.
• Key Cautions:
  • Alpha-blockers: Postural hypotension. ⚠️ Tamsulosin: Intraoperative Floppy Iris Syndrome (IFIS).
  • Anticholinergics: Dry mouth, constipation, blurred vision, cognitive issues (elderly), urinary retention risk in BPH.
  • Mirabegron: May ↑ BP.

⭐ Tamsulosin is notorious for causing Intraoperative Floppy Iris Syndrome (IFIS), a crucial consideration before cataract surgery.

High‑Yield Points - ⚡ Biggest Takeaways

• BPH: α1-blockers for rapid symptom relief; 5α-reductase inhibitors for prostate size reduction.
• OAB: Antimuscarinics (e.g., Oxybutynin) are first-line; Mirabegron (β3-agonist) is an alternative.
• Urinary Retention: Bethanechol (muscarinic agonist) for non-obstructive, often post-operative, retention.
• Tamsulosin: Uroselective α1A/α1D blocker, less hypotension.
• Finasteride: Inhibits 5α-reductase, ↓DHT, shrinks prostate.
• Antimuscarinic ADRs: Dry mouth, blurred vision, constipation, cognitive issues (elderly).
• Mirabegron: β3-agonist for OAB, can ↑BP_._