Urecholine
Urecholine
Generic Name
Urecholine
Mechanism
- Direct M3 receptor stimulation → ↑ intracellular Ca²⁺ → smooth‑muscle contraction
- No significant nicotinic activity, minimizing neuromuscular side‑effects
- Reversible agonism (receptor occupancy ≈ 30–50 %) allowing titration of effect
- Rapid onset (≈15 min after oral dosing) and transient receptor desensitization mitigated by intermittent dosing
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral: 85 % bioavailability; peak plasma concentration Tₘₐₓ ≈ 0.5–1 h |
| Distribution | Volume of distribution ≈ 0.6 L/kg; moderate protein binding (≈ 20 %) |
| Metabolism | Phase II glucuronidation (UGT1A4) and minor oxidation (CYP3A4); minimal CYP450 involvement |
| Elimination | Renal excretion: 75 % unchanged, 25 % as glucuronide; half‑life ≈ 4 h (shorter in advanced CKD) |
| Special Populations | Reduced clearance in CKD stage 3–5; dosage adjustment advised |
Indications
- Acute urinary retention (both male and female)
- Detrusor under‑activity in post‑operative patients
- Functional constipation refractory to laxatives (off‑label evidence)
- Idiopathic lower urinary tract symptoms under specialist supervision
Contraindications
- Contraindicated in patients with:
- Severe uncontrolled asthma or COPD
- Ocular myasthenia gravis
- Severe gastric acid reflux unresponsive to anticholinergics
- Warnings:
- Possible cholinergic crisis with co‑administration of cholinesterase inhibitors or high‑dose neuraminidase inhibitors
- May precipitate urinary incontinence or bladder overactivity in patients with neurogenic bladder
- Precautions:
- Use with caution in pregnancy (category C); lactation exposure minimal
- Avoid in patients with renal impairment > Stage 3 without dose adjustment
Dosing
| Condition | First Dose | Maintenance | Administration Notes |
| Acute urinary retention | 5 mg PO | 5 mg q6 h as needed | Initiate after bladder scan confirms residual volume ≥ 300 mL |
| Detrusor under‑activity | 5 mg PO daily | 5–10 mg daily | Titrate by 5 mg increments every 3 days |
| Functional constipation | 5 mg PO twice daily | 5–10 mg BID | Take with food to reduce GI upset |
• Route: Oral tablets (5 mg), chewable formulation available for post‑operative patients
• Formulation: 100 mg and 500 mg tablets for intravenous use (bolus 10 mg IV over 30 min for severe retention)
Adverse Effects
Common (≥ 5 %)
• Nausea, vomiting, abdominal cramps
• Diarrhea, increased stool frequency
• Excessive salivation, lacrimation
• Dizziness, blurred vision
Serious (≤ 1 %)
• Bradycardia or sinus arrest (especially in patients on β‑blockers)
• Severe hypotension from vasodilation
• Urinary retention paradox (bladder over‑activity)
• Anaphylactoid reaction (rash, angioedema)
Rare (≤ 0.1 %)
• Severe cholinergic crisis (yawning, hyperthermia, seizures)
• Acute interstitial nephritis
Monitoring
- Baseline: Serum creatinine, electrolytes, ECG (HR, PR interval)
- During therapy:
- Urine output (≥ 300 mL/h post‑dose)
- Bladder ultrasound to track residual volume
- Serum BNP if heart failure co‑present
- Lab monitoring: BUN/creatinine every 2 weeks first month, then quarterly in CKD patients
- Adjuncts: Pulse oximetry if respiratory status is precarious
Clinical Pearls
- “Urecholine on a Stop‑Watch”: Because the half‑life is short, patients report quicker symptom relief but may need more frequent dosing for lasting effect.
- Tailored for CKD: Reduce dose by 50 % in patients with eGFR < 30 mL/min/1.73 m²; consider a 2‑hour extended‑release formulation if renal clearance remains sub‑optimal.
- Combination therapy: Pair with a short‑acting antimuscarinic (e.g., tolterodine) in cases of over‑activity to blunt unwanted detrusor contraction while retaining urinary retention benefits.
- Patient education: Instruct on “safety‑first” signs: chest pain, faintness, or extreme sweating—promptly report these as possible cholinergic crisis.
- Surgical setting: Administer pre‑operative dose 1–2 h before epidural or spinal anesthesia to pre‑empt postoperative urinary retention.
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• *For reference, see: “Textbook of Clinical Pharmacology, 7th ed.”, “Urologic Pharmacotherapy: Emerging Agents” (2023).*