PNS Pharmacology: Cholinergic and Adrenergic Receptor Subtypes

By stimulating $M_{3}$ receptors in the bladder, bethanechol causes:

1. Detrusor muscle contraction, which increases bladder pressure.
2. Relaxation of the trigone and sphincter muscles, which allows urine to exit the body.

Clinical Considerations for Bethanechol

• Administration: Usually taken orally (PO) 1 hour before meals or 2 hours after meals to prevent nausea and vomiting.
• Contraindications: Do not use in patients with physical urinary obstructions, weak bladder walls, intestinal obstructions, or active asthma.
• Adverse Effects: Patients may experience "cholinergic" effects, including decreased blood pressure, bradycardia, increased salivation, abdominal cramps, and diarrhea.

Critical Safety Note: In the event of a Bethanechol overdose (characterized by excessive salivation, sweating, bradycardia, or hypotension), the antidote is Atropine, a muscarinic blocker.

Parasympatholytics: Muscarinic Antagonists

Parasympatholytics (anticholinergics) block muscarinic receptors, effectively inhibiting parasympathetic activity. These are frequently used to treat Overactive Bladder (OAB) by inducing bladder relaxation.

Agent Selectivity in OAB Treatment

Not all anticholinergics are equal; their selectivity determines their side effect profile:

• Highly $M_{3}$ Selective: Darifenacin targets the bladder specifically, which may reduce systemic side effects like dry mouth or constipation.
• Non-selective: Agents like Oxybutynin, Tolterodine, Fesoterodine, and Trospium block multiple muscarinic subtypes, often leading to more widespread side effects.

Common Side Effects of Anticholinergics

Because these drugs block $M_{3}$ receptors throughout the body, patients often experience:

• Dry mouth (salivary gland blockade)
• Constipation (GI motility blockade)
• Blurred vision and mydriasis (eye muscle blockade)
• Urinary retention (bladder relaxation)

Warning: Avoid combining anticholinergics with other drugs that have similar properties, such as certain antihistamines or tricyclic antidepressants (TCAs), as this can lead to toxicity.

Adrenergic Receptors

The sympathetic nervous system utilizes adrenergic receptors to mediate responses to epinephrine and norepinephrine.

Alpha ($\alpha$) Receptors

• $\alpha_{1}$ Receptors: These are critical in the genitourinary system. Activation of $\alpha_{1}$ causes contraction/constriction of the prostate, male sex organs (ejaculation), and the bladder (trigone and sphincter). This action promotes urinary retention. Conversely, blocking $\alpha_{1}$ receptors promotes voiding.

Beta ($\beta$) Receptors

• $\beta_{1}$: Primarily located in the heart.
• $\beta_{2}$: Primarily located in the lungs (bronchodilation).
• $\beta_{3}$: Located in the bladder. Mirabegron is a selective $\beta_{3}$ agonist used for OAB. Unlike anticholinergics, it works by relaxing the detrusor muscle, allowing the bladder to fill more comfortably without the "drying" side effects of muscarinic blockers.

Summary Table of Clinical Applications