Anticholinergics / antispasmodics

Introduction

Anticholinergics are drugs that inhibit the action of acetylcholine (ACh) at muscarinic receptors, leading to reduced parasympathetic activity in various organ systems. Within this broad class, antispasmodics are agents used specifically to relieve smooth muscle spasms, particularly in the gastrointestinal (GI), genitourinary (GU), and biliary tracts.

Their clinical value extends across multiple domains:

• Gastrointestinal disorders: irritable bowel syndrome, peptic ulcer disease, functional GI pain.

• Genitourinary conditions: overactive bladder, urinary incontinence, renal colic.

• Respiratory and neurologic conditions: adjunctive role in COPD, Parkinson’s disease, and motion sickness.

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Mechanism of Action

• Blockade of muscarinic receptors (M1–M5) in smooth muscle, secretory glands, and the central nervous system.

• Results in:

  • Reduced GI motility and secretions.

  • Relaxation of bladder detrusor muscle.

  • Pupil dilation (mydriasis) and decreased accommodation (cycloplegia).

  • Decreased bronchial secretions and airway resistance.

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Classification of Anticholinergics / Antispasmodics

1. Belladonna Alkaloids (Natural Antimuscarinics)

• Generics: atropine, hyoscyamine, scopolamine.

• Uses:

  • Atropine: bradycardia, organophosphate poisoning, pre-anesthetic to reduce secretions.

  • Hyoscyamine: GI spasms, irritable bowel syndrome.

  • Scopolamine: motion sickness, postoperative nausea.

• Adverse Effects: Dry mouth, blurred vision, tachycardia, urinary retention, confusion (especially elderly).

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2. Synthetic Antispasmodics (GI and Biliary Tract)

• Dicyclomine: Used in irritable bowel syndrome (IBS) to reduce bowel spasms.

• Propantheline: Decreases gastric secretions and motility (less common today).

• Glycopyrrolate: Preoperative secretion control, adjunct for peptic ulcer disease, also used in anesthesia.

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3. Urinary Antispasmodics (Overactive Bladder Therapy)

• Oxybutynin: Reduces detrusor overactivity; available in oral and transdermal formulations.

• Tolterodine, fesoterodine: Selective bladder antimuscarinics, fewer CNS effects.

• Solifenacin, darifenacin: M3-selective agents → more bladder-specific, fewer systemic adverse effects.

• Trospium chloride: Quaternary amine, less CNS penetration, preferred in elderly to reduce cognitive adverse effects.

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4. Respiratory Anticholinergics (Bronchodilators)

• Ipratropium bromide, tiotropium, aclidinium, umeclidinium: Used in COPD and asthma (though mainly categorized under bronchodilators, they are anticholinergics).

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5. Neurologic / Antiparkinsonian Anticholinergics

• Trihexyphenidyl, benztropine, biperiden: Used in Parkinson’s disease (especially tremor-predominant) and drug-induced extrapyramidal symptoms.

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Therapeutic Indications

1. Gastrointestinal disorders

   • Irritable bowel syndrome (IBS): dicyclomine, hyoscyamine.

   • Peptic ulcer disease (historical use, now less common due to PPIs/H2 blockers).

   • Functional abdominal pain/spasms.

2. Genitourinary conditions

   • Overactive bladder / urge incontinence: oxybutynin, tolterodine, solifenacin.

   • Neurogenic bladder.

   • Adjunct in renal or biliary colic.

3. Respiratory conditions

   • COPD: ipratropium, tiotropium.

   • Asthma (adjunctive role): ipratropium.

4. Neurological conditions

   • Parkinson’s disease: trihexyphenidyl, benztropine.

   • Drug-induced extrapyramidal symptoms (antipsychotics).

5. Other uses

   • Motion sickness: scopolamine.

   • Pre-anesthetic medication: atropine, glycopyrrolate.

   • Organophosphate poisoning: atropine.

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Contraindications

• Narrow-angle glaucoma (risk of acute angle closure).

• Urinary retention (e.g., prostatic hypertrophy).

• Severe paralytic ileus or GI obstruction.

• Myasthenia gravis (worsens weakness).

• Caution in elderly (risk of confusion, delirium, falls).

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Adverse Effects (Anticholinergic Syndrome)

• Peripheral:

  • Dry mouth (xerostomia).

  • Blurred vision, mydriasis, photophobia.

  • Constipation.

  • Urinary retention.

  • Tachycardia.

• Central (especially with lipid-soluble agents like scopolamine, oxybutynin, trihexyphenidyl):

  • Sedation or agitation.

  • Hallucinations, confusion.

  • Memory impairment.

• Mnemonic: “Dry as a bone, blind as a bat, hot as a hare, red as a beet, mad as a hatter.”

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Clinical Considerations

1. Drug selection by organ system:

   • GI spasms: dicyclomine, hyoscyamine.

   • Bladder overactivity: solifenacin, darifenacin (M3-selective, better tolerability).

   • COPD: tiotropium (long-acting, once daily).

   • Parkinson’s disease: trihexyphenidyl, benztropine.

2. Age considerations:

   • Elderly patients are highly sensitive to central anticholinergic effects (confusion, delirium). Use bladder-selective or peripherally acting agents (e.g., trospium, glycopyrrolate).

3. Combination therapy:

   • Often used with other drug classes (e.g., combined with analgesics for renal colic).

4. Risk-benefit balance:

• Benefits in spasm control vs. high risk of side effects (especially cognitive decline in older adults).

• Deprescribing is often recommended in polypharmacy to reduce “anticholinergic burden.”