• Clinical science

Muscarinic antagonists (Antimuscarinic agents)

Abstract

Muscarinic antagonists (antimuscarinic agents) are a group of anticholinergic drugs that competitively inhibit postganglionic muscarinic receptors. As such, they have a variety of applications that involve the parasympathetic nervous system. Which organ systems are most affected by an antimuscarinic agent depends on the specific characteristics of the agent, particularly its lipophilicity. Lipophilic agents (i.e., atropine or benztropine) are able to cross the blood-brain barrier and therefore affect the central nervous system (CNS) in addition to other organ systems. Less lipophilic agents (i.e., ipratropium or butylscopolamine) are administered if the CNS does not need to be targeted, specifically for respiratory (e.g., asthma), gastrointestinal (e.g., irritable bowel syndrome), or genitourinary applications (e.g., urinary incontinence). Numerous adverse effects have been reported, the most common of which is dry mouth. An overdose can result in anticholinergic syndrome, which manifests in disorientation, hyperthermia, tachycardia, and/or coma. To avoid toxicity, it is especially important to consider the anticholinergic effects of other drug classes before administering muscarinic antagonists.

Overview

Mechanism of action

Anticholinergic agents block the neurotransmitter acetylcholine in the central and the peripheral nervous system. Muscarinic antagonists (the majority of anticholinergic drugs) inhibit the effect of acetylcholine on muscarinic receptors, and antinicotinic agents inhibit the effects of acetylcholine on nicotinic receptors (mostly skeletal muscle relaxants). Antinicotinic agents are discussed in the learning card on skeletal muscle relaxants.

Effects of muscarinic antagonists

Muscarinic receptors Organ/Tissue Effects
M1, M4, M5

Central nervous system

  • Influences neurologic function (e.g., cognitive impairment)
M2

Heart

M3

Smooth muscle

Exocrine glands

  • ↓ Secretions (sweat)

Important muscarinic antagonists

Chemical characteristics Drug Effect Indication

Tertiary amines

Lipophilic (good oral bioavailability and CNS penetration)

  • CNS depression
  • ↓ Vestibular disturbances (antiemetic)
  • Premedication prior to intubation
    • Sedation
    • Amnesia
    • Decreases secretions
  • Motion sickness
  • Ophthalmology
    • Therapeutic use: in patients with uveitis
    • Diagnostic use: pupillary dilation to allow ocular fundus examination and cycloplegia to allow refractory testing
    • Tropicamide: short duration of action → 6 hours
    • Cyclopentolate: duration of action → 1 day
    • Homatropine: duration of action → 2–3 days
  • ↓ Cholinergic overactivity in CNS
  • ↓ Tone and motility of smooth muscle cells
  • ↑ Sphincter tone

Quarternary amines

Hydrophilic (poor oral bioavailability and CNS penetration)

  • ↓ Tone and motility of the gut (antispasmodic effect)
  • Methscopolamine
  • Pirenzepine
  • Propantheline
  • Glycopyrrolate
  • Bronchodilation

References:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]

Side effects

Antimuscarinic side effects

Side effect Contraindications
Impaired secretion by exocrine glands
  • Dry mouth and sore throat
  • ↓ Respiratory tract secretions
  • Hyperthermia and warm, dry skin
  • Acute asthma
  • Respiratory distress
Cardiovascular system
  • Tachycardia
Decreased smooth muscle tone
Eye
CNS

"Blind as a bat (mydriasis), mad as a hatter (delirium), red as a beet (flushing), hot as a hare (hyperthermia), dry as a bone (decreased secretions and dry skin), the bowel and bladder lose their tone (urinary retention and paralytic ileus), and the heart runs alone (tachycardia).”

Anticholinergic syndrome (overdose)

References:[1][2][17][18][19][20]

We list the most important adverse effects. The selection is not exhaustive.