Muscarinic antagonists

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.

Mechanism of action

• Anticholinergic agents block the neurotransmitter acetylcholine in the central and peripheral nervous system.
  • Muscarinic antagonists: inhibit the effect of acetylcholine on muscarinic receptors (the majority of anticholinergic drugs)
  • Antinicotinic agents: inhibit the effects of acetylcholine on nicotinic receptors (mostly skeletal muscle relaxants).
• Antinicotinic agents are discussed in the “Skeletal muscle relaxants” article; the effects of muscarinic receptors are discussed in the “Autonomic nervous system” article.

Effects of muscarinic antagonists

Important muscarinic antagonists

References:^{[1][2][3][4][5][6][7]}

Side effects of antimuscarinic agents

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)

• Etiology
  • Belladonna poisoning
  • Jimson weed/Angel's trumpet (Datura stramonium) poisoning: The plant contains alkaloids, such as atropine and scopolamine, which lead to anticholinergic intoxication and mydriasis (“gardener's pupil”).
  • Medications
    • Anticholinergic agents (e.g., atropine, benztropine, trihexyphenidyl)
    • Drugs with anticholinergic properties
      • Tricyclic antidepressives (predominantly doxepin, amitriptyline, imipramine, and trimipramine)
      • Antipsychotics; (e.g., clozapine, quetiapine)
      • First-generation antihistamines (e.g., promethazine, dimenhydrinate)
• Clinical features
  • Dry mouth, warm, flushed skin, thirst, tachycardia, arrhythmias, mydriasis, confusion, and agitation
  • Possibly anticholinergic delirium: Excessive use of tricyclic antidepressants (or other medications with significant anticholinergic effects) can cause life-threatening delirium, hallucinations, and psychomotor symptoms.
• Diagnostics
  • Clinical findings and history of exposure
  • Electrocardiogram: to rule out QRS, QTc interval prolongation, and other arrhythmias
• Treatment: antidote for purely anticholinergic poisoning (e.g. atropine): physostigmine
• Differential diagnosis: See “Differential diagnosis of drug intoxication” and “Differential diagnosis of drug-induced hyperthermia.”

References:^{[1][8][9][10]}

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