15. Muscarinic receptor antagonists

Last updated on April 4, 2021 at 13:38

This class of drugs are competitive antagonists of muscarinic receptors, so they decrease parasympathetic activation. Because of this are they called anticholinergics, and sometimes parasympatholytics or cholinolytics. They are mostly non-selective (meaning they act on all muscarinic receptor subtypes, not just one subtype), but a few are selective.

They have the following effects (mostly the opposite of the parasympathetic system):

  • Mydriasis, increased intraocular pressure, cycloplegia (they block accommodation), decreased tear secretion, photophobia
  • Tachycardia
  • Bronchodilation, decreased bronchial secretion
  • Decreased gastrointestinal secretion, decreased motility and peristalsis, constriction of sphincters
  • Relaxation of detrusor muscle
  • Decreased sweating, hyperthermia in high doses (due to the decreased sweating)

Generally speaking are the parietal cells and CNS innervated by M1, heart innervated by M2, while M3 innervates the rest, e.g. the eye, GI tract, bronchial smooth muscle and salivary gland secretion.

These are the most important drugs:

  • Tertiary compounds
    • Atropine
    • Scopolamine
    • Cyclopentolate
    • Homatropine
    • Tropicamide
    • Oxybutinin
    • Tolterodine
    • Benztropine
    • Biperiden
  • Quaternary compounds
    • Ipratropium (bromide)
    • Tiotropium (bromide)
    • Butylscopolamine
  • M1-selective antagonists
    • (Pirenzepine)

Atropine and scopolamine are natural compounds from the plant Atropa Belladonna.

Indications:

Atropine has many uses:

  • Sinus bradycardia
  • Cholinergic poisoning
  • Premedication before intubation (decreases salivary and respiratory secretions)
  • Uveitis

Scopolamine is used to treat motion sickness, often as a transdermal patch.

Homatropine and tropicamide are used to treat uveitis and to induce pupil dilation and cycloplegia (paralysis of the ciliary muscle) for diagnostic purposes.

Ipratropium (bromide) and tiotropium (bromide) are used as bronchodilators to treat COPD and bronchial asthma when given as inhalation.

Centrally-acting muscarinic antagonists like benztropine and biperiden can be used to treat Parkinson’s.

Butylscopolamine is related to scopolamine but does not cross the BBB and therefore only acts peripherally. It relaxes smooth muscle and is used to treat colicky pain, like biliary colic, ureteric colic, and intestinal colic.

Oxybutinin and tolterodine are used to treat bladder incontinence.

Pirenzepine is unique in that it is a selective muscarinic subtype 1 (M1) antagonist. It inhibits gastric secretions and is used against peptic ulcers and has few side-effects. It is very rarely used nowadays so I don’t think it’s worth learning.

Like for the parasympathomimetics there is significant overlap between the indications here. 

Pharmacokinetics:

All of them contain a tertiary ammonium group except for butylscopolamine, ipratropium, and tiotropium. The quaternary amine drugs are hydrophilic and therefore poorly absorbed and unable to cross the blood-brain barrier to have any effects on the CNS.

Drugs with the tertiary ammonium group are lipophilic and can cross the BBB and will have CNS effects. Tertiary ammonium drugs are also much better absorbed through the GI tract than quaternary drugs. Scopolamine can even be absorbed transdermally.

Atropine has a short half-life of only 2 hours, except when used in eyedrops, where the half-life is 72 hours. It’s 50% metabolized in the liver and 50% excreted unchanged by the kidneys.

Side effects:

It’s important to know the side effects of anticholinergics well.

  • Dry mouth
  • Dry eyes
  • Headache
  • Mydriasis
  • Tachycardia
  • Urinary retention
  • Constipation
  • CNS side effects (for tertiary compounds)
    • Mostly in elderly
    • Confusion
    • Disorientation
    • Delirium
    • Hallucination

Atropine poisoning

The symptoms of atropine poisoning/anticholinergic overdose are similar to the side effects of parasympatholythics except more severe:

  • Dry mouth
  • Mydriasis
  • Tachycardia
  • Hot, dry, red skin
  • Hyperthermia
  • Urinary retention
  • Confusion, hallucination, convulsion

Atropine intoxication is treated with physostigmine, diazepam and cooling.

Tricyclic antidepressants, low-potency first-generation antipsychotics, second-generation antipsychotics and first-generation antihistamines have anticholinergic effect and can also cause anticholinergic overdose.


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14. Cholinergic agonists and cholinesterase inhibitors

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16. Neuromuscular blocking agents

2 thoughts on “15. Muscarinic receptor antagonists”

  1. Hello! Was just wondering, should it not be spinchter constriction in the GI, on the effect of cholinergic antagonists? I see you have written relaxation of spinchters!

    (Love your notes!!)

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