15. Muscarinic receptor antagonists

Last updated on November 24, 2019 at 13:33

This class of drugs are competitive antagonists of muscarinic receptors, so they decrease parasympathetic activation. Because of this are they called 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, relaxation 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
  • Quaternary compounds
    • Ipratropium (bromide)
    • Tiotropium (bromide)
  • M1-selective antagonists
    • Pirenzepine

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

Indications:

Atropine is used to treat sinus bradycardia and anticholinesterase/cholinergic poisoning. It is also used as premedication prior to intubation to decrease salivary, respiratory and gastric secretion.

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

Homatropine and tropicamide are used to treat eye infections and to induce pupil dilation and cycloplegia (paralysis of the ciliary muscle).

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

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.

Centrally-acting muscarinic antagonists like scopolamine can be used to treat Parkinson’s, however they have so many peripheral side effects, so they’re not widely used.

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

Pharmacokinetics:

All of them contain a tertiary ammonium group except for 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:

  • Dry mouth
  • Mydriasis
  • Tachycardia
  • Urinary retention

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

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