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AUTONOMIC PHARMACOLOGY | MUSCARINIC ANTAGONISTS

Autonomic Pharmacology | Muscarinic Antagonists Medical Editor: Gerard Jude Loyola

OUTLINE
I) CHOLINERGIC PHYSIOLOGY (C) QUATERNARY AMINES
(A) ACETYLCHOLINE-RELEASING III) ANTICHOLINERGIC TOXICITY
NEURONS (A) SYMPTOMS
II) TYPES OF MUSCARINIC ANTAGONISTS (B) CAUSES
(A) MUSCARINIC RECEPTORS (C) ANTIDOTE
(B) TERTIARY AMINES IV) REVIEW QUESTIONS

I) CHOLINERGIC PHYSIOLOGY
Table 1. Effects of acetylcholine in different organs.
(A) ACETYLCHOLINE-RELEASING NEURONS
NEURONS/ REMARKS
ORGANS

Basal ganglia Controlled by a balance of dopamine and

acetylcholine
In certain diseases, there is alteration in
the balance leading in alteration of
movement

Emetic center or Found in the medulla

the vomiting Contains a lot of muscarinic receptors
center Controls our vomiting response
Triggered by vestibular dysfunction,
stretching or irritation of particular factors
in the GI tract or higher level of
functioning

Eye Pupil: Causes pupil constriction

Ciliaris: Causes contraction of ciliaris
o Pulls the angle where the aqueous
humor → increases aqueous humor
drainage
Lens: Causes lens accommodation

Lacrimal and Stimulation causes lacrimation (↑tear

salivary glands production) and salivation (↑salivary
production)
CN VII (lacrimal gland)
CN IX (salivary gland)

Vagus nerve Heart: Works on the bundle system (SA

node, AV node) to slow down HR and CO
o To conserve energy for resting and
digesting
Smooth muscle bronchiole:
Bronchoconstriction
Liver: Increase bile release which is
involved in digestion
Stomach: Increase motility and secretions

Skin There is sympathetic neurons but they

Figure 1. Effects of cholinergic neurons in different organs.
release acetylcholine
Anticholinergic drugs act like a parasympatholytic; Involved in sweating
o Trying to inhibit the parasympathetic nervous system
Sacral nerves Supplies the lower abdomen (bladder +
(S2-S4) lower parts of the colon)
Acetylcholine-releasing neurons, muscarinic and nicotinic
Bladder: Causes contraction of the
receptors in the CNS:
detrusor muscle → urination
Lower GIT: Increases GI motility

(1) Summary of cholinergic effects:

Regulates movements Decrease HR and CO

Induce vomiting Bronchoconstricts
Constricts pupil Increase bile secretion
Increase aqueous drainage Increase GI motility and secretion
Accommodation of the lens Increase sweating
Increase lacrimation and salivation Induce urination

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 II) TYPES OF MUSCARINIC ANTAGONISTS
(A) MUSCARINIC RECEPTORS

Figure 2. Inhibitory (left) and stimulatory (right) muscarinic receptors.

Muscarinic receptors are G-protein receptors
(1) Inhibitory receptors (M2R, M4R)
o Coupled with G-inhibitory proteins
o Primary organ is the heart
o When ACh is released from the post-ganglionic
neuron, it binds to M2R or M4R → ↓cAMP → ↓PK →
cell hyperpolarization → ↓HR and CO
 Also ↑K efflux → hyperpolarization → ↓HR and CO
(2) Stimulatory receptors (M1R, M3R, M5R)
o Coupled with G-stimulatory proteins
o When ACh is released from the post-ganglionic
neuron, it binds to these stimulatory receptors →
↑cAMP → ↑PK → ↑contraction, secretion etc.
o Bladder: Causes ↑contractility of the detrusor muscle
→ ↑urination
o GIT: ↑contractility and secretions
Muscarinic antagonists block the aforementioned
reactions

(B) TERTIARY AMINES

Tertiary amines are lipophilic → easier to cross the BBB → affects the CNS
(1) Atropine
Blocks the muscarinic receptors in the pupil and ciliaris
AfraTafreeh.com
 causes pupil dilation and decrease drainage in the
canal shunt
o ↓aqueous humor drainage → blurred vision, and
increase IOP
o !! Be careful to patients with narrow-angle glaucoma
Blocks muscarinic receptors in the lacrimal gland →
↓lacrimation  may dry out the eyes
Blocks muscarinic receptors in the salivary gland →
↓salivation
o Indicated in:
 Situations where patients drool a lot
 Pre-op vs pre-intubation to clear-up upper airway
secretions
Oppose the M2R in the AV and SA node → ↑HR and
↑CO
o First-line for patients with symptomatic bradycardia
Cholinergic agonists (cholinesterase) → cholinergic
crisis
o Atropine as an antidote to cholinergic crisis

(2) Scopolamine
Blocks muscarinic receptor in the emetic center
o When there is a lot of acetylcholine in the emetic
center
o Inhibit vomiting type of process
Indicated in (1) patients with motion sickness (d/t
vestibular dysfunction) or (2) post-operative nausea
and vomiting (PONV)

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(3) Benztropine & Trihexyphenidyl

Recall that movement is modulated by balance of
dopamine and ACh
In states where there is a massive reduction of dopamine,
acetylcholine may be overpowering
o Can reduce tremors in Parkinson’s by inhibiting
acetylcholine
 Recall that in Parkinson’s, the neurons in the
substantia nigra degenerate leading to reduction
in dopamine
o Can alleviate EPS (extrapyramidal symptoms)
caused by antipsychotics in patients who are delirious
or with psychiatric disorders

(4) Oxybutynin, Tolteradine, Solfenacin (5) Dicyclomine & Hyoscyamine

Inhibits contraction in the bladder Indicated in patients have GI spasms or diarrhea
Indicated in patients with urinary incontinence or o Benefits patients with IBS-D → ↓spasms and diarrhea
urgency (overactive bladder) o Recall that IBS has two types:
 (1) IBS-C with predominant constipation,
 (2) IBS-D with predominant diarrhea

(C) QUATERNARY AMINES

Figure 3. Quaternary amines.

Quaternary amines are hydrophilic → difficulty penetrating the CNS
(1) Glycopyrrolate
Indicated for patients with a lot of drooling (e.g. cerebral
palsy or psychiatric disorders that causes a lot of
drooling)
o Inreased respiratory secretions can clog endotracheal
tubes → cause pneumonia
Helpful in pre-op situation or pre-intubation to clear up
respiratory secretions
(2) Ipratropium & Tiotropium
In the bronchioles, ACh promotes bronchoconstriction →
causes difficulty in ventilation in diseases such as COPD
and asthma
These drugs inhibit bronchoconstriction → better air
movement
Ipratropium: short-acting muscarinic antagonist (SAMA)
Tiotropium: long-acting muscarinic antagonist (LAMA)

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 III) ANTICHOLINERGIC TOXICITY

(A) SYMPTOMS (B) CAUSES

Antimuscarinic agents
Tricyclic antidepressants
Antipsychotics
First-gen antihistamines
Belladonna plant

Either these drugs are taken two much or mixed together

can cause anticholinergic toxicity.

(C) ANTIDOTE
Physostigmine
o Cholinergic agonist
o Will do everything opposite of anticholinergic toxicity

Figure 4. Symptoms of anticholinergic toxicity.

Delirium, alterned mental status → seizures (rarely but
possible)
o Although ACh is involved in regulating movement, it
also affects cognition AfraTafreeh.com
Massive pupil dilation
Blurry vision
o Due to ciliaris not contracting and/or inability of the
lens to accommodate
o !! Contraindicated in patients with narrow-angle
glaucoma (high IOP)
Severe dry eyes and dry mouth
Tachycardia (↑↑↑HR) and hypertension (↑↑↑CO)
Bronchodilation
Little sweating
o Body cannot be cooled down through evaporative
cooling → hyperthermia (↑↑↑T)
Severe constipation
o Due to inadequate GI contraction
o !! Contraindicated in patients with small bowel
obstruction, large bowel obstruction, or ileus
Severe retention
o !! Contraindicated in patients with BPH

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IV) REVIEW QUESTIONS

1) Sarin is a nerve gas that is an organophosphate
cholinesterase inhibitor. Which agent could be used
as an antidote to sarin poisoning?
a. Pilocarpine
b. Carbachol
c. Atropine
d. Physostigmine.

2) A patient with asthma was prescribed a β2 agonist

for acute relief of bronchospasm, but did not respond
to treatment. Which drug is the most likely next
option for this patient?
a. Benztropine
b. Ipratropium
c. Oxybutynin
d. Physostigmine

3) A 50-year-old male who is noncompliant with

medications was recently diagnosed with COPD. His
physician would like to prescribed an inhaled
anticholinergic that is dosed once or twice daily.
Which drug is most appropriate for this patient?
a. Atropine
b. Ipratropium
c. Tiotropium
d. Trospium

4) Which is the most effective drug for motion sickness

for a person planning to go on a cruise?
a. Atropine
b. Fesoterodine
c. Scopolamine
d. Tropicamide

5) Which drug is useful in treating sinus bradycardia?

a. Atropine
b. Cisatracurium
c. Neostigmine
d. Succinylcholine

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