Chapter 14
Muscarinic Agonists and
Antagonists
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Cholinergic Drugs
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Agents that influence the activity of
cholinergic receptors
Most mimic or block the actions of
acetylcholine.
Cholinesterase inhibitors
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Indirectly prevent the breakdown of acetylcholine
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Cholinergic Drugs
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Toxicology encompasses
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Nicotine
Insecticides
Chemical warfare
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Tips for Understanding the
Cholinergic Drugs
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Know the receptors that the drug affects.
Know the normal responses to activation of
those receptors.
Know whether the drug in question increases
or decreases receptor activation.
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Master Keys to Cholinergic Drugs
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Master Keys to Cholinergic Drugs
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Muscarinic Agonists and Antagonists
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Muscarinic agonists
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Bethanechol
Other muscarinic agonists
Toxicology of muscarinic agonists
Muscarinic antagonists (anticholinergic drugs)
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Atropine
Anticholinergic drugs for overactive bladder (urge
incontinence)
Other muscarinic antagonists
Toxicology of muscarinic antagonists
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Tips for Understanding the
Cholinergic Drugs
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Bethanechol (prototype drug)
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Selective agonist at muscarinic cholinergic receptors
Refer to Table 14-2.
Note the effects muscarinic receptors can produce.
Bethanechol activates muscarinic receptors (agonist).
Know which receptors a drug interacts with
(Table 14-2) and what those receptors do (Table 14-2).
You can predict the types of responses you might expect
from bethanechol.
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Muscarinic Agonists and Antagonists
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Muscarinic agonists
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Bethanechol
Other muscarinic agonists
Toxicology of muscarinic agonists
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Muscarinic Agonists and Antagonists
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Principal structures affected by muscarinic
activation
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Heart: bradycardia
Exocrine glands: increase sweating, salivation,
bronchial secretions, and secretion of gastric acid
Smooth muscles
• Contraction in lung (constriction)
• GI tract (increased tone/motility)
• Bladder (contraction of detrusor)
• Vascular (relaxation, vasodilation, hypotension)
• Eye (pupillary constriction and ciliary contraction)
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Muscarinic Agonists
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Bethanechol
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Pharmacologic effects
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Mechanism of action
Pharmacokinetics
Therapeutic uses
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Urinary retention
Gastrointestinal uses
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Muscarinic Agonists
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Adverse effects
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Cardiovascular system
Alimentary system
Urinary tract
Exacerbation of asthma
Dysrhythmias in hyperthyroid patients
Preparations, dosage, and administration
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Fig. 14-1. Structures of muscarinic agonists.
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Other Muscarinic Agonists
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Cevimeline
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Actions and uses
Adverse effects
Drug interactions
Preparations, dosage, and administration
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Other Muscarinic Agonists
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Pilocarpine
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Acetylcholine
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Glaucoma
Miosis
Muscarine
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Present in poisonous mushrooms
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Overactive Bladder
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Also known as urgency incontinence,
detrusor instability, and sometimes “can’thold-it-anymore” incontinence
Four major symptoms: urinary urgency,
urinary frequency, nocturia, and urge
incontinence
Urge incontinence often results from
involuntary contractions of the bladder
detrusor.
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Overactive Bladder
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Affects up to one-third of Americans
Can develop at any age, but is most
predominant in elderly patients
Two modes of treatment: behavioral therapy
and drug therapy
If ineffective—percutaneous tibial nerve
stimulation (PTNS) may be tried.
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Competitively block the actions of
acetylcholine at muscarinic receptors
Most muscarinic receptors on structures
innervated by parasympathetic nerves
Also known as parasympatholytic drugs,
antimuscarinic drugs, muscarinic blockers,
and anticholinergic drugs
Anticholinergic drugs: produce selective
blockade of muscarinic receptors—not all
cholinergic receptors
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Certain drugs (antihistamines, tricyclic
antidepressants, phenothiazine
antipsychotics) have prominent
antimuscarinic actions.
Use with caution—or not at all—with patients
receiving other muscarinic antagonists.
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Atropine
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Best known muscarinic antagonist
Found in nature
Mechanism of action
• No direct effect of its own
• Muscarinic receptor blockade
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Muscarinic Antagonists
(Anticholinergic Drugs)

Atropine
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Pharmacologic effects (receptor blockade)
• Heart
• Exocrine glands
• Smooth muscle
• Eye
• CNS
• Dose dependency of muscarinic blockade
• Pharmacokinetics
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Atropine (cont’d)
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Therapeutic uses
• Preanesthetic medication
• Disorders of the eye
• Bradycardia
• Intestinal hypertonicity and hypermotility
• Muscarinic agonist poisoning
• Peptic ulcer disease
• Asthma
• Biliary colic
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Atropine (cont’d)
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Adverse effects
• Xerostomia (dry mouth)
• Blurred vision and photophobia
• Elevation of intraocular pressure
• Urinary retention
• Constipation
• Anhidrosis
• Tachycardia
• Asthma
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Muscarinic Antagonists
(Anticholinergic Drugs)
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Atropine (cont’d)
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Drug interactions
• Avoid combining atropine with other drugs capable of
causing muscarinic blockade
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Preparations, dosage, and administration
• General systemic therapy
• AtroPen for cholinesterase inhibitor poisoning
• Ophthalmology
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Anticholinergic Drugs for
Overactive Bladder
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Overactive bladder (OAB): characteristics and
overview of treatment
Introduction to anticholinergic therapy of OAB
Specific anticholinergic drugs for OAB

Oxybutynin (Ditropan, Oxytrol, Gelnique)
• Syrup
• Extended-release tablets
• Transdermal patch and gel
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Anticholinergic Drugs for
Overactive Bladder
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Specific anticholinergic drugs for OAB
(cont’d)
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Darifenacin
Solifenacin
Tolterodine
• Immediate-release tablets
• Extended-release capsules
Trospium
Fesoterodine
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Other Muscarinic Antagonists
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Scopolamine
Ipratropium bromide
Antisecretory anticholinergics
Dicyclomine
Pirenzepine and telenzepine
Mydriatic-cycloplegics
Centrally acting anticholinergics
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Toxicology of Muscarinic Agonists
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Source of muscarinic poisoning
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Symptoms
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Direct-acting muscarinic agonists
Cholinesterase inhibitors
Result from excessive activation of muscarinic
receptors
Treatment

Muscarinic blocking agent, such as atropine
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Toxicology of Muscarinic Antagonists
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Sources of antimuscarinic poisoning
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Natural products
Selective antimuscarinic drugs
Drugs with pronounced antimuscarinic properties
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Toxicology of Muscarinic Antagonists
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Symptoms
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Dry mouth
Blurred vision
Photophobia
Hyperthermia
CNS effects
Hot, dry, and flushed skin
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Toxicology of Muscarinic Antagonists
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Treatment
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Physostigmine
Inhibitor of acetylcholinesterase
Warning

Differentiate between poisoning and an actual
psychotic episode!
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