chapter 14

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 14

Muscarinic Agonists and Antagonists

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Cholinergic Drugs Agents that influence the activity of

cholinergic receptors Most mimic or block the actions of

acetylcholine. Cholinesterase inhibitors

Indirectly prevent the breakdown of acetylcholine


Cholinergic Drugs Toxicology encompasses

Nicotine Insecticides Chemical warfare


Tips for Understanding the Cholinergic Drugs

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.


Master Keys to Cholinergic Drugs


Muscarinic Agonists and Antagonists Muscarinic agonists

Bethanechol Other muscarinic agonists Toxicology of muscarinic agonists

Muscarinic antagonists (anticholinergic drugs) Atropine Anticholinergic drugs for overactive bladder (urge

incontinence) Other muscarinic antagonists Toxicology of muscarinic antagonists


Tips for Understanding the Cholinergic Drugs

Bethanechol (prototype drug) 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.


Muscarinic Agonists and Antagonists Muscarinic agonists

Bethanechol Other muscarinic agonists Toxicology of muscarinic agonists


Muscarinic Agonists and Antagonists Principal structures affected by muscarinic

activation 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)


Muscarinic Agonists Bethanechol

Mechanism of action Pharmacologic effects

Pharmacokinetics Therapeutic uses

Urinary retention Gastrointestinal uses


Muscarinic Agonists Adverse effects

Cardiovascular system Alimentary system Urinary tract Exacerbation of asthma Dysrhythmias in hyperthyroid patients

Preparations, dosage, and administration


Fig. 14-1. Structures of muscarinic agonists.


Other Muscarinic Agonists Cevimeline

Actions and uses Adverse effects Drug interactions Preparations, dosage, and administration


Other Muscarinic Agonists Pilocarpine

Glaucoma Acetylcholine

Miosis Muscarine

Present in poisonous mushrooms


Overactive Bladder Also known as urgency incontinence,

detrusor instability, and sometimes “can’t-hold-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.


Overactive Bladder 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.


Muscarinic Antagonists(Anticholinergic Drugs)

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



Certain drugs (antihistamines, tricyclic antidepressants, phenothiazine antipsychotics) have prominent antimuscarinic actions.

Use with caution—or not at all—with patients receiving other muscarinic antagonists.



Atropine Best known muscarinic antagonist Found in nature Mechanism of action

• No direct effect of its own• Muscarinic receptor blockade



Atropine Pharmacologic effects (receptor blockade)

• Heart• Exocrine glands• Smooth muscle• Eye• CNS• Dose dependency of muscarinic blockade• Pharmacokinetics



Atropine (cont’d) Therapeutic uses

• Preanesthetic medication• Disorders of the eye• Bradycardia• Intestinal hypertonicity and hypermotility• Muscarinic agonist poisoning• Peptic ulcer disease• Asthma• Biliary colic



Atropine (cont’d) Adverse effects

• Xerostomia (dry mouth)• Blurred vision and photophobia• Elevation of intraocular pressure• Urinary retention• Constipation• Anhidrosis• Tachycardia• Asthma



Atropine (cont’d) Drug interactions

• Avoid combining atropine with other drugs capable of causing muscarinic blockade

Preparations, dosage, and administration• General systemic therapy• AtroPen for cholinesterase inhibitor poisoning• Ophthalmology


Anticholinergic Drugs for Overactive Bladder

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


Anticholinergic Drugs for Overactive Bladder

Specific anticholinergic drugs for OAB (cont’d) Darifenacin Solifenacin Tolterodine

• Immediate-release tablets• Extended-release capsules

Trospium Fesoterodine


Other Muscarinic Antagonists Scopolamine Ipratropium bromide Antisecretory anticholinergics Dicyclomine Pirenzepine and telenzepine Mydriatic-cycloplegics Centrally acting anticholinergics


Toxicology of Muscarinic Agonists Source of muscarinic poisoning

Direct-acting muscarinic agonists Cholinesterase inhibitors

Symptoms Result from excessive activation of muscarinic

receptors Treatment

Muscarinic blocking agent, such as atropine


Toxicology of Muscarinic Antagonists Sources of antimuscarinic poisoning

Natural products Selective antimuscarinic drugs Drugs with pronounced antimuscarinic properties


Toxicology of Muscarinic Antagonists Symptoms

Dry mouth Blurred vision Photophobia Hyperthermia CNS effects Hot, dry, and flushed skin


Toxicology of Muscarinic Antagonists Treatment

Physostigmine Inhibitor of acetylcholinesterase

Warning Differentiate between poisoning and an actual

psychotic episode!

chapter 14

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muscarinic receptors

effects muscarinic receptors

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ciliary contraction

master keys