copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 14 muscarinic agonists and...
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 14
Muscarinic Agonists and Antagonists
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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
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3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Cholinergic Drugs
Toxicology encompasses Nicotine Insecticides Chemical warfare
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4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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.
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6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Master Keys to Cholinergic Drugs
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7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Master Keys to Cholinergic Drugs
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8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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.
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10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Agonists and Antagonists
Muscarinic agonists Bethanechol Other muscarinic agonists Toxicology of muscarinic agonists
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11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
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12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Agonists
Bethanechol Mechanism of action
Pharmacologic effects Pharmacokinetics
Therapeutic uses Urinary retention Gastrointestinal uses
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Muscarinic Agonists
Adverse effects Cardiovascular system Alimentary system Urinary tract Exacerbation of asthma Dysrhythmias in hyperthyroid patients
Preparations, dosage, and administration
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14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fig. 14-1. Structures of muscarinic agonists.
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Other Muscarinic Agonists
Cevimeline Actions and uses Adverse effects Drug interactions Preparations, dosage, and administration
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Other Muscarinic Agonists
Pilocarpine Glaucoma
Acetylcholine Miosis
Muscarine Present in poisonous mushrooms
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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.
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18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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.
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19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Antagonists(Anticholinergic Drugs)
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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21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Antagonists(Anticholinergic Drugs)
Atropine 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 Pharmacologic effects (receptor blockade)
• Heart• Exocrine glands• Smooth muscle• Eye• CNS• Dose dependency of muscarinic blockade• Pharmacokinetics
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23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Antagonists(Anticholinergic Drugs)
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
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24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Antagonists(Anticholinergic Drugs)
Atropine (cont’d) Adverse effects
• Xerostomia (dry mouth)• Blurred vision and photophobia• Elevation of intraocular pressure• Urinary retention• Constipation• Anhidrosis• Tachycardia• Asthma
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25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Muscarinic Antagonists(Anticholinergic Drugs)
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
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26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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Anticholinergic Drugs for Overactive Bladder
Specific anticholinergic drugs for OAB (cont’d) Darifenacin Solifenacin Tolterodine
• Immediate-release tablets• Extended-release capsules
Trospium Fesoterodine
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28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Other Muscarinic Antagonists
Scopolamine Ipratropium bromide Antisecretory anticholinergics Dicyclomine Pirenzepine and telenzepine Mydriatic-cycloplegics Centrally acting anticholinergics
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29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Toxicology of Muscarinic Antagonists
Sources of antimuscarinic poisoning Natural products Selective antimuscarinic drugs Drugs with pronounced antimuscarinic properties
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Toxicology of Muscarinic Antagonists
Symptoms Dry mouth Blurred vision Photophobia Hyperthermia CNS effects Hot, dry, and flushed skin
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Toxicology of Muscarinic Antagonists
Treatment Physostigmine Inhibitor of acetylcholinesterase
Warning Differentiate between poisoning and an actual
psychotic episode!