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Chapter 14

Muscarinic Agonists and Antagonists

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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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Cholinergic Drugs

Toxicology encompasses Nicotine Insecticides Chemical warfare

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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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Master Keys to Cholinergic Drugs

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Master Keys to Cholinergic Drugs

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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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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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Muscarinic Agonists and Antagonists

Muscarinic agonists Bethanechol Other muscarinic agonists Toxicology of muscarinic agonists

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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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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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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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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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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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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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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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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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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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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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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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Other Muscarinic Antagonists

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

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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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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!