Transcript Chapter_014
Chapter 14 Muscarinic Agonists and Antagonists Copyright © 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 2 Cholinergic Drugs Toxicology encompasses Nicotine Insecticides Chemical warfare Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 4 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 5 Master Keys to Cholinergic Drugs Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 6 Master Keys to Cholinergic Drugs Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 7 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 8 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 9 Muscarinic Agonists and Antagonists Muscarinic agonists Bethanechol Other muscarinic agonists Toxicology of muscarinic agonists Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 10 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) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 11 Muscarinic Agonists Bethanechol Pharmacologic effects Mechanism of action Pharmacokinetics Therapeutic uses Urinary retention Gastrointestinal uses Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 12 Muscarinic Agonists Adverse effects Cardiovascular system Alimentary system Urinary tract Exacerbation of asthma Dysrhythmias in hyperthyroid patients Preparations, dosage, and administration Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 13 Fig. 14-1. Structures of muscarinic agonists. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 14 Other Muscarinic Agonists Cevimeline Actions and uses Adverse effects Drug interactions Preparations, dosage, and administration Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 15 Other Muscarinic Agonists Pilocarpine Acetylcholine Glaucoma Miosis Muscarine Present in poisonous mushrooms Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 16 Overactive Bladder 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 17 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 18 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 19 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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 20 Muscarinic Antagonists (Anticholinergic Drugs) Atropine Best known muscarinic antagonist Found in nature Mechanism of action • No direct effect of its own • Muscarinic receptor blockade Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 21 Muscarinic Antagonists (Anticholinergic Drugs) Atropine Pharmacologic effects (receptor blockade) • Heart • Exocrine glands • Smooth muscle • Eye • CNS • Dose dependency of muscarinic blockade • Pharmacokinetics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 22 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 23 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 24 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 25 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 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 26 Anticholinergic Drugs for Overactive Bladder Specific anticholinergic drugs for OAB (cont’d) Darifenacin Solifenacin Tolterodine • Immediate-release tablets • Extended-release capsules Trospium Fesoterodine Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 27 Other Muscarinic Antagonists Scopolamine Ipratropium bromide Antisecretory anticholinergics Dicyclomine Pirenzepine and telenzepine Mydriatic-cycloplegics Centrally acting anticholinergics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 28 Toxicology of Muscarinic Agonists Source of muscarinic poisoning Symptoms Direct-acting muscarinic agonists Cholinesterase inhibitors Result from excessive activation of muscarinic receptors Treatment Muscarinic blocking agent, such as atropine Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 29 Toxicology of Muscarinic Antagonists Sources of antimuscarinic poisoning Natural products Selective antimuscarinic drugs Drugs with pronounced antimuscarinic properties Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 30 Toxicology of Muscarinic Antagonists Symptoms Dry mouth Blurred vision Photophobia Hyperthermia CNS effects Hot, dry, and flushed skin Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 31 Toxicology of Muscarinic Antagonists Treatment Physostigmine Inhibitor of acetylcholinesterase Warning Differentiate between poisoning and an actual psychotic episode! Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 32