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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 7 Anticholinergic (Parasympatholytic) Bronchodilators
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Clinical Indications for Use Indication for anticholinergic bronchodilator COPD maintenance Indication for combined anticholinergic and β-agonist bronchodilators COPD + airflow obstruction Anticholinergic nasal spray Allergic and nonallergic perennial rhinitis + common cold
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Specific Anticholinergic (Parasympatholytic) Agents Atropine sulfate Not recommended for inhalation Ipratropium bromide Available as MDI, nasal spray, and SVN solution Quaternary ammonium derivative of atropine Distribution limited to lung when inhaled
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Specific Anticholinergic (Parasympatholytic) Agents Ipratropium + albuterol Synergistic effect in COPD Glycopyrrolate Used parenterally to reverse neuromuscular blockade Not approved for inhalation Tiotropium bromide Longer-acting (up to 24 hours) quaternary ammonium derivative of atropine
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Clinical Pharmacology Structure-activity relations Atropine and scopolamine Tertiary ammonium compounds Tertiary ammonium compounds Easily absorbed in bloodstream Easily absorbed in bloodstream Quaternary forms poorly absorbed in bloodstream (better for inhalation)
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Pharmacological Effects Anticholinergic (antimuscarinic) agents Tertiary ammonium compounds Respiratory tract Respiratory tract CNS CNS Eyes Eyes Cardiac Cardiac Gastrointestinal Gastrointestinal Genitourinary Genitourinary
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Pharmacological Effects Quaternary ammonium compounds Respiratory tract Respiratory tract CNS CNS Eyes Eyes Cardiac Cardiac Gastrointestinal Gastrointestinal Genitourinary Genitourinary
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Mode of Action Parasympathetic innervation causes basal level bronchomotor tone Parasympatholytic bronchodilators block this tone Degree of bronchodilation depends on amount of parasympathetic tone present
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Mode of Action Vagally mediated reflex bronchoconstriction Irritant aerosols, cold air, high flows, smoke, fumes, histamine release Afferent impulse to CNS = reflex cholinergic efferent impulse = bronchospasm + cough + mucus Can be blocked by competitive inhibitors of acetylcholine
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Receptor Subtypes Muscarinic M 1 Parasympathetic ganglia Parasympathetic ganglia Facilitate neurotransmission and bronchoconstriction Facilitate neurotransmission and bronchoconstriction Cause secretion and rhinitis in nose Cause secretion and rhinitis in nose M 2 Inhibit continued use of acetylcholine Inhibit continued use of acetylcholine Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for M 1 and M 3 ) Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for M 1 and M 3 ) M 3 Smooth airway muscle Smooth airway muscle Cause bronchoconstriction Cause bronchoconstriction Cause secretion and rhinitis in nose Cause secretion and rhinitis in nose
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Adverse Effects Changes in BP, EKG, or HR not usually seen No worsening of ventilation-perfusion abnormalities No tolerance/loss of protection Side effects: Dry mouth (most common) Mydriasis (eyes should be protected) SVN: also pharyngitis, dyspnea, flulike symptoms, bronchitis, upper respiratory infection
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Clinical Application Use in COPD More potent bronchodilators than β adrenergics in emphysema/bronchitis FDA approved specifically for COPD Tiotropium maintains higher PFT levels than ipratropium
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Clinical Application Use in asthma No label indication for asthma in United States Antimuscarinics not clearly superior to β agonists in asthma May be useful in: Nocturnal asthma Nocturnal asthma Psychogenic asthma Psychogenic asthma Asthmatics being treated for another condition with β blockers Asthmatics being treated for another condition with β blockers As an alternative to theophylline As an alternative to theophylline In acute/severe episodes not responding to β agonist In acute/severe episodes not responding to β agonist
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Combination Therapy β-Adrenergic and anticholinergic agents in COPD Additive effect of β agonists and anticholinergics Additive effect of β agonists and anticholinergics Mean peak increases: –31 to 33% for combined drugs –24 to 25% for ipratropium alone –24 to 27% for albuterol alone
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Administration Sequence of administration No data to support either drug being administered first No data to support either drug being administered first Not an issue when using Combivent Not an issue when using Combivent β Agonist may be given first because β Agonist may be given first because More rapid onset Distributed in large and small airways
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Respiratory Care Assessment Anticholinergic bronchodilator therapy Assess effectiveness based on indication for use Monitor flow rates Perform respiratory assessment Breath sounds, auscultation, respiratory rate (pre- and posttreatment) Assess pulse Subjective reaction
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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Respiratory Care Assessment Anticholinergic bronchodilator therapy (continued) Arterial blood gases/SpO 2 Long term: PFTs Instruct/verify correct use of delivery device For long-acting drugs: Ongoing lung function over time Ongoing lung function over time Concomitant β-agonist use/nocturnal symptoms Concomitant β-agonist use/nocturnal symptoms Exacerbations/hospitalizations Exacerbations/hospitalizations Absences from work/school Absences from work/school
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