Rau Ch. 7 Anticholinergic Bronchodilators PDF

Chapter 7 ANTICHOLINERGIC (PARASYMPATHOLYTIC) BRONCHODILATORS Copyright © 2016, Elsevier Inc. All rights reserved. 1  LETS REVIEW THE PARASYMPATHOLYTIC RESPONSE Anticholinergic bronchodilators are specifically parasympatholytic, that is, antimuscarinic, agent...

Chapter 7 ANTICHOLINERGIC (PARASYMPATHOLYTIC) BRONCHODILATORS Copyright © 2016, Elsevier Inc. All rights reserved. 1  LETS REVIEW THE PARASYMPATHOLYTIC RESPONSE Anticholinergic bronchodilators are specifically parasympatholytic, that is, antimuscarinic, agents, blocking the effect of acetylcholine at the cholinergic (muscarinic) receptors on bronchial smooth muscle 2 Copyright © 2016, Elsevier Inc. All rights reserved. 2 CLINICAL INDICATIONS Indication for anticholinergic bronchodilator FOR USE COPD maintenance Ipratropium bromide may be used in some individuals with asthma Indication for combined anticholinergic and β-agonist bronchodilators COPD with airflow obstruction Also used in cases of severe asthma not responsive to β-agonist therapy Anticholinergic nasal spray Allergic and nonallergic perennial rhinitis and the common cold Copyright © 2016, Elsevier Inc. All rights reserved. 3  INHALED ANTICHOLINERGIC BRONCHODILATOR Ipratropium bromide AGENTS Atrovent Ipratropium bromide and albuterol Combivent, Duoneb, Combivent Respimat Aclidinium bromide Tudorza Pressair Tiotropium bromide Spiriva Umeclidinium bromide Incruse Ellipta Umeclidinium bromide and vilanterol Anoro Ellipta Copyright © 2016, Elsevier Inc. All rights reserved. 4  IPRATROPIUM BROMIDE (ATROVENT HFA) Available as: MDI: 17 μg/puff, 2 puffs qid SVN solution: 0.2% solution (0.5 mg) qid Nasal spray (rhinopathies and rhinorrhea) Approved for the maintenance treatment of airflow obstruction in COPD Quaternary ammonium derivative of atropine Distribution is limited to lung when inhaled Does not distribute well across lipid membranes Copyright © 2016, Elsevier Inc. All rights reserved. 5  IPRATROPIUM AND ALBUTEROL (COMBIVENT HFA, DUONEB, COMBIVENT RESPIMAT) Available as: Combivent: 18 μg ipratropium and 90 μg albuterol/puff, 2 puffs qid Duoneb: 0.5 mg ipratropium and 2.5 mg albuterol Combivent Respimat: 20 μg ipratropium and 100 μg albuterol/puff, qid Combination therapy more effective in stable COPD than either agent alone Copyright © 2016, Elsevier Inc. All rights reserved. 6 ONCE-DAILY ANTICHOLINERGIC BRONCHODILATORS Tiotropium bromide (Spiriva) M1 and M3 selectivity DPI: 18 μg/inhalation, once daily Umeclidinium bromide (Incruse Ellipta) DPI: 62.5 μg/inhalation, once daily Umeclidinium bromide and vilanterol (Anoro Ellipta) DPI: 62.5 μg umeclidinium and 25 μg vilanterol/puff, once daily Copyright © 2016, Elsevier Inc. All rights reserved. 7  ACLIDINIUM BROMIDE (TUDORZA PRESSAIR) Approved for the maintenance treatment in COPD Available as: DPI: 400 μg/inhalation, 1 inhalation bid Potent antagonist for all muscarinic receptors Very low and transient systemic exposure Reduced potential for side effects Copyright © 2016, Elsevier Inc. All rights reserved. 8  PHARMACOLOGICAL EFFECTS Anticholinergic (antimuscarinic) agents Tertiary ammonium compound effects Respiratory tract Central nervous system Eyes Cardiac Gastrointestinal Genitourinary Copyright © 2016, Elsevier Inc. All rights reserved. 9 PHARMACOLOGICAL EFFECTS (CONT.) Quaternary ammonium compound effects when inhaled Respiratory tract – bronchodilation Central nervous system – no effect Eyes – Pupillary dilation and lens paralysis Cardiac – no effect (Basically) Gastrointestinal – dry mouth Genitourinary – usually no effect Side effects are localized to the site of drug exposure Copyright © 2016, Elsevier Inc. All rights reserved. 10  MODE OF ACTION Parasympathetic innervation causes increase basal level bronchomotor tone Parasympatholytic bronchodilators block this tone Degree of bronchodilation depends on the amount of parasympathetic tone present Copyright © 2016, Elsevier Inc. All rights reserved. 11 ANTICHOLINERGIC AGENT Figure 7-2 Conceptual overview of the action of anticholinergic (parasympatholytic) bronchodilating agents in preventing cholinergic-induced bronchoconstriction. Ach, Acetylcholine. Copyright © 2016, Elsevier Inc. All rights reserved. 12  VAGALLY MEDIATED REFLEX BRONCOCONSTICTION Irritant aerosols, cold air, high airflow rates, smoke, fumes, histamine release Afferent impulse to CNS → reflex cholinergic efferent impulse → constriction of airway smooth muscle → mucus and cough Can be blocked by competitive inhibitors of acetylcholine Copyright © 2016, Elsevier Inc. All rights reserved. 13 MECHANISM OF ACTION Figure 7-3 Mechanism of vagally mediated reflex bronchoconstriction induced by nonspecific stimuli on sensory C-fibers. Ach, Acetylcholine; CNS, central nervous system; SP, substance P. Copyright © 2016, Elsevier Inc. All rights reserved. 14  RECEPTOR SUBTYPES Muscarinic M1 Parasympathetic ganglia Facilitate neurotransmission and bronchoconstriction Cause secretion and rhinitis in the nose – (GUT) M2 Inhibit continued use of acetylcholine Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for M1 and M3) M3 Smooth airway muscle and submucosal glands Cause bronchoconstriction Cause secretion and rhinitis in the nose Copyright © 2016, Elsevier Inc. All rights reserved. 15 MUSCARINIC RECEPTORS Figure 7-4 Identification and location of muscarinic receptor subtypes M1, M2, and M3 in the vagal nerve, submucosal gland, and bronchial smooth muscle in the airway, showing nonspecific blockade by anticholinergic drugs such as ipratropium. Ach, Acetylcholine. Copyright © 2016, Elsevier Inc. All rights reserved. 16  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) Cough Mydriasis (eyes should be protected) SVN: also pharyngitis, dyspnea, flulike symptoms, bronchitis, upper respiratory infection Copyright © 2016, Elsevier Inc. All rights reserved. 17  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 Copyright © 2016, Elsevier Inc. All rights reserved. 18  CLINICAL APPLICATION Use in asthma No label indication for asthma in the United States Antimuscarinics not clearly superior to β-agonists for asthma May be useful in: Nocturnal asthma Psychogenic asthma Asthmatics being treated for another condition with β-blockers An alternative to theophylline Acute/severe episodes not responding to β-agonist Copyright © 2016, Elsevier Inc. All rights reserved. 19  COMBINATION THERAPY β-Adrenergic and anticholinergic agents in COPD Complementary sites of action Mechanisms of action: separate and complementary 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 Copyright © 2016, Elsevier Inc. All rights reserved. 20  ADMINISTRATION  Sequence of administration No data to support either drug being administered first Not an issue when using Combivent β-Agonist may be given first because: More rapid onset Distributed in large and small airways Copyright © 2016, Elsevier Inc. All rights reserved. 21  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 Copyright © 2016, Elsevier Inc. All rights reserved. 22  RESPIRATORY CARE ASSESSMENT (CONT.) Anticholinergic bronchodilator therapy (Cont.) Arterial blood gases/SpO2 Long term: PFTs Instruct/verify correct use of delivery device For long-acting drugs: Ongoing lung function over time Concomitant β-agonist use/nocturnal symptoms Exacerbations/hospitalizations Absences from work/school Copyright © 2016, Elsevier Inc. All rights reserved. 23