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Clinical Indications for UseClinical Indications for Use
Indication for anticholinergic bronchodilatorIndication for anticholinergic bronchodilator COPD maintenanceCOPD maintenance
Indication for combined anticholinergic and Indication for combined anticholinergic and
β-agonist bronchodilatorsβ-agonist bronchodilators COPD with airflow obstructionCOPD with airflow obstruction
Anticholinergic nasal sprayAnticholinergic nasal spray Allergic and nonallergic perennial rhinitis and the Allergic and nonallergic perennial rhinitis and the
Specific Anticholinergic Specific Anticholinergic (Parasympatholytic) Agents(Parasympatholytic) Agents
Atropine sulfateAtropine sulfate Not recommended for inhalationNot recommended for inhalation
Ipratropium bromideIpratropium bromide Available as MDI, SVN solution, and nasal sprayAvailable as MDI, SVN solution, and nasal spray Quaternary ammonium derivative of atropineQuaternary ammonium derivative of atropine Distribution is limited to lung when inhaledDistribution is limited to lung when inhaled
Parasympatholytic bronchodilators block this Parasympatholytic bronchodilators block this tone.tone.
Degree of bronchodilation depends on the Degree of bronchodilation depends on the amount of parasympathetic tone present.amount of parasympathetic tone present.
Figure 7-2 Figure 7-2 Conceptual overview of the action of anticholinergic (parasympatholytic) Conceptual overview of the action of anticholinergic (parasympatholytic) bronchodilating agents in preventing cholinergic-induced bronchoconstriction. bronchodilating agents in preventing cholinergic-induced bronchoconstriction. Ach,Ach, Acetylcholine.Acetylcholine.
Figure 7-3 Figure 7-3 Mechanism of vagally mediated reflex bronchoconstriction induced Mechanism of vagally mediated reflex bronchoconstriction induced by nonspecific stimuli on sensory C-fibers. by nonspecific stimuli on sensory C-fibers. Ach,Ach, Acetylcholine; Acetylcholine; CNS,CNS, central central nervous system; nervous system; SP,SP, substance P. substance P.
• Facilitate neurotransmission and bronchoconstrictionFacilitate neurotransmission and bronchoconstriction
• Cause secretion and rhinitis in the noseCause secretion and rhinitis in the nose MM22
• Inhibit continued use of acetylcholineInhibit continued use of acetylcholine
• Blockade may enhance acetylcholine release, counteracting Blockade may enhance acetylcholine release, counteracting bronchodilation (tiotropium is selective for Mbronchodilation (tiotropium is selective for M11 and M and M33))
MM33
• Smooth airway muscle and submucosal glandsSmooth airway muscle and submucosal glands
• Cause bronchoconstrictionCause bronchoconstriction
• Cause secretion and rhinitis in the noseCause secretion and rhinitis in the nose
Figure 7-4 Figure 7-4 Identification and location of muscarinic receptor subtypes MIdentification and location of muscarinic receptor subtypes M11, M, M
22, and M, and M33 in the in the
vagal nerve, submucosal gland, and bronchial smooth muscle in the airway, showing vagal nerve, submucosal gland, and bronchial smooth muscle in the airway, showing nonspecific blockade by anticholinergic drugs such as ipratropium. nonspecific blockade by anticholinergic drugs such as ipratropium. Ach,Ach, Acetylcholine. Acetylcholine.
Changes in BP, EKG, or HR not usually seenChanges in BP, EKG, or HR not usually seen No worsening of ventilation-perfusion No worsening of ventilation-perfusion
abnormalitiesabnormalities No tolerance/loss of protectionNo tolerance/loss of protection Side effects:Side effects:
Dry mouth (most common)Dry mouth (most common) CoughCough Mydriasis (eyes should be protected)Mydriasis (eyes should be protected) SVN: also pharyngitis, dyspnea, flulike symptoms, SVN: also pharyngitis, dyspnea, flulike symptoms,
Use in COPDUse in COPD More potent bronchodilators than β-adrenergics in More potent bronchodilators than β-adrenergics in
emphysema/bronchitisemphysema/bronchitis FDA approved specifically for COPDFDA approved specifically for COPD Tiotropium maintains higher PFT levels than Tiotropium maintains higher PFT levels than
Figure 7-6 Figure 7-6 Effect of the Effect of the ββ agonist metaproterenol and the anticholinergic ipratropium on forced agonist metaproterenol and the anticholinergic ipratropium on forced expiratory volume in 1 second expiratory volume in 1 second (FEV(FEV
11) in patients with chronic obstructive pulmonary disease ) in patients with chronic obstructive pulmonary disease
(COPD) after 90 days of treatment (*(COPD) after 90 days of treatment (*PP less than 0.01; less than 0.01; ††PP less than 0.05). (From Tashkin DP, less than 0.05). (From Tashkin DP, Ashutosh K, Bleecker ER, et al: Comparison of the anticholinergic bronchodilator ipratropium Ashutosh K, Bleecker ER, et al: Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease: a 90-day multi-center bromide with metaproterenol in chronic obstructive pulmonary disease: a 90-day multi-center study, study, Am J Med Am J Med 81(suppl 5A):59, 1986. From Excerpta Medica, Inc.)81(suppl 5A):59, 1986. From Excerpta Medica, Inc.)
Use in asthmaUse in asthma No label indication for asthma in the United StatesNo label indication for asthma in the United States Antimuscarinics not clearly superior to β-agonists for Antimuscarinics not clearly superior to β-agonists for
asthmaasthma May be useful in:May be useful in:
• Nocturnal asthmaNocturnal asthma
• Psychogenic asthmaPsychogenic asthma
• Asthmatics being treated for another condition with β-blockersAsthmatics being treated for another condition with β-blockers
• An alternative to theophyllineAn alternative to theophylline
• In acute/severe episodes not responding to β-agonistIn acute/severe episodes not responding to β-agonist
β-Adrenergic and anticholinergic agents in β-Adrenergic and anticholinergic agents in COPDCOPD Complementarily sites of action Complementarily sites of action Mechanisms of action: separate and Mechanisms of action: separate and
complementarycomplementary• Additive effect of β-agonists and anticholinergicsAdditive effect of β-agonists and anticholinergics
Mean peak increases:Mean peak increases:– 31 to 33% for combined drugs31 to 33% for combined drugs– 24 to 25% for ipratropium alone24 to 25% for ipratropium alone– 24 to 27% for albuterol alone24 to 27% for albuterol alone
Sequence of administrationSequence of administration No data to support either drug being No data to support either drug being
administered firstadministered first Not an issue when using CombiventNot an issue when using Combivent β-Agonist may be given first becauseβ-Agonist may be given first because
• More rapid onsetMore rapid onset
• Distributed in large and small airwaysDistributed in large and small airways
Respiratory Care AssessmentRespiratory Care Assessment
Anticholinergic bronchodilator therapyAnticholinergic bronchodilator therapy Assess effectiveness based on indication for use Assess effectiveness based on indication for use Monitor flow ratesMonitor flow rates Perform respiratory assessmentPerform respiratory assessment Breath sounds, auscultation, respiratory rate Breath sounds, auscultation, respiratory rate
(pre- and posttreatment)(pre- and posttreatment) Assess pulseAssess pulse Subjective reactionSubjective reaction
Long term: PFTsLong term: PFTs Instruct/verify correct use of delivery deviceInstruct/verify correct use of delivery device For long-acting drugs:For long-acting drugs:
• Ongoing lung function over time Ongoing lung function over time