Atrovent

Pronunciation

Generic Name: Ipratropium Bromide
Class: Antimuscarinics/Antispasmodics
Molecular Formula: C20H30BrNO3•H2O
CAS Number: 66985-17- 9

Introduction

Bronchodilator; a nonselective, competitive antagonist at muscarinic receptors.2 224 225 232

Uses for Atrovent

Bronchospasm in COPD

Long-term treatment of reversible bronchospasm associated with COPD,1 2 4 58 76 114 115 118 120 121 122 123 124 127 128 130 228 230 244 245 253 254 255 256 257 258 259 260 261 262 263 267 278 281 285 292 293 294 including chronic bronchitis1 2 4 36 55 61 76 90 116 117 119 120 121 124 125 129 131 281 and emphysema.1 2 4 90 91 119 120 125 281 343 344 345 347

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Fixed combination with albuterol sulfate is used for the symptomatic management of bronchospasm associated with COPD in patients who continue to have evidence of bronchospasm despite the regular use of an orally inhaled bronchodilator and who require a second bronchodilator.320 347

Bronchospasm in Asthma

Has been used for symptomatic treatment of acute or chronic bronchial asthma;36 55 56 76 91 92 115 124 125 129 153 161 162 164 180 181 211 225 228 268 302 303 331 336 337 β2-adrenergic agonist bronchodilators generally preferred initially for relief of bronchospasm in asthmatic patients.161 164 225 257 268 302 303 331 337

May be useful as alternative therapy in adults experiencing adverse effects (e.g., tachycardia, arrhythmia, tremor) with a β-adrenergic agonist.331 336 337

Some clinicians consider ipratropium as adjunctive therapy in patients with moderate or severe exacerbations (peak expiratory flow rate ≤80% of predicted) of asthma who fail to respond adequately to β-adrenergic agonists and corticosteroids.331 337

May be useful for prevention or reversal of bronchospasm induced by β-adrenergic blocking agents (e.g., propranolol) in asthmatic patients; β-adrenergic bronchodilators generally ineffective for this indication in such patients.31 191 194 225 268

Atrovent Dosage and Administration

Administration

Administer by oral inhalation using an oral aerosol inhaler1 10 320 or via nebulization.4 281 329

Oral Inhalation via Metered-dose Aerosol

Ipratropium Bromide

Aerosol delivers ≥200 metered sprays per canister.1

Patient should be instructed to clear excessive sputum from chest before inhalation.10

Shake well immediately prior to use.1 10 320 Actuate aerosol inhaler 3 times prior to the initial use or if it has not been used for >24 hours.1

Do not use mouthpiece for other aerosol drugs.1

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed around it.10 348 To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.1 10 348 Inhale slowly and deeply through the mouth while actuating the inhaler.1 10 Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.1 10

Allow ≥15 seconds to elapse between subsequent inhalations from the aerosol inhaler.10 348

Wash the mouthpiece in hot running water as needed.10 348 If soap is used, rinse mouthpiece thoroughly with plain water.10 348

Ipratropium Bromide and Albuterol Sulfate

Aerosol delivers ≥200 metered sprays per canister.346

Shake well immediately prior to use.346 Actuate 3 times prior to the initial use or if it has not been used for >24 hours.346 Do not use actuator provided for other aerosol drugs.346 To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.346

Exhale deeply and place mouthpiece of the inhaler into the mouth.346 Inhale slowly and deeply through the mouth while actuating the inhaler.346 Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.346 Allow approximately 2 minutes to elapse and repeat the procedure.346 Rinse the mouthpiece in hot water as needed.346 If soap is used, rinse the mouthpiece thoroughly with plain water.346 When dry, replace the cap on the mouthpiece when the inhaler is not in use.346

Oral Inhalation via Nebulization

Ipratropium Bromide

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.4 328 350

Use care when a face mask is used to avoid leakage since transient blurred vision and other adverse effects may result if the drug enters the eyes.2 225 250 275 328 350 (See Ocular Effects under Cautions.) Use of a mouthpiece may avoid inadvertent entry of drug into the eye.4

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.4 15 328 Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.4 328

Duration of treatment usually is about 5–15 minutes.4 328

Ipratropium Bromide and Albuterol Sulfate

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.328

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.328 Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.328

Duration of treatment usually is about 5–15 minutes.328

Clean the nebulizer after use according to the manufacturer’s instructions.328

Dosage

Available as ipratropium bromide.

Dosage of oral inhalation aerosol expressed in terms of the monohydrate.1 320

Dosage of inhalation solution for nebulization expressed in terms of anhydrous drug.4 329 330

Using in vitro testing at an average flow rate of 3.6 L per minute for an average of ≤15 minutes, the Pari-LC Plus nebulizer delivered at the mouthpiece approximately 46 or 42% of the original dosage of albuterol or ipratropium bromide, respectively.327

Pediatric Patients

COPD
Inhalation

Patients ≥12 years of age: 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg via the mouthpiece).1 2 320 Additional inhalations should not exceed 216 mcg (12 inhalations) of ipratropium bromide in 24 hours.1 320

Patients ≥12 years of age: 500 mcg (contents of 1 unit-dose vial) 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.4 329

Adults

COPD
Inhalation

Initially, 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg from the mouthpiece).1 2 320 Additional inhalations should not exceed 216 mcg (12 inhalations) in 24 hours.1 320

Initially, 500 mcg 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.4 329 With ipratropium bromide in fixed combination with albuterol sulfate (DuoNeb), 500 mcg 4 times daily.327 Additional inhalations should not exceed 6 inhalations daily.327

Prescribing Limits

Pediatric Patients

COPD
Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours.1 320

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.320

500 mcg 3–4 times daily via a nebulizer in patients ≥12 years of age.4 329

Adults

COPD
Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours;1 320 frequency of administration should not exceed 4 times daily.1 267 323

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.320

500 mcg 3–4 times daily via a nebulizer.4 329

Special Populations

Geriatric Patients

Dosage adjustments based solely on age are not necessary.1 4

Cautions for Atrovent

Contraindications

  • Known hypersensitivity to the drug or any other component of the formulation, or to atropine or its derivatives.1 4 329

  • Known hypersensitivity to soya lecithin or related food products, including soybeans and peanuts.1 277 320

Warnings/Precautions

Warnings

Acute Bronchospasm

Delayed onset of action; not indicated for initial treatment.1 4 Generally should not be used alone for the management of acute bronchospasm, when a rapid response is required.1 4 164 225

Sensitivity Reactions

Immediate hypersensitivity reactions, including rash, angioedema of the tongue, lips, and face, urticaria, bronchospasm, oropharyngeal edema, and anaphylactic reaction.1 4 196 213 277 285 320 329

Possible paradoxical bronchospasm.1 4 190 191 196 270 271 272 273 320

General Precautions

Worsening COPD

Contact a clinician immediately if a previously effective dosage regimen fails to provide the usual relief (e.g., need to increase the dose or frequency of administration of the drug).1 Do not increase the dose or frequency of inhalation without consultation with a clinician.1

Ocular Effects

Possible temporary blurred vision,1 2 4 10 328 349 mydriasis,1 225 250 275 ocular pain,4 328 329 349 conjunctival or corneal congestion associated with visual halos or colored images,1 or precipitation or worsening of angle-closure glaucoma4 173 329 337 349 following inadvertent contact of ipratropium with the eyes.4 190 191 328 349

Minimize ocular exposure by using a mouthpiece rather than a face mask during administration via a nebulizer.4 190 191 329 During oral inhalation of aerosol, close eyes.1 2 Inhalation aerosol should not be administered using the open-mouth technique in these patients with angle-closure glaucoma.173 190 191 Use with caution in patients with angle-closure glaucoma.1 4

Genitourinary Effects

Possible urinary retention/difficulty,1 4 251 252 320 329 urinary tract infection,4 320 329 or dysuria.4 320

Use with caution in patients with bladder neck obstruction or prostatic hypertrophy.1 4 190 191 225 329

Cardiovascular Effects

Possible adverse cardiovascular effects (e.g., tachycardia, palpitations, aggravated hypotension or hypertension).1 4 329

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.1

Lactation

Use with caution.1 2 4 329

Pediatric Use

Safety and efficacy of oral inhalation not established in children <12 years of age.1 4 320 329

Hepatic Impairment

Use with caution.4 329

Renal Impairment

Use with caution.4 329

Common Adverse Effects

Bronchitis, upper respiratory tract infection,320 cough,1 2 4 87 120 285 and dryness of the mouth,1 2 14 16 60 90 120 127 throat,1 75 90 or tongue87 with ipratropium aerosol. Adverse effects resulting in discontinuance of nebulized ipratropium most frequently include bronchitis, dyspnea, and bronchospasm.4 329

Interactions for Atrovent

Limited systemic absorption following oral inhalation; interactions with systemically administered drugs unlikely.2 190 191

Specific Drugs

Drug

Interaction

Comments

Antimuscarinic agents

Potential pharmacodynamic interaction (additive effects)1 320

Caution advised with concomitant administration1

Methylxanthine derivatives

No adverse drug interactions reported115 120 121 132 157 158 149 187 220 261 305 329

β-Adrenergic agonists

Potential pharmacodynamic interaction (additive effects)4 6 133 147 152 155 225 228 246 248 260 262 278 279 285 287 288 289

If concomitant therapy is required, consider cautious use of cardioselective β-adrenergic blocking agents115 132 139 146 153 154 181 216

Corticosteroids

No adverse drug interactions reported91 115 119 120 121 124 132 153 154 160 329

Cromolyn sodium

No adverse drug interactions reported132 159

Atrovent Pharmacokinetics

Absorption

Bioavailability

Only minimally absorbed into systemic circulation following oral inhalation.1 2 4 6 14 106 228 229 230

Onset

Bronchodilation evident within 15 minutes following oral aerosol inhalation1 2 111 120 230 and within 15–30 minutes following oral inhalation via nebulization.4 86 281

Duration

Bronchodilation generally persists for 3–4 hours following oral aerosol inhalation1 2 111 120 230 and for 4–5 hours following nebulization.4 86 281

Distribution

Extent

Does not readily penetrate the CNS.2 4 12 It is not known whether the drug crosses the placenta or is distributed into milk.1 4 6

Plasma Protein Binding

0–9%.1 4

Elimination

Metabolism

Metabolized partially to at least 8 metabolites.4 8 106

Elimination Route

Excreted principally in feces as unchanged drug.2 3 6 7 107 109 Following oral inhalation of radiolabeled ipratropium bromide, about 69 and 3.2% of the dose was excreted in feces and urine, respectively, within 6–7 days.6 106 109 Undergoes some biliary elimination.6 7

Half-life

1.6 hours (t½β with IV administration).4 190 229

Stability

Storage

Oral Inhalation

15–30 °C (metered-dose inhalers or inhalation solution of ipratropium bromide).1 3 4 281 320

2–25°C (oral inhalation solution of ipratropium bromide in fixed combination with albuterol sulfate); protect from light.327 328

Actions

  • A nonselective competitive antagonist at muscarinic receptors present in airways and other organs.2 224 225 232

  • Relaxes smooth muscles of bronchi and bronchioles.1 2 4 6

  • Blocks acetylcholine-induced stimulation of guanyl cyclase and reduces formation of cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction.1 2 4 6

  • Exhibits greater antimuscarinic activity on bronchial smooth muscle than on secretory (e.g., salivary, gastric) glands.6 7 12 16 18 34 225

  • Tolerance to bronchodilating effect does not develop with prolonged use.4 14 90 91 92 115 116 117 118 119 120 121 168 225 278

Advice to Patients

  • Importance of providing patients with a copy of the manufacturer’s patient information.1 4

  • Importance of using proper administration technique.1 4

  • Importance of advising patients that oral inhalation is not intended for occasional use.1 4 Use consistently throughout the course of therapy for maximum effectiveness.1 4

  • Importance of contacting a clinician if symptoms of COPD are not relieved by usually effective doses or if they worsen.1 Do not increase the dosage or frequency of administration without consultation with a clinician.1

  • Importance of advising patients to close their eyes during oral inhalation of aerosol1 2 to avoid inadvertent contact of the drug with the eyes and subsequent adverse effects.1 10

  • Importance of contacting a clinician immediately if ocular symptoms develop.1

  • Importance of advising patients that blurring of vision, precipitation or aggravation of narrow angle glaucoma, mydriasis, visual halos, colored images in association with conjunctival or corneal congestion, or eye pain or discomfort may result from contact of the inhalation solution with the eyes.1

  • Importance of informing clinicians if ocular adverse effects develop.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.320

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ipratropium Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Aerosol

18 mcg/metered spray

Atrovent (with chlorofluorohydrocarbon propellants and soya lecithin)

Boehringer Ingelheim

Solution, for nebulization

0.02%*

Atrovent (preservative-free)

Boehringer Ingelheim

Ipratropium Bromide Inhalation Solution (preservative-free)

Alpharma, Dey, Holopack, Nephron, Novex, Roxane, RxElite, Teva, Warrick

Ipratropium Bromide Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation Only

Aerosol

18 mcg with Albuterol Sulfate 90 mcg (of albuterol) per metered spray

Combivent (with chlorofluorohydrocarbon propellants and soya lecithin)

Boehringer Ingelheim

Solution, for nebulization

0.5 mg with Albuterol Sulfate 2.5 mg (of albuterol) per 3 mL

DuoNeb

Dey

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Combivent 18-103MCG/ACT Aerosol (BOEHRINGER INGELHEIM): 15/$238.33 or 44/$679.95

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 90/$80.86 or 270/$228.18

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 180/$148.24 or 540/$424.54

Ipratropium Bromide 0.02% Solution (NEPHRON PHARMACEUTICALS CORP.): 63/$14.99 or 125/$19.97

Ipratropium-Albuterol 0.5-2.5 (3)MG/3ML Solution (MYLAN): 90/$39.99 or 270/$99.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 2002 Mar 27.

2. Boehringer Ingelheim. Atrovent product monograph. Ridgefield, CT; 1987 Feb.

3. Boehringer Ingelheim. Atrovent product information form for American Hospital Formulary Service. Ridgefield, CT; 1987 Feb.

4. Boehringer Ingelheim. Atrovent (ipratropium bromide) 0.02% inhalation solution prescribing information. Ridgefield, CT; 1998 Oct.

5. Budavari S, O’Neil MJ, Smith A et al, eds. The Merck index. 11th ed. Rahway, NJ: Merck & Co., Inc; 1989:4956-7.

6. Pakes GE, Brogden RN, Heel RC et al. Ipratropium bromide: a review of its pharmacological properties and therapeutic efficacy in asthma and chronic bronchitis. Drugs. 1980; 20:237-66. [IDIS 124386] [PubMed 6448137]

7. Bauer R, Banholzer R, Grieben C et al. Ipratropium bromide. In: Goldberg ME, ed. Pharmacological and biochemical properties of drug substances. 1979; 2:489-515.

8. Deckers W. The chemistry of new derivatives of tropane alkaloids and the pharmacokinetics of a new quaternary compound. Postgrad Med J. 1975; 51(Suppl 7):76-81. [PubMed 134360]

9. Winthrop-Breon. How to correctly use your Tornalate (bitolterol meyslate) metered dose inhaler. New York; 1985 Jan.

10. Boehringer Ingelheim. Questions and answers about Atrovent (ipratropium bromide) inhalation aerosol 18 mcg per puff. Ridgefield, CT; 1987 Mar.

11. Brown JH. Atropine, scopolamine, and related antimuscarinic drugs. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:159-60.

12. Englehardt A. Pharmacology and toxicology of Atrovent. Scand J Respir Dis. 1979; 103(Suppl):110-5.

13. Bauer R, Kuhn FJ, Stockhaus K et al. Allgemeine Pharmakologie und seckretionshemmende Wirkung von (8r)-3α-Hydroxy-8-isopropyl- 1αH,5αH-tropaniumbromid-()tropat (Ipratropiumbromid). (German; with English abstract.) Arzneim-Forsch. 1976; 26:974-80.

14. Gross NJ, Skorodin MS. Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis. 1984; 129:856-70. [IDIS 185268] [PubMed 6372560]

15. Genentech, Inc. Patient information booklet: your guide to Pulmozyme (dornase alfa) therapy for cystic fibrosis (CF). South San Francisco, CA; 1994.

16. Bleichert A. Zur Frage der Nebenwirkungen anticholinerger Drogen in Abhängigkeit von der Applikationsart: inhalation versus intravenöse Injektion von Ipratropiumbromid. (German; with English abstract.) Arzneim-Forsch. 1976; 26:1010-3.

17. Otto P. Untersuchungen über die Hemmung der Magensaftsekretion beim Menschen durch den Atropinabkömmling N-Isopropyl-nortropintropasäureester-brommethylat. (German; with English abstract.) Arzneim-Forsch. 1973; 23:1334-6.

18. Bauer R, Püschmann S, Wick H et al. Wirkung von (8r)-3α-Hydroxy-8-isopropyl-1αH,5αH-tropaniumbromid-()- tropat (Ipratropiumbromid) auf Spasmen des Tracheobronchialbaumes und die Bronchialsekretion, die Speichelsekretion, EKG und Herzfrequenz. (German; with English abstract.) Arzneim-Forsch. 1976; 26:981-5.

19. Morris HG. Review of ipratropium bromide in induced bronchospasm in patients with asthma. Am J Med. 1986; 81(Suppl 5A):36-44. [IDIS 228924] [PubMed 2947459]

20. Cockcroft DW, Ruffin RE, Hargreave FE. Effect of Sch1000 in allergen-induced asthma. Clin Allergy. 1978; 8:361-72. [PubMed 152170]

21. Bandouvakis J, Cartier A, Roberts R et al. The effect of ipratropium and fenoterol on methacholine- and histamine-induced bronchoconstriction. Br J Dis Chest. 1981; 75:295-305. [PubMed 6457620]

22. Woenne R, Kattan M, Orange RP et al. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. J Allergy Clin Immunol. 1978; 62:119-24. [IDIS 115343] [PubMed 149804]

23. Giulekas D, Tsakalos N, Georgopoulos D et al. Effect of ipratropium bromide on repeated methacholine challenges. Ann Allergy. 1985; 55:835-9. [IDIS 209734] [PubMed 2934009]

24. Larsson K. Ipratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction. J Asthma. 1987; 24:29-35. [PubMed 2975285]

25. de Vries K. The protective effect of inhaled Sch 1000 MDI on bronchoconstriction induced by serotonin, histamine, acetylcholine and propranolol. Postgrad Med J. 1975; 51(Suppl 7):106.

26. Nolte D. The action of Sch 1000 MDI on experimental bronchoconstriction induced by various types of nonspecific and pharmacodynamic irritants in young asthmatics. Postgrad Med J. 1975; 51(Suppl 7):103.

27. Beumer HM. The antagonistic effect of several doses of inhaled Sch 1000 administered by metered dose inhaler (MDI) on a Bird respirator on acetylcholine-induced bronchospasm. Postgrad Med J. 1975; 51(Suppl 7):101-2.

28. Harnett J, Spector SL. Blocking effect of SCH 1000, isoproterenol, and the combination on methacholine and histamine inhalations. J Allergy Clin Immunol. 1976; 57:261.

29. Kersten W. The role of Sch 1000 MDI in preventing a rise in total airways resistance (Rt) induced by inhaled allergen in patients with atopic asthma. Postgrad Med J. 1975; 51(Suppl 7):103.

30. Killian D, Mellon A, Hargreave FE. Protective effect of drugs on histamine-induced asthma. J Allergy Clin Immunol. 1976; 57:263.

31. Germouty J. The possible antagonism between Sch 1000 MDI and beta-blocking agents. Postgrad Med. 1975; 51(Suppl 7):103.

32. Chan-Yeung M. The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma. Chest. 1977; 71:320-3. [PubMed 138577]

33. Tullett WM, Patel KR, Berkin KE et al. Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma. Thorax. 1982; 37:737-40. [PubMed 6218645]

34. Hartley JPR, Davies BH. Cholinergic blockade in the prevention of exercise-induced asthma. Thorax. 1980; 35:680-5. [PubMed 6449753]

35. Borut TC, Tashkin DP, Fischer TJ et al. Comparison of aerosolized atropine sulfate and Sch 1000 on exercise-induced bronchospasm in children. J Allergy Clin Immunol. 1977; 60:127-33. [IDIS 92840] [PubMed 141471]

36. Poppius H, Salorinne Y, Viljanen AA. Inhalation of a new anticholinergic drug, Sch 1000, in asthma and chronic bronchitis: effect on airway resistance, thoracic gas volume, blood gases and exercise-induced asthma. Bull Physiopathol Resp. 1972; 8:643-52.

37. Poppius H, Salorinne Y, Viljanen AA. The role of Sch 1000 MDI in preventing exercise-induced asthma. Postgrad Med J. 1975; 51(Suppl 7):105.

38. Weinberg EG. Experience with Sch 1000 MDI in the treatment of exercise-induced asthma in children. Postgrad Med J. 1975; 51(Suppl 7):128.

39. Thomson NC, Patel KR, Kerr JW. Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. Thorax. 1978; 33:694-9. [PubMed 154747]

40. Sanguinetti CM, De Luca S, Gasparini S et al. Evaluation of Duovent in the prevention of exercise-induced asthma. Respiration. 1986; 50(Suppl 2):181-5. [PubMed 2951802]

41. Dry J, Pradalier A, Leynadier F et al. Recherche d’une prévention de la bronchoconstriction induite par une épreuve d’efforts chez l’asthmatique par un atropinique de synthèse: le Sch 1000. (French; with English abstract.) Thérapie. 1977; 32:181-8.

42. Anderson S, Seale JP, Ferris L et al. An evaluation of pharmacotherapy for exercise-induced asthma. J Allergy Immunol. 1979; 64:612-24.

43. Poppius H, Sovijärvi ARA, Tammilehto L. Controlled study on the preventing effect of inhaled ipratropium powder on asthma induced by breathing cold air during exercise. Respiration. 1984; 46(Suppl):45-6. [PubMed 6436932]

44. Wolkove N, Kreisman H, Frank H et al. The effect of ipratropium on exercise-induced bronchoconstriction. Ann Allergy. 1981; 47:311-5. [IDIS 164243] [PubMed 6459045]

45. Scano G, Stendardi L, Gigliotti G et al. Comparative effects of SCH 1000 and fenoterol after histamine-induced bronchoconstricition in asymptomatic asthmatics. Intl J Clin Pharmacol Ther Toxicol. 1984; 22:81-5.

46. Dorward AJ, Patel KR. A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma. Clin Allergy. 1982; 12:355-61. [PubMed 6214337]

47. Yeung R, Nolan GM, Levison H. Comparison of the effects of inhaled SCH 1000 and fenoterol on exercise-induced bronchospasm in children. Pediatrics. 1980; 66:109-14. [IDIS 116640] [PubMed 6447269]

48. Nair N, Townley RG, Watt G et al. Protection by ipratropium bromide and metaproterenol against methacholine and histamine bronchoconstriction. Clin Allergy. 1984; 24:11-9.

49. Clarke PS, Jarrett RG, Hall GJL. The protective effect of ipratropium bromide aerosol against bronchospasm induced by hyperventilation and the inhalation of allergen, methacholine and histamine. Ann Allergy. 1982; 48:180-3. [IDIS 149911] [PubMed 6461281]

50. Cockcroft DW, Killian DN, Mellon JJA et al. Protective effect of drugs on histamine-induced asthma. Thorax. 1977; 32:429-37. [PubMed 145036]

51. Gayrard P, Orehek J, Charpin J et al. The prevention of the bronchoconstrictor effects of deep inspiration or of cigarette smoking in asthmatic patients by Sch 1000. Postgrad Med J. 1975; 51(Suppl 7):102-3.

52. Widdicombe JG. Reflex control of tracheobronchial smooth muscle in experimental and human asthma. In: Lichtenstein LM, Austen KF, eds. Asthma: physiology, immunopharmacology, and treatment. New York: Academic Press; 1977:225-31.

53. Islam MS, Ulmer WT. Influence of the inhalative aerosol Atrovent on airway resistance and intrathoracic gas volume in healthy volunteers of different ages. Respiration. 1984; 45:225-31. [PubMed 6235557]

54. Douglas NJ, Sudlow MF, Flenley DC. Effect of an inhaled atropinelike agent on normal airway function. J Appl Physiol. 1979; 46:256-62. [PubMed 154492]

55. Thiessen B, Pedersen OF. A double blind cross-over study of maximal expiratory flows and arterial blood gas tensions in normals, asthmatics and bronchitis after salbutamol and ipratropin. Scand J Respir Dis. 1979; 103(Suppl):170-7.

56. Partridge MR, Saunders KB. Site of action of ipratropium bromide and clinical and physiological determinants of response in patients with asthma. Thorax. 1981; 36:530-3. [PubMed 6458921]

57. Hensley MJ, O’Cain CF, McFadden ER Jr et al. Distribution of bronchodilatation in normal subjects: beta agonist versus atropine. J Appl Physiol. 1978; 45:778-82. [PubMed 730574]

58. Günther W, Kamburoff PL. The bronchodilator effect of a new anticholinergic drug, Sch 1000. Curr Med Res Opin. 1974; 2:281-7. [PubMed 4416109]

59. Böhning W, Fabel H. Comparison of the onset of action of Sch 1000 and orciprenaline given by metered dose inhaler (MDI). Postgrad Med J. 1975; 51(Suppl 7):95.

60. Gross HJ. Dose-response study of the effect of Sch 1000 MDI on forced vital capacity (FVC), FEV10, maximal midexpiratory flow (MMEF) and heart rate, ECG and blood pressure. Postgrad Med J. 1975; 51(Suppl 7):95-6.

61. Heller KF. Changes in total airways resistance (Rt) and thoracic gas volume (TGV) following Sch 1000 MDI or placebo. Multiple dose study over 12 hours. Postgrad Med J. 1975; 51(Suppl 7):96.

62. Irsigler G. Flow volume curves and changes in FEV10 forced vital capacity (FVC), mid and slow vital capacity (Mid VC and SVC) in patients with bronchial asthma or chronic bronchitis and emphysema following increasing dosages of Sch 1000 MDI. Postgrad Med J. 1975; 51(Suppl 7):96.

63. Loddenkemper R. Dose- and time-response of Sch 1000 MDI on total (Rt) and expiratory (Rt) airways resistance in patients with chronic bronchitis and emphysema. Postgrad Med J. 1975; 51(Suppl 7):97.

64. Bell JA, Bluestein BM, Danta I et al. Effect of inhaled ipratropium bromide on tracheal mucociliary transport in bronchial asthma. Mt Sinai J Med. 1984; 51:215-7. [PubMed 6233486]

65. Foster WM, Langenback EG, Glaser ML et al. Acute effect of ipratropium bromide at therapeutic dose on mucus transport of adult asthmatics. Eur J Respir Dis. 1983; 64(Suppl 128):554-7.

66. Francis RA, Thomson ML, Pavia D et al. Ipratropium bromide: mucociliary clearance rate and airway resistance in normal subjects. Br J Dis Chest. 1977; 71:173-8. [PubMed 142502]

67. Pavia D, Bateman JRM, Sheahan NF et al. Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction. Thorax. 1979; 34:501-7. [PubMed 159510]

68. Ruffin RE, Wolff RK, Dolovich MB et al. Aerosol therapy with Sch 1000: short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects. Chest. 1978; 73:501-6. [PubMed 344012]

69. Wanner A. Effect of ipratropium bromide on airway mucociliary function. Am J Med. 1986; 81(Suppl 5A):23-7. [IDIS 228922] [PubMed 2947458]

70. Iravani J, Melville GN. Ciliary movement following various concentrations of different anticholinergic and adrenergic bronchodilator solutions in animals. Postgrad Med J. 1975; 51(Suppl 7) 108. Abstract No. 4/3.

71. Matthys H, Müller M, Konietzko N et al. Tracheobronchial clearance studies with and without Sch 1000 using99mtechnetium sulphate (99mTc) particles. Postgrad Med J. 1975; 51(Suppl 7):108.

72. Matthys H, Müller M, Konietzko N. Quantitative and selective bronchial clearance studies using99mTc-sulfate particles. Scand J Respir Dis. 1974; 55(Suppl 85):33-45.

73. Foster WM, Bergofsky EH, Bohning DE et al. Effect of adrenergic agents and their mode of action on mucociliary clearance in man. J Appl Physiol. 1976; 41:146-52. [PubMed 956095]

74. Pavia D, Thomson ML. Inhibition of mucociliary clearance from the human lung by hyoscine. Lancet. 1971; 1:449-50. [PubMed 4100417]

75. Ghafouri MA, Patil KD, Kass I. Sputum changes associated with the use of ipratropium bromide. Chest. 1984; 86:387-93. [IDIS 189614] [PubMed 6236043]

76. Chervinsky P. Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator. J Allergy Clin Immunol. 1977; 59:22-30. [PubMed 137921]

77. Puchelle E, Uffholtz H. Sputum viscoelasticity following administration of Sch 1000 MDI. Postgrad Med J. 1975; 51(Suppl 7):109.

78. Krieger E, Reitberger U. Sputum rheology following treatment with Sch 1000 MDI and orciprenaline MDI. Postgrad Med J. 1975; 51(Suppl 7):108.

79. Stresemann E. Total airways resistance (Rt), sputum volume and rheology in patients with chronic bronchitis following treatment with Sch 1000 MDI and placebo. Postgrad Med J. 1975; 51(Suppl 7):110.

80. May CS, Palmer KNV. Effect of aerosol ipratropium bromide (Sch 1000) on sputum viscosity and volume in chronic bronchitis. Br J Clin Pharmacol. 1977; 4:491-2. [PubMed 143293]

81. Coleman AJ, Leary UP, Kaul DS. Haemodynamic effects of Sch 1000 in normal subjects. Postgrad Med J. 1975; 51(Suppl 7):121.

82. Fabel H, Hartmann W, Wettengel R. Effects on central haemodynamics and blood gas tensions following increasing doses of inhaled Sch 1000 MDI in patients with chronic obstructive lung disease. Postgrad Med. 1975; 51(Suppl 7):121.

83. Grimaud C, Nicholi MM, Delpierre S et al. Action of Sch 1000 MDI on blood gas tensions and alveolar ventilation in patients with chronic obstructive airway disease (COAD). Postgrad Med J. 1975; 51(Suppl 7):121.

84. Maesen FPV, Buytendijk HJ. Pulmonary haemodynamics and blood gas tensions in patients with chronic obstructive airways disease (COAD) following inhalation of a new parasympatholytic bronchodilator. Postgrad Med J. 1975; 51(Suppl 7):123.

85. Marcq M, Minette A. Effects of Sch 1000 inhalation on arterial blood gases in patients with reversible airway obstruction. Acta Tuberc Pneumol Belg. 1975; 66:429-33. [PubMed 131480]

86. Gross NJ, Petty TL, Friedman M et al. Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1989; 139:188-91. [IDIS 249894] [PubMed 2912339]

87. Wieser 0, Königshofer R. Dose-response study of Sch 1000 MDI on heart rate, ECG and blood pressure in healthy volunteers. Postgrad Med J. 1975; 51(Suppl 7):125. [PubMed 1219669]

88. Wettengel R. The effects of Sch 1000 MDI in patients with mitral stenosis. Postgrad Med J. 1975; 51(Suppl 7):125. [PubMed 1219669]

89. Sill V, Voelkel N, Siemssen S et al. Effects of Sch 1000 MDI on the pulmonary circulation under hypoxic conditions. Postgrad Med J. 1975; 51(Suppl 7):125. [PubMed 1219669]

90. Brinkmann O. The results of long-term treatment with Sch 1000 MDI on repeated measurements of FEV10, total airways resistance (Rt), haematological and biochemical tests in patients with chronic bronchitis and emphysema. Postgrad Med J. 1975; 51(Suppl 7):130.

91. Haslreiter E. Haematological and biochemical monitoring during long-term treatment with Sch 1000 MDI in patients with chronic bronchitis and emphysema. Postgrad Med J. 1975; 51(Suppl 7):130-1.

92. Jilg J. Long-term treatment with Sch 1000 MDI in outpatients with chronic bronchitis. Postgrad Med J. 1975; 51(Suppl 7):131.

93. Chapman KR, Smith DL, Rebuck AS et al. Hemodynamic effects of inhaled ipratropium bromide, alone and combined with an inhaled beta2-agonist. Am Rev Respir Dis. 1985; 132:845-7. [IDIS 206364] [PubMed 2864891]

94. Bleichert A. The effects of atropine sulphate MDI and Sch 1000 MDI in low and very high dosages on salivation and pulse rate in healthy volunteers. Postgrad Med J. 1975; 51(Suppl 7):112.

95. Sackner MA, Friedman M, Silva G et al. The pulmonary hemodynamic effects of aerosols of isoproterenol and ipratropium in normal subjects and patients with reversible airway obstruction. Am Rev Respir Dis. 1977; 116:1013-22. [PubMed 145195]

96. Simonsson BG, Jonson B, Ström B. Bronchodilatory and circulatory effects of inhaling increasing doses of an anti-cholinergic drug, ipratropium bromide (SCH 1000). Scand J Respir Dis. 1975; 56:138-49. [PubMed 1162305]

97. Kühns K, Stolte A. Controlled trial of Sch 1000 MDI in hypertensive patients as assessed by measurements of blood pressure and pulse rate at rest and during exercise. Postgrad Med J. 1975; 51(Suppl 7):123.

98. Anderson WM. Hemodynamic and non-bronchial effects of ipratropium bromide. Am J Med. 1986; 81(Suppl 5A):45-53. [IDIS 228925] [PubMed 2947460]

99. Seider N, Abinader EG, Oliven A. Cardiac arrhythmias after inhaled bronchodilators in patients with COPD and ischemic heart disease. Chest. 1993; 104:1070-4. [IDIS 320969] [PubMed 8404168]

100. Dotevall G, Walan A. Long-term effect of ipratropium bromide on gastric secretion. Arzneimittelforschung. 1978; 28:2163-5. [PubMed 159057]

101. Scherberger RR, Kaess H, Brückner S. Untersuchengen uber die Wirkung eines Anticholinergikums in Verbindung mit ein Tranquilizer auf die Magensaftsekretion beim Menschen. (German; with English abstract.) Arzneim-Forsch. 1975; 25:1460-3.

102. Scheufler G. Ophthalmotonometry, pupil diameter and visual accommodation following repeated administration of Sch 1000 MDI in patients with glaucoma. Postgrad Med J. 1975; 51(Suppl 7):132.

103. Thumm HW. Ophthalmic effects of high doses of Sch 1000 MDI in healthy volunteers and patients with glaucoma. Postgrad Med J. 1975; 51(Suppl 7):132-3.

104. Molkenboer JFWM, Lardenoye JG. The effects of Atrovent in micturition function, double blind cross-over study. Scand J Respir Dis. 1979; 103(Suppl):154-8.

105. Shenfield GM, Evans ME, Paterson JW. Absorption of drugs by the lung. Br J Clin Pharmacol. 1976; 3:583-9. [PubMed 22216498]

106. Adlung J, Höhle KD, Zeren S et al. Untersuchungen zur Pharmakokinetik und Biotransformation von Ipratropiumbromid am Menschen. (German; with English abstract). Arzneimittelforschung. 1976; 26:1005-10. [PubMed 134721]

107. Rominger KL. Chemistry and pharmacokinetics of ipratropium bromide. Scand J Respir Dis. 1979; 103(Suppl):116-29.

108. Davies DS. Pharmacokinetics of inhaled substances. Scand J Respir Dis. 1979; 103(Suppl):44-9.

109. Wahl D. Pharmacokinetics (absorption-distribution-metabolism-excretion) of 14C- labelled Sch 1000 administered by inhalation, orally and intravenously. Postgrad Med J. 1975; 51(Suppl 7):93-4.

110. Förster HJ, Kramer I, Pook KH et al. Untersuchungen zur Pharmakokinetik und Biotransformation von Ipratropiumbromid bei Ratte und Hund. (German; with English abstract.) Arzneim-Forsch. 1976; 26:992-1005.

111. Loddenkemper R. Ipratropiumbromid, ein anticholinergischer Bronchodilatator: verhalten des Atemwegwiderstandes nach Inhalation verschiedener Dosierungen bei Patienten mit reversibler Atemwegobstruktion. (German; with English abstract.) Arzneim-Forsch. 1976; 26:1017-20.

112. Ikeda A, Nishimura K, Koyama H et al. Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD. Chest. 1995; 107:401-5. [IDIS 342515] [PubMed 7842768]

113. Massey KL, Gotz VP. Ipratropium bromide. Drug Intell Clin Pharm. 1985; 19:5-12. [IDIS 194752] [PubMed 3155676]

114. Lulling J, Delwiche JP, Ledent C et al. Controlled trial of the effect of repeated administration of ipratropium bromide on ventilatory function of patients with severe chronic airways obstruction. Br J Dis Chest. 1980; 74:135-41. [PubMed 6448618]

115. Cockcroft DW, Cotton DJ, Berscheid BA. Long-term efficacy and safety of inhaled SCH 1000, an anticholinergic bronchodilator. Curr Ther Res. 1982; 31:138-47.

116. Cummiskey J, Keelan P. Study of Sch 1000 MDI used in therapeutic doses in patients with chronic bronchitis. Postgrad Med J. 1975; 51(Suppl 7):130.

117. Minette A. Haematological and biochemical results during long-term treatment with Sch 1000. Postgrad Med J. 1975; 51(Suppl 7):131.

118. Ulmer UT. Repeated measurements of total airways resistance (Rt) intrathoracic gas volume (TGV), PaO2, PaCO2 and clinical features in patients with chronic obstructive lung disease during long-term treatment with Sch 1000 inhalations. Postgrad Med J. 1975; 51(Suppl 7):133.

119. Zeren S. Haematological and biochemical values in patients with chronic bronchitis and emphysema treated with Sch 1000 MDI over 3 months. Postgrad Med J. 1975; 51(Suppl 7):133-4.

120. Tashkin DP, Ashutosh K, Bleecker ER et al. Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease. Am J Med. 1986; 81(Suppl 5A):81-90. [IDIS 228930] [PubMed 2947465]

121. Ashutosh K, Lang H. Comparison between long-term treatment of chronic bronchitic airway obstruction with ipratropium bromide and metaproterenol. Ann Allergy. 1984; 53:401-6. [IDIS 192916] [PubMed 6238558]

122. Krieger E. The effect of 2 different types of bronchodilators on FEV1-0, vital capacity (VC), and clinical features of airways obstruction in patients with chronic obstructive airways disease. Postgrad Med J. 1975; 51(Suppl 7):115.

123. Böhning W, Fabel H. Comparison of the onset of action of Sch 1000 and orciprenaline given by metered dose inhaler (MDI). Postgrad Med J. 1975; 51(Suppl 7):95.

124. Baigelman W, Chodosh S. Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma. Chest. 1977; 71:324-8. [PubMed 138578]

125. Kummer F. The acute effect of an adrenergic and a parasympatholytic bronchodilator on obstructive lung disease as assessed by total airways resistance (Rt) in a double blind study. Postgrad Med J. 1975; 51(Suppl 7):115.

126. Douglas NJ, Davidson I, Sudlow MF et al. Bronchodilatation and the site of airway resistance in severe chronic bronchitis. Thorax. 1979; 34:51-6. [PubMed 155891]

127. Poppius H, Salorinne Y. Comparative trial of a new anticholinergic bronchodilator, Sch 1000, and salbutamol in chronic bronchitis. Br Med J. 1973; 4:134-6. [PubMed 4584707]

128. Chapman TT. The effect of Sch 1000 MDI and salbutamol MDI on ventilatory function in patients with chronic bronchitis assessed by spirometry. Postgrad Med J. 1975; 51(Suppl 7):112-3.

129. Petrie GR, Palmer KNV. Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma. Br Med J. 1975; 1:430-2. [PubMed 1090337]

130. Jenkins CR, Chow CM, Fisher BL et al. Comparison of ipratropium bromide and salbutamol by aerosolized sodium. Aust N Z J Med. 1981; 11:513-6. [PubMed 6459776]

131. Maesen FPV. Comparison of the effects of Sch 1000 MDI and fenoterol MDI in patients with bronchial asthma and chronic bronchitis. Postgrad Med J. 1975; 51(Suppl 7):116. [PubMed 1114147]

132. Marlin GE, Bush DE, Berend N. Comparison of ipratropium bromide and fenoterol in asthma and chronic bronchitis. Br J Clin Pharmacol. 1978; 6:547-9. [IDIS 108925] [PubMed 153146]

133. Baronti A, Grieco A. A comparative trial of bronchodilator effects of fenoterol and SCH 1000 in chronic bronchitis. (Italian; with English abstract.) Bull Eur Physiopathol Respir. 1976; 12:533-43.

134. Minette A, Marcq M. Experience with Atrovent in coal miners. Scand J Respir Dis. 1979; 103(Suppl):192-9.

135. Jaffé GV, Grimshaw JJ, Cox GA. A comparative trial of Atrovent and Ventolin in chronic bronchitis. Practitioner. 1980; 224:433-6. [IDIS 112831] [PubMed 6448997]

136. Addis GJ, Barclay J, Chang EM. Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol. Eur J Clin Pharmacol. 1979; 16:97-100. [IDIS 142145] [PubMed 159182]

137. Longhini E, Bozzoni M, Mastropasqua B et al. Evaluation of the intensity and duration of the bronchodilatory action of fenoterol–ipratropium bromide in combination compared with terbutaline and placebo in patients with chronic obstructive lung disease. Respiration. 1986; 50(Suppl 2):169-72. [PubMed 2951799]

138. Jenkins CR, Chow CM, Fisher BL et al. Ipratropium bromide and fenoterol by aerosolized solution. Br J Clin Pharmacol. 1982; 14:113-5. [IDIS 153784] [PubMed 6213250]

139. Marangio E, Pesci A, Mori A et al. Clinical physiological data on the bronchodilator effect of Duovent versus salbutamol in chronic obstructive lung disease. Respiration. 1986; 50(Suppl 2):165-8. [PubMed 2951798]

140. Macaluso S, Del Torre L. Efficacy and compliance to prolonged Duovent treatment of bronchospasm. Respiration. 1986; 50(Suppl 2):222-5. [PubMed 2951810]

141. Cecere I, Funaro G, De Cataldis G et al. Long-term treatment with ’Duovent’ in elderly patients affected by chronic obstructive lung disease. Respiration. 1986; 50(Suppl 2):245-8. [PubMed 2951815]

142. Aquilina R, Bergero F, Noceti P et al. Protective effect of Duovent versus salbutamol in long-term treatment. Respiration. 1986; 50(Suppl 2):240- 4. [PubMed 2951814]

143. Petrie GR, Palmer KNV. Comparative trial of Sch 1000 MDI and salbutamol MDI in chronic bronchitis and bronchial asthma. Postgrad Med J. 1975; 51(Suppl 7):117.

144. Guttersohn J, Joos H, Herzog H. The effect of Raw on Sch 1000 MDI or fenoterol MDI and the combined administration of subthreshold dosages of both compounds. Postgrad Med J. 1975; 51(Suppl 7):113.

145. Kaik G. The effect on total airways resistance (Rt) of adding Sch 1000 MDI to beta- adrenergics, and vice versa, in patients with chronic bronchitis and emphysema. Postgrad Med J. 1975; 51(Suppl 7):114.

146. Marlin GE, Berend N, Harrison AC. Combined cholinergic antagonist and β2-adrenoceptor agonist bronchodilator therapy by inhalation. Aust N Z J Med. 1979; 9:511-4. [PubMed 161170]

147. Sergysels R, Schandevyl SW, Yernault JC et al. The complementary effects of an anticholinergic and sympathicomimetic drug inhalation in patients with severe chronic obstructive lung disease. Acta Tuberc Pneumol Belg. 1976; 67:163-73. [PubMed 138353]

148. Verstraeten JM. Bronchial response of asthmatic and bronchitic patients to fenoterol MDI with or without subsequent Sch 1000 MDI. Postgrad Med J. 1975; 51(Suppl 7):120. [PubMed 1219668]

149. Wildbolz U, Kyd K, Scherrer M. Ipratropium in addition to theophylline- sustained betastimulation. Lung. 1977; 154(2):141-2.

150. Casali L, Grassi C, Rampulla C et al. Clinical pharmacology of a combination of bronchodilators. Int J Clin Pharmacol Biopharm. 1979; 7:277-80.

151. Easton PA, Jadue C, Dhingra S et al. A comparison of the bronchodilating effects of a beta-2 adrenergic agent (albuterol) and an anticholinergic agent (ipratropium bromide), given by aerosol alone or in sequence. N Engl J Med. 1986; 315:735-9. [IDIS 220447] [PubMed 2943994]

152. Leitch AG, Hopkin JM, Ellis DA et al. The effect of aerosol ipratropium bromide and salbutamol on exercise and tolerance in chronic bronchitis. Thorax. 1978; 33:711-3. [PubMed 154748]

153. Lightbody IM, Ingram CG, Legge JS et al. Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis. Br J Dis Chest. 1978; 72:181-6. [PubMed 151547]

154. Brown IG, Chan CS, Kelly CA et al. Assessment of the clinical usefulness of nebulised ipratropium bromide in patients with chronic airflow limitation. Thorax. 1984; 39:272-6. [PubMed 6232724]

155. Petrie GR, Palmer KNV. Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma. Br Med J. 1975; 1:430-2. [PubMed 1090337]

156. Baronti A, Grieco A, Lelli M et al. Comparison of bronchodilator effects of Duovent and reproterol in patients with chronic reversible airway obstruction. Respiration. 1986; 50(Suppl 2):173-6. [PubMed 2951800]

157. Kreisman H, Frank H, Wolkove N et al. Anticholinergic therapy in bronchial asthma. Synergistic effect of ipratropium and theophylline. Am Rev Respir Dis. 1978; 117:142.

158. Lefcoe NM, Toogood JH, Blennerhassett G et al. The addition of an oral beta agonist plus theophylline in asthma and bronchitis. Chest. 1982; 82:300-5. [IDIS 158732] [PubMed 6213382]

159. Rasmussen FV, Madsen L, Bundgaard A. Combined effect of an anticholinergic drug ipratropium bromide and disodium cromoglycate in exercise induced asthma. Scand J Respir Dis. 1979; 103(Suppl):159-62.

160. Ajewski Z, Popiak B. The relation between permanent administration of Atrovent and the dose of steroids in chronic bronchitis. Scand J Respir Dis. 1979; 103(Suppl):205.

161. National Asthma Education Program, National Institutes of Health. Executive summary: guidelines for the diagnosis and management of asthma. US Department of Health and Human Services, Public Health Service, National Institutes of Health. Publication No.. 94-3042A. 1994 Jul.

162. Hockley B, Johnson NM. A comparison of three high doses of ipratropium bromide in chronic asthma. Br J Dis Chest. 1985; 79:379-84. [PubMed 2932138]

163. Gross NJ. Sch 1000: a new anticholinergic bronchodilator. Am Rev Respir Dis. 1975; 112:823-8. [PubMed 128306]

164. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 1995 Jan:77-100. NIH/NHLBI Publication No. 95-3659.

165. Storms WW, DoPico GA, Reed CE. Aerosol Sch 1000: an anticholinergic bronchodilator. Am Rev Respir Dis. 1975; 111:419-22. [PubMed 123712]

166. Yeager H Jr, Weinberg RM, Kaufman LV et al. Asthma: comparative bronchodilator effects of ipratropium bromide and isoproterenol. J Clin Pharmacol. 1978; 16:198-204.

167. McFadden ER Jr, Gilbert IA. Exercise-induced asthma. N Engl J Med. 1994; 330:1362-7. [IDIS 329312] [PubMed 8152449]

168. Storms WW, Bodman SF, Nathan RA et al. Use of ipratropium bromide in asthma. Am J Med. 1986; 81(Suppl 5A):61-6. [IDIS 228927] [PubMed 2947462]

169. Ruffin RE, Fitzgerald JD, Rebuck AS. A comparison of the bronchodilator activity of Sch 1000 and salbutamol. J Allergy Clin Immunol. 1977; 59:136-41. [PubMed 137922]

170. Laitinen LA, Poppius H, Haahtela T. Comparison of ipratropium bromide and salbutamol in a long-term trial in asthmatic and bronchitic patients in a cold climate. Scand J Respir Dis. 1979; 103(Suppl):163-9.

171. Ullah MI, Newman GB, Saunders KB. Influence of age on response to ipratropium and salbutamol in asthma. Thorax. 1981; 36:523-9. [PubMed 6458920]

172. Bell R, Sahay JN, Barber PV et al. A therapeutic comparison of ipratropium bromide and salbutamol in asthmatic patients. Curr Med Res Opin. 1982; 8:242-6. [PubMed 6217949]

173. Hall SK. Acute angle-closure glaucoma as a complication of combined β-agonist and ipratropium bromide therapy in the emergency department. Ann Emergency Med. 1994; 23:884-7.

174. Leahy BC, Gomm SA, Allen SC. Comparison of nebulized salbutamol with nebulized ipratropium bromide in acute asthma. Br J Dis Chest. 1983; 77:159-63. [PubMed 6223651]

175. Jindal SK, Malik SK. Clinical experience with terbutaline sulphate and ipratropium bromide in bronchial asthma. Indian J Chest Dis Allied Sci. 1979; 21:130-3. [PubMed 160398]

176. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation solution prescribing information. In: Krogh CME, ed. Compendium of pharmaceuticals and specialties 1995. 30th ed. Ottawa, Ontario: Canadian Pharmaceutical Association; 1995:130-1.

177. Emirgil C, Dwyer K, Baskette P et al. A new parasympatholytic bronchodilator: a study of its onset of effect after inhalation. Curr Ther Res. 1975; 17:215-24. [PubMed 805016]

178. Schlueter DP, Neumann JL. Double blind comparison of acute bronchial and ventilation-perfusion changes to Atrovent and isoproterenol. Chest. 1978; 73:982-3. [IDIS 107413] [PubMed 150323]

179. Vlagopoulos T, Townley R, Ghazanshahi S et al. Comparison of the onset of action and bronchodilation effects of the anticholinergic agent SCH 1000 with isoproterenol. J Allergy Clin Immunol. 1975; 55:99.

180. Ahonen A, Alanko K, Mattson K. Bronchodilator action of two different doses of ipratropium bromide (Sch 1000) compared with fenoterol and placebo. Curr Ther Res. 1978; 24:65-75.

181. Spector S, Ball E Jr. Bronchodilating effects of aerosolized Sch 1000 and atropine sulfate in asthmatics. Chest. 1975; 68:426.

182. Rebuck AS, Gent M, Chapman KR. Anticholinergic and sympathomimetic combination therapy of asthma. J Allergy Clin Immunol. 1983; 71:317-23. [IDIS 167773] [PubMed 6219156]

183. Flint KC, Hockley B. A comparison between a combination of ipratropium bromide plus fenoterol single metered dose inhaler (Duovent) and salbutamol in asthma. Postgrad Med J. 1983; 59:724-5. [PubMed 6227877]

184. Anderson G, Jariwalla AG, Turnbull P et al. The effects of fenoterol, ipratropium bromide and their combination in asthma and chronic bronchitis. IRCS Med Sci. 1981; 9:251.

185. Alanko K, Sahlström K, Härkonen R. Combination of fenoterol and ipratropium bromide in the treatment of bronchial asthma. Eur J Respir Dis. 1983; 64(Suppl 128):546-7.

186. Bruderman I, Cohen-Aronovski R, Smorzik J. A comparative study of various combinations of ipratropium bromide and metaproterenol in allergic asthmatic patients. Chest. 1983; 83:208-10. [IDIS 165425] [PubMed 6217951]

187. Kreisman H, Cohen C, Ghezzo H et al. Combined therapy with ipratropium and theophylline in asthma. Ann Allergy. 1984; 52:90-3. [IDIS 182121] [PubMed 6230034]

188. Bonsignore G, Bellia V, Peralta G et al. The combination of fenoterol and ipratropium bromide in bronchial asthma: comparison of the acute effects of two different dosages. Respiriration. 1986; 50(Suppl 2):148-51.

189. Frith PA, Ruffin RE, Cockcroft DW et al. A comparison of the protective effect of sch 1000 and fenoterol against bronchoconstriction induced by histamine and methacholine. J Allergy Clin Immunol. 1978; 61:175.

190. Boehringer Ingelheim, Ridgefield, CT: Personal communication.

191. Reviewers’ comments (personal observations).

192. Rebuck AS, Marcus HI. Sch 1000 in psychogenic asthma. Scand J Respir Dis. 1979; 103(Suppl):186-91.

193. Schuh S, Johnson DW, Callahan S et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. J Pediatr. 1995; 126:639-45. [IDIS 345503] [PubMed 7699549]

194. Desche P, Cournot A, Duchier J et al. Airway responses to salbutamol and to ipratropium bromide after non-selective and cardioselective beta-blocker. Eur J Clin Pharmacol. 1987; 32:343-6. [IDIS 231909] [PubMed 2886341]

195. Gross NJ, Bankwala Z. Effects of an anticholinergic bronchodilator on arterial blood gases of hypoxemic patients with chronic obstructive pulmonary disease. Comparison with a beta-adrenergic agent. Am Rev Respir Dis. 1987; 136:1091-4. [IDIS 236089] [PubMed 3118746]

196. Fine SR. Possible reactions to soya lecithin in aerosols. J Allergy Clin Immunol. 1991; 87:600. [IDIS 277823] [PubMed 1825215]

197. Canadian Thoracic Society Workshop Group. Guidelines for the assessment and management of chronic obstructive pulmonary disease. CMAJ. 1992; 147:420-8. [IDIS 300998] [PubMed 1498754]

198. Kosche F, Stemmann EA. Peak flow measurements following Sch 1000 MDI in children with reversible airways obstruction. Postgrad Med J. 1975; 51(Suppl 7):127.

199. Kunkel G, Rudolph R, Stock U. Dose-titration and long-term studies in asthmatic children. Postgrad Med J. 1975; 51(Suppl 7):127.

200. Logvinoff-Poidatz M, Geubelle F. Effects of Sch 1000 MDI on the lung function in asthmatic children. Postgrad Med J. 1975; 51(Suppl 7):127.

201. Pulejo R, Romano L, Noto M. Double-blind study with Duovent and placebo in 20 asthmatic children. Respiration. 1986; 50(Suppl 2):236-9. [PubMed 2951813]

202. Bratteby LE, Foucard T, Lönnerholm G. Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma. Eur J Respir Dis. 1986; 68:239-47. [PubMed 2874047]

203. Groggins RC, Milner AD, Stokes GM. Bronchodilator effects of clemastine, ipratropium bromide, and salbutamol in preschool children with asthma. Arch Dis Child. 1981; 56:342-4. [IDIS 133079] [PubMed 6455096]

204. Henry RL, Hiller EJ, Milner AD et al. Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life. Arch Dis Child. 1984; 59:54-7. [IDIS 181272] [PubMed 6230059]

205. Beck R, Robertson C, Galdès-Sebaldt M et al. Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. J Ped. 1985; 107:605-8.

206. Hofmann D, Wönne R. Action of Sch 1000 MDI and fenoterol on bronchial obstruction induced by allergen challenge. Postgrad Med J. 1975; 51(Suppl 7):126.

207. Stemmann EA, Kosche F, Braun SH. The assessment of Sch 1000 MDI and/or beta-adrenergics in asthmatic children. Postgrad Med J. 1975; 51(Suppl 7):128.

208. Lin MT, Lee-Hong E, Collins-Williams C. A clinical trial of the bronchodilator effect of Sch 1000 aerosol in asthmatic children. Ann Allergy. 1978; 40:326-32. [PubMed 347990]

209. Turner M. Compatibility of nebuliser solutions. Aust J Hosp Pharm. 1987; 17:241-2.

210. Lahdensuo A, Viljanen AA, Muittari A. A comparative study on the effect of Sch 1000 MDI, salbutamol and placebo MDI in bronchial asthma. Postgrad Med J. 1975; 51(Suppl 7):116. [PubMed 1114147]

211. Rebuck AS, Chapman KR, Abboud P et al. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med. 1987; 82:59-64.

212. Lichterfeld A. Safety of Atrovent. Scand J Respir Dis. 1979; 103(Suppl):143-6.

213. Connolly CK. Adverse reaction to ipratropium bromide. BMJ. 1982; 285:934-5. [IDIS 158336] [PubMed 6214296]

214. Farrow PR, Fancourt GJ. Does ipratropium bromide by nebulizer and face-mask have local ocular effects? Human Toxicol. 1986; 5:53-4.

215. Iacono M, Johnson GJ, Bury RW. An investigation of the compatibility of ipratropium and sodium cromoglycate nebuliser solutions. Aust J Hosp Pharm. 1987; 17:158-60.

216. Nadel JA. Ipratropium bromide nebuliser therapy and airway submucosal gland secretion. Lancet. 1982; 2:823. [IDIS 158268] [PubMed 6126694]

217. Friberg S, Graff-Lonnevig V. Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study. Ann Allergy. 1989; 62:131-4. [IDIS 300746] [PubMed 2521989]

218. Sarafana L, Clark GC, Stötzer H. Toxikologische untersuchungen mit ipratropiumbromid. (German; with English abstract.) Arzneim-Forsch. 1976; 26:985-9.

219. Niggeschulze A, Palmer AK. Reproduktionstoxikologische untersuchungen mit ipratropiumbromid. (German; with English abstract.) Arzneim-Forsch. 1976; 26:989.

220. Kreisman H, Frank H, Wolkove N et al. Synergism between ipratropium and theophylline in asthma. Thorax. 1981; 36:387-91. [PubMed 6458919]

221. Allen CJ, Campbell AH. Dose response of ipratropium bromide assessed by two methods. Thorax. 1979; 34:137-9.

222. Reisman J, Galdes-Sebalt M, Kazim F et al. Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. J Allergy Clin Immunol. 1988; 81:16-20. [IDIS 316647] [PubMed 2963059]

223. DeStefano G, Bonetti S, Bonizzato C et al. Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children. Ann Allergy. 1990; 65:260-2. [IDIS 274039] [PubMed 2145790]

224. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 30th ed. London; The Pharmaceutical Press, 1992:427.

225. Gross NJ. Ipratropium bromide. N Engl J Med. 1988; 319:486-94. [IDIS 244946] [PubMed 2970009]

226. Howarth PH, Durham SR, Lee TH et al. Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. Am Rev Respir Dis. 1985; 132:986-92. [IDIS 208125] [PubMed 2932989]

227. Ind PW, Dixon CMS, Fuller RW et al. Anticholinergic blockade of propranolol induced bronchoconstriction. Thorax. 1986; 41:718.

228. Mann KV, Leon AL, Tietze KJ. Use of ipratropium bromide in obstructive lung disease. Clin Pharm. 1988; 7:670-80. [IDIS 245585] [PubMed 2977109]

229. Ensing K, de Zeeuw RA, Nossent GD et al. Pharmacokinetics of ipratropium bromide after single dose inhalation and oral and intravenous administration. Eur J Clin Pharmacol. 1989; 36:189-94. [IDIS 253059] [PubMed 2524387]

230. Anon. Ipratropium. Med Lett Drugs Ther. 1987; 29:71-2. [PubMed 2885730]

231. Fisons. Tilade (nedocromil sodium) inhalation aerosol patient information. (undated).

232. Lammers JWJ, Minette P, McCusker M et al. The role of pirenzepine-sensitive (M1) muscarinic receptors in vagally mediated bronchoconstriction in humans. Am Rev Respir Dis. 1989; 139:446-9. [IDIS 251249] [PubMed 2521552]

233. Wesseling G, Mostert R, Wouters EFM. A comparison of the effects of anticholinergic and β2-agonist and combination therapy on respiratory impedance in COPD. Chest. 1992; 101:166-73. [IDIS 290181] [PubMed 1530836]

234. Gross NJ, Co E, Skorodin MS. Cholinergic bronchomotor tone in COPD: estimates of its amount in comparison with that in normal subjects. Chest. 1989; 96:984-7. [PubMed 2805869]

235. Magnussen H, Nowak D, Wiebicke W. Effect of inhaled ipratropium bromide on the airway response to methacholine, histamine, and exercise in patients with mild bronchial asthma. Respiration. 1992; 59:42-7. [PubMed 1533724]

236. Peters MJ, Breslin ABX, Berend N. The effect of anticholinergic and beta-agonist pretreatment of bronchoconstriction induced by N-formyl-methionyl-leucyl-phenylalanine. Eur Respir J. 1989; 2:946-9. [PubMed 2532605]

237. Polosa R, Phillips GD, Rajakulasingam K et al. The effect of inhaled ipratropium bromide alone and in combination with oral terfenadine on bronchoconstriction provoked by adenosine 5′-monophosphate and histamine in asthma. J Allergy Clin Immunol. 1991; 87:939-47. [IDIS 282514] [PubMed 1673977]

238. Crimi N, Palermo F, Oliveri R et al. Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma. Eur Respir J. 1992; 5:560-5. [PubMed 1535321]

239. Georgopoulos D, Giulekas D, Ilonidis G et al. Effect of salbutamol, ipratropium bromide and cromolyn sodium on prostaglandin F-induced bronchospasm. Chest. 1989; 96:809-14. [IDIS 305764] [PubMed 2529105]

240. Crimi N, Palermo F, Oliveri R et al. Influence of antihistamine (astemizole) and anticholinergic drugs (ipratropium bromide) on bronchoconstriction induced by substance P. Ann Allergy. 1990; 65:115-20. [IDIS 297046] [PubMed 1696438]

241. McManus MS, Koenig JQ, Altman LC et al. Pulmonary effects of sulfur dioxide exposure and ipratropium bromide pretreatment in adults with nonallergic asthma. J Allergy Clin Immunol. 1989; 83:619-26. [IDIS 252672] [PubMed 2522475]

242. Watson WTA, Becker AB, Simons FER. Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma. J Allergy Clin Immunol. 1988; 82:1012-8. [IDIS 312158] [PubMed 2974463]

243. Quieffin J, Hunter J, Schechter MT et al. Aerosol pentamidine-induced bronchoconstriction: predictive factors and preventive therapy. Chest. 1991; 100:624-27. [IDIS 288845] [PubMed 1832372]

244. Gross NJ. The influence of anticholinergic agents on treatment for bronchitis and emphysema. Am J Med. 1991; 91(Suppl 4A):11-2S.

245. Karpel JP, Pesin J, Greenberg D et al. A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD. Chest. 1990; 98:835-9. [IDIS 274905] [PubMed 2145136]

246. Kalra L, Bone MF. The effect of nebulized bronchodilator therapy on intraocular pressures in patients with glaucoma. Chest. 1988; 93:739-41. [IDIS 311621] [PubMed 2964995]

247. D’Arcy PF. Glaucoma associated with nebulised ipratropium and salbutamol. Int Pharm J. 1992; 6:53.

248. Shah P, Dhurjon L, Metcalfe T et al. Acute angle closure glaucoma associated with nebulised ipratropium bromide and salbutamol. BMJ. 1992; 304:40-1. [IDIS 290228] [PubMed 1531182]

249. Reuser T, Flanagan DW, Borland C et al. Acute angle closure glaucoma occurring after nebulized bronchodilator treatment with ipratropium bromide and salbutamol. J R Soc Med. 1992; 85:499-500. [PubMed 1404209]

250. Roberts TE, Pearson DJ. Wide eyed and breathless. BMJ. 1989; 299:1348.

251. Pras E, Stienlauf S, Pinkhas J et al. Urinary retention associated with ipratropium bromide. DICP. 1991; 25:939-40. [IDIS 285270] [PubMed 1835224]

252. Lozewicz S. Bladder outflow obstruction induced by ipratropium bromide. Postgrad Med J. 1989; 65:260-1. [PubMed 2480586]

253. Skorodin MS. Pharmacotherapy for asthma and chronic obstructive pulmonary disease. Arch Intern Med. 1993; 153:814-28. [IDIS 312555] [PubMed 8096690]

254. Ferguson GT, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med. 1993; 328:1017-22. [IDIS 312147] [PubMed 8450855]

255. Listello D, Glauser F. COPD: primary care management with drug and oxygen therapies. Geriatrics. 1992; 47:28-38. [IDIS 306254] [PubMed 1446842]

256. Chapman KR. Therapeutic algorithm for chronic obstructive pulmonary disease. Am J Med. 1991; 91(Suppl 4A):17-23S.

257. Chapman KR. The role of anticholinergic bronchodilators in adult asthma and chronic obstructive pulmonary disease. Lung. 1990; 168(Suppl):295-303. [PubMed 2143551]

258. Braun SR, Levy SF, Grossman J. Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study. Am J Med. 1991; 91(Suppl 4A):28-32S.

259. Braun SR, McKenzie WN, Copeland C et al. A comparison of the effect of ipratropium and albuterol in the treatment of chronic obstructive airway disease. Arch Intern Med. 1989; 149:544-7. [IDIS 252403] [PubMed 2521997]

260. Shrestha M, O’Brien T, Haddox R et al. Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to β-agonist therapy. Ann Emerg Med. 1991; 20:1206-9. [PubMed 1835324]

261. Nishimura K, Koyama H, Ikeda A et al. Is oral theophylline effective in combination with both inhaled anticholinergic agent and inhaled β2-agonist in the treatment of stable COPD? Chest. 1993; 104:179-84. (IDIS 317807)

262. LeDoux EJ, Morris JF, Temple WP et al. Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled metaproterenol in COPD. Chest. 1989; 95:1013-6. [IDIS 255395] [PubMed 2523291]

263. Karpel JP. Bronchodilator responses to anticholinergic and beta-adrenergic agents in acute and stable COPD. Chest. 1991; 99:871-6. [IDIS 280296] [PubMed 1672634]

264. Weintraub SJ, Eschenbacher WL. The inhaled bronchodilators ipratropium bromide and metaproterenol in adults with CF. Chest. 1989; 95:861-4. [IDIS 305627] [PubMed 2522385]

265. Sanchez, I, Holbrow J et al. Acute bronchodilator response to a combination of beta- adrenergic and anticholinergic agents in patients with cystic fibrosis. J Pediatr. 1992; 120:486-8. [IDIS 292645] [PubMed 1531677]

266. Sanchez I, De Koster J, Holbrow J et al. The effect of high doses of inhaled salbutamol and ipratropium bromide in patients with stable cystic fibrosis. Chest. 1993; 104:842-6. [IDIS 319959] [PubMed 8365299]

267. American Thoracic Society. ATS Statement: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(Suppl):S78-120.

268. Corbridge TC, Hall JB. The assessment and management of adults with status asthmaticus. Am J Respir Crit Care Med. 1995;151:1296-1316.

269. O’Driscoll BR, Taylor R, Horsley MG et al. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet. 1989; 1:1418-20. [IDIS 256594] [PubMed 2567431]

270. Bryant DH, Rogers P. Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma. Chest. 1992; 102:742-7. [IDIS 302744] [PubMed 1387604]

271. O’Callaghan C, Milner AD, Swarbrick A. Paradoxical bronchoconstriction in wheezing infants after nebulised preservative free iso-osmolar ipratropium bromide. BMJ. 1989; 299:1433-4. [IDIS 261395] [PubMed 2532940]

272. Van Bever HP, Desager KN. Paradoxical bronchoconstriction in wheezing infants after nebulised ipratropium bromide. Br Med J. 1990; 300:397-8.

273. Milner AD, O’Callaghan C. Paradoxical bronchoconstriction in wheezing infants after nebulised ipratropium bromide. Br Med J. 1990; 300:398.

274. Markus HS. Paralytic ileus associated with ipratropium. Lancet. 1990; 355:1224.

275. Tuohy PG. Ipratropium and the eye. N Z Med J. 1989; 102:386. [IDIS 260010] [PubMed 2529459]

276. O’Driscoll BR. Supraventricular tachycardia caused by nebulised ipratropium bromide. Thorax. 1989; 44:312. [PubMed 2527421]

277. Bone WD, Amundson DF. An unusual case of severe anaphylaxis due to ipratropium bromide inhalation. Chest. 1993; 103:981-2.

278. Levin DC, Little KS, Laughlin KR et al. Ipratropium bromide solution in COPD augments extent and duration of FEV1 increases achieved by albuterol up to 85 days. Chest. 1993; 104(Suppl):112S.

279. Karpel J, Kotch A, Zinney M et al. Comparison of ipratropium, theophylline plus B-agonist, and all three in patients with COPD. Chest. 1993; 104(Suppl):112S.

280. Mulherin D, FitzGerald MX. Meconium ileus equivalent in association with nebulised ipratropium bromide in cystic fibrosis. Lancet. 1990; 355:552.

281. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation solution product monograph. Ridgefield, CT; 1993 Nov.

282. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation solution product information. Ridgefield, CT; 1993 Dec.

283. Hampson NB, Mueller MP. Cooling of metered-dose inhalers decrease pressure output from canisters. N Engl J Med. 1989; 320:321. [IDIS 250265] [PubMed 2563147]

284. Lourenco RV, Cotromanes E. Clinical aerosols: I. characterization of aerosols and their diagnostic uses. Arch Intern Med. 1982; 142:2163-72. [PubMed 6753780]

285. Combivent Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone: an 85-day multicenter trial. Chest. 1994; 105:1411-9. [IDIS 329783] [PubMed 8181328]

286. Watson WTA, Shuckett P, Becker AB et al. Effect of nebulized ipratropium bromide on intraocular pressure in children. Chest. 1994; 105:1439-41. [IDIS 329785] [PubMed 8181333]

287. Armstrong GP, Braatvedt GD. Nebulised bronchodilators and eye complications. New Ethicals. 1994; 31:41-2.

288. Packe GE, Cayton RM, Mashhoudi N. Nebulised ipratropium bromide and salbutamol causing closed-angle glaucoma. Lancet. 1984; 2:691. [IDIS 190415] [PubMed 6147708]

289. Malani JT, Robinson GM, Seneviratne EL. Ipratropium bromide induced angle closure glaucoma. N Z Med J. 1982; 95:749. [IDIS 161512] [PubMed 6216428]

290. Kil H, Rooke GA, Ryan-Dykes MA et al. Effect of prophylactic bronchodilator treatment on lung resistance after tracheal intubation. Anesthesiology. 1994; 81:43-8. [IDIS 332910] [PubMed 8042809]

291. Nisar M, Earis JE, Pearson MG et al. Acute bronchodilator trials in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1992; 146:555-9. [IDIS 301641] [PubMed 1387772]

292. Jacobs M. Maintenance therapy for obstructive lung disease. Postgrad Med. 1994; 95:87-99. [IDIS 331162] [PubMed 8202425]

293. Fromm RE Jr, Varon J. Acute exacerbations of obstructive lung disease. Postgrad Med. 1994; 95:101-6. [IDIS 331163] [PubMed 7911236]

294. Anthonisen NR, Connett JE, Kiley JP et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. JAMA. 1994; 272:1497-505. [IDIS 338253] [PubMed 7966841]

295. Yang SC, Yang SP, Lee TS. Nebulized ipratropium bromide in ventilator-assisted patients with chronic bronchitis. Chest. 1994; 105:1511-5. [IDIS 329788] [PubMed 8181345]

296. Mulpeter KM, Walsh JB, O’Connor M et al. Ocular hazards of nebulized bronchodilators. Postgrad Med J. 1992; 68:132-3. [PubMed 1533281]

297. Diamond L, Dockhorn RJ, Grossman J et al. A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the the common cold. J Allergy Clin Immunol. 1995; 95:1139-46. [IDIS 348619] [PubMed 7751531]

298. Bronsky EA, Druce H, Findlay SR et al. A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis. J Allergy Clin Immunol. 1995; 95:1117-22. [IDIS 348615] [PubMed 7751528]

299. Inoue H, Aizawa H, Takata S et al. Ipratropium bromide protects against bronchoconstriction during bronchoscopy. Lung. 1994; 172:2930-8.

300. Lee H, Amon S, Silverman M. Bronchodilator aerosol adminstered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome. Arch Dis Child. 1994; 70:F218-22.

301. Brundage KL, Mohsini KG, Froese AB et al. Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia. Am Rev Respir Dis. 1990; 142:1137-42. [IDIS 273832] [PubMed 2146910]

302. Anon. Drugs for asthma. Med Lett Drug Ther. 1995; 37:1-4.

303. Goldstein RA, Paul WE, Metcalfe DD et al. Asthma. Ann Intern Med. 1994; 121:698-708. [IDIS 33939] [PubMed 7944080]

304. Wilkie RA, Bryan MH. Effect of bronchodilators on airway resistance in ventilation-dependent neonates with chronic lung disease. J Pediatr. 1987; 111:278-82. [IDIS 233441] [PubMed 2956405]

305. Karpel JP, Kotch A, Zinny M et al. A comparison of inhaled ipratropium, oral theophylline plus inhaled β-agonist, and the combination of all three in patients with COPD. Chest. 1994; 105:1089-94. [IDIS 328134] [PubMed 8162730]

306. Lehrer PM, Hochron SM, Rausch L et al. Effects of aerosol ipratropium bromide on cardiac vagal tone. Chest. 1994; 105:1701-4. [IDIS 332082] [PubMed 8205863]

307. Eedy DJ, Bartan K, Stanford CF. Ipratropium bromide/terbutaline. Postgrad Med J. 1988; 64:306-7. [PubMed 2973007]

308. Liggett SB, Daughaday CC, Senior RM. Ipratropium in patients with COPD receiving cholinesterase inhibitors. Chest. 1988; 94:210-2. [IDIS 243553] [PubMed 2968227]

309. Ashutosh K, Dev G, Steele D. Nonbronchodilator effects of pirbuterol and ipratropium in chronic obstructive pulmonary disease. Chest. 1995; 107:173-8. [IDIS 341534] [PubMed 7813271]

310. Patel KR, Tullett WM. Bronchoconstriction in response to ipratropium bromide. BMJ. 1983; 286:1318. [IDIS 170238] [PubMed 6220756]

311. Jolobe OMP. Adverse reaction to ipratropium bromide. BMJ. 1982; 285:1425-6.

312. Meyer JM, Wenzel CL, Kradjan WA. Salmeterol: a novel, long-acting beta 2-agonist. Ann Pharmacother. 1993; 27:1478-87. [IDIS 323106] [PubMed 7905757]

313. Kelly HW. Issues and advances in the pharmacotherapy of asthma. J Clin Pharm Ther. 1992; 17:271-81. [IDIS 304352] [PubMed 1361192]

314. British Thoracic Society. Guidelines on the management of asthma. Thorax. 1993; 48(Suppl 2):S1-24.

315. Svedmyr N. Action of corticosteroids on beta-adrenergic receptors: clinical aspects. Am Rev Respir Dis. 1990; 141:S31-8.

316. Anon. Salmeterol. Med Lett Drugs Ther. 1994; 36:37-9. [PubMed 7909139]

317. Johnson ME. A multicentre study to compare the efficacy and safety of salmeterol xinofoate and nedocromil sodium via metered-dose inhalers in adults with mild-to-moderate asthma. Eur J Clin Res. 1994; 5:75-85.

318. O’Connor BJ, Aikman SL, Barnes PJ. Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma. N Engl J Med. 1992; 327:1204-8. [IDIS 304091] [PubMed 1357551]

319. Reviewers’ comments (personal observations) on salmeterol 12:12.

320. Boehringer Ingelheim Pharmaceuticals. Combivent (ipratropium bromide and albuterol sulfate) inhalation aerosol prescribing information.Ridgefield, CT; 2001 Sep.

321. Combivent Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone; an 85-day multicenter trial. Chest. 1994; 105: 1411-9.

322. Key Pharmaceuticals. Proventil HFA (albuterol sulfate) inhalation aerosol for oral inhalation prescribing information. Kenilworth, NJ; 1996 Aug. (reference 181 from albuterol)

323. Siafakas NM, Vermeire P, Pride NB et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J. 1995: 8; 1398-420.

324. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

325. Boehringer Ingelheim Pharmaceuticals. Atrovent (ipratropium bromide) Nasal Spray 0.03% prescribing information. In: Physicians’ desk reference. 54th ed. Montvale, NJ: Mecial Economics Company. 2000:791-2.

326. Boehringer Ingelheim Pharmaceuticals. Atrovent (ipratropium bromide) Nasal Spray 0.06% prescribing information. In: Physicians’ desk reference. 54th ed. Montvale, NJ: Medical Economics Company. 2000:792-4.

327. Dey Laboratories. DuoNeb (ipratropium bromide/albuterol sulfate) inhalation solution prescribing information. Napa, CA; 2005 Apr.

328. Dey. DuoNeb (albuterol sulfate/ipratropium bromide) inhalation solution patient instructions. Napa, CA: 2005 Apr.

329. Dey. Ipratropium bromide 0.02% inhalation solution prescribing instructions. Napa, CA: 1998 Apr.

330. Dey,L.P. Napa, CA: Personal communication.

331. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2002 Feb. NIH/NHLBI Publication No. 02-3659. Available at: http://www.ginasthma.com. Accessed Sep. 26, 2002

332. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2001. Available at: http://www.goldcopd.com/workshop/index.html. Accessed Sep. 26, 2002.

333. Veterans’ Health Administration Department of Veteran Affairs. The pharmacologic management of chronic obstructive pulmonary disease. Washington, DC: Veterans’ Health Administration; 1999 June. Pharmacy Benefits Management No. 99-0012. Available at http://www.vabpm.org. Accessed Sep. 30, 2002.

334. Veterans’ Health Administration, Department of Veterans’ Affairs. VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease: complete summary. Washington, DC: Veterans’ Health Administration; 1999 Aug.

335. Snow V, Lascher S, Mottur-Pilson C for the Joint Expert Panel of Chronic Obstructive Pulmonary Disease of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Clinical Practice Guideline, pt.1. Ann Intern Med. 2001; 134:595-9. [IDIS 462483] [PubMed 11281744]

336. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2003 Nov 21. NIH/NHLBI Publication No. 02-3659 (updated 2004). Available at: http://www.ginasthma.com. Accessed Sep 22, 2004.

337. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma. Update on selected topics 2002. Bethesda, Md: National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Coordinating Committee; 2003 Jun. Available from National Heart, Lung, and Blood Institute Information Center, NIH Publication No. 02-5074. Also available at . Accessed 2004 Sep. 15.

338. Boehringer Ingelheim. Spiriva HandiHaler (tiotropium bromide) inhalation powder prescribing information. Ridgefield, CT; 2004 Jan.

339. Vincken W, van Noord JA, Greefhirst APM et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J

340. Casaburi R, Mahler DA, Jones PW et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructuve pulmonary disease. Eur Respir J. 2002; 19:217-24. [IDIS 514612] [PubMed 11866001]

341. Anon. Tiotropium (Spiriva) for COPD. Med Lett Drugs Ther. 2004: 46:41-2.

342. Hvizdos KM, Goa KL. Tiotropium bromide. Drugs. 2002; 62:1195-203. [PubMed 12010082]

343. ATS/ERS Standards for the diagnosis and management of patients with COPD. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available from website. Accessed Dec. 8, 2004.

344. O’Donnell DE, Aaron S, Bourbeau J et al. State of the art compendium: Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease. Can Respir J. 2004; 11 (Suppl. B):7B-59B.

345. Celli BR, Macnee W. Standard for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23:932-46. [PubMed 15219010]

346. Boehringer Ingleheim. Combivent (albuterol sulfate/ipratropium bromide) inhalation aerosol patient instructions for use. Ridgefield, CT: 2001 Sep.

347. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2005 Sep. Available at: . Accessed Oct. 5, 2005.

348. Boehringer Ingleheim. Atrovent (ipratropium bromide) inhalation aerosol patient instructions for use. Ridgefield, CT: 2002 Mar. 27.

349. Dey. Ipratropium bromide inhalation solution 0.02% patient instructions. Napa, CA: 1998 Apr.

350. Boehringer Ingelheim. Atrovent (ipratropium bromide) 0.02% inhalation solution patient instructions. Ridgefield, CT; 1998 Oct.

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