Dr. Paul Answers Your Questions About Asthma. Watch The Video

Generic Name: Metaproterenol Sulfate
Class: Selective beta-2-Adrenergic Agonists
VA Class: RE102
CAS Number: 5874-97-5

Introduction

Bronchodilator; less selective than relatively selective β2-adrenergic agonists (e.g., albuterol).b c f h i j k

Uses for Alupent

Bronchospasm in Asthma

Symptomatic management of bronchospasm in patients with reversible, obstructive airway disease (e.g., asthma).146 c g Manufacturer recommends against use with other β-adrenergic bronchodilators.c f (See Specific Drugs under Interactions.)

Slideshow: Asthma: 10 Things You Need To Do To Keep It In Check

Current asthma management guidelines and most clinicians recommend anti-inflammatory therapy with an orally inhaled corticosteroid as first-line therapy for long-term control of persistent asthma, supplemented by intermittent, as-needed use of a short-acting, inhaled β2-agonist.j o

The National Asthma Education and Prevention Program (NAEPP) does not recommend nonselective β-adrenergic agonists, including metaproterenol,j k for treatment of asthma because of the associated potential for excessive cardiac stimulation, particularly in high doses.j

Bronchospasm in COPD

Symptomatic management of reversible bronchospasm in patients with COPD, including chronic bronchitis and emphysema.146 Manufacturer recommends against use with other β-adrenergic bronchodilators.c f (See Specific Drugs under Interactions.)

Alupent Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response.146 c f g

Administration

Administer orally146 f or by oral inhalation via metered-dose inhaler or nebulizer.145 c

Oral Inhalation

Metered-dose Inhaler

Oral inhalation aerosol delivers approximately 0.65 mg from mouthpiece per metered spray; 7-g or 14-g canister delivers 100 or 200 metered sprays, respectively.c

Administer inhalation aerosol only with actuator provided by manufacturer.d

Shake the inhaler well before use.d

Avoid spraying aerosol into eyes.d

Place the mouthpiece of the inhaler well into the mouth with lips closed around it.d Exhale through nose as completely as possible.d Inhale slowly and deeply through mouth.d Actuate aerosol inhaler, hold breath for few seconds, withdraw mouthpiece, and exhale slowly.d

Allow ≥2 minutes to elapse between inhalations from aerosol inhaler.d

Clean inhalation aerosol inhaler by removing metal canister and running warm water through plastic mouthpiece.d If soap used, rinse thoroughly with plain water.d

Dosage

Available as metaproterenol sulfate; dosage expressed in terms of metaproterenol sulfate.145 c f

Pediatric Patients

Bronchospasm in Asthma
Oral

Oral solution in children <6 years of age (limited experience): 1.3–2.6 mg/kg daily.f

Oral solution in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.f

Conventional tablets in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.146

Oral solution in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.f

Conventional tablets in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.146

Oral Inhalation

Inhalation aerosol in children ≥12 years of age: 1.3 or 1.95 mg (2 or 3 inhalations).c Usually no need to repeat dosing more often than every 3–4 hours.c d If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.c d

0.4 or 0.6% inhalation solution for nebulization in children ≥12 years of age: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.145 Usually no need to repeat dosing more often than every 4 hours.145 g

Adults

Bronchospasm in Asthma
Oral

Usually, 20 mg 3 or 4 times daily.146 f

Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations).c Usually no need to repeat dosing more often than every 3–4 hours.d If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.c d

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.145 Usually no need to repeat dosing more often than every 4 hours.145 g

Bronchospasm in COPD
Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations).c Usually no need to repeat dosing more often than every 3–4 hours.d If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.c d

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.145 Usually no need to repeat dosing more often than every 4 hours.145 g

Prescribing Limits

Pediatric Patients

Bronchospasm
Asthma
Oral Inhalation

Inhalation aerosol in children ≥12 years of age: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.c

Adults

Bronchospasm in Asthma
Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.d

Bronchospasm in COPD
Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.d

Cautions for Alupent

Contraindications

Arrhythmias associated with tachycardia.145 146 c f

Known hypersensitivity to metaproterenol or any ingredients in formulation.145 146 c f

Warnings/Precautions

Warnings

Acute or Worsening Asthma

Oral inhalation therapy intended for acute symptomatic relief of bronchospasm.126 134 135

Failure to respond to previously effective dosage of metaproterenol may indicate seriously worsening asthma.112 126 134 135 Contact a clinician if control of mild asthma deteriorates. Reevaluate asthma therapy and institute alternative regimens or therapy.112 126 134 135

Excessive Doses

Fatalities have been associated with excessive use of inhaled sympathomimetic drugs; cardiac arrest occurred in several cases.145 c

Paradoxical Bronchospasm

Possible life-threatening, acute paradoxical bronchospasm.b c Occasionally occurs after repeated or excessive use of orally inhaled sympathomimetic amines.b g

Discontinue therapy immediately if bronchoconstriction occurs and institute alternative therapy.b c

Cardiovascular Effects

Possible clinically important cardiovascular effects, including cardiac arrhythmias (e.g., tachycardia), changes in BP, and related symptoms.146 b c f

Cautious use recommended in patients with cardiovascular disorders (e.g., ischemic heart disease, CAD, cardiac arrhythmias, hypertension, CHF).145 146 c f

Sensitivity Reactions

Rarely, immediate hypersensitivity reactions can occur.c f

Possible acute bronchospasm.b c (See Paradoxical Bronchospasm under Cautions.)

General Precautions

Nervous System Effects

In high doses, possible CNS stimulation.b

Cautious use recommended in patients with seizure disorders and those with sensitivity to sympathomimetic amines.146 c

Metabolic Effects

Possible hypokalemia, which may increase risk of adverse cardiovascular effects.k l m

Cautious use recommended in patients with diabetes mellitus or hyperthyroidism.145 146 c f

Specific Populations

Pregnancy

Category C.c f g

Lactation

Not known whether metaproterenol is distributed into milk.c f g With oral inhalation solution, use caution.g Administer oral solution or inhalation aerosol to nursing women only if potential benefits to the woman outweigh the possible risk to infant.c f

Pediatric Use

Safety and efficacy of oral inhalation aerosol or solution for nebulization not established in children <12 years of age.c g

Safety and efficacy of oral tablets not established in children <6 years of age.146 b Safety and efficacy of oral solution demonstrated in limited number of pediatric patients <6 years of age.f

Common Adverse Effects

Inhalation aerosol: Nervousness, c headache,c dizziness,c palpitations,c GI distress,c tremor,c throat irritation,c nausea,c vomiting,c cough,c asthma exacerbation.c

Inhalation solution: Nervousness,g tachycardia,g tremor,g nausea.g

Oral tablets: Nervousness,146 tachycardia,146 tremor,146 headache,146 palpitations,146 nausea,146 GI distress,146 dizziness,146 asthma exacerbation, 146 insomnia,146 fatigue,146 diarrhea,146 bad taste,146 vomiting,146 drowsiness,146 syncope,146 hypertension,146 pruritus,146 appetite changes,146 dry throat,146 fever.146

Oral solution: Tachycardia,f nervousness,f tremor,f nausea,f headache.f

Interactions for Alupent

Specific Drugs

Drug

Interaction

Comments

Antidepressants, tricyclic

Increased effect on vascular system146 c f

Use caution146 c f

β-Adrenergic blocking agents

Antagonism of pulmonary effects, bronchospasmb n

If concomitant use necessary, use cardioselective β-adrenergic blocker without intrinsic sympathomimetic activity (e.g., metoprolol, atenolol, esmolol); use low dosages initially and titrate upward with cautionn

MAO inhibitors

Increased effect on vascular system 146 c f

Use caution146 c f

Methylxanthine derivatives

Pharmacokinetic interaction unlikelye

Potential for increased cardiotoxic effects (e.g., arrhythmias)100 101 102 146 c g

Sympathomimetic agents

Additive effects and possible toxicityb c f

Concomitant use not recommendedc f

Exercise extreme care and allow sufficient time to elapse prior to administration of another sympathomimetic agent146 c (See Duration under Pharmacokinetics)

Alupent Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability about 10%.f h

Onset

Oral inhalation aerosol: ≤1 minute.b

Oral: ≤15–30 minutes.146 b

Oral inhalation solution: ≤5–30 minutes.b g

Oral or oral inhalation: Peak effect ≤1 hour.b

Duration

Oral: ≤4 hours for oral solution and ≥4 hours for tablets.146 f

Oral inhalation aerosol: About 1–2.5 hours.c

Oral inhalation solution: 4–6 hours.g

Bronchodilating effect of metaproterenol persists for ≥1 hour longer than that of equipotent doses of isoproterenol.b

Distribution

Extent

Not known if metaproterenol is distributed into milk.c

Plasma Protein Binding

Approximately 10–15%.i

Elimination

Metabolism

Following oral administration, extensively metabolized in GI tract to sulfate conjugate.c i Following oral inhalation, may be excreted as glucuronic acid conjugates.145 147

Elimination Route

Oral: Excreted in urine (approximately 40%) mostly as sulfate metabolite.147 f i

Half-life

Biphasic: Terminal half-life 1.5–6 hours.h i

Stability

Storage

Oral

Solution and Tablets

Tight, light-resistant containers at 15–30°C.146 f Protect from moisture.146

Oral Inhalation

Oral inhalation aerosol: 15–25°C; avoid excessive humidity.c

Oral inhalation solution: ≤25°C.145 Discard solution if pinkish or darker than slightly yellow in color or if it contains a precipitate.g

Actions

  • Stimulates β-adrenergic receptors with little or no effect on α-adrenergic receptors.b

  • Less selectivity for β2-receptors than albuterol.b j More selectivity for β2-receptors than isoproterenol.c f i

  • Stimulates the production of cyclic adenosine-3′,5′-monophosphate (cAMP),146 b f which mediates bronchial smooth muscle relaxation and inhibition of release of proinflammatory mediators from mast cells in airways.146 b c f

  • Decreases airway resistance.c f g

  • In high doses, may cause CNS stimulation and some cardiostimulatory effects, which may result in tachycardia and hypertension.b

  • Possible development of tolerance to bronchodilatory effects with prolonged therapy exceeding recommended dosages.b

Advice to Patients

  • Importance of adherence to dosing schedules of metaproterenol and concomitant therapy, including not exceeding recommended dosage or frequency of use unless otherwise instructed by a clinician.b f

  • Importance of using extreme care when considering administration of additional sympathomimetic agents.f Importance of allowing a sufficient interval of time to elapse before administering another sympathomimetic agent.f (See Specific Drugs under Interactions.)

  • Importance of contacting clinician if asthmatic symptoms worsen or adverse reactions or diminished response occurs with usual dosage;b f g do not increase dose or frequency of administration.c f

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

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

  • Importance of advising patients of other important precautionary information.146 c f g (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

Metaproterenol Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

10 mg/5 mL*

Metaproterenol Sulfate Syrup

Novex, Par, Silarx

Tablets

10 mg*

Metaproterenol Sulfate Tablets

Par, Teva, Watson

20 mg*

Metaproterenol Sulfate Tablets

Par, Teva, Watson

Oral Inhalation

Aerosol

0.65 mg/metered spray

Alupent (with chlorofluorohydrocarbon propellants)

Boehringer Ingelheim

Solution, for nebulization

0.4%

Metaproterenol Sulfate Inhalation Solution

Dey

0.6%

Metaproterenol Sulfate Inhalation Solution

Dey

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation solution prescribing information. Ridgefield, CT; 1995 July.

101. Joseph X, Whitehurst VE, Bloom S et al. Enhancement of cardiotoxic effects of β-adrenergic bronchodilators by aminophylline in experimental animals. Fundam Appl Toxicol. 1981; 1:443-7. [PubMed 6136445]

102. Anon. Interaction between methyl xanthines and beta adrenergic agonists. FDA Drug Bull. 1981; 11:19-20. [PubMed 6119269]

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

104. Lourenco RV, Cotromanes E. Clinical aerosols: I. characterization of aerosols and their diagnostic uses. Arch Intern Med. 1982; 142:2163-92. [PubMed 6753780]

105. Guill MF, Maloney MJ, DuRant RH. Comparison of inhaled metaproterenol, inhaled atropine sulfate, and their combination in treatment of children with acute asthma. Ann Allergy. 1987; 59:367-71. [IDIS 246510] [PubMed 3318574]

106. Nussbaum E, Eyzaguirre M, Galant SP. Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma. Pediatrics. 1990; 85:1072-5. [IDIS 270835] [PubMed 2187175]

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

108. Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs. 1991; 42:895-912. [PubMed 1723379]

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

110. Lipworth BJ. Risks versus benefits of inhaled β2-agonists in the management of asthma. Drug Safety. 1992; 7:54-70. [PubMed 1346963]

111. Sears MR, Taylor DR, Print CG et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 1990; 336:1391-6. [IDIS 275192] [PubMed 1978871]

112. Anon. Warnings from the CSM. Int Pharm J. 1991; 5:247-8.

113. Spitzer WO, Sussa S, Ernst P et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med. 1992; 326:501-6. [IDIS 291894] [PubMed 1346340]

114. Palmer JBD, Jenkins MM. β2-agonists in asthma. Lancet. 1991; 337:43. [IDIS 275815] [PubMed 1670660]

115. Dahl R. β2-agonists in asthma. Lancet. 1991; 337:43. [IDIS 275815] [PubMed 1670660]

116. Löfdahl CG, Svedmyr N. Beta agonists—friends or foes? Eur Respir J. 1991; 4:1161-5. Editorial.

117. Kamada AK, Spahn JD, Blake KV. Salmeterol: its place in asthma management. Ann Pharmacother. 1994; 28:1100-2. [IDIS 335815] [PubMed 7803888]

118. Wanner A. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? Yes. Am J Respir Crit Care Med. 1995; 151:597-9. [IDIS 344522] [PubMed 7881643]

119. Sears MR. Is the routine use of inhaled β-adrenergic agonists appropriate in asthma treatment? No. Am J Respir Crit Care Med. 1995; 151:600-1. [IDIS 344523] [PubMed 7881644]

120. Lai CKW, Twentyman OP, Holgate ST. The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the asssociated change in nonspecific bronchial responsiveness. Am Rev Respir Dis. 1989; 140:917-23. [IDIS 310468] [PubMed 2572192]

121. Suissa S, Ernst P, Boivin JF et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994; 149(3 Part 1):604-10. [IDIS 327105] [PubMed 8118625]

122. 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]

123. Cockcroft DW, McParland CP, Britto SA et al. Regular inhaled salbutamol and airway responsiveness to allergen. Lancet. 1993; 342:833-7. [IDIS 320479] [PubMed 8104272]

124. Mullen ML, Mullen B, Carey M. The association between β-agonist use and death from asthma: a meta-analytic integration of case-control studies. JAMA. 1993; 270:1842-5. [IDIS 320909] [PubMed 8105113]

125. Reviewers’ comments (personal observations) on Salmeterol 12:12.

126. 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.

127. Devoy MAB, Fuller RW, Palmer JBD. Are there any detrimental effects of the use of inhaled long-acting β2-agonists in the treatment of asthma? Chest. 1995; 107:1116-24.

128. McFadden ER Jr. Perspectives in β2-agonist therapy: vox clamantis in deserto vel lux in tenebris? J Allergy Clin Immunol. 1995; 95:641-51.

129. Crane J, Burgess C, Pearce N et al. Asthma deaths in New Zealand. BMJ. 1992; 304:1307. [IDIS 296806] [PubMed 1606438]

130. Crane J, Pearce N, Flatt A et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet. 1989; 1:917-22. [IDIS 254874] [PubMed 2565417]

131. Pearlman DS, Chervinsky P, LaForce C et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992; 327:1420-5.

132. D’Alonzo GE, Nathan RA, Henochowicz S et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994; 271:1412-6.

133. Drazen JM, Israel E, Boushey HA et al. Comparison of regularly scheduled with as- needed use of albuterol in mild asthma. N Engl J Med. 1996; 335:841-7.

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

135. 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 from website. Accessed Sep. 26, 2002

136. 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 from website. Accessed Sep. 26, 2002.

137. 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.

138. 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 from website. Accessed Sep. 30, 2002.

139. 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.

140. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Mar.

141. 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.

142. 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. [PubMed 15340581]

143. 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]

144. 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 from website. Accessed Oct. 5, 2005.

145. Dey. Metaproterenol sulfate (0.4 and 0.6%) inhalation solution. Napa , CA; 1998 Apr.

146. Par Pharmaceuticals. Metaproterenol tablets prescribing information. Spring Valley, NY; 2000 Sep.

147. MacGregor TR, Nastasi L, Farina PR et al. Isolation and characterization of metaproterenol-3-O-sulfate: a conjugate of metaproterenol in human urine. Drug Metab Dispos. 1983; 160:568-73.

b. AHFS drug information 2007. McEvoy GK, ed. Metaproterenol. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1321-3.

c. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Feb.

d. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation aerosol patient instructions. Ridgefield, CT; 1999 Feb.

e. Upton RA. Pharmacokinetic interactions between theophylline and other medication. Clin Pharmacokinet. 1991; 20:66-80. [PubMed 1674242]

f. Apotex Corporation. Metaproterenol sulfate oral solution prescribing information. Weston, FL; 2005 May.

g. Dey. Metaproterenol sulfate (0.4 and 0.6%) inhalation solution prescribing information. Napa , CA; 2006 Jan.

h. Kelly HW. New β2-adrenergic agonist aerosols. Clin Pharm. 1985; 4:393-403. [PubMed 2864159]

i. Hatch F, McKellop K, Hansen G et al. Relative bioavailability of metaproterenol in humans utilizing a single-dose, stable isotope approach. J Pharm Sci. 1986; 75:886-90. [PubMed 3783458]

j. National Asthma Education Program Expert Panel Report. Executive summary: guidelines for the diagnosis and management of asthma—update on selected topics 2002. NIH Publication No. 02-5075. Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 2002 Jun.

k. Burgess CD, Windom HH, Pearce N et al. Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma. Am Rev Respir Dis. 1991; 143(2):444-6. [PubMed 1671326]

l. Gelmont DM, Balmes JR, Yee A. Hypokalemia induced by inhaled bronchodilators. Chest. 1988; 94:763-6. [PubMed 3168573]

m. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of β-agonists in patients with asthma and COPD. Chest. 2004; 125:2309-21. [PubMed 15189956]

n. Tafreshi MJ, Weinacker AB. Beta-adrenergic-blocking agents in bronchospastic diseases: a therapeutic dilemma. Pharmacotherapy. 1999; 19:974-8. [PubMed 10453968]

o. 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. 2006 Nov. Available from website. Accessed Aug 9, 2007.

Hide
(web2)