Paradoxical bronchoconstriction caused by β2-adrenoceptor agonists

Introduction: Salbutamol and terbutaline are short-acting β2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β2 adrenergic agonists. Methods: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured. Results: On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV1 at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use. Conclusion: Salbutamol and terbutaline are generally well-tolerated β2 adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.

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Transdermal Nitroglycerine in the Management of Pain Associated with Primary Dysmenorrhoea: A Multinational Pilot Study

Journal of International Medical Research ◽

10.1177/030006059702500106 ◽

1997 ◽

Vol 25 (1) ◽

pp. 41-44 ◽

Cited By ~ 16

Author(s):

O Ré ◽

Keyword(s):

Nitric Oxide ◽

Pain Relief ◽

Muscle Relaxation ◽

Nitric Oxide Donor ◽

Controlled Study ◽

Smooth Muscle Relaxation ◽

Uterine Contractility ◽

Double Blind ◽

Patch Application ◽

Endogenous Nitric Oxide

Endogenous nitric oxide mediates smooth-muscle relaxation with subsequent vasodilatation in the vascular, pulmonary, gastrointestinal and genitourinary tissues. Transdermal nitroglycerine (a nitric oxide donor) has been found effective in inhibiting uterine contractility during premature labour. Sixty-five women with histories of moderate-to-severe pain associated with menses were treated with nitroglycerine patches that delivered 0.2 or 0.1 mg/h. Patches were applied as necessary during the first 3 days of the menstrual cycle for up to three consecutive cycles. Pain intensity was assessed at baseline and at 30 min and at 1, 2 and 4 h after patch application. Most patients obtained pain relief with the first dose of the first day. Pain relief was satisfactory to excellent in 90% of the patients. Headache was reported by 20% of the patients, most often in patients using two consecutive patches. A randomized, double-blind, placebo-controlled study is underway in an attempt to confirm the above findings.

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Nociceptive mechanisms modulate ozone-induced human lung function decrements

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.5.1863 ◽

1998 ◽

Vol 85 (5) ◽

pp. 1863-1870 ◽

Cited By ~ 38

Author(s):

Anthony N. Passannante ◽

Milan J. Hazucha ◽

Philip A. Bromberg ◽

Elston Seal ◽

Larry Folinsbee ◽

...

Keyword(s):

Lung Function ◽

Intermittent Exercise ◽

Forced Expiratory Volume ◽

Endogenous Opioids ◽

Functional Responses ◽

Double Blind ◽

C Fibers ◽

Impaired Lung Function ◽

Opioid Receptor Agonists ◽

Double Blind Crossover Study

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535–1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18–59 yr) known to be “weak” (WR; n = 20) and “strong” O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0.42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 μg/kg iv) or saline. O3 exposure significantly ( P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma β-endorphin levels were not related to an individual’s O3responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.

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Prevention of Recurrent Urinary Tract Infections in Girls

PEDIATRICS ◽

10.1542/peds.59.4.562 ◽

1977 ◽

Vol 59 (4) ◽

pp. 562-565

Author(s):

Jacob A. Lohr ◽

Donna H. Nunley ◽

Stuart S. Howards ◽

Raymond F. Ford

Keyword(s):

Urinary Tract ◽

Adverse Reactions ◽

Low Dose ◽

Double Blind ◽

Urinary Tract Abnormality ◽

History Of ◽

The Difference ◽

Tract Infections ◽

Blind Crossover Study ◽

Double Blind Crossover Study

Eighteen girls between the ages of 3 and 13 years—with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality—were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk.

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THE HEART PRELOAD AND AFTERLOAD INTERACTION AND RR INTERVALS UNDER HARD NORMOBARICHYPOXIA EXPOSURE IN HEALTHY YOUNG PERSONS

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf11340-49 ◽

2013 ◽

Vol 11 (3) ◽

pp. 40-49

Author(s):

Aleksandr Sergeyevich Radchenko ◽

N. S. Borisenko ◽

A. I. Kalinichenko ◽

Yu Yu Rodionova ◽

Yuriy Nikolayevich Korolev ◽

...

Keyword(s):

Diastolic Pressure ◽

Function Analysis ◽

Muscle Relaxation ◽

Left Ventricular ◽

Smooth Muscle Relaxation ◽

Peripheral Vascular ◽

Oxyhemoglobin Saturation ◽

Respiration Frequency ◽

Transfer Function Analysis ◽

Before And After

The study wThe left ventricular end diastolic pressure (EDP) fluctuations, specific peripheral vascular resistance (SPR) and cardiointervals (RR) on the respiration frequency under hard normobaric hypoxia (FIO2 = 0.1) were studied. 7 young men (volunteers) were subject to series of hard hypoxic exposures (6 weeks, every other day, intermittently by 6 × 5 min – FIO2 = 0.1). The hypoxic tests (HT1 and HT2) – FIO2 = 0.1, 15 min continuously) were performed before and after each series. SаO2 at the last 3 m of the tests on average was 82.5 % and 92.0 % respectively (Р < 0.05). During HT1 and HT2 (in comparison with inactivity) were increased: angle of max QRS vector (VQRS) in the frontal plain (68.5° ± 16.68 and 72.94° ± 15.32; 69.62° ± 22.4 and 74.45° ± 17.98 respectively), minutes blood flow (MBF) (6.41 ± 1.98 l/min and 6.87 ± 1.27 l/min; 5,27 ± 1,02 l/min and 5.67 ± 1.19 l/min respectively) (Р < 0.05). SPR was decreased too (27.39 ± 5.45 s.u. and 25.62 ± 4.96 s.u.; 30.59 ± 6.34 s.u. and 27.93 ± 5.77 s.u. respectively) (Р < 0.05). By means of transfer function analysis was shown that EDP fluctuations at HT2 significantly outpace by time (phase) the SPR and RR fluctuations on the respiration frequency (1.19 s ± 0.64 and 1.99 s ± 0.63 or 94.39° ± 43.3 and 125.4° ± 7.54; 1.65 s ± 1.28 and 2.22 s ± 0.87 or 101.4° ± 59.6 and 152.7° ± 21.26 respectively) (Р < 0.05). The increased oxyhemoglobin saturation is a trigger of artery wall smooth muscle relaxation mechanisms and this one is changes the background for beat to beat baroreflex realization on the respiration frequency.

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Adverse Pulmonary Responses to Aspirin and Acetaminophen in Chronic Childhood Asthma

PEDIATRICS ◽

10.1542/peds.71.3.313 ◽

1983 ◽

Vol 71 (3) ◽

pp. 313-318

Author(s):

Thomas J. Fischer ◽

Timothy D. Guilfoile ◽

Hemant H. Kesarwala ◽

John G. Winant ◽

Gregory L. Kearns ◽

...

Keyword(s):

Pulmonary Function ◽

Flow Rate ◽

Past History ◽

Forced Expiratory Volume ◽

Base Line ◽

Double Blind ◽

Asthmatic Children ◽

Significant Difference ◽

History Of ◽

Expiratory Flow

Because aspirin (ASA) is often reported to have an adverse effect on pulmonary function in children with chronic asthma, acetaminophen is commonly used as an ASA substitute in these children. To study acetaminophen effects on pulmonary functions, double-blind, oral challenges of ASA (600 mg), acetaminophen (600 mg), or lactose were administered on separate days to 25 chronic asthmatics, ten boys and 15 girls, ranging in age from 8 to 18 years (mean age ± 1 SD: 12.5 ± 2.8 years). No patient had a past history of adverse reactions to either drug. Forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), maximal mid-expiratory flow rate (FEF25-75), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and flow volume curves were measured at base line and ½, 1, 2, 3, and 4 hours after ingestion of drug or placebo. Persistent decreases from base line FEV1 (> 20%) or FEF25-75 (> 30%) occurred in four ASA- and two acetaminophen-challenged patients. One ASA-sensitive patient was placebo intolerant; another reacted to acetaminophen. The acetaminophen responses were of less intensity than the ASA responses. Analysis of group mean pulmonary function responses to ASA, acetaminophen, and lactose showed no significant difference among the three agents at any time. Aspirin should be used cautiously in asthmatic children. Acetaminophen appears to be an adequate, although not completely, innocuous ASA substitute.

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Treatment of Chronic Childhood Asthma With Beclomethasone Dipropionate Aerosol: I. A Double-Blind Crossover Trial in Nonsteroid-Dependent Patients

PEDIATRICS ◽

10.1542/peds.60.1.7 ◽

1977 ◽

Vol 60 (1) ◽

pp. 7-13

Author(s):

Robert Klein ◽

David Waldman ◽

Harvey Kershnar ◽

William Berger ◽

Anne Coulson ◽

...

Keyword(s):

Beclomethasone Dipropionate ◽

Placebo Treatment ◽

Forced Expiratory Volume ◽

Adrenal Function ◽

Double Blind ◽

Medication Score ◽

Hormone Responses ◽

The Mean ◽

Double Blind Crossover Study ◽

Chronic Childhood

Twenty-two children with chronic asthma requiring daily administration of bronchodilators but not steroids were administered 400 µg of beclomethasone dipropionate aerosol (BDA) or a placebo (vehicle) in a double-blind crossover study. The experimental design consisted of four study periods (four weeks each): (1) baseline, (2) BDA or placebo treatment, (3) washout, (4) BDA or placebo treatment. Evaluation of effectiveness was assessed by daily symptom and medication scores, Wright Peak Flow (WPF) measurements three times each day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal measurement of cortisol level, intravenous (IV) metyrapone tests, and IV adrenocorticotropic hormone responses. Quantitative throat cultures for Candida were taken monthly. Twenty-one of 22 patients correctly identified BDA. The mean weekly symptom score was 76.5 ± 10.8 (mean ± SE) during placebo compared to 21.3 ± 5.3 during BDA therapy (P < .005). The number of attacks per week was 7.1 ± 1.4 in those receiving placebo and 1.6 ± 0.6 in those receiving BDA (P < .005). Mean medication score was 39.6 ± 3.6 during placebo and 21.6 ± 1.3 during BDA therapy (P < .005). Mean weekly average WPF measurements increased 33% with BDA therapy compared to placebo. Eighty percent of patients showed an increase in forced expiratory volume in one second and in maximum midexpiratory flow rate during BDA therapy. All throat cultures were negative. No pituitary-adrenal function suppression was noted in any of the parameters studied. BDA was shown to be highly effective in controlling asthma and produced no adverse effects.

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Effectiveness of Terbutaline and Theophylline Alone and in Combination in Exercise-Induced Bronchospasm

PEDIATRICS ◽

10.1542/peds.67.4.508 ◽

1981 ◽

Vol 67 (4) ◽

pp. 508-513

Author(s):

Gail G. Shapiro ◽

Joseph J. McPhillips ◽

Kevin Smith ◽

Clifton T. Furukawa ◽

William E. Pierson ◽

...

Keyword(s):

Drug Administration ◽

Study Drug ◽

Forced Expiratory Volume ◽

Exercise Tests ◽

Double Blind ◽

Study Drug Administration ◽

Before And After ◽

Forced Expiratory Flow ◽

Exercise Induced ◽

Better Than

Theophylline and terbutaline, alone and in combination, were evaluated for effectiveness in treating exercise-induced bronchospasm (EIB) when used at doses that should be tolerated by adolescents taking them intermittently: theophylline, 250 mg (fast release), and terbutaline, 2.5 mg. Twenty-one subjects, 12 to 19 years of age, with EIB performed standardized exercise tests on four separate days and received either theophylline, terbutaline, the combination, or placebo in a prerandomized double-blind manner prior to exercise. Exercise tests were performed two and five hours after each study drug administration. Blood samples were drawn before and again two and five hours after drug administration for theophylline level. Pulmonary function [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow rate (FEF25% to 75%)] was recorded before and after exercise. All of the active treatments were better than placebo in diminishing EIB. The combination was statistically better than terbutaline or theophylline alone. The effect of theophylline was not significantly different from that of terbutaline. The combination induced significantly more tremor than either agent individually. Either drug alone or the two in combination is effective for diminishing EIB. Although the combination may have additive properties for some patients, the increased incidence of tremor may diminish its appeal. Either drug alone or in combination is effective in decreasing EIB for at least five hours, which makes them practical choices for treatment of school-aged children.

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Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia

Advances in Preventive Medicine ◽

10.1155/2015/351059 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Kevin D. Ballard ◽

Lindsay Lorson ◽

C. Michael White ◽

Paul D. Thompson ◽

Beth A. Taylor

Keyword(s):

Smooth Muscle ◽

Arterial Stiffness ◽

Serum Lipids ◽

Pulse Wave ◽

Short Term ◽

Double Blind ◽

Simvastatin Treatment ◽

Time Interaction ◽

Before And After ◽

History Of

Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n=115) completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P=0.01) following simvastatin treatment but not placebo (drug ∗ time interaction:P=0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P≥0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r=-0.207,P=0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

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Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.1.g32 ◽

2001 ◽

Vol 280 (1) ◽

pp. G32-G42 ◽

Cited By ~ 43

Author(s):

Ya-Ping Fan ◽

Sushanta Chakder ◽

Feng Gao ◽

Satish Rattan

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Muscle Relaxation ◽

Smooth Muscle Relaxation ◽

No Production ◽

Muscarinic Agonist ◽

Basal Tone ◽

Before And After ◽

Oxide Synthase ◽

Nanc Relaxation

We examined the effect of endotoxin lipopolysaccharide (LPS) on the basal tone and on the effects of different stimuli and agonists and transcriptional and translational expression of nitric oxide (NO) synthase (NOS) isozymes in the lower esophageal sphincter (LES), pyloric sphincter (PS), and internal anal sphincter (IAS). NO release was also examined before and after LPS. LPS caused a dose-dependent fall in the basal tone and augmentation of the relaxation caused by nonadrenergic, noncholinergic (NANC) nerve stimulation in the LES and IAS. In the PS, LPS had no significant effect on the basal tone and caused an attenuation of the NANC relaxation and an augmentation of the contractile response of muscarinic agonist. Interestingly, the smooth muscle relaxation by atrial natriuretic factor was suppressed in the LES and IAS but not in the PS. These changes in the sphincteric function following LPS may be associated with increase in the inducible NOS (iNOS) expression since they were blocked by iNOS inhibitorl-canavanine. Augmentation of NANC relaxation in the LES and IAS smooth muscle by LPS may be due to the increased activity of neuronal NOS and NO production.

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