Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects

Higbee, Martin D.; Kumar, M Arun; Galant, Stanley P.

doi:10.1016/0091-6749(82)90028-8

Cited by 102 publications

(27 citation statements)

References 10 publications

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“…Theophylline increases the secretion of adrenaline from the adrenal medulla [40,41], although the increase in plasma concentration is small and insufficient to account for any significant bronchodilator effect [42]. The release of catecholamines may only be relevant when aminophylline is given intravenously.…”

Section: Increased Catecholamine Releasementioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

248

107

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T Th he eo op ph hy yl ll li in ne e i in n t th he e m ma an na ag ge em me en nt t o of f a as st th hm ma a: : t ti im me e f fo or r r re ea ap pp pr ra ai is sa al l? ?P.J. Barnes*, R.A. Pauwels** Theophylline is now considered to be a bronchodilator, but it is increasingly recognized that theophylline has other anti-asthma activities, which may be more important. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. These clinical pharmacological observations are substantiated by experimental animal and in vitro data showing that theophylline has several anti-inflammatory activities relevant to asthma. These include the inhibition of cytokine synthesis and release, the inhibition of inflammatory cell activation and microvascular leakage, and the prevention of airway hyperresponsiveness induced by airway inflammation. Theophylline appears to have immunomodulatory effects, even at relatively low plasma concentrations.Based on these considerations, theophylline can be regarded as a useful alternative to other anti-inflammatory drugs for the chronic treatment of mild to moderate asthma. Theophylline should be used at lower doses to achieve plasma concentrations of 5-10 mg·l -1 , which will avoid the risk of side-effects.Further studies are required to evaluate the role of low-dose theophylline as an adjunct to low-dose inhaled steroids in the management of chronic asthma. It may now be appropriate to re-evaluate the role of theophylline in asthma management.

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Section: Increased Catecholamine Releasementioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

248

107

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“…The proposed mechanism for bronchodilatation involves the non-selective inhibition of phosphodiesterase isoenzymes, 131 in particular, the inhibition of phosphodiesterase-IV, which reduces the intracellular degradation of cAMP. 132 Other mechanisms include increased respiratory drive and diaphragmatic contractility, 133 stimulation of endogenous catecholamine release, 134 prostaglandin antagonism, 135 and inhibition of afferent neuronal activity. 136 In addition, theophylline is known to have anti-inflammatory and immunomodulatory effects, although the contributions of these mechanisms to its therapeutic effects in children with asthma have not been studied.…”

Section: Methylxanthinesmentioning

confidence: 99%

Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

Nievas

Anand

2013

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVES An increasing prevalence of pediatric asthma has led to increasing burdens of critical illness in children with severe acute asthma exacerbations, often leading to respiratory distress, progressive hypoxia, and respiratory failure. We review the definitions, epidemiology, pathophysiology, and clinical manifestations of severe acute asthma, with a view to developing an evidence-based, stepwise approach for escalating therapy in these patients. METHODS Subject headings related to asthma, status asthmaticus, critical asthma, and drug therapy were used in a MEDLINE search , supplemented by a manual search of personal files, references cited in the reviewed articles, and treatment algorithms developed within Le Bonheur Children's Hospital. RESULTS Patients with asthma require continuous monitoring of their cardiorespiratory status via noninvasive or invasive devices, with serial clinical examinations, objective scoring of asthma severity (using an objective pediatric asthma score), and appropriate diagnostic tests. All patients are treated with β-agonists, ipratropium, and steroids (intravenous preferable over oral preparations). Patients with worsening clinical status should be progressively treated with continuous β-agonists, intravenous magnesium, helium-oxygen mixtures, intravenous terbutaline and/or aminophylline, coupled with high-flow oxygen and non-invasive ventilation to limit the work of breathing, hypoxemia, and possibly hypercarbia. Sedation with low-dose ketamine (with or without benzodiazepines) infusions may allow better toleration of non-invasive ventilation and may also prepare the patient for tracheal intubation and mechanical ventilation, if indicated by a worsening clinical status. CONCLUSIONS Severe asthma can be a devastating illness in children, but most patients can be managed by using serial objective assessments and the stepwise clinical approach outlined herein. Following multidisciplinary education and training, this approach was successfully implemented in a tertiary-care, metropolitan children's hospital. INDEX TERMS asthma, child, critical care, infant, respiratory failure, status asthmaticus J Pediatr Pharmacol Ther 2013;18(2):88-104

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“…Several other mechanisms have, therefore, been proposed to explain how methylxanthines exert their bronchodilator effect. These include antagonism of adenosine receptors (Fredholm, 1980), increased secretion of endogenous catecholamines (Higbee et al, 1982), inhibition of constrictor prostanoid formation (Horrobin et al, 1977) and a reduction in intracellular Ca24 concentrations (Kolbeck et al, 1979). To date, none of these proposed mechanisms of action is, in its own right, wholly satisfactory (Persson, 1985).…”

Section: Introductionmentioning

confidence: 99%

Effects of phosphodiesterase inhibitors on normal and chemically‐skinned isolated airway smooth muscle

Bryson¹,

Rodger²

1987

British J Pharmacology

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1 The effects of three phosphodiesterase inhibitors (papaverine, igobutyl methyl xanthine (IBMX) and SKF 94120) were examined on tension responses and cyclic nucleotide content (both cyclic AMP and cyclic GMP) of normal and Triton X-100 skinned isolated trachealis of the guinea-pig. 2 The three inhibitors were approximately equipotent in eliciting concentration-dependent relaxation of histamine-induced contractions of the trachealis. 3 Papaverine-induced relaxation was associated with concentration-related increases in the levels of both cyclic nucleotides. 4 IBMX at low concentrations (1 gmol 1-') produced significant relaxation (36%) of histaminecontracted trachealis without changing cyclic nucleotide levels. At a ten fold higher concentration IBMX-induced relaxation (95%) was associated with a selective increase in tissue cyclic GMP levels.Only at the highest concentration tested (100 gmol I-) did IBMX increase cyclic AMP levels significantly.5 SKF 94120(1 pmol 1-') elicited a 23% relaxation of the contracted trachealis without altering the tissue content ofeither cyclic nucleotide. At the two higher concentrations tested (10 and 100 pmol 1 -'), SKF 94120-induced relaxation was accompanied by a selective increase in the levels of cyclic AMP. 6 In the skinned trachealis Ca2" (10 and 20 gmol I ')-induced contractions were significantly inhibited by the calmodulin antagonist calmidazolium (10 gtmol 1I-') and by cyclic AMP (10 pmol 1 1'), the catalytic subunit of cyclic AMP-dependent protein kinase (0.1 pmol I') and cyclic GMP (10 pmol l'). 7 Papaverine (1O00Imoll-') significantly inhibited (31 ± 6%) the Ca2t-induced contractions of the skinned trachealis. Both IBMX and SKF 94120 were without effect. 8 It is concluded that cyclic nucleotide-dependent mechanisms have an inhibitory action on the biochemical processes that lead to contraction of the guinea-pig trachealis. The results suggest that a functional sarcoplasmic reticular and/or plasma membrane is essential for the expression of IBMXand SKF 94120-induced relaxation. This is not the case for papaverine. The results also highlight the fact that significant relaxant responses of airway smooth muscle can be produced by phosphodiesterase-inhibiting drugs without concomitant elevations in tissue cyclic nucleotide content.

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Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects

Cited by 102 publications

References 10 publications

Theophylline in the management of asthma: time for reappraisal?

Theophylline in the management of asthma: time for reappraisal?

Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

Effects of phosphodiesterase inhibitors on normal and chemically‐skinned isolated airway smooth muscle

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