Aminophylline toxicity—how many hospital asthma deaths does it cause?

Eason, John; Markowe, Hugh L.J.

doi:10.1016/s0954-6111(89)80035-6

Cited by 27 publications

(10 citation statements)

References 31 publications

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“…Several deaths have been reported after intravenous aminophylline. In one study of 43 asthma deaths in southern England, there was a significantly greater frequency of toxic theophylline concentrations (21%) compared with matched controls (7%) [124]. These concerns have lead to the view that intravenous aminophylline should be reserved for the few patients with acute severe asthma who fail to show a satisfactory response to nebulized β-agonists.…”

Section: Acute Severe Asthmamentioning

confidence: 99%

“…There has recently been concern that theophylline, even at therapeutic concentrations, may lead to behavioural disturbance and learning difficulties in school children [142][143][144], although a carefully designed study could not confirm this [145]. At high concentrations, convulsions and cardiac arrhythmias may occur, and there is concern that intravenous aminophylline administered in the emergency room may be a contributory factor to the deaths of some patients with severe asthma [124].…”

Section: Side-effectsmentioning

confidence: 99%

See 1 more Smart Citation

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

249

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: Acute Severe Asthmamentioning

confidence: 99%

Section: Side-effectsmentioning

confidence: 99%

Theophylline in the management of asthma: time for reappraisal?

Barnes¹,

Pauwels²

1994

Eur Respir J

249

107

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“…Theophylline Can cause adverse effects due to theophylline toxicity. Eason and Markowe, 1989 Montelukast Increased risk of ecchymosis. Aypak et al, 2013 Methotrexate May cause elevation of liver enzymes and hepatotoxicity.…”

Section: -Lipoxygenase Inhibitorsmentioning

confidence: 99%

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

Iqbal

Baker

Khan

et al. 2017

British J Pharmacology

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Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL-C). For~50 years, HDL-C has been considered as the atheroprotective 'good' cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL-C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL-C levels. Based on these data, the significance of HDL-C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL-C functionality, rather than HDL-C concentration, is important for the CVD-preventive qualities of HDL-C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL-C. Our survey indicates that HDL-C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of antiinflammatory drugs to either prevent HDL-C clearance or improve the function and production of HDL-C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL-C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD. LINKED ARTICLES IntroductionThere have been several sharp turns in the evidence trail marking the atheroprotective role of high density lipoproteins (HDLs). Very early studies on dyslipidaemia highlighted the positive correlation between total triglycerides (TGs) with the risk of developing cardiovascular disease (CVD). Since the mid-1970s, numerous epidemiological and animal studies, including the Framingham Study (Gordon et al., 1977), reported that HDL cholesterol (HDL-C) has the strongest inverse relationship with the development of CVD of the known serum lipid factors (Badimon et al., 1990;Rubin et al., 1991;Liu et al., 1994;Plump et al., 1994). This association is underpinned by reverse cholesterol transport (RCT) -a process by which HDL-C transfers the cholesterol from peripheral cells, for example, lipid-laden foam cells, to the liver for secretion into bile and faeces. The promotion of RCT is considered a major anti-atherogenic function of HDL-C (Gofman et al., 1966;Miller and Miller, 1975;Rhoads et al., 1976). Based on these findings, interventions to increase the levels of HDL-C were developed but found to be ineffective for preventing cardiovascular outcomes in several large clinical trials (Brousseau et al., 2004;McKenney et al., 2006;Barter et al., 2007;Boden et al., 2011;Lü...

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“…Several deaths have been reported after intravenous aminophylline. In one study of 43 asthma deaths in southern England there was a significantly greater frequency of toxic theophylline concentrations (21%) compared with matched controls (7%) [ 96 ]. These concerns have lead to the view that intravenous aminophylline should be reserved for the few patients with acute severe asthma who fail to show a satisfactory response to nebulized β 2 -agonists.…”

Section: Clinical Usementioning

confidence: 99%

Theophylline

Barnes

2010

Pharmaceuticals

103

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Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is markedly reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) and blood concentrations are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids and in COPD patients with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism.

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Aminophylline toxicity—how many hospital asthma deaths does it cause?

Cited by 27 publications

References 31 publications

Theophylline in the management of asthma: time for reappraisal?

Theophylline in the management of asthma: time for reappraisal?

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

Theophylline

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