- Alveolar liquid clearance in lung injury: Evaluation of the impairment of the β2-adrenergic agonist response in an ischemia-reperfusion lung injury model. [Journal Article]
- RPRespir Physiol Neurobiol 2018 Aug 29
- While alveolar liquid clearance (ALC) mediated by the β2-adrenergic receptor (β2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury mode...
While alveolar liquid clearance (ALC) mediated by the β2-adrenergic receptor (β2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury models, this response might disappear. Indeed, we have shown that in an ischemia-reperfusion-induced lung injury model, β2-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the β2-AR could explain the lack of response to β2-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in β2-AR concentration or affinity in the injured transplanted lungs compared to the native lungs. Furthermore, we could not enhance ALC in transplanted lungs with dcAMP + aminophylline, a treatment that bypasses the β2-adrenergic receptor and is known to stimulate ALC in normal lungs. However, transplantation decreased αENaC expression in the lungs by 50%. We conclude that the lack of response to β2-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the β2-adrenergic receptors but is attributable to decreased expression of the ENaC channel, which is essential for sodium transport and alveolar liquid clearance in the lung.
- Intravenous Regadenoson with Aminophylline Reversal is Safe and Equivalent to Intravenous Adenosine Infusion for Fractional Flow Reserve Measurements. [Journal Article]
- CCClin Cardiol 2018 Aug 19
- CONCLUSIONS: For FFR measurement, regadenoson and adenosine are equivalent hyperemic agents. Regadenoson with aminophylline reversal may be considered as an alternative to adenosine for FFR measurements. This article is protected by copyright. All rights reserved.
- Acute hemodynamic effects of methylxanthine therapy in preterm neonates: Effect of variations in subgroups. [Journal Article]
- JTJ Trop Pediatr 2018 Jul 30
- CONCLUSIONS: Caffeine has similar effects on cardiac parameters as aminophylline; however, caffeine-treated small-for-gestation stratification gave rise to significant cardiac variations.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- An expert panel considers use of aminophylline to be acceptable during breastfeeding. Maternal aminophylline use may occasionally cause stimulation and irritability and fretful sleep in infants. N...
An expert panel considers use of aminophylline to be acceptable during breastfeeding. Maternal aminophylline use may occasionally cause stimulation and irritability and fretful sleep in infants. Newborn and especially preterm infants are most likely to be affected because of their slow elimination and low serum protein binding of theophylline. There is no need to avoid aminophylline products; however, keep maternal serum theophylline concentrations in the lower part of the therapeutic range and monitor the infant for signs of theophylline side effects. Infant serum theophylline concentrations can help to determine if signs of agitation are due to theophylline. Avoiding breastfeeding for 2 hours after intravenous or 4 hours after an immediate-release oral aminophylline product can decrease the dose received by the breastfed infant.
- No Requirement for Targeted Theophylline Levels for Diuretic Effect of Aminophylline in Critically Ill Children. [Journal Article]
- PCPediatr Crit Care Med 2018; 19(8):e425-e432
- CONCLUSIONS: Aminophylline administration provided a measure of increased diuresis, regardless of dosage, and theophylline trough levels. Therefore, achieving a prescribed therapeutic trough level may not be necessary for full diuretic effect. Because, as opposed to the diuretic effect, the side effect profile of aminophylline is dose-dependent, low maintenance dosing may optimize the balance between providing adjunctive diuretic effect while minimizing the risk of toxicity.
- Aminophylline and Ephedrine, but Not Flumazenil, Inhibit the Activity of the Excitatory Amino Acid Transporter 3 Expressed in Xenopus Oocytes and Reverse the Increased Activity by Propofol. [Journal Article]
- BRBiomed Res Int 2018; 2018:6817932
- We investigated the effects of flumazenil, aminophylline, and ephedrine on the excitatory amino acid transporter type 3 (EAAT3) activity and the interaction with propofol. EAAT3 was expressed in the ...
We investigated the effects of flumazenil, aminophylline, and ephedrine on the excitatory amino acid transporter type 3 (EAAT3) activity and the interaction with propofol. EAAT3 was expressed in the Xenopus oocytes. L-Glutamate-induced membrane currents were measured using the two-electrode voltage clamp at various drug concentrations. Oocytes were preincubated with protein kinase C- (PKC-) activator, or inhibitor, and phosphatidylinositol 3-kinase (PI3K) inhibitor. To study the interaction with propofol, oocytes were exposed to propofol, propofol + aminophylline, or ephedrine. Aminophylline and ephedrine significantly decreased EAAT3 activity. Aminophylline (95 μM) and ephedrine (1.19 μM) significantly decreased Vmax, but not Km of EAAT3, for glutamate. The phorbol 12-myristate-13-acetate-induced increase in EAAT3 activity was abolished by aminophylline or ephedrine. The decreased EAAT3 activities by PKC inhibitors (staurosporine, chelerythrine) and PI3K inhibitor (wortmannin) were not significantly different from those by aminophylline or ephedrine, as well as those by PKC inhibitors or PI3K inhibitor + aminophylline or ephedrine. The enhanced EAAT3 activities induced by propofol were significantly abolished by aminophylline or ephedrine. Aminophylline and ephedrine inhibit EAAT3 activity via PKC and PI3K pathways and abolish the increased EAAT3 activity by propofol. Our results indicate a novel site of action for aminophylline and ephedrine.
- What do Cochrane systematic reviews say about cardiac arrest management? [Review]
- SPSao Paulo Med J 2018; 136(2):170-176
- CONCLUSIONS: This review included nine Cochrane systematic reviews that provided a diverse range of qualities of evidence (unknown to high) regarding interventions that are used in management of cardiac arrest. High-quality evidence was found by two systematic reviews as follows: (a) increased survival until hospital discharge with continuous compression, compared with interrupted chest compression, both administered by an untrained person and (b) no difference regarding the return of spontaneous circulation, comparing aminophylline and placebo, for bradyasystolic patients under cardiac arrest. Further studies are needed in order to reach solid conclusions.
- Efficacy and safety profile of xanthines in COPD: a network meta-analysis. [Review]
- EREur Respir Rev 2018 Jun 30; 27(148)
- Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofyllin...
Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.
- Evaluation of the Effect of Aminophylline in Reducing the Incidence of Acute Kidney Injury After Cardiac Surgery. [Journal Article]
- APAnesth Pain Med 2017; 7(4):e21740
- CONCLUSIONS: Aminophylline in cardiac surgery can reduce the frequency of acute kidney injury according to RIFLE criteria and could be used in the prevention of AKI as a safe and efficient modality in high-risk patients. Also, the use of this drug may reduce the need for inotropic medication at the time of surgery, intensive care unit stay length, and extubation time.
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- Factors affecting the efficacy and safety of aminophylline in treatment of apnea of prematurity in neonatal intensive care unit. [Journal Article]
- PNPediatr Neonatol 2018 Mar 30
- CONCLUSIONS: Infants with apnea and gestational age >30.36 weeks, body weight at initiation of aminophylline treatment above 1.69 kg, and birth weight >1.48 kg are suitable for treatment with aminophylline. Monitoring of serum theophylline concentration should be implemented in the absence of clinical response or in case of suspected adverse reactions.