Cardiotoxicodynamics

Menke, Nathan B.; Walsh, Steven J.; King, Andrew

doi:10.1016/j.emc.2015.04.007

Cited by 6 publications

(3 citation statements)

References 99 publications

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“…One of the major adverse effects of methylxanthines is cardiac toxicity. In human, acute toxicity of methylxanthines cause functional alteration of cardiac physiology such as tachycardia and arrhythmia [ 1 , 21 ] rather than the structural alteration of heart. However, animal studies have shown association of methylxanthines with structural cardiac defect [ 37 , 38 ] and systematic review has shown cardiovascular malformations as a teratogenic effect of maternal caffeine ingestion in human [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

Basnet

Zizioli

Guarienti

et al. 2017

BMC Pharmacol Toxicol

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BackgroundZebrafish embryos are emerging as a model for pharmacological and toxicological studies. We used zebrafish embryos to study the general toxicity and cardiovascular effects of eight methylxanthines: aminophylline, caffeine, diprophylline, doxofylline, etophylline, 3-isobutyl-1-methylxanthine (IBMX), pentoxifylline and theophylline.MethodsMicroinjections of the eight methylxanthines were performed in 1-2 cell stage zebrafish embryos and the general toxicity and cardiovascular effects were analyzed at different time points. Embryotoxicity and teratogenicity were evaluated to understand the general toxicity of these compounds. Structural and functional alterations of the heart were evaluated to assess the cardiovascular effects.ResultsOur results showed different activity patterns of the methylxanthines drugs. Caffeine, IBMX, pentoxifylline and theophylline were highly embryotoxic and teratogenic; aminophylline, doxofylline and etophylline were embryotoxic and teratogenic only at higher doses, and diprophylline showed a minimal (<10%) embryotoxicity and teratogenicity. Most of these drugs induced structural alteration of the heart in 20-40% of the injected embryos with the maximum dose. This structural alteration was fatal with the embryos ultimately dying within 120 hpf. All the drugs induced a transient increase in heart rate at 48 hpf which returned to baseline within 96 hpf. This functional effect of methylxanthines showed similarity to the studies done in humans and other vertebrates.ConclusionOur results indicate the potential toxicity and teratogenicity of different methylxanthines in the embryos during embryonic development, the most sensitive period of life. Although interspecies differences need to be considered before drawing any conclusion, our study elucidated that a single exposure of methylxanthines at therapeutic range could induce cardiac dysfunction besides causing embryotoxicity and teratogenicity. Of all the drugs, diprophylline appeared to be safer, with lower degree of embryotoxicity, teratogenicity and cardiac toxicity as compared to other methylxanthines.Electronic supplementary materialThe online version of this article (10.1186/s40360-017-0179-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Cardiac toxicity and hemodynamic perturbations are two major aspects of methylxanthine toxicity [ 21 ]. Tachydysrhythmias which includes sinus tachycardia and premature ventricular contraction are the most common dysrhythmia observed with methylxanthines toxicity [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

Basnet

Zizioli

Guarienti

et al. 2017

BMC Pharmacol Toxicol

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“…[70,71] It is worthy of mention that generally, methylxanthines, including theophylline and aminophylline, are known to increase heart rate in human subjects. [76] This effect is well-documented and is attributed to their action as adenosine receptor antagonists, which leads to an increase in sympathetic activity. In contrast, doxofylline appears to be unique among methylxanthines in that it does not have any effect on heart rate in human subjects.…”

Section: Doxofylline Versus Theophylline In Respiratory Carementioning

confidence: 98%

Doxofylline: Advancing and Empowering Equitable Asthma and COPD Management Beyond Tradition

Cazzola,

Page,

Calzetta

et al. 2024

Advanced Therapeutics

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Doxofylline, a newer methylxanthine derivative, has garnered increasing attention for its distinct pharmacological properties and therapeutic advantages over traditional agents such as theophylline. This paper provides a comprehensive review of the pharmacological characteristics and clinical efficacy of doxofylline, elucidating why it represents a significant advancement in methylxanthine therapy. Moreover, attention is given to the economic considerations surrounding its utilization, particularly in low‐ and medium‐income countries where access to healthcare resources is limited. The affordability, improved tolerability, and dosing convenience of doxofylline make it a promising candidate for addressing the substantial burden of asthma and COPD in resource‐constrained settings.

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Successful treatment of flecainide-induced cardiac arrest with extracorporeal membrane oxygenation in the ED

Reynolds

Judge

2015

The American Journal of Emergency Medicine

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Cardiotoxicodynamics

Cited by 6 publications

References 99 publications

Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

Doxofylline: Advancing and Empowering Equitable Asthma and COPD Management Beyond Tradition

Successful treatment of flecainide-induced cardiac arrest with extracorporeal membrane oxygenation in the ED

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