Potential mechanisms underlying the effects of lipid emulsion against theophylline-induced toxicity

• Published in: The American journal of emergency medicine Vol. 45; pp. 629 - 630
• Main Authors: Lee, Soo Hee, Sohn, Ju-Tae
• Format: Journal Article
• Language: English
• Published: Philadelphia Elsevier Inc 01.07.2021; Elsevier Limited
• Subjects: Adenosine; Adrenergic receptors; Asthma; Catecholamines; Chronic obstructive pulmonary disease; Cyclic AMP; Cyclic GMP; Distributive shock; Drug dosages; Emergency medical care; Endothelium; Glycogen; Glycogen synthase kinase 3; Kinases; Lipid emulsion; Lipids; Lung diseases; Mitochondria; Nitric oxide; Obstructive lung disease; Phosphodiesterase; Phosphorylation; Smooth muscle; Theophylline; Toxicity; Vasodilation; Distributive shock; Theophylline; Lipid emulsion
• ISSN: 0735-6757; 1532-8171
• DOI: 10.1016/j.ajem.2020.11.042

Theophylline, a bronchodilator used to treat asthma and chronic obstructive pulmonary disease, has a narrow safety margin and the following mechanisms of action: phosphodiesterase inhibition associated with increased cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP) level, adenosine receptor inhibition, and improved endogenous catecholamine release associated with beta-adrenoceptor activation [2]. The direct mechanism of lipid emulsion treatment as a non-specific antidote for drug toxicity includes inotropic effects, nitric oxide (NO) release inhibition, fatty acid supply, mitochondrial dysfunction attenuation, and glycogen synthase kinase-3β phosphorylation [3]. Altogether, lipid emulsion-mediated inhibition of NO-induced vasodilation may contribute to treat distributive shock, which is partially mediated via augmented NO-induced vasodilation induced by toxic theophylline doses. [...]studies regarding lipid emulsion effects on hemodynamic changes induced by toxic doses of theophylline-induced NO-mediated vasodilation are needed.