Drug–drug interactions between propofol and ART drugs: Inhibiting neuronal activity by affecting glucose metabolism

Abstract

BackgroundThe use of two or more drugs carries the potential risk of drug–drug interactions (DDIs), which may result in adverse reactions. Some human immunodeficiency virus (HIV)‐infected patients who receive antiretroviral therapy (ART) may require general anesthesia with propofol (PRL) before undergoing surgical treatment. Both PRL and ART drugs may lead to neuronal dysfunction, which can be accompanied by energy metabolism disorders. Neurons take in glucose mainly through glucose transporter 3 (Glut3) which is specifically expressed on the cell membranes of neurons. However, to date, no study has examined whether the DDIs of PRL and ART drugs interfere with glucose metabolism and Glut3 expression in neurons.MethodsAn in vitro model was constructed using the primary cultures of neurons. PRL and ART drugs (EFV, AZT, and 3TC), were added at different concentrations (low, medium, and high). The neurons were exposed to the drugs for 1, 4, 8, and 12 h. The optimal drug concentration and exposure time were selected. The cellular survival rate, glucose concentration, electrophysiology, and the expression of Glut3 were detected.ResultsThere were no significant changes in the cellular survival rates of the neurons that were exposed to both PRL and ART drugs at low concentrations for 1 h. However, the survival rates of the neurons decreased significantly as the drug concentrations and durations increased. The glucose concentration of the neurons that were exposed to both PRL and the ART drugs was significantly decreased. The glucose concentration of the neurons was not affected by any individual drug. The amplitude of the action potential and the expression of Glut3 were decreased in the neurons that were exposed to both PRL and ART drugs.ConclusionsThe main adverse reactions induced by the DDIs between PRL and the ART drugs were decreased glucose metabolism and neuronal damage, which were caused by inhibiting the expression of Glut3. More importantly, we found that decreases in glucose metabolism predated neuronal damage.

A Retrospective Analysis of Central and Peripheral Metabolic Characteristics in Patients with Cryptococcal Meningitis

“…Even worse, peripheral metabolic disorders can lead to CNS damage [ 31 ]. Our previous study confirmed that the disruption of glucose metabolism predated neuronal damage [ 32 ], which suggested that correcting the disruption of energy metabolism may save neurons and avoid damage to multiple organ systems. Therefore, maintaining central/peripheral metabolic homeostasis for patients with CM is extremely important to protect the nervous system and to improve their prognosis.…”

“…Our results also suggested that the structural damage leading from C. neoformans may lead to higher protein elevation. The long-term disturbance of energy metabolism in the CNS may be a crucial factor leading to structural damage [ 32 ]. The energy utilization of the brain is mainly dependent on ATP, which mainly comes from glucose [ 51 , 52 ].…”