ABSTRACT
Background: Drug-drug interactions (DDIs) have the potential to result in severe adverse drug events and profoundly affect patient outcomes. The pivotal role community pharmacists assume in recognizing and effectively managing these interactions necessitates a comprehensive understanding and heightened awareness of their implications. Such knowledge and awareness among community pharmacists are fundamental for ensuring the delivery of safe and efficacious care to patients. Aim: This study aimed to assess the knowledge of community pharmacists in Jeddah, Saudi Arabia, regarding drug-drug interactions (DDIs). Method: A cross-sectional survey was administered to a cohort of 147 community pharmacists through the utilization of a self-administered questionnaire. The questionnaire encompassed a comprehensive range of 30 multiple-choice questions, encompassing various facets pertaining to drug-drug interactions (DDIs). Results: A total of 147 community pharmacists working in Jeddah City, Saudi Arabia, completed the survey. The majority of them were male (89.1%, n = 131), and had bachelor's degrees in pharmacy. Results showed that the lowest correct response of DDIs was between Theophylline/Omeprazole, while the highest was between amoxicillin and acetaminophen. Results revealed that among the 28 drug pairs, only six pairs were determined correctly by most participants. The study found that majority of the studied community pharmacist could not determine the correct answer on drug-drug interaction knowledge, as also seen with the measured below half mean DDIs knowledge of 38.22 ± 22.0 (min = 0, max = 89.29, median = 35.71). Conclusion: The study highlights the need for ongoing training and education programs for community pharmacists in Saudi Arabia to enhance their knowledge and understanding of DDIs, ultimately leading to improved patient care and safety.
ABSTRACT
Epilepsy is a complex neurological condition characterized by repeated spontaneous seizures and can be induced by initiating seizures known as status epilepticus (SE). Elaborating the critical molecular mechanisms following SE are central to understanding the establishment of chronic seizures. Here, we identify a transient program of molecular and metabolic signaling in the early epileptogenic period, centered on day five following SE in the pre-clinical kainate or pilocarpine models of temporal lobe epilepsy. Our work now elaborates a new molecular mechanism centered around Wnt signaling and a growing network comprised of metabolic reprogramming and mTOR activation. Biochemical, metabolomic, confocal microscopy and mouse genetics experiments all demonstrate coordinated activation of Wnt signaling, predominantly in neurons, and the ensuing induction of an overall aerobic glycolysis (Warburg-like phenomenon) and an altered TCA cycle in early epileptogenesis. A centerpiece of the mechanism is the regulation of pyruvate dehydrogenase (PDH) through its kinase and Wnt target genes PDK4. Intriguingly, PDH is a central gene in certain genetic epilepsies, underscoring the relevance of our elaborated mechanisms. While sharing some features with cancers, the Warburg-like metabolism in early epileptogenesis is uniquely split between neurons and astrocytes to achieve an overall novel metabolic reprogramming. This split Warburg metabolic reprogramming triggers an inhibition of AMPK and subsequent activation of mTOR, which is a signature event of epileptogenesis. Interrogation of the mechanism with the metabolic inhibitor 2-deoxyglucose surprisingly demonstrated that Wnt signaling and the resulting metabolic reprogramming lies upstream of mTOR activation in epileptogenesis. To augment the pre-clinical pilocarpine and kainate models, aspects of the proposed mechanisms were also investigated and correlated in a genetic model of constitutive Wnt signaling (deletion of the transcriptional repressor and Wnt pathway inhibitor HBP1). The results from the HBP1-/- mice provide a genetic evidence that Wnt signaling may set the threshold of acquired seizure susceptibility with a similar molecular framework. Using biochemistry and genetics, this paper outlines a new molecular framework of early epileptogenesis and advances a potential molecular platform for refining therapeutic strategies in attenuating recurrent seizures.
