Phd in PHARMACOLOGY AND TOXICOLOGY

Thesis title: Farmacologia e tossicologia clinica nella gestione neuro-anestesiologica e respiratoria: integrazione tra ricerca e pratica assistenziale.

The neuroanesthesiological and respiratory management of critically ill patients remains one of the most complex challenges in intensive care medicine. Clinical pharmacology and toxicology play a crucial role in ensuring effective and safe treatment; however, their application is often complicated by the highly unstable pathophysiological conditions of these patients, who frequently present with neuromuscular disorders and respiratory complications. This research focuses on the integration of pharmacology, toxicology, and clinical practice in neuroanesthesiological and respiratory management, aiming to refine therapeutic strategies to optimize patient care in the intensive care setting. Specifically, the study examines pharmacological agents used for anesthesia, pain management, and mechanical ventilation, as well as their effects on the central nervous system, respiratory function, and muscle physiology. It provides an in-depth analysis of key pharmacological classes, including anesthetics, sedatives, analgesics, neuromuscular blocking agents, and drugs supporting respiratory function. Each class is evaluated not only in terms of pharmacodynamics and pharmacokinetics but also with regard to toxicity risks and drug interactions—critical factors in the management of intensive care therapies. Furthermore, the study investigates the impact of neuromuscular disorders, such as myasthenia gravis and muscular dystrophy, on anesthetic and respiratory pharmacology. These conditions add significant complexity to therapeutic management, emphasizing the necessity of personalized pharmacological approaches. The findings highlight that a thorough understanding of each patient’s specific characteristics, combined with continuous monitoring of neurological and respiratory functions, is key to improving clinical outcomes. Moreover, the study explores the interplay between the gut microbiome and pharmacological responses in critically ill patients, with particular attention to drug modulation through interactions with enteric microorganisms. Preliminary results suggest that the microbiome significantly influences drug efficacy, as well as susceptibility to adverse effects and toxicity. This opens new avenues for integrating personalized medicine into intensive care, considering not only the patient’s genetic profile but also their microbiota composition. Finally, the thesis addresses future challenges in clinical pharmacology and toxicology research, including the emergence of novel pharmacological therapies and the expanding knowledge of microbiome interactions. Pharmacogenomics, advanced monitoring technologies, and artificial intelligence have the potential to revolutionize personalized treatment, enhancing the management of respiratory and neurological complications in critically ill patients. In particular, the use of in vivo and in vitro experimental models, combined with omics-based analysis, could facilitate the development of more targeted and safer therapeutic approaches, minimizing adverse effects while maximizing therapeutic efficacy. In conclusion, the integration of pharmacology, toxicology, and clinical research represents a promising path toward advancing neuroanesthesiological and respiratory management in critically ill patients, with significant implications for improving clinical practice and long-term patient outcomes.