Ateneo - UPO

Characterization of toxic effects induced by xenobiotic exposure. Methods and approaches used in the toxicological evaluation. Mechanisms underlying xenobiotic adverse effects, with particular attention to drugs. Main organ toxicities: type of induced damage and substances involved, with a particular focus to drugs. Principles of pharmacokinetics and pharmacodynamics.

1. W. Balduini, L. G. Costa; Tossicologia generale e applicata ai farmaci; Edra, 2015.
2. C. Cicala, M. Collino, A. Ialenti; Farmacologia generale; UTET Università, 2023.
3. lecture notes and supplementary teaching materials provided by the professor via the DIR platform.

The course aims to provide knowledge of toxicodynamic and toxicokinetic mechanisms regulating the toxic effects produced by natural and synthetic xenobiotics, with particular regard to drugs, and of the methodologies used for the toxicological risk assessment from exposure to toxic agents.The course provides the methodological tools required for analysis and processing of experimental data for quantitative determination of pharmacokinetic and pharmacodynamic parameters.The 6 ECTS credits (CFU) for the course are distributed as follows: 3 ECTS of delivery-based teaching (DE) through classroom lectures on the principles of toxicology, and 3 ECTS of interactive teaching (DI) focused on pharmacodynamics, pharmacokinetics, and practical data analysis.

There are no formal prerequisites but the course requires basic knowledge of pharmacology.

The course consists of face-to-face lectures and classroom exercises. In the event of a new epidemiological emergency, all lectures will be delivered remotely through audio and video lessons uploaded to the Moodle platform (www.dir.uniupo.it).

Teaching materials will be made available to the student on the Moodle platform (www.dir.uniupo.it)Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services-students-physical-or-learning-disabilitiesStudents with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

The examination consists of a written test followed by an oral test. The written test assesses students’ ability to apply the knowledge acquired during practical exercises and consists of one exercise on receptor binding and one on pharmacokinetics. Each exercise is awarded 15 points if it is completed fully and correctly. The written test is passed if the overall score is at least 18/30. The written test is selective: failure to reach the 18/30 threshold precludes access to the oral examination. During the written test, only the use of a scientific calculator is permitted. Consulting books, lecture notes, personal notes, or electronic devices is strictly prohibited.
In the oral examination, students are asked questions about the main topics covered during the course. The oral test aims to verify the level of knowledge and understanding of the course content and to assess independent judgement, learning capacity, and communication skills.
To pass the examination, students must have passed the written test and demonstrate knowledge and understanding of at least the fundamental concepts of the syllabus. To achieve a high grade, students must be able to use their knowledge and understanding of the course content independently, and to engage in an in-depth discussion of aspects related to the topics covered.

1. General principles of toxicology 2. Mutagenesis and carcinogenesis 3. Developmental toxicology 4. Toxicology in drug development 5. Pharmacovigilance and phytovigilance 6. Classification of adverse drug reactions 7. Allergic reactions to drugs 8. Pharmacogenetics 9. Toxic responses of the liver 10. Toxic responses of the kidney 11. Toxic responses of the respiratory system 12. Toxic responses of the cardiovascular system 13. Principles of the receptor binding technique: the Scatchard graph, the affinity constant and the maximum number of binding sites, IC50 determination. 14. Principles of pharmacokinetics. Single intravenous or oral administration: determination of plasma half-life, plasma and renal clearance, and volume of distribution. Continuous infusion: calculation of plasma concentration at steady state. Repeated administration intravenously and orally: determination of maximum and minimum plasma concentration at steady state.Integration of the gender dimension: The course will address gender differences in toxicological responses, analysing how biological factors (sex) and sociocultural factors (gender) influence the toxicokinetics and toxicodynamics of xenobiotics, with particular reference to organ susceptibility and to the differing incidence of adverse reactions between men and women in pharmacovigilance reporting.

KNOWLEDGE AND UNDERSTANDINGThe student at the end of the teaching will know concepts relative to: - types of toxic effects and factors influencing xenobiotic toxicity; - general principles governing the estimation of the risk deriving from the exposure to chemical agents; - molecular and toxicokinetic mechanisms underlying the toxic effects induced by xenobiotics, with a particular focus on drugs. CAPACITY TO APPLY KNOWLEDGE AND UNDERSTANDINGThe student can demonstrate to apply the theoretical contents through examples of toxic agents in the context of clinical, environmental and occupational toxicology. The student is in possession of the methodological tools required for solving pharmacokinetic and pharmacodynamic questions through experimental data processing. JUDGMENT SKILLS AND COMMUNICATION SKILLSThe student is able to communicate the knowledge acquired through the examination interview. In addition, the student is able to demonstrate that she/he can connect the different topics covered through a "transversal" logic so as to combine the different fields of the discipline. Minimum level of sufficiency: upon completion of the course, students must demonstrate knowledge of basic toxicological definitions and the main mechanisms of organ damage. To pass, they must correctly perform calculation procedures in the written exercises (pharmacokinetics and binding) and answer fundamental theoretical questions during the oral interview, demonstrating a basic understanding of the subject.Advanced level: upon completion of the course, students must demonstrate a critical, cross-disciplinary perspective. The advanced level is characterised by rigorous methodological precision in the written exam and the ability to link pharmacokinetic parameters with toxicological consequences in the oral exam. Independent judgement in the analysis of complex cases, and the use of rigorous, fluent technical-scientific language in both written and oral forms, will be assessed.