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. Pharmacovigilance: definition, aims, methodological tools, reference legislation, compilation of ADR reporting forms. Principles of pharmacokinetics.

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. Pharmacokinetics lecture notes and supplementary teaching materials provided by the professor via the DIR platform.

The basic principles of toxicokinetics and toxicodynamics that account for natural and synthetic xenobiotic toxic effects with special attention to drugs. Methodologies used to assess the risk of toxic substance exposure. Acquisition of the theoretical and methodological principles underlying pharmacovigilance. In addition, the course intends to provide the methodological tools required for analysis and processing of experimental data for quantitative determination of pharmacokinetic parameters. The 10 ECTS credits (CFU) for the course are distributed as follows: 8 ECTS of delivery-based teaching (DE) through classroom lectures and 2 ECTS of interactive teaching (DI) through practical pharmacokinetics exercises.

There are no preparatory requirements but optimal use of the course requires basic knowledge of anatomy, physiology, biochemistry, general pharmacology and pharmacognosy.

The course is structured in classroom lectures. In case of a new epidemiological emergency, all the lessons will be conducted remotely through audio/video lessons which will be uploaded to the Moodle platform (www.dir.uniupo.it).  Practical exercises will be also planned to take place in the classroom. In case of a new epidemiologica emergency, practical exercises will be conducted remotely via Google Meet (https://meet.google.com).

Slides and all other materials will be available on the DIR platform (Didattica in Rete, 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-disabilities. Students 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 exam consists of a written test comprising 1 exercise of pharmacokinetics and 2 open questions on topics indicated in the course program and given during lectures. Each of them will be scored from 0 to 30. The written test is passed if the overall mean assessment will be equal or higher than 18 points out of 30 points. Incoming Erasmus students are given the option of taking the written exam in English.
The use of a scientific calculator is permitted during the written examination. The consultation of textbooks or notes is not allowed.
The achievement of excellence (30/30 and potentially cum laude) is determined by students' ability to produce written answers that demonstrate complete and in-depth mastery of the subject.
To obtain the highest marks, open-ended responses must be logically structured and capable of establishing critical connections between different areas of the syllabus (for instance, correlating pharmacokinetic parameters with the molecular mechanisms of organ toxicity). The following criteria will be decisive for the awarding of honours (lode):
1. Absolute precision and methodological rigour in the written resolution of the pharmacokinetics exercise;
2. The completeness and analytical depth of the answers to theoretical questions;
3. The use of impeccable, precise and appropriate written technical-scientific language within the specialised context of Toxicology and Pharmacovigilance.

General principles of toxicology; mutagenesis and carcinogenesis; developmental toxicology; toxicology in drug development; classification of advers drug reactions; drug allergic reactions; pharmacogenetics; organ toxicology: hepatotoxicity, renal toxicity, respiratory system toxicity; cardiovascular toxicity; drugs of abuse toxicity; metals and pesticides toxicities; antidotes; toxicity of biotechnological drugs; drug interactions, pharmacoepidemiology; systematic reviews and meta-analyses; pharmacovigilance (active and passive), phytovigilance and cosmetics vigilance; ecopharmacovigilance.
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 intravenous or oral administrations: determination of maximum and minimum plasma concentration at the 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 students 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.APPLYING KNOWLEDGE AND UNDERSTANDINGThe students will have the tools for evaluating the risk/benefit of drugs, and understanding the role of toxicology in the drug discovery and development process. The students will have the toolsfor solving pharmacokinetic and pharmacodynamic questions through experimental data processing.LIFELONG LEARNING SKILL, MAKING JUDGEMENTS, COMMUNICATIONThe students will be familiar with the key aspects of fundamental toxicology, and will have developed an insight in concepts and methods that will make the student able to critically assess new results in the field.Minimum level of sufficiency: upon completion of the course, students must demonstrate, through the written exam, knowledge of the fundamental definitions of toxicology and the purposes of pharmacovigilance. To achieve a passing grade, they must be able to describe correctly the main mechanisms of organ toxicity and solve the pharmacokinetics exercise by correctly applying basic calculation procedures.Advanced level: upon completion of the course, students must demonstrate a critical and integrated understanding of the subject, and be able to correlate pharmacokinetic parameters with toxicological risk within the written exam. They must be capable of critically analysing complex pharmacovigilance cases, applying current regulations and using rigorous, precise written technical-scientific language.