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.

- Cassarett and Doull: Elementi di tossicologia, Casa Editrice Ambrosiana.
- Walter Balduini, Lucio Costa: Tossicologia generale e applicata ai farmaci, Edizioni EDRA.
-Rossi F.; Cuomo V.; Riccardi C. Farmacologia. Principi di base e applicazioni terapeutiche, Edizioni Minerva medica.
-Lecture notes provided in class.

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.

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

The course is structured in frontal lessons and classroom exercises. In case of a new Covid-19 emergency, lessons will be provided remotely via Google Meet (https://meet.google.com).

The slides of the individual lessons and other materials provided will be available on DIR platform (Didattica in Rete, www.dir.uniupo.it).

The exam consists of a written test followed by an oral test.
In the written test the student's ability to apply the knowledge acquired during practical exercises is assessed and consists of 1 exercise of receptor binding and 1 exercise of pharmacokinetics. For each of the two exercises, 15 marks are awarded if resolved completely and without errors. The written test is passed if the overall mark is not less than 18 points out of 30. Only those who pass the written exam will have access to the oral exam.

The oral exam consists of questions on topics covered in the Toxicology module. The oral exam aims to verify the level of knowledge and understanding of the course contents and to assess the independence of judgment, the ability to learn and the communicative ability.
The oral exam is passed if the mark is not less than 18 points out of 30. To achieve a high mark in the oral exam, the student must be able to use his / her own knowledge and understanding of teaching contents in an autonomous way in order to face an in-depth discussion on aspects related to the covered topics.

The final mark will be the arithmetic mean of marks on the two exams (written and oral).

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.

KNOWLEDGE AND UNDERSTANDING
The student at the end of the teaching knows 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 UNDERSTANDING
The 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 SKILLS
The student is able to demonstrate that he/she can connect the different topics covered through a "transversal" logic so as to combine the different fields of the discipline. The student can communicate the knowledge acquired through the examination interview.