TOXICOLOGY

The aims of the course are the following:

- to learn the basic principles of toxicology both in toxicokinetics and toxicodynamics

- to learn how evaluate drug’s toxicity and in particular methods and assays useful to perform this evaluation in drug discovery processes

- To learn the role of drug interactions in determining an increasing risk of adverse effects

-To learn the toxicological profile of the principal drug classes currently adopted in clinics

- To understand the neurobiological basis and pharmacological treatment of drug abuse

Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes with respect to previous statements, in line with the programme planned and outlined in the syllabus

The course will consist of lectures

A specific section of the course will be dedicated to discuss the potential applications of preclinical toxicology’s assays in the context of drug discovery processes

Learning assessment may also be carried out on line, should the conditions require it.

General principles of toxicology and classification of toxic effects . Adverse Drug Reactions in Clinical Practice. Factors That Contribute to ADRs. Over Prescribing and Drug Interactions: the role of pharmacogenetics. Allergic Reactions. Idiosyncratic Reactions. Immediate vs. Delayed Hypersensitivity Reactions. Medication warnings and Pharmacovigilance. Clinical trials design and ADRs. Teratogenesis.

Predictive toxicology: risk evaluation, LOEL, LOAEL, NOEL, NOAEL, NEL, Safety and ADI. Dose-Response. Types of Dose-Response Relationships. Concentration-Effect and Presence at the Receptor Site. Criteria for Measurement. LD50 (Lethal Dose 50%). Definition. ED50 (Effective Dose 50%), and TI (Therapeutic Index).

Role of preclinical toxicology in drug discovery processes: methods and assays. Molecular and cellular mechanisms of toxicity. General mechanisms of cellular damage. Free radicals. Molecular mechanisms of genotoxicity. Mutagenicity. Carcinogenicity.

Toxicological profile of therapeutic agents currently used for the treatment of neurological and psychiatric disorders (antidepressants, benzodiazepines, antipsychotics, antiparkinsonian agents, antidementia drugs analgesic drugs). Toxicological profile of antibiotics, antiviral agents (with a focus on anti-HIV ed anti-HBV ed anti-HCV drugs), antifungal agents and antineoplastic drugs.

Neurobiological basis and pharmacological treatment of drug abuse. Tolerance and dependence. general principles. Classification and toxicology of drugs of abuse.

1- Goodman & Gilman's - The Pharmacological Basis of Therapeutics.

2- Rossi, Cuomo, Riccardi – Farmacologia (Principi di base ed applicazioni terapeutiche)

3- Cantelli Forti et al., - Tossicologia cellulare e molecolare. Ed UTET