Academic Year 2023/2024 - Teacher: FILIPPO CARACI

Expected Learning Outcomes

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

Course Structure

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

Required Prerequisites

Basic knowledge of pharmacology and biochemistry

Attendance of Lessons

Mandatory attendance according to the rules of the teaching regulations of the CdS in CTF as reported in the link:

Detailed Course Content

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.

Textbook Information

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


Course Planning

 SubjectsText References
1Principi generali di tossicologia. Meccanismi molecolari e cellulari di tossicità. Tossicologia dei chemioterapici.3
2Aree della tossicologia. Classificazione degli effetti tossici. Reazioni allergiche,idiosincrasia, tossicità immediata e ritardata, reversibile, irreversibile, locale, sistemica. 3
3Interazioni tra farmaci. Variabilità della risposta tossicologica: aspetti farmacocinetici e farmacodinamici 1-3
4Tossicologia predittiva. Valutazione del rischio. Soglia di tossicità, effetti privi di soglia. LOEL, LOAEL, NOEL, NAEL, NEL.1-3
5Relazione dose-effetto. Curve dose-risposta. Margine di sicurezza, ADI. Principi e definizioni della farmacovigilanza.1-3
6Meccanismi generali di danno cellulare. Radicali liberi. Meccanismi di genotossicitá, mutagenesi, cancerogenesi e teratogenesi1-3
7Profilo tossicologico dei farmaci utilizzati per il trattamento delle patologie del SNC e delle patologie cardiovascolari, profilo tossicologico dei farmaci antibatterici, antivirali, antimicotici ed antineoplastici1-3
8Tossicologia delle sostanze d’abuso. Meccanismi delle tossicodipendenze.. Classificazione delle sostanze d'abuso. Potenziale tossicomanigeno.1-2

Learning Assessment

Learning Assessment Procedures

Oral Exam

CInAP support will be required in presence of specific teaching activities related to specific needs

Examples of frequently asked questions and / or exercises

Allergic reactions Idiosyncrasy Immediate and delayed reversible, irreversible, local, systemic toxicity Interactions between drugs and aspects of pharmacogenetics. Teratogenesis Adverse reactions and principles and definitions of pharmacovigilance. LOEL LOAEL NOEL, NOAEL Preclinical Toxicology in Drug Development. Molecular and cellular mechanisms of toxicity. General mechanisms of cell damage. Free radicals. Mechanisms of genotoxicity, mutagenesis Therapeutic uses and toxicity from antineoplastic drugs Therapeutic uses and antimicrobial drug toxicity Pharmacokinetic interactions Pharmacodynamic interactions Neurobiological basis of the neurotoxic action of drugs of abuse Cellular and molecular mechanisms of toxicity Adverse reactions related to CYP450 inhibition Toxicity profile of tricyclic antidepressants Adverse reactions of antivirals Adverse reactions of anti-HCV drugs