Medicine and Surgery

The program of the Pharmacology and Toxicology course is carried out through 3 years, starting from the second trimester of the 3rd year to the first trimester of the 5th year. A section of the program (Research and development, pharmacokinetics, and the study of antinflammatory drugs, drugs for reumathological diseases, HIV drugs, and drugs for central nervous system pathologies) will be administered in the integrated course of Pharmacology and Toxicology. The remaining sections will be administered as parts of the Integrated Pathology 1 course (drugs for the cardiovascular and pulmonary system diseases), Integrated Pathology 2 course (drugs for renal and renal tube pathologies) and Integrated Pathology 3 course (drugs for endocrinological and gastroenteric diseases). The Integrated course of Pharmacology and Toxicology includes 5 teaching units: Unit 1 (16 hours) will focus on research, drug development, post-marketing monitoring, and antibiotics. Unit 2 (8 hours) will focus on anti-inflammatory drugs, anti H1-drugs and anti-malaria drugs. Unit 3 (4 hours) will focus on drugs for HIV therapy and on the therapy of complex bacterial diseases, including endocarditis and meningitis. Unit 4 (24 hours) will focus on drugs for the therapy of neurological diseases Unit 5 (23 hours) will focus on drugs for the therapy of psychiatric diseases Unit 1: Research and drug development, drug post-marketing monitoring, antibiotics. This unit will be administered during the second trimester of the 3rd year of the Medicine and Surgery study course. The Unit is developed in 3 sections: Section 1.1 (4 hours) will focus on research, drug development and post-marketing monitoring. The main part of the teaching will focus on the pre-clinic and clinic phases in drug development with particular reference to the type and design of non-clinical and clinical studies requested for drug development, the tools to interpret study results, and European guidelines for the redaction of the marketing authorisation dossier. Differences in the development of chemical drugs and biotechnological drugs will be described, with a dedicated focus on advanced therapy medicinal products (ATMPs). The legislation on innovative drugs will be discussed, together with the available tools aiming at facilitating development and authorisation of innovative drugs. The Section will also focus on the Competent Authorities for the release of the marketing authorisation (MA) of medicinal products in Europe, US and Japan. There are two ways to obtain a MA: via the Centralised Procedure or via a non-centralised procedure. The latter includes the Decentralised Procedure, the Mutual Recognition Procedure, and the National Procedure. The section will deal with the legal provisions and responsibilities for the competent authority and MA holders in both systems. Post-marketing activities and safety monitoring of authorised medicinal products in Europe will represent the object of the last part of this section, that will deal with the responsibilities of the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency, the Eudravigilance system for reporting of adverse reactions to medicinal products, and the redaction and use of the Periodic Safety Update Report (PSUR). Section 1.2 (8 hours) will deal with Pharmacokinetics and focus on absorption, distribution, metabolism and excretion of drugs. The section will address the role and importance of pharmacokinetic studies in drug development and in particular for the selection of the correct posology and the identification of drug-drug interactions. Several examples will be given of how the pharmacokinetics knowledge is reflected in the relevant sections of the Summary of Product Characteristics (SmPC). The section will focus on bioequivalence studies and their role in the clinical development of drugs. Differences between generics and biosimilar drugs will also be addressed. Section 1.3 (6 hours): Antibiotics. The section will deal with the different antibiotic classes (bacterial wall synthesis inhibitors, agents destroying bacterial cellular membrane stability, protein synthesis inhibitors, anti-metabolites, DNA and RNA synthesis inhibitors), and relevant therapeutic guidelines. Mechanism of action, indication and adverse effects of each antibiotic will be described. The concept of antibiotic potency, and its measurement will be discussed. Focus will be on bacterial resistance generation and transmission. In addition, diagnostic techniques, including fast microbiology, will be presented together with how to interpret the molecular antibiogram and to formulate a correct antibiotic therapy. This unit will be administered during the second semester of the 3rd year of the Medicine and Surgery course of study. Unit 2 (4 hours) will deal with the study of non-steroid anti-inflammatory drugs (NSAD and COXIB), anti-H1 drugs, and anti-malaria drugs. All drugs will be discussed, in terms of mechanism of action, drug-drug interactions, adverse effects and place in therapy. Contraindications and, if relevant, off-label use will also be discussed. This unit will be administered during the second semester of the 4th year of the Medicine and Surgery course of study. Unit 3 (4 hours) will deal with the study of the antiretroviral drugs and guidelines for HIV therapy, including pre-exposure prophylaxis. All drugs used in the therapy of the disease will be discussed, in terms of mechanism of action, drug-drug interactions, adverse effects and place in therapy. Contraindications and, if relevant, off-label use will also be discussed. The unit also includes the description and discussion of two serious bacterial infections, which often needs polytherapy: endocarditis and meningitis. This unit will be administered during the second semester of the 4th year of the Medicine and Surgery course of study Unit 4 (25 hours) will deal with the study of neurologic drugs. The Unit will include 2 sub-sections 4.1 Drugs for neurodegenerative diseases 4.2 Drugs for non-degenerative neurologic diseases 4.3 Analgesic drugs and anaesthetics Section 4.1 Drugs for neurodegenerative diseases.The Unit will deal with drugs for Parkinson disease, atypical parkinsonism and dementia. The Unit will start with a discussion on the etiopathogenesis and clinical development of the disease in order to allow the understanding of the drugs mechanism of action and clinical use. The genetic forms of the diseases will be described as extrapolation to idiopathic forms is possible in terms of molecular mechanisms and drug targets. For each disease the relevant European and/or US clinical guidelines will be presented and the strength of the evidence on which treatment recommendations are based will be discussed. Students will thus be available to critically understand and apply the guidelines recommendation in their future clinical practice. All drugs used in the therapy of the disease will be discussed, in terms of mechanism of action, indication drug-drug interactions, adverse effects and place in therapy. Contraindications and, if relevant, off-label use will also be discussed. Dementia and Alzheimer disease. The discussion will start with the classification and description of the different dementia forms. In particular, focus will be on fronto-temporal dementia and Alzheimer disease. Main challenges in clinical studies in Alzheimer disease will be addressed and the recent failures of monoclonal antibodies trials will be discussed. The issue of the identification of prognostic biomarkers aimed at the enrichment of the patient population recruited in clinical trials will also be discussed. All drugs will be described in terms of mechanism of action, adverse effects and contraindications. Drugs under development will also be discussed Drugs for non-degenerative neurologic diseases Drugs for the therapy of epilepsy. The different forms of epilepsy and epileptic syndromes according to the ILAE classification will be described. This will allow the understanding of the mechanism of action and clinical use of antiepileptic drugs in the different forms and epileptic syndromes. The European clinical guidelines will be used to discuss the pharmacotherapy according to the individual syndrome. Drugs will be described in terms of mechanism of action, adverse events and contraindications. Given that polytherapy is often used, drug-drug interactions will be discussed in details, and instructions for dosage decrease will be given. The mechanisms of resistance to therapy will be addressed and therapeutic strategies to overcome resistance will be discussed. The challenges of treating paediatric patients will be discussed together with the possibility to extrapolate efficacy and safety data from adults to children. Drugs for prophylaxis and therapy of migraine Students will be introduced to the pathophysiology of migraine. Drugs will be discussed based on their mechanism of action, clinical use and adverse reactions. In particular focus will be on the new monoclonal antibodies against calcitonin gene-related peptide (CGRP) and on the action on the trigeminal system. Analgesic and anaesthetics The discussion will start with the description of nociceptive pathways and main regulatory nuclei in the brain and spinal cord. This will form the bases for the understanding of the mechanism of action of analgesics. The following classes of drugs will be studied: NSAD, cannabinoids, and opioids. Anaesthetic drugs will be discussed separately. The clinical use, antalgic potency, dose equivalence, mechanism of action and adverse events and contraindications will be discussed for each class of analgesic drugs. Focus will be on therapeutic cannabis, and its approved indications in Italy. Anaesthetic drugs. The discussion will start with the description of the principles of general and local anaesthesia. Students will be introduced to: anaesthesia stages, differential sensitivity of neurons to anaesthetics, neuroanatomic substrate of anaesthesia and the activating ascending system. Anaesthetic drugs will be discussed in terms of mechanism of action, route of administration and adverse events. Neuroleptoanalgesia indications and contraindications will also be discussed. Local analgesia techniques will be described, including: troncular anaesthesia, epidural and thecal anaesthesia. Mechanisms of action and adverse events of local anaesthetics will be described. Unit 5 (23 hours) will deal with drugs for psychiatric disorders The Unit will include drugs for the therapy of: • Schizophrenia • Mood disorders • Anxiety disorders Schizophrenia. Students will be introduced to the pathophysiological bases of schizophrenia, involved neurotransmitters and brain pathways. Recent understanding of the molecular mechanisms of the disease will also be discussed. The role of brain dopaminergic, serotoninergic and glutamatergic pathways in the disease, and their modulation by antipsychotic drugs will be discussed. This will form the basis for the understanding of the mechanism of action of antipsychotic drugs and the rational for their use. The standard classification of antipsychotic drugs will used to introduce neuroleptics and atypical antipsychotics. Focus will be on partial dopaminergic and serotoninergic agonists recently approved in Europe. All drugs will be discussed in terms of their clinical use, adverse effects and contraindications. Clinical cases will be used to teach student how to optimize therapy in individual patients Mood disorders. The DSM V classification will be followed. Major depressive disorder. The study will start with the description of the neuroanatomic and pathophysiologic bases of major depression and its correlation with anxiety disorders and stress axis. Focus will be on reward and anti-reward systems and role of glucocorticoid s and stress on neurodevelopment and neurodegeneration in the hippocampus. This will build the basis for the understanding of the mechanism of action and use of antidepressant drugs. Particular attention will be given to the molecular mechanisms underlying the long latency of antidepressant clinical efficacy will be addressed, together with the therapeutic strategies to achieve symptom control and decrease the risk of suicide. All classes of antidepressant drugs will be described in terms of mechanism of action, clinical indicatio0ns, adverse effects and contraindications. Bipolar disorders. The DSM V classification will be used to describe the disorders. The European guidelines for the treatment of bipolar disorders will be described and all drugs will be addressed in terms of mechanism of action, clinical use, adverse reactions, and contraindications. Anxiety disorders. The DSM V classification will be used to describe the disorders. The obsessive-compulsory disorder and the post-traumatic stress disorders will also be discussed. Benzodiazepines will be classified according to their pharmacokinetics and clinical use. Their mechanism of action, adverse events and contraindications will be discussed

Basic knowledge of cell biology (cell structures and organels, cell transport mechanisms, DNA transcription and translation), essential knowledge; human anatomy and physiology (central and peripheral nervous system, sistema nervoso centrale e periferico, excretory organs: kidney and liver), important knowledge; fundamentals of micobiology (classification and characteristics of the main bacterial pathogens), important knowledge; fundamentals of organic chemistry, useful knowledge. All pre-requisites will be briefly re-cap to the students to facilitate understanding of the topics of the course.

PowerPoint presentations of the Course lessons Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill Education, XIV edition, 2023

Class attendance is mandatory, according to the Faculty rules

Final examination will take into account: i. active partecipation during lessons (25%) ii. results from written examination (50%). Multiple choice-quizzes will be the standard prove for units 1, 2 and 3. Duration of the written examination will be 10 minutes for each unit. At least 4 correct answers are required to pass the test. In case the student will fail the written exam, he will be offered oral examination. iv. oral examination (25%). This will be the standard procedure for unit 4 and 5, aimed at assessing the student communication skills of scientific themes. Among the aims of this exam are: the evaluation of students’ critical capacity, ability to apply the acquired knowledge to individual clinical cases, and communicate appropriately using both scientific as well as patient-friendly language. For the oral examination, some of the elements that will be taken into consideration are: the logic applied to the resolution of the question; the adequacy of the response in relation to the knowledge the student should have acquired at the end of the course; the use of appropriate scientific language. In-coming international students who will request, have the possibility to pass the exam in English. In this case, only oral examination will be offered.

Frontal lections and clinical case discussions with students. These will allow to obtain points 1 and 2 of learning objectives (see section on learning objectives awaited). Tutorials on how to navigate through the EMA, AIFA, and main scientific societies' websites, to find international therapy guidelines, will allow to obtain point 5 of learning objectives. Multiple-choice quizzes and/or short scientific reports will teach students how to integrate the knowledge derived from attending the course to formulate judgements based on the available data. (point 3 of learning objectives). Students will also be requested to discuss some scientific articles and translate their content into patient and relative-friendly information, in order to accomplish point 4 of learning objectives.