Università degli Studi di Roma "Tor Vergata"

DESCRIPTION OF TEACHING MODULE: Pharmacogenomics Programme Definitions of Key Terms and Basic genetics Principles. The genetic inter-individual variability and the concepts of polymorphism and mutation. Principal types of genetic polymorphysms. Haplotypes. Methodological Approaches to study inter-individual genetic variability The role of genetic variability in the response to drugs, both in terms of efficacy and toxicity The concept of genomic biomarker Different types of genetic testing and their correct use in clinical practice. Concept of Analytical Validity, Clinical Validity and Clinical Utility for Genomic Biomarkers The definitions of pharmacogenetics/pharmacogenomics (PGt, PGx) The principles and applications of human genetics and genomics in drug therapy optimization, patient care, and counseling. Pharmacogenetics testing and clinical utility: various illustrative examples in details of application of Pharmacogenomics in safety and efficacy of drugs in different fields: -Oncology (Irinotecan, 5FU, Tamoxifen, Cetuximab, Herbitux..) -Cardiovascular diseases (Warfarin, Statins, Clopidogrel) -Infectious diseases (Hiv: Abacavir, Nevirapine, HCV: Peg Interferon..) - Therapy of pain and anhestesia Applications of PGx in Drug Discovery and Clinical Trials. From Genotyping to Drug Label-Challenges; Pharmacogenomics: The Regulatory Environment

DIDACTIC MATERIALS: PDF slides Files by Prof Borgiani and advised scientific papers on the argument

Pharmacodynamics: relationship dose/effects; series of doses; ED50, LD50, Therapeutic window; Receptors: Classification, Structural, Functional Organization And Pharmacological Modulation; Ionotropic Receptors And Metabotropic Receptors; Methods For The Study Of Membrane Receptors;Protein Kinases And Their Role In Signal Transduction; Regulation Of Intracellular Calcium Homeostasis; Voltage-Deprendent Ion Channels; Neurotransporters: Molecular Structure, Activation Mechanisms And Pharmacological Modulation Of Neurotransporters; Neurotransmitters: Cholinergic Transmission, Catecholaminergic Transmission, Serotonergic Transmission, Gabaergic Transmission, Excitatory Amino Acid Transmission, Nitric Oxide, Opioid System, Cannabinoids; Tolerance, Drug Dependence, Prescription Medicines And Otc Medicines; Clinical Trials (placebo, randomization, blind design, ethics); Homeopathic School; Introduction To Toxicology; Toxicokinetics, Mechanisms Of Toxicity, Cellular Toxicity, Genetic Toxicology, Carcinogenesis, Mechanisms And Pathogenesis Of Developmental Toxicity; Basis Of Adverse Drug Reaction: Drug Allergy, Drug Idiosyncrasy; Target Organ Toxicity Induced By Drugs. Scope and aims of pharmacokinetics; Utility of pharmacokinetics in pharmacotherapy and drug development; Pharmacokinetic parameters (Ke, Clearance, Vd, t1/2); Steady-state; Relationship between persistence in the body and effect; Passage through biological membranes; Cell barriers; Absorption, Biological dosage (bioassay), Bioavailability, Pre-systemic elimination; Binding to plasma proteins and Pharmaco-toxicological consequences of plasma protein binding displacement, Drug interactions; Accumulation and storage tissues; Renal and biliary excretion; Dose-concentration relationship, saturation kinetics; Kinetic variability: influence of genetic factors, interactions, pathologies; Metabolism of drugs; Enzymatic induction: mechanisms and kinetics, pharmacological and toxicological consequences; Enzymatic inhibition: mechanisms and kinetics, pharmacological and toxicological consequences, main inhibitors of CYP450; Genetic polymorphism of metabolizing enzymes.

Goodman and Gilman: The pharmacological basis of therapeutics, XI ed. McGraw-Hill; Clementi F., Fumagalli G.: Farmacologia generale e molecolare, III ed. UTET.