Applied pharmacology

A.Y. 2019/2020
7
Max ECTS
56
Overall hours
SSD
BIO/14
Language
Italian
Learning objectives
The goal of the course is to acquire the knowledge required to understand the experimental approaches used in basic and clinical pharmacology research. Theorical and practical aspects of pharmacological research will be tasked. The Course takes the move from the knowledge already acquired by the student in order to understand how to study the activity of a drug and which criteria are typically followed in the development of a new biologically active molecule. The Course will provide a practical approach to pharmacology with the goal of learning how to design and validate experimental protocol and present the results obtained rather than extensively survey the pharmacological protocols available. The discussion of specific topics will be implemented through the reading and presentation of scientific papers.
Expected learning outcomes
The student will learn of the critical steps to attend a Pharmacological Research laboratory. He/she will learn how to examine the state of the art to develop a specific research activity. He/she will learn the general features related to the different experimental models (acellular, cellular, isolated and in vivo organs) and to clinical studies. He/she will learn how to critically examine the results of a scientific experiment and will be given examples of the different types of experimental models
Course syllabus and organization

Linea AL

Responsible
Lesson period
First semester
Course syllabus
Organization of an experimental research: criteria and principles. Acquisition of data from scientific literature; structure and analysis of scientific works; consultation of databases.Preparation of a scientific manuscript.

In vitro methods: Investigation of drug-receptor interactions: use of receptorial analysis techniques (saturation and displacement binding), meaning of the parameters obtained. Tests on isolated organs, use of cell cultures

In vivo methods: Use of laboratory animals: legislation and criteria. In vivo tests for the determination of pharmacological activity, related to selected classes of drugs. Biological variability; elaboration and statistical analysis of experimental results.
Study of dose-response relationships: achievement and use of pharmacodynamic activity parameters of agonists and antagonists. Pharmacogenetics and pharmacogenomics
Study methods for platelet function
Study methods of drugs with analgesic and anti-inflammatory activity
Study methods for psychiatric diseases: genetic models and environmental models General considerations and applications.
Study methods of drugs with anxiolytic and hypnotic activity
Study methods of drugs with antidepressant activity
Methods of studying drugs with antipsychotic activity
Study of drug dependence. Animal models for the study of drugs of abuse and methods for the study of drugs that act on gratification mechanisms. Methods of identifying new substances of abuse and their study.
Study of adaptive mechanisms in the action of psychotropic drugs
Drug study methods for neurodegenerative diseases.
Study methods of drugs of natural origin. Methods of studying drugs that act at the peripheral level.
Imaging techniques applied to pharmacology
Biomarkers in psychiatric research and their clinical implications
Prerequisites for admission
Knowledge of the topics studied during the curriculum of the previous years is required.
Teaching methods
The major aim is to understand the methodologies of basic and clinical pharmacological experimentation. The course is aimed at the study of pharmacology in its theoretical and practical aspects. The program is based on the cultural preparation already largely acquired by the student in order to understand how the action of drugs can be studied and what are the criteria for the development and characterization of new molecules with therapeutic activity. The course will try to provide a practical approach to the subject aimed not only at the acquisition of methodologies, but also and above all, at the design of experimental protocols, their validation and the presentation of the results. The discussion of the main topics of the course will be implemented through the presentation of original scientific articles with interactive critical discussion.
Bibliography
Clementi, Fumagalli - Farmacologia Generale e Molecolare, UTET Quarta edizione
Rossi, Cuomo, Riccardi - Farmacologia: principi di base e applicazioni terapeutiche - II edizione, Edizioni Minerva Medica.
Assessement methods and criteria
The exam consists of a written test. The test includes 3 open questions and 15 multiple choice questions. For each open question a score from 0 to 5 will be assigned (maximum 15 points) while for multiple choice questions 1 point will be awarded for the right answer, -0.5 for each wrong answer and 0 points for no answer. The test must be completed in 1 hour.
BIO/14 - PHARMACOLOGY - University credits: 7
Lessons: 56 hours
Professor: Fumagalli Fabio

Linea MZ

Responsible
Lesson period
First semester
Course syllabus
Introduction. Drug Development
Drug molecular targets. Receptors.
Receptor studies: Binding, Dose-Response, Potency and Efficacy.
Agonist, Partial Agonist, Antagonist, Inverse Agonist, Allosteric Modulators.
Drug-Receptor Interaction Theories, Theory of induction and Selection.
Statistic: Measures of centrality and dispersion, Normal Distribution. Inferent Statistic: the null hypothesis, Type I and Type II Errors. Test Potency; Sample size. t-Test. ANOVA. Linear and non-Linear Regression. Correlation. Models for the analysis of Experimental Data.
Safety in the pharmacological lab. Common risks in the lab. Groups of Biological Risk. Personal and Lab Protection.
Experimental Design.
Laboratory Animals: the 3 R.
Acellular Preparations for Pharmacological Studies. Protein Determination.
Buffers and Temperature sensitivity.
Homogenization. Centrifugation. Subcellular Fractions Separation.
Examples of Acellular Preparation: Ligands of H1 Receptor
Protein expression for Pharmacological Studies. Recombinant Proteins. Expression Systems. Vectors. Transfection. Transient and Permanent Expression. Selectable Markers. Protein Purification. Quality Control: Western Blot.
Examples of Acellular Preparation: Muscarinic Receptor Ligands Evaluation. Expression and Purification of 5-LO. Flap Identification and the Development of Leukotriene Synthesis Inhibitors that do not interact with 5-LO
Cellular preparations for Pharmacological Studie: General Aspects. The development of Cellular Cultures. Cell Culture Media: Serum and Defined Media. Contamination. Primary Cultures and Cellular Lines. Transformation in a cellular line: immortalised Cell Lines. Counting Cells.
Examples of Cellular Preparations of Pharmacological Interest: Platelets. Aggregation. Activity of NO-donor compounds. Polymorphonuclear Leukocytes: Purification and Identification. ROS Determination: Effect PDE4 inhibitors. Intacellular Calcium Ion Determination: FURA-2. Calibration and Concentration Determination. Activation of Gq-coupled Receptors. Extracellular Sodium and Intracellular Calcium Levels.
Tissues and Isolated Organs Preparations: Instrumentation, Incubation Media, Transducers. Electrical Stimulation. Incubations or Superfusion of Isolated Organs: Concentration or Amount of Administered Substance. Bracketing, Four Points Bioassay.
Examples of Tissues Preparations of Pharmacological Interest: guinea-pig ileum. Activity of Cholin Esters. Selective antagonist avaluation with the guinea-pig ileum.
Examples of Tissues Preparations of Pharmacological Interest: Vascular Preparation. Aorta rings: the Role of Endothelium. The Isolated and Perfused Heart. Cardiac Effects of anti asthmatic drugs. Complex models: Neutrophil Activation and Coronary effects.
In vivo pre-clinical pharmacology studies. Laboratory Animals: pros and cons. Animal Models. Spontaneous and Pharmacologically-Induced Pathologies. Genetically modified animals as animal models of Pathologies. Normalization of data. Drug administration in Experimental Animals: Oral, Peritoneal, Endovenous. Anesthesia. Final Report.
Examples in Preclinical Pharmacological Studies: Myocardial Ischemia from Descending Coronary Artery Ligation.
Clinical Pharmacology. Ethics Committee and Informed consent. Placebo and placebo effect. Randomized clinical studies, iBlind, Double-Blind, Crossover. Good Clinical Practice. C.R.O.
General aspects of Clinical Studies. Phase 0. Phase I, II e III. Pharmacovigilance. Adverse Drug Reactions Classification. Risk and Probability. Odds Ratio. Relative and Absolute Risk. Risk/benefit ratio. Number Needed to Treat. The results of a Clinical Study.
Use of scientific literature databases
Molecular Imaging in Oncological and Pulmonary Pharmacology. Bioluminescence. NIRF probes.
Methodologies in Lipid Metabolism studies. Chromatographical analysis. Lipids as biomarkers.
Applied Pharmacology in Pulmonary Drug Discovery.
Prerequisites for admission
Knowledge of the topics studied during the curriculum of the previuos years is required.
Teaching methods
Frontal lesson. Group work and open discussion.
Bibliography
Clementi, Fumagalli
FARMACOLOGIA GENERALE E MOLECOLARE
UTET Quarta edizione


D. Michael Salmon
PRACTICAL PHARMACOLOGY for the PHARMACEUTICAL SCIENCES
WILEY

Slides available at the Course official web site:
http://asalafalmz.ariel.ctu.unimi.it
Assessement methods and criteria
Knowledge will be assessed with a written test, carried out directly on computers located in IT classrooms, accessed using username and password of the institutional email. The test is structured in two parts: the first part is a multiple choice test with 15 questions in 20 minutes, and the second part proposes 3 open questions that can be discussed in an hour. Passing of the first part is mandatory in order to seat in the second part, that takes place immediately after the first part. Scoring of the first part is generated automatically assigning 1 point for each correct answer, -0.5 for each wrong answer, while no answer is scored 0. The test is passed with a score of 9 or above. Scoring of the first part accounts for 30% of the final score. 8 tests are programmed during the Academic Year, according to the avalability of IT classrooms.
BIO/14 - PHARMACOLOGY - University credits: 7
Lessons: 56 hours
Professor(s)
Reception:
Wednesday at 10.30 am upon appointment by writing to the institutional email
Via Balzaretti 9