PHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRY I
Learning outcomes of the course unit
This course provides an introduction to Medicinal Chemistry and is integrated with the Medicinal Chemistry courses delivered in the following years.
The course provides the knowledge and understanding of the basic chemical and toxicological concepts related to drugs and drug action, to be applied to the study of the classes of drugs presented in the systematic part of the course. The acquired knowledge and methodology allow the student to analyze, describe and discuss, with proper language, the most relevant aspects of drug structure and action.
Besides the knowledge on general aspects of drug activity, the student will learn in detail the most important drugs belonging to the therapeutic classes treated, with particular consideration for their name, molecular formula, mechanism of action, therapeutic application, metabolic fate and toxicity.
At the end of the course the student is expected to:
1. Understand how the structural, chemical and physicochemical properties of a drug affect its biological activity, pharmacokinetic behavior, adverse reactions and interaction with other drugs.
For the classes of drugs treated during the course: know names of drugs, simple formulas, origin and application. Understand (recognize, explain and discuss) complex formulas, structure-activity relationships, chemical, physicochemical toxicological and metabolic properties of drugs (Knowledge and understanding).
2. For drugs treated and their structural analogs: go from formula to name and vice versa. Infer chemical and physicochemical properties of drugs and discuss how they can affect biological properties, including metabolism and toxicity (Applying knowledge and understanding).
3. Draw consequences on the use of drugs based on their structural, chemical and physicochemical properties. Properly answer to questions, suggestions and criticisms, and formulate opinions on the topics treated in the course (Making judgements).
4. Report with proper language, to specialists and non-specialists, knowledge and concepts related to the classes of drugs treated during the course (Communication skills).
5. Learn to infer general rules/concepts from examples. Learn to search and critically evaluate sources of information and literature (Learning skills).
Basic notions of general and organic chemistry, physiology and biochemistry. Chemical equilibrium, equilibria in solution, and in particular acid/base equilibria and redox reactions. Knowledge of functional groups of organic chemistry and their properties, in particular reactivity and acid/base profile. Nomenclature of heterocycles. Knowledge of structure and function of proteins, sugars, lipids and nucleic acids. Basic concepts of cell and organ physiology.
Course contents summary
The first lessons deal with general concepts on drugs, such as names/nomenclature and origin of drugs, and structural, chemical and physicochemical properties affecting drug action. Relevant mechanisms of action are also discussed, as well as an introduction to structure-activity relationships is presented. Drug absorption, distribution, metabolism and excretion, with particular emphasis on metabolic reactions are treated in the general part of the course. Prodrug strategies will also be discussed, with examples of activation mechanisms.
The second part of the course deals with the most relevant classes of antibacterial, antiprotozoal, antifungal, anthelmintic, antiparasitic, antiviral and anticancer classes of drugs. For each class the chemical formulas of the most important drugs are described and commented, as well as the most relevant information on the mechanism of action, therapeutic application, structure-activity relationships, chemical and physicochemical properties, metabolic reactions and toxicity is provided.
Names and classification of drugs
Origin of drugs
Chemical and physicochemical properties influencing drug action
Moments of drug action: the pharmaceutical, pharmacodynamic and pharmacokinetic phases.
Membrane crossing and protein binding
Drug metabolism and elimination
Drug toxicity and drug resistance, in particular antibiotic resistance.
Drug targets: membranes, receptors, enzymes, nucleic acids.
Mechanisms of drug action
Isosteres and bioisosteres
Antibacterial agents: sulfa-drugs, beta-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, oxazolidinones; antimicrobial peptides, glyco- and lipopeptides.
Antimycobacterial and leprostatic agents
Antiprotozoal drugs: nitro-heterocyclic drugs, antimalarial drugs; other antiprotozoal agents.
Antifungal drugs: azoles, allylamines, polyenic drugs, other antifungal agents.
Insecticides: pyrethrum and derivatives
Antiviral drugs: anti-herpetic, anti-HIV, anti-flu, drugs for hepatitis B and C; drugs against coronavirus infections, other antiviral agents.
Anticancer drugs: alkylating agents, intercalating agents, antimetabolites, antimitotics, DNA-polymerase and topoisomerase inhibitors, tyrosine kinase inhibitors; other anticancer agents.
Thomas L. Lemke, David A. Williams, Victoria F. Roche, S. William Zito: Foye’s Principi di Chimica Farmaceutica, sesta edizione italiana; Piccin, Padova.
John M. Beale, Jr., John H. Block: Wilson & Gisvold Chimica Farmaceutica; Casa Editrice Ambrosiana, Milano.
Alberto Gasco, Fulvio Gualtieri, Carlo Melchiorre: Chimica Farmaceutica, seconda edizione; Casa Editrice Ambrosiana, Milano.
G. L. Patrick: Introduzione alla chimica farmaceutica, terza edizione; Edises Napoli.
Slides commented during the course are available to students before the beginning of the course at the Elly website.
Teacher-led lessons (72 hours corresponding to 9 CFU) with slides reporting the major concepts and information described and discussed during each lesson. Chemical structures and mechanisms will be also illustrated at the blackboard. The student is expected to study and understand the content of lessons using the textbook and the material provided through the ELLY platform (slides). The teacher is available for explanation and discussion at the end of the lesson or by appointment (e-mail request). In case the sanitary emergence will continue, lessons will be in mixed mode (presence + online) or completely online. The way in which lessons will be delivered will be publicized through the degree web site.
Assessment methods and criteria
The oral examination will be preceded by a written questionnaire (5 open questions) about the most relevant concepts/knowledge presented during the course. The questionnaire will take about 15 minutes. If the answers will be evaluated sufficient (usually 3 correct answers), the student will pass to the oral examination. With questions related to all the topics treated during the course, the level of knowledge and comprehension of the contents of the course achieved by the student will be evaluated. The ability of the student to apply the acquired knowledge and understanding will be also assessed through connections among topics. In case the sanitary emergency will continue, it will be possible to sustain online examinations though MS Teams software ((http://selma.unipr.it for user guide). Online exams will be structured in the same way as those in presence, with the only difference that the initial questionnaire will not be performed. In this case the teacher will check basic knowledge and understanding through oral questions.