PHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRY I
Learning outcomes of the course unit
This course provides an introduction to Medicinal Chemistry and is integrated with the other Medicinal Chemistry courses delivered in the following years.
The course aims at providing the students with the knowledge and understanding of the basic chemical and toxicological concepts of drugs, to be applied to the study of the classes of drugs presented during 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, metabolic transformation, adverse reactions and interaction with other drugs.
For the classes of drugs treated during the course: know the names, 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 (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. Answer properly to questions, suggestions and criticisms (Communication skills).
5. Learn to infer general rules from examples. Learn to search and critically evaluate reliable sources of information and literature (Learning skills).
Basic notions of general and organic chemistry, physiology and biochemistry. Chemical equilibrium, equilibrium in solution, and in particular acid/base equilibria. Knowledge of functional groups of organic chemistry and their properties, mostly 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 topics on drugs, such as names and origin of drugs, and structural, chemical and physicochemical properties affecting drug action. The most important 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 describes the most relevant classes of antibacterial, antiprotozoal, antifungal, anthelmintic, 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 about 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
Moments of drug action: the pharmaceutical, pharmacodynamic and pharmacokinetic phases.
Drug targets: membranes, receptors, enzymes, nucleic acids.
Mechanisms of drug action
Structure and action of drugs
Chemical and physicochemical properties influencing 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; 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, 2013.
John M. Beale, Jr., John H. Block: Wilson & Gisvold Chimica Farmaceutica; Casa Editrice Ambrosiana, Milano, 2014.
Alberto Gasco, Fulvio Gualtieri, Carlo Melchiorre: Chimica Farmaceutica; Casa Editrice Ambrosiana, Milano, 2015.
G. L. Patrick: Introduzione alla chimica farmaceutica, seconda edizione; Edises Napoli, 2010.
Slides commented during the course will be available for the students before the beginning of the course at the Elly website.
Teacher-led lessons (72 hours corresponding to 9 CFU) with slides summarizing the major points described and discussed during each lesson. Chemical structures and mechanisms will be also illustrated on the blackboard. The student is expected to study and understand the content of the 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, during lesson breaks or by appointment (e-mail request).
Assessment methods and criteria
The oral examination will be preceded by a written questionnaire (5 short essay questions) about the most relevant aspects of the topics treated during the course. The questionnaire will be given at the beginning of the exam and it will take about 15 minutes. If the answers to the questionnaire will be sufficient (usually 3 correct answers), the student will be allowed to sustain to the oral part of the examination. The answers to questions related to all the topics treated during the course will be used to evaluate the knowledge and comprehension of the contents of the course achieved by the student. The ability of the student to apply the acquired knowledge and understanding will be also assessed through connections among topics.