Learning objectives
SUPPLEMENT TO PHARMACEUTICAL CHEMISTRY:
The course aims at providing the necessary methodological tools for understanding the molecular basis of drug action, with particular the drugs included in the program.
Knowledge and understanding: the relationships between chemical structure and pharmaceutical, pharmacodynamic and pharmacokinetic properties,the study of the chemical and physico-chemical properties of the drugs, the mechanism of action, the most important biotransformations and metabolic considerations, the classification of the drugs and the nomenclature.
Applying knowledge and understanding: through the frequency of the course the student will be able to apply his knowledge to the interpretation of the mechanism of action and the pharmacological profile of the drugs and their metabolic characteristics, the discussion of the structure-activity relationships, the definition of a correct nomenclature according to international rules, the ability to communicate with people in different areas such as pharmacology, pharmaceutical technology, biotechnology.
Communication skilles: being treated the acquisition of a formally correct language, is stimulated the ability to express the contents in a clear way.
BIOTECHNOLOGICAL DRUGS: At the end of the course the student will be familiar with basic notions on the production of biotech proteins and engineered microorganisms and on their therapeutic and diagnostic application. The examples of biotech drugs presented during the course will provide not only specific information on these drugs, but also an overview on the variety of products, production, purification and characterization techniques and application of the biotech products currently available. At the end of the course, the student is expected to:
1. Know and understand the processes, techniques and specific issues related to the production, purification, characterization, and use of biotech drugs. Know in detail the structure, properties, functions, production and application of biotech drugs treated during the course. Know the definition and examples of biosimilar and biobetter drugs and understand the rationale for pegylation and hyper-glycosylation of drugs, production of fusion proteins and conjugation of small molecules with macromolecules (Knowledge and understanding).
2. Interpret and critically comment information on biotech drugs treated during the course, also in the wider context of production and use of biotech pharmaceuticals. Apply acquired notions to the understanding of strategies for protein modification aimed at improving specific properties (Applying knowledge and understanding).
3. Identify relevant properties of specific biotech drugs and make inference on their production, potential for structural modification and application. Analyze pros and cons of techniques for the production of biotech drugs. 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 biopharmaceuticals, concerning both general aspects on the production/management of biotech drugs and detailed information on the drugs treated during the course (Communication skills).
5. Autonomously deepen his/her knowledge and expertise in the development and application of biotech drugs, using bibliographic resources and integrating information from other disciplines (Learning skills).
Prerequisites
Basic knowledge of pharmaceutical chemistry, biochemistry, organic chemistry is required for Selected Topics of Pharmaceutical Chemistry. In particular, knowledge of the functional groups of organic chemistry and of heterocyclic rings is required, necessary to understand the structure of drugs, and of the main metabolic reactions.
For the part of Biotechnological Drugs: Basic concepts of general, organic and medicinal chemistry, biochemistry, pharmacology and immunology are required to understand the structure, action, application and other relevant aspects of biotechnological drugs. In particular, the student should be familiar with structure and function of amino acids and proteins, nucleotides, DNA and RNA, and the processes of DNA replication and transcription and of protein synthesis. Knowledge of basic principles of immunology, structure and function of antibodies is also required. Acid-base equilibria, redox reactions, functional groups of organic chemistry and of the mechanisms of action of drugs are further prerequisites of the course.
Course unit content
- The course of Selected Topics of Medicinal Chemistry integrates with the courses of Pharmaceutical and Toxicological Chemistry I and II for the treatment of the main classes of drugs. It includes some drugs with activity on the cardiovascular system (drugs used in the treatment of hyperlipoproteinemia and antithrombotic drugs), drugs of the endocrine system and drugs active on the immune and inflammatory responses.
- The first part of the course of Biotechnological. D. provides basic knowledge on biotech methodologies and biotechnology-related techniques, and on their application to the design, production, downstream processing and characterization of biopharmaceuticals. The process and rationale of drug pegylation are described, with examples of pegylated drugs, as well as other strategies to prolong the half-life of biotech drugs. Examples of biosimilar and biobetter drugs are also presented and discussed, in comparison with generic drugs. Basic notions related to diagnostic and analytical application of protein biologics are also provided. The second part of the course covers the most important biotech drugs used in several therapeutic areas, including hormones, enzymes, cytokines, vaccines, monoclonal antibodies and immunoconjugates. Engineered microorganisms and nucleic acids used as vaccines are also described and discussed. For each drug, relevant aspects related to structural properties, production, mechanism of action, therapeutic application, as well as pharmacokinetics and toxicity are described. Immunoconjugates and radioimmunoconjugates are presented, with examples of drugs used in the clinics. Structure-activity and structure-property relationships are discussed to rationalize the design of analogs of physiological proteins with modified or improved pharmacodynamic and/or pharmacokinetic properties.
Full programme
Supplement to Pharmaceutical Chemistry:
Antilipoproteinemic drugs and inhibitors of cholesterol synthesis: Bile acid sequestrants, HMG-CoA reductase inhibitors, cholesterol absorption inhibitors, fibrates, nicotinic acid.
Insulin and medications used to treat diabetes.
Corticosteroids: Biosynthesis of corticosteroids. Development of corticosteroid drugs. SAR.
Thyroid function and thyroid medications.
Calcium homeostasis: pharmacological therapies for osteoporosis, for hyperparathyroidism, for hypoparathyroidism, for hypercalcaemia.
Female sex hormones: estrogenic and progestinic substances.
Male sex hormones: androgenic substances.
Non-steroidal anti-inflammatory drugs: Antipyretic analgesics. Anti-inflammatory analgesics. COX-2 inhibitors. Drugs for the treatment of arthritis. Antithrombotic drugs: anticoagulants, antiaggregants and fibrinolytics.
Biotechnological Drugs:
Introduction to biotechnology. Basic concepts of molecular biotechnology. Production of biotech products: cultivation and downstream processing. Biophysical and biochemical analyses of recombinant proteins. Chemical and physicochemical properties and reactivity of recombinant proteins; stability of proteins and mechanisms of degradation. Pharmacokinetics and metabolic processes. Immunogenicity of biopharmaceuticals. Pegylation of therapeutic proteins. Fusion proteins and soluble receptors. Biosimilars and biobetters.
Hormones: insulin, growth hormone, follicle-stimulating hormone.
Cytokines: interleukins (IL-1, IL-2) and derivatives; interferons; hematopoietic growth factors (erythropoietin).
Blood proteins: tissue-type plasminogen activator, clotting factors (IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase.
Recombinant vaccines: genetically improved live vaccines against salmonella and cholera; vector vaccines; genetically improved subunit vaccines against hepatitis B, papillomavirus and diphtheria; glycoconjugated vaccines against pneumococcus and meningococcus. RNA-based vaccines.
Monoclonal antibodies, immunoconjugates and radioimmunoconjugates; murine, chimeric, humanized, human, bispecific antibodies and antibody fragments; naming of monoclonal antibodies, rituximab, ofatumumab, obinutuzumab, emicizumab, ibritumomab tiuxetan, brentuximab vedotin, basiliximab, infliximab, adalimumab, certolizumab pegol, abciximab, ibalizumab.
Soluble receptors: etanercept.
Fusion proteins: denileukin diftitox
Bibliography
Gasco, Gualtieri, Melchiorre: "Chimica Farmaceutica", casa Editrice Ambrosiana.
W.O. Foye: “Principi di Chimica Farmaceutica”, Piccin.
M.L. Calabrò: "Compendio di Biotecnologie Farmaceutiche"; EdiSES, Napoli, 2008.
A.J. Crommelin, R.D. Sindelar, B. Meibohm: "Pharmaceutical Biotechnology: Fundamentals and Applications", Fifth Edition, Springer, 2019.
Per consultation and further information:
E. Vegeto, A. Maggi, P. Minghetti: "Farmaci biotecnologici e terapia personalizzata. Aspetti farmacologici e clinici." Casa Editrice Ambrosiana, 2019.
Slides commented during the lessons will be available for students before the beginning of the course at the Elly web site.
Teaching methods
Selected topics of Medicinal Chemistry: Through oral lessons with slides will be presented and discussed matters relating to the course content.
Biotechnological Drugs: Teacher-led lessons (40 hours corresponding to 5 ECTS) with slide projection. The student is expected to study using the textbook and the additional material provided on the ELLY platform (slides and supplementary material). The teacher is available for explanations and discussion of the course contents at the end of the lesson, or by appointment (e-mail request).
Assessment methods and criteria
The achievement of the objectives of the course is checked by oral examination. The markes obtained in the two modules will be mediated.
For Supplement to Pharmaceutical Chemistry, through questions regarding the course topics will be determined knowledge and understanding of the student.
Through questions about the connections between different topics, the interpretation of the action and the pharmacological profile of drugs, the structure-activity relationships and structure-pharmacokinetic properties will be cheked the skills of the student. This is the minimum threshold for the exam to be sufficient.
For Biotechnological Drugs: An oral examination, with questions related to all the topics treated during the course, will assess the knowledge and comprehension of the contents of the course achieved by the student. The ability of the student to apply his/her knowledge is evaluated through connections among topics and personal comments/judgements related to the content of the course. Preparation is considered sufficient if the student proves knowledge and understanding of the basic aspects of each topic and is able to apply this knowledge into a simple discussion. During the examination, use of a proper terminology and language will be also assessed. The grade for the course of Supplement to Pharmaceutical Chemistry/Biotechnological Drugs will be the average grade obtained for the two modules.
Other information
Selected topics of Medicinal Chemistry: Lectures are conducted with the aid of slides whose contents are available to students. The teaching material available online is not a replacement but a supplementary of reference texts, and a guide to a better understanding of the topics to be studied.
Biotecnological Drugs: Teacher-led lessons (40 hours corresponding to 5 ECTS) with slide projection. The student is expected to study using the textbook and the additional material provided on the ELLY platform (slides and supplementary material). The teacher is available for explanations and discussion of the course contents at the end of the lesson, or by appointment (e-mail request).
