MOLECULAR PHARMACOLOGY



Faculty of Science and Technology / Degree in Biochemistry and Molecular Biology



Academic year: 2020/21 Year: 4 ECTS Credits: 4.5



Module lecturers: Rebeca Diez-Alarcia, PhD (Coordinator for 2023/24 course), Rafael Rodríguez-Puertas, PhD, and Leyre Urigüen, PhD. All of them are Staff Scientist at the Department of Pharmacology of the School of Medicine and Nursing of the University of the Basque Country (UPV / EHU).



Context: The Degree in Biochemistry and Molecular Biology, aims to train professionals who have the theoretical and practical training necessary to:

- Understand, generate and communicate knowledge related to biological processes at the molecular level.

- Apply this knowledge to the experimental work carried out in research laboratories.



The fourth and last course of the degree, where Molecular Pharmacology is included as an optional module, allows the student to deepen their knowledge of advanced aspects of Biochemistry and Molecular Biology and their professionalization, especially through the end-of-degree work and the optional modules.

Molecular Pharmacology seeks to understand the cellular and molecular mechanisms of basic biological processes, as well as their dysfunction under pathophysiological conditions, and their relation with the action of drugs. For developing these aims, a multidisciplinary approach is applied, exploring these biological processes both in vitro and in vivo.

The syllabus of the Molecular Pharmacology course covers the general common processes of drugs, referring to Pharmacodynamics (action and mechanism of action) and Pharmacokinetics (processes of absorption, distribution, metabolism and excretion of drugs), as well as the molecular aspects of the interaction of drugs with their biological targets. These concepts are structured in several introductory lectures (ADME), to then go on to more specific lectures focused on the: Introduction to the pharmacology of the vegetative and peripheral nervous system, Pharmacology of the central nervous system, analgesic, anti-inflammatory and immunomodulatory drugs, Pharmacology of the digestive, respiratory and cardiovascular systems, Pharmacology of antimicrobials and anticancer drugs, Pharmacogenomics, and Development of new drugs.

LECTURES

- INTRODUCTION to PHARMACOLOGY

LECTURE 1. Introduction to Pharmacology. General concepts. General cycle of drugs in the body.



- BASIC PRINCIPLES OF BIOAVAILABILITY AND PHARMACOKINETICS (ADME)

LECTURE 2. Absorption and distribution of drugs. Passage of drugs through biological barriers (Blood-brain barrier. Placental barrier). Diffusion through lipids. Transport mediated by transporters. Administration routes. Absorption kinetics. Bioavailability. Distribution of drugs into the body. Volume of distribution.

LECTURE 3. Metabolism and excretion of drugs. Pharmacological metabolism. Biotransformation sites and pathways. Factors that modify the metabolism of drugs. Renal excretion and excretion by other routes. Elimination kinetics.



- MOLECULAR ASPECTS OF THE INTERACTION OF DRUGS and THEIR BIOLOGICAL TARGETS.

LECTURE 4. Mechanisms of action of drugs. Fundamentals of drug-receptor interaction. Nomenclature and classification of receptors. Concept of agonism and antagonism in relation to the pharmacodynamic effect. Quantification of the response: dose-effect curve. Radioligand binding studies.

LECTURE 5. Molecular aspects of the interaction of drugs with their pharmacological targets. Places of action of drugs. Ion channels. Enzymes. Transporter families. Receptors. Other targets of drug action.



- DRUGS THAT ACT ON RECEPTORS, CHANNELS AND TRANSPORTERS:

LECTURE 6. Introduction to the pharmacology of the autonomic nervous system. Organization of the autonomic nervous system. Neurotransmission. Concept and characteristics of neurotransmitters.

LECTURE 7. Cholinergic and muscarinic receptors. Pharmacology of the parasympathetic nervous system. Direct and indirect action of parasympathomimetic drugs. Cholinomimetic and muscarinic drugs.

LECTURE 8. Alpha and beta adrenergic receptors. Pharmacology of the sympathetic nervous system. Sympathomimetic amines with indirect action. Sympatholytic drugs. Alpha-1 and 2-receptor antagonists. Beta-1 and 2-receptor antagonists. Drugs that modulate noradrenergic transmission.

LECTURE 9. Introduction to the pharmacology of the central nervous system. Mechanism of action of synapses and neurotransmitters.

LECTURE 10. Opioid receptors as a molecular target. Opioid drugs. Classification of opioid analgesics: mu opioid receptor agonists (morphine and others). Opioid antagonists.

LECTURE 11. The GABAA receptor as a molecular target. Anxiolytic and hypnotic drugs. Anxiolytic drugs: benzodiazepines. Sedative-hypnotic drugs.

LECTURE 12. Enzymes, receptors and transporters of biogenic amines as molecular targets. Antidepressant, antimanic and antipsychotic drugs.

LECTURE 13. Pharmacology of neurological disorders. Antiepileptic drugs. Drugs used in Parkinson's disease. Drugs used in Alzheimer's disease. Antioxidant drugs used in neurodegenerative processes.

LECTURE 14. Voltage-dependent sodium channel. Local and general anaesthetics.

LECTURE 15. Intracellular receptors as pharmacological targets. Steroidal anti-inflammatory drugs. Mineralocorticoids and glucocorticoids.

LECTURE 16. The proton pump and other useful targets in the pharmacology of the digestive and respiratory system.



- ENZYMES AS TARGETS OF DRUG ACTION.

LECTURE 17. Cyclooxygenase. Non-steroidal anti-inflammatory drugs (NSAIDs).

LECTURE 18. The Renin-Angiotensin System, guanylate cyclase and other useful targets in the pharmacology of Cardiovascular System.



- OTHER PHARMACOLOGICAL TARGETS / ANTI-INFECTIOUS AND ANTI-TUMOR CHEMOTHERAPY.

LECTURE 19. Pharmacological targets for anti-infective chemotherapy. Beta lactam antibiotics. Aminoglycosides. Tetracyclines. Chloramphenicol. Macrolide antibiotics and other antibiotics.

LECTURE 20. Pharmacological targets for antiviral treatment. Antiviral drugs for HIV (antiretrovirals). Other antiviral drugs.

LECTURE 21. Pharmacological targets for antineoplastic treatment. Cytostatics. Hormones. New drugs in oncology.



- BIODRUGS / PHARMACOGENETICs.

LECTURE 22. Pharmacogenetics and pharmacogenomics. Principles of gene therapy. Pharmacogenetics. Genetics factors influencing response to drugs. Genetic polymorphisms in pharmacokinetics and pharmacodynamics.



- DEVELOPMENT OF NEW DRUGS.

*LECTURE 23. Development of new drugs. Identification and validation of pharmacological targets. Preclinical research and clinical research.

*This subject has been replaced by a visit to the laboratories of the pharma company FAES FARMA S.A. which would take place at the end of the lecture sessions.

DELIVERY: Lectures and student-driven presentations.



LECTURES

_ 23 lectures

_ 3 research talks (seminars, S). Each lecturer gives a talk focused on areas of active research within the field of MOLECULAR PHARMACOLOGY, which seek to delve into the most practical and translational aspects of the theoretical concepts.

S1. Pharmacology of neurological disorders. R&D in Alzheimer's disease. R. Rodríguez

S2. Functional selectivity. R. Diez-Alarcia

S3. Cannabis and psychosis. L. Urigüen

_ VISITS to LABORATORIES*

Two VISITS to the RESEARCH LABORATORIES (2.5 hours each) of the Pharmacology Department of the Faculty of Medicine are established:

1- Simulation of three types of radioligand binding experiments for drug screening.

2- Visits to the research facilities of the Neuropsychopharmacology, and Neurochemistry and Neurodegeneration groups at the Medical School, describing the different experimental techniques and methodologies that are routinely used and their relevance within research in molecular pharmacology.



_ COMPUTER SESSIONS (2 sessions, 2.5 hours each):

1- Data analysis of the radioligand binding experiments seen in Visit 1.

2- Use of search engines and specialized databases for the resolution of cases and problems based on the knowledge acquired in lectures.



Notes:

- Attendance at lectures and participation in class are not compulsory but considered for the evaluation.

- Both laboratory visits and computer sessions are mandatory.

- Both for visits to the laboratories and computer sessions, students will be divided into two groups.



STUDENT-DRIVEN PRESENTATIONs

Each student should present in class a critical review of an up to date and relevant scientific article related to Molecular Pharmacology. The presentation will last approximately 10 minutes and should include not only the description of the article, but also its benefits and shortcomings of its approach and development, and its bench to bedside relevance.

• Continuous Assessment System
• Final Assessment System
• Tools and qualification percentages:
  • Written test to be taken (%): 70
  • Individual works (%): 30

CONSTINUOUS ASSESSMENT



OFFICIAL EXAMINATION PERIOD // ASSESSMENT METHOD: Coursework 1, Examination 1

_ Examination will consist of a written exam (10 short questions) weighting 70% of the final mark. Failure to attend to the official exam will be considered as a resignation (for both, the mixed and the final assessment method). In this case, the mark will be “not taken”.

_ Coursework will consist of an oral presentation weighting 30% of the final mark. Student-driven presentation of a critical review of an up to date and relevant scientific article related to Molecular Pharmacology.



Students will have the right to be evaluated through the final evaluation system, regardless of whether they have participated or not in the continuous evaluation system. Students must submit a signed document to the coordinator lecturer during the first 9 weeks of the semester asking for a Final Assessment Method.



Attendance and class participation will be taken into account without a certain proportion for slight variations during the evaluation process.



COVID-19: In the event that sanitary conditions prevent the face-to-face evaluation, a non-face-to-face evaluation will be activated. Students will be informed promptly.

EXTRAORDINARY CALL



_ Examination will consist of a written exam (10 short questions) weighting 100% of the final mark.

Laboratory coat is required for laboratory visit 1.

Basic bibliography

1. Pharmacology. 8th Ed. Rang & Dale. Ed. Elsevier. ISBN-10: 0702053627; ISBN-13: 978-0702053627

4. Principles of Pharmacology. The phathophysiologic basis of drug therapy. Third Edition. David E. Golan, Armen H. Tashjian, Ehrin J. Armstrong, and April W. Armstrong. 2012. ISBN 978-1-60831-270-2.

5. General and Molecular Pharmacology: Principles of Drug Action. Ed. Francesco Clementi and Ed. Guido Fumagalli. Wiley, 2015. ISBN: 978-1-118-76857-0.

In-depth bibliography

1. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Ed. L Brunton, B Chabner, B KnollmanEd. Mac Graw Hill (2011). ISBN 9780071624428.
2. The Biochemical Basis of Neuropharmacology. JR Cooper, FE Bloom, RH Roth. Oxford University Press (2003). ISBN: 9788415419501.
3. From molecules to networks. An introduction to cellular and molecular neurosciencie. JH Byrne, R Heidelberger, MN Waxham (2014). Academic Press. ISBN: 9780123741325.
4. Neurobiology of Brain Disorders. Biological Basis of Neurological and Psychiatric Disorders. M Zigmond, J Coyle, L Rowland (2014). Academic Press. ISBN: 9780123982704.

Journals

Reviews:
- Nature Reviews Drug discovery
- Trends in Pharmacological Sciences
- Current Opinion on Pharmacology
- Pharmacogenetics

Web addresses

http://www.pharmgkb.org/index.jsp
http://www.iuphar.org/