60/56/73 - PHARMACOLOGICAL METHODOLOGIES WITH PRACTICE
Academic Year 2015/2016
Free text for the University
ENRICO SANNA (Tit.)
- Teaching style
- Lingua Insegnamento
|[60/56] INDUSTRIAL BIOTECHNOLOGY||[60/56-00 - Ord. 2013] PERCORSO COMUNE||6||56|
Aim of the course is to provide fundamental concepts of the general pharmacology as well as the more recent advancements on the molecular and cellular mechanisms underlying the action of different classes of drugs. Several theoretical and methodological aspects related to the application of molecular biotechnology to the pharmacological research will be illustrated, including production of recombinant drugs, inhibitors of the genetic code, and the principles of gene therapy.
The student will acquire the fundaments of the molecular and cellular mechanisms of action of several classes of drugs that may be useful in order to understand their pharmacological effects on the organism. The student will acquire a sufficient knowledge to understand the potentiality of the application of molecular biotechnology in the development and production of novel drugs. The student will be able to perform in laboratory “in vitro” tests for the quantitative and qualitative analysis of the molecular and cellular action of certain classes of drugs.
This course aims at stimulating both independent, through the lectures, and team work during the laboratory activity.
Students should have already acquired fundaments of Biochemistry, Molecular Biology and Cellular Physiology.
Lectures (32 hours, 4 CFU)
- Principles of Pharmacodynamics. Concept of drug. Concept of drug receptor and its properties. Theory of drug-receptor interaction. Receptor binding, dissociation constant (KD), saturation curve and linear transformation of Scatchard. Dose-response relationship, potency and efficacy. Full, partial and inverse agonists. Competitive and non-competitive agonists. Therapeutic index. Mechanisms of membrane receptor plasticity. Receptor desensitization, tolerance, tachyphyilaxis.(2 hours)
- Principle of Pharmacokinetics . Administration, absorption, distribution of drugs. Models of drug distribution. Systems of drug release. (2 hours)
- Drug receptors. General concepts on cell-cell signaling and membrane receptor. Ionotropic receptors. G protein-coupled receptors. Adenilate cyclase and cAMP/PKA cascade. Phospholipase C and Ca2+/PKC cascade. Receptor for growth factors. Ras-dependent and Ras-independent pathway. The MAP kinase pathway. Insulin and diabetes. The cytokine receptors. Alpha interferon and erythropoietin. Intracellular receptors for hormones and vitamins. Androgen and anabolic steroids. (6 hours)
- Principles of cellular pharmacology. Mechanisms of excitation, secretion and muscle contraction. Pharmacology of voltage-dependent ion channels. Ca2+ channel antagonists. Local anesthetics. (6 hours)
- Pharmacology of the autonomic nervous system. Pharmacology of the cholinergic system. Pharmacology of the adrenergic system. (6 hours)
- Inhibitors of the genetic code. Gene arrays in the search for candidate genes. Antisense oligonucleotides. Small interference RNA (siRNA), ribozymes, aptamers. Pharmacokinetics of antisense oligonucleotides. (2 hours)
- Principles of gene therapy. General concepts. Methodological aspects for its application: ex vivo and in vivo gene therapy. Application to proliferant tumor therapy. (2 hours)
- Transgenic mice as experimental models in pharmacology. Methodologies for creating transgenic mice. Knock-out and knock-in mice. The Cre-loxP system for generating cell-specific and inducible knock-out mice. Site-directed mutagenesis. Chimeras for characterizing the site of drug-receptor interaction. (6 hours)
Laboratory of Pharmacology (24 hours)
- The receptor binding. Preparation of synaptosomes from rat brain using a discontinuous sucrose gradient. The receptor binding reaction. Analysis of data and construction of the saturation curve and linear transformation of Scatchard.
- Determination of protein content (of the rat synaptosome preparation) by the Lowry method.
- Expression of human recombinant GABA-A receptors in Xenopus laevis oocytes. Isolation of Xenopus oocytes, treatment with collagenase, and microinjection of cDNA encoding for the different subunits of the human GABA-A receptor. The voltage-clamp methods for recording the function of recombinant GABA-A receptors expressed in oocytes. Study of the action of agonists and modulatory drugs acting at the GABA-A receptor (benzodiazepines, barbiturates, general anesthetics).
The course comprises 32 hours (4 CFU) of lectures and 24 hours (2 CFU) of laboratory activity. Lectures, lasting 2 hours each, will be using PowerPoint presentations. Laboratory activity is divided in lessons of 4 hours each and will be carried out in the laboratory of Biology.
Verification of learning
Students will have to give a final oral examination in which they will have to demonstrate to have acquired the basic concepts of the different subjects presented during lectures and laboratory activity: principles of pharmacodynamics and pharmacokinetics; molecular and cellular pharmacology; pharmacology of the autonomous nervous system; pharmacological biotechnologies, methodologies presented during laboratory activity.
EVALUATION CRITERIA FOR LEARNING ASSESSMENT
The final grade takes into account several factors:
Quality of the knowledge, skills, competences:
a) appropriateness, accuracy and consistency of knowledge
b) appropriateness, accuracy and consistency of abilities
c) appropriateness, accuracy and consistency of ability to apply knowledge and understanding
a) Ability of expression;
b) Proper use of the specific language of the discipline;
c) Logical skills and inherent consequentiality in communicating;
d) Ability to connect different subjects by finding the common points and establish a consistent overall design, i.e. taking care of structure, organization and logical connections of speech;
f) Ability to summarize also through the use of specific symbolism of each discipline and graphic expression of ideas and concepts, for example in form of formulas, schemes, equations.
Availability to exchange and interact with the teacher during the interview.
a) critical thinking;
b) ability of self-evaluation.
Consequently, the judgment can be:
a) Sufficient (from 18 to 20/30)
The candidate demonstrates little acquisition of theoretical knowledge, superficial level, many gaps. Modest communicative abilities, but still sufficient to support a coherent dialogue, logical capacity and consequentiality in fitting the subjects of elementary level; poor capacity of synthesis and rather stunted ability of graphical expression, scanty interaction with the teacher during the interview.
b) Moderate (21 to 23)
The applicant demonstrates a moderate acquisition of knowledge but lack of expatiation, a few gaps; communicative abilities more than sufficient to support a coherent dialogue; acceptable mastery of the scientific language, logical capacity and consequentiality in fitting the subjects of moderate complexity, good enough capacity of synthesis and acceptable ability of graphical expression.
c) Good (24 to 26)
The candidate demonstrates a rather large wealth of knowledge, moderate in-depth, with small gaps; satisfactory mastery of the communicative abilities and meaningful scientific language; dialogical ability and critical thinking well detectable, good capacity of synthesis and more than acceptable ability of graphical expression.
d) Outstanding (27 to 29)
The candidate demonstrates a very extensive wealth of notions, high in-depth, with marginal gaps; remarkable ability in communicating and high mastery of scientific language; remarkable dialogical capacity, good competence and relevant aptitude for logical synthesis, high capacity of synthesis and graphical expression.
e) Excellent (30)
The candidate demonstrates a wealth of very extensive and in-depth knowledge, irrelevant gaps, high capacity and high mastery in communicating through the scientific language; excellent dialogical ability and marked aptitude to make connections among different subjects, excellent ability to synthesize and very familiar with the graphical expression.
The praise is attributed to the candidates clearly above average, and whose notional, expressive, conceptual, logical limits, if any, as a whole are completely irrelevant.
- Golan et al., Principi di farmacologia, II Ed., Casa Editrice Ambrosiana
- Rossi, Cuomo & Riccardi, Farmacologia, II Ed., Edizioni Minerva Medica
- Rang et al., Farmacologia, VI Ed., Masson
- Goodman & Gilman. Le basi farmacologiche della terapia, XII Ed., Zanichelli
The professor will provide integrative books and the most recent scientific publication on specific subjects discussed during the lectures. Copies of PowerPoint presentations will eventually also be provided. Examples of written examinations with the indication of the right answer will also be provided.