84352 - Fundamentals of Pharmacology

Learning outcomes

Use appropriate terminology to define a drug or a medicinal substance from a clinical and regulatory perspective. Compare and contrast the mechanism of action of the main classes of drugs. Identify and describe the mechanism of action, therapeutic use and side effects of selected classes of drugs. Describe the principles of pharmacokinetics, and understand the implications for the choice of the route of administration and dosing regimen. Recognize the different phases of a clinical trial, and understand the basis for the evaluation of the risk-to-benefit and cost-to-benefit ratio of a medication. Discuss regulatory and scientific aspects concerning herbal products. Read and interpret literature pertaining to a clinical trial. Describe the criteria for the commercialization, dispensing and reimbursement of medications. Discuss the general approach to the correct prescription of a drug, taking into account the variability in drug responses in the population. Discuss pharmacological and regulatory issues related to drug abuse and doping.

Course contents

1. Drugs in medicine: definitions and regulatory aspects
   1. Definition of drug, medicinal product, food supplement, homeopathic product, herbal product, radiopharmaceutical within the current European regulatory framework
   2. Marketing authorization process for medicinal products in the European Union
   3. Summary of the Product Characteristics and European Public Assessment Report by the European Medicines Agency as sources of information for prescribers
   4. Dispensation and reimbursement criteria of medicinal products
   5. Drugs as sources of harm: poisoning, drug abuse and doping
2. Pharmacodynamics
   1. Mechanisms of drug action and the dose-response curve:
      • agonists, partial agonists, antagonists and inverse agonists: the examples of the opioid receptors and of the GABA receptor complex
      • pharmacodynamics as the key to understand the risk/benefit balance: compare and contrast the meaning of the terms “activity”, “efficacy” and “effectiveness” in a clinical setting; drugs with large and narrow therapeutic index
   2. Examples of classes of drugs with different mechanisms of action:
      • drugs acting via membrane receptors: drugs acting on adrenoceptors and acetylcholine receptors
      • drugs acting via enzyme inhibition: non-steroidal antinflammatory drugs, ACE inhibitors
      • drugs mimicking hormonal action: steroids, insulin, levothyroxine

      3. Medicinal products that are not drugs and act via different mechanisms

3. Pharmacokinetics
   1. The entry of a drug into the human body and its fate:
      • how absorption depends on route of administration: the pharmacokinetic curve: reasons why noradrenaline and acetylcholine are not ideal drugs
      • distribution and volume of distribution (Vd)
      • metabolism and excretion
   2. Main pharmacokinetic parameters and their clinical meaning: bioavailability and area under the curve (AUC), Vd, Cmax, tmax, clearance, half-life
   3. Examples of classes of drugs targeting specific compartments/organs thanks to their pharmacokinetic properties: agents with central action used to treat Parkinson’s disease; curaric agents (acting in peripheral compartments); drugs used in general and local anaesthesia; antiasthmatic agents; nitrate derivatives used in angina (sublingually or transdermally) and hypertensive emergencies (intravenously); drugs distributed only in the central compartment (heparin).
4. Drug development: a process where scientific evidence and ethical aspects must be well balanced
   1. The evaluation of the risk-benefit profile of a medicinal product in the different phases of drug development: therapeutic index; number needed to treat, number needed to harm; the importance of pharmacovigilance after marketing authorization and the active role of prescribers
   2. Sustainable healthcare for all citizens: key elements to evaluate the cost-benefit profile of a medicinal product (cost-efficacy and cost-utility studies) and the degree of therapeutic innovation; equivalent products and biosimilar products
   3. The critical appraisal of scientific literature for clinical practice:
      • definition of conflict of interest and identification of independent sources of drug information
      • strengths and limitations of the evidence-based approach
      • the key role of evidence evaluation when prescribing off-label
5. The variability in drug response

1. The WHO approach to prescribing and the concept of essential medicines
2. Drug prescription in a population where one size does not fit all:

• Pharmacogenetics; 
• Age-related issues: children and elderly patients; Comorbidity (e.g. kidney and liver disease);
• Pregnancy and lactation;
• Concomitant medication and likelihood of drug interactions;
• The importance of therapeutic monitoring.

Readings/Bibliography

Suggested texbooks:

1) Waller and Sampson, Medical Pharmacology and Therapeutics. 5^th Edition. 2018. Elsevier (or previous Editions).

2) Goodman and Gilman’s Manual of Pharmacology and Therapeutics. 2^nd Edition. 2014. The McGraw-Hill Companies.

Teaching methods

Interactive lectures where general rules are derived from practical examples taken from everyday experience.

Attending lessons plays an important role in the learning process. During the lessons, the teacher guides the students in the critical analysis of the teaching materials and provides opportunities for online formative assessment.

Teaching material and slides are made available to the students via the moodle platform (Virtuale).

The basic principles learned during this course will provide the basis for the courses of pharmacology in the subsequent years.

Attendance to learning activities is mandatory; the minimum attendance requirement to be admitted to the final exam is 60% of lessons. For Integrated Courses (IC), the 60% attendance requirement refers to the total amount of I.C. lessons. Students who fail to meet the minimum attendance requirement will not be admitted to the final exam of the course and will have to attend relevant classes again during the next academic year.

Professors may authorise excused absences upon receipt of proper justifying documentation, in case of illness or serious reasons. Excused absences do not count against a student’s attendance record to determine their minimum attendance requirement.

Assessment methods

The final examination consists of an oral dissertation concerning a single medicinal product (or a drug class) selected from a list agreed every year during the lectures. The time allowed for the presentation is 20 minutes maximum (15 min presentation + 5 min questions). Use of original slides, specifically prepared by the student, is allowed during the presentation.

The student is asked to demonstrate skills in terms of synthesis, analysis and critical appraisal of the selected topic, by considering at least four of the following six items covered during the lessons:

- Characterization of pharmacokinetic aspects of the selected drug(s);

- Characterization of pharmacodynamic aspects of the selected drug(s);

- Identification of factors explaining clinical variability in drug response;

- Evaluation of the risk / benefit ratio of the drug by identifying appropriate sources of information;

- Identification of the innovative aspects of a medicinal product for a given therapeutic indication;

- Regulatory and/or ethical aspects related to preclinical studies and/or clinical trials required to obtain marketing authorization.

The presentation will be scored considering the following aspects:

• clarity and style of the presentation
• completeness of coverage of the four selected items (considering the time limit indicated above)
• critical assessment by the student of the selected sources of information and ability to link specific aspects of the selected drugs to theoretical concepts illustrated during the lessons

Final grades will be assigned according to the following criteria:

o Outstanding (30L): full achievement of the learning outcomes. The presentation is clear, in professional style with no significant inaccuracies. When asked on specific aspects of the presentation, the student shows ability to promptly frame the topic and full understanding of the underlying theoretical concepts presented during the lessons. Ability to analyze and connect independently the different topics. Concepts in the right succession with some original elaboration by the student and full command of the specific language.

o Excellent (29-30): full achievement of the learning outcomes. The presentation is clear, in professional style with only minor inaccuracies. When asked on specific aspects of the presentation, the student shows ability to frame the topic and full understanding of the underlying theoretical concepts presented during the lessons. Ability to analyze and connect independently the different topics. Concepts in the right succession with some original elaboration by the student and full command of the specific language.

o Very good (27-28): very good level of achievement of the learning outcomes. The presentation is clear, in professional style although with some inaccuracies. When asked on specific aspects of the presentation, the student shows ability to frame the topic and adequate understanding of the underlying theoretical concepts presented during the lessons. Ability to analyze and connect independently the different topics. Concepts in the right succession with very good command of the specific language.

o Good (23-26): good level of achievement of the learning outcomes. The presentation may be clear, but with some significant inaccuracies. When asked on specific aspects of the presentation, the student shows good understanding of the underlying theoretical concepts presented during the lessons. Concepts are presented in the right succession with good command of the specific language. Ability to analyze and link concepts after input from the teacher.

o Sufficient (18-22): sufficient level of achievement of the learning outcomes. The presentation is unclear in the way it is presented and shows some significant inaccuracies/errors. When asked on specific aspects of the presentation, the student shows sufficient understanding of the underlying theoretical concepts presented during the lessons. Exposition of concepts and language acceptable as a whole.

o Insufficient (<18): failure to achieve the learning outcomes. The presentation is unclear in the way it is presented and shows several errors. When asked on specific aspects of the presentation, the student shows insufficient understanding of the underlying theoretical concepts presented during the lessons. Serious and repeated conceptual errors.

Teaching tools

Students are encouraged to attend the lectures with a printout of the relevant file downloaded from moodle or bringing electronic devices to access the relevant material during the lecture. This will allow easier interaction with the teacher when asked to discuss a problem.

Also e-learning material (including scientific literature and self-assessment tools) will be provided.

Office hours

See the website of Elisabetta Poluzzi

See the website of Fabrizio De Ponti

See the website of Fabrizio De Ponti