LEARNING OUTCOMES

The aim of this course is to provide the students with knowledge about fundamental concepts of the main pharmacological classes, the basic concepts of pharmacokinetics and pharmacodynamics, correlated to the study and the development of new drugs, and the methodologies of pharmacological experimentation. The course will be focused to study cellular molecular mechanisms of the action of drugs, deepening their receptorial mechanisms and signal transduction. Moreover, the course will underline the progresses, obtained using new technologies, molecular biology and biotechnology, towards the investigation of innovative pharmaceuticals molecules and the finding of new therapeutic targets.

AIMS AND LEARNING OUTCOMES

The main learning outcome of the Pharmacology course is acquisition of all the basic information about the drugs of current use and of innovative conception as far as their chemical composition, clinical indications, therapeutic activity, adverse reactions and toxicity.

In detail the student have to get knowledge on:

the molecular and cellular targets that mediate the drug effects;

administration modality and the fate of the drugs within the body, inclding the mechaisms of drug distribution, metabolism amd elimination;

the mechanisms mediating the development of the adverse drug reactions and their toxic effects; the possible causes of hydiosyncratic and allergig reactions toward drugs, included principle of pharmacogenetics and of drug-drug interactions.

TEACHING METHODS

Frontal lessons and laboratory.

SYLLABUS/CONTENT

GENERAL PHRMACOLOGY

1) Introduction to the pharmacology and its sub-branches, definition of drug and toxic agent, active component and excipient. Cell diversity as main target of the action of the drugs.

The different phases of drug development. The origin of the drugs (pharmacognosy) (2 hours)

PHARMACOKINETICS

2) Different routes of drug administration, absorption of drugs and the conditions that may modulate it, bioavailability and bioequivalence. Drug distribution and redistribution (2 hours)

3) Drug metabolism: phase 1 e phase 2 enzymes. Drug excretion and its modulation, individual factors that may modify the responses to the drugs (2 hours)

MECHANISM OF ACTION OF THE DRUGS

4-5) THE DRUG-RECEPTOR INTERACTION (4 hours)

Qualitative and quantitative characteristics – gradual and quantal responses, the concept of receptor affinity, Bmax, intrinsic activity, efficacy, and potency - techniques to measure receptor density, saturation curves, Scatchard analysis to determine Bmax and Kd, concentration-effect curves, up e down-regulation – agonism e antagonism – structure-activity relationship – therapeutic index

6) DRUG EFFECTS (2 hours)

Receptor- and non-receptor-mediated mechanisms. Different receptor classes. Pharmacoallergy, idiosyncrasy, tolerance, dependence, pharmacogenetics, pharmacogenomics.

DRUG MOLECULAR TARGETS

7) G protein coupled receptors, mechanisms of activation and signal transduction pathways; pharmacological modulation (2 hours)

8) Growth factor receptors endowed with intrinsic tyrosine kinase activity, signal transduction pathways; pharmacological modulation (2 hours)

9) Intracellular receptors, signal transduction pathways; pharmacological modulation (2 hours)

10) Ion channels and ionotropic receptors; pharmacological modulation (2 hours)

11) ionic pumps and transporters; pharmacological modulation (2 hours)

12) Pharmacological modulation of the enzyme activity (2 hours)

13) Molecular targets of the neurotransmission and their pharmacological modulation: the noradrenergic neurotransmission (2 hours)

14) Molecular targets of the neurotransmission and their pharmacological modulation: the cholinergic neurotransmission (2 hours)

15) Molecular targets to control inflammation and NSAIDs (2 hours)

16) Pharmacological control of cell proliferation (2 hours)

RECOMMENDED READING/BIBLIOGRAPHY

F. Clementi, G. Fumagalli. Farmacologia generale e molecolare. (Quarta Edizione) UTET.