4029 - TOXICOLOGY
Academic Year 2019/2020
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ANNAROSA CARTA (Tit.)
- Teaching style
- Lingua Insegnamento
|[50/22] PHARMACY||[22/00 - Ord. 2014] PERCORSO COMUNE||8||64|
The objective of the course of Toxicology is to provide the student with an appropriate knowledge of the manifestation of toxic effects generated in man and in experimental animals by environmental substances or drugs. The course will be divided in two parts to allow students to acquire the principles of general toxicology, with a particular attention to the highlight differences and similarities between general pharmacology and general toxicology. Further attention will be given to the use of experimental data generated in a simulated test of toxicity. The data will be elaborated statistically and plotted in graphs. The path of a xenobiotic through the body will be described, including the different phases of toxicocinetic, from absorption to distribution, storage, metabolism and clearance. The second part of the course will deal with toxic effects caused by drugs or other toxic substances in specific organs or systems. Particular attention will be given to the mechanism of toxicity that occur a molecular or subcellular level exploiting the relationship between the pharmacological and toxic effect of drugs. At completition of this course the student will have acquired the necessary basic knowledge on the mechanism of toxicity either at cellular level or at organ level and will be able to use it to foresee the consequences of an accidental exposition to elevated doses of drugs or of toxic substances but also to foresee the eventual toxic effect of an unwonted administration of a combination of drugs. In addition, the student will have developed skills in evaluating the consequences of an accidental exposition of a population or an individual to a toxic substance, being able to quantify levels of risk either at qualitative level (frequency of appearance) or at quantitative level (intensity of damage). The final exam will allow to the evaluate the communicative skills of the student as far as regards the use of an adequate terminology in the description of a) toxicity mechanism at cellular of organ level; b) model of toxicity exposition in a population; c) experimental models in which drugs or experimental drugs are tested.
The course of Toxicology is a relatively complex course because the delivered contents can only be optimally acquired only by students who will have passed the prior exams that are considered mandatory by the teaching board. Indeed, this course is finalized to provide the tools to understand the xenobiotic interaction with the body, and how a toxic effect will develop either at the cellular level or at the organ level. Therefore, the knowledge of general and inorganic chemistry is required, as well as organic chemistry, anatomy, biochemistry and physiology.
The course is divided into two parts: General Toxicology and Organ Toxicology.
The first illustrates how a molecule interacts with the host starting from absorption surface to the elimination route. The second part will deal with the systematic examination of main organ toxicity.
Principle of General Toxicology: classification of toxic agents; exposure types and administration routes, duration and frequency of toxic agents exposure. Classification of the toxic effects induced by drugs: mechanisms of action, excessive and prolonged exposure, enzymatic deficiency, hypersensitivity reactions.
Dose-response: gradual and quantal; pharmaceutical safety and therapeutic index (TI: LD50 / ED50). LT 50. Evaluation of toxic effects. Use of animals in pre-clinic toxicology.
Drug/Toxic agent-receptor interaction: type of receptors and chemical interactions between drug and receptor; binding; dose-response curve; agonist, antagonist (competitive, non competitive), partial agonist or inverse agonist.
Mechanism of toxicity: metabolic activation and toxic effect of free radicals. Toxicity as a consequence of cellular dysfunction and wrong reparation.
Predictive toxicology and risk evaluation: risk assessment; drug structure/drug activity relationship, in vitro and in vivo test, epidemiology, NOEL, NOAEL, LOAEL, FEL LOEL.
Absorption, distribution and excretion of toxics.
Biotransformation of xenobiotics: Phase I and Phase II reactions.
Toxicokinetics: Classical and physiology toxicokinetics. Apparent volume of distribution, cleareance and relative persistence of a specific toxic expressed as "half-life" (T0.5).
2nd part, organ toxicity.
Toxic Responses of the Blood: Blood as a target organ. Hematopoiesis. Treatment of anaemia and toxic effects of iron therapy, anticoagulants, antifibrinolytics, antiaggregants. Hypoxia.
Toxic Responses of the Immune System: Methods to assess immunocompetence. Immune modulation by therapeutic agents. Hypersensitivity, Autoimmunity.
Toxic Responses of the Respiratory System: General principles in phatogenesis of lung damage caused by chemicals. Acute and chronic responses of the lungs to injuries. Agents known to produce lung injuries in humans.
Toxic Responses of the Kidney: Assessment of renal toxicity. Phatophysiologic responses of the kidney. Biochemical mechanism/mediators of renal cell injury. Specific nefrotoxicity by thearapeutic agents.
Toxic Responses of the Liver : Liver phisiology and phatophisiology. Mechanism of liver toxicity by chemical and therapeutic agents. Critical factors in toxicant-induced liver injuries: biotransformation, alteration of the blood efflux. Steatosis, cholestasis, necrosis, cirrhosis. Toxicity of nonsteroidal antinflammatory agents/analgesics.
Toxic Responses of the Nervous System. Neuronopathies. Assonopathies. Myelinopathies. Neurotransmission-associated neurotoxicity. Chemicals that induce neurotoxicity (antidepressant, antipsychotics, antiparkinson, hypnotic, ansiolythic).
Toxic Responses of the Heart and circuolation system.
Toxicity of drugs of abuse: nicotine, opioids, cocaine, other psychostimulants, ethanol and alcoholic beverages, cannabinoids.
The course consists of 64 hs of frontal lesson. Two hour lessons will be provided three days a week and the course will be completed in about 3 months. During the teaching the student will have chances to interact with the professor, in order to gain further details on the subjects exposed.
Verification of learning
The evaluation of the student knowledge of course contents will be performed frequently during the lessons through questions aimed to check the assimilation of the content delivered in terms of knowledge and ability to use them in a discussion. A more formal assessment will be performed at the end of the first part of the course (general toxicology). This test will consist of 6 questions to be answered with a short reply aimed to check knowledge and ability to use the course content for solving simple problems. The second test will consist of 6 questions related to to the toxicokinetic (ADME). The tirth test will consist of 6 questions related to systemic toxicology. The evaluation of the results of the test will contribute to the final evaluation.
The final vote, expressed in 18-30/30 will be formulated taking into account this basic scheme.
Sufficient to discrete (18-23/30): The student shows to have acquired a sufficient level of knowledge of contents and a sufficient ability in communicating and using them in a discussion or in the process of solving simple problems.
Good (from 24 to 27/30). The student shows to have acquired an almost complete level of knowledge of contents and good ability in communicating and using them in a discussion or in the process of solving relatively complex problems.
Optimum to excellent (28-30/30): The student shows to have acquired a complete level of knowledge of contents and an optimal ability to communicate and using them in a discussion or in the process of promptly solving simple and complex problems without any hesitation.
The “laude” will be given only to excellent students that are well above average in understanding and using the contents delivered in this course and in those delivered in previous courses.
Casarett & Doull’s: Tossicologia: i fondamenti dell’azione delle sostanze tossiche. EMSI Roma
A copy of the slides presented in the frontal lessons will be provided, every two/three lessons, to three students in chargo of distributing the material among the colleagues.