Pharmacy

The Pharmaceutical and Toxicological Chemistry I course provides the student with the foundations for understanding the therapeutic action of drugs at a chemical level. At the end of this course the student will be able to understand the events that take place inside the human body from the administration of the drug to its elimination. To make better use of the notions of this course, the teaching program is shared into two sections: the part of General Pharmaceutical Chemistry leads the student through the general knowledge that underlies the action of the drug; the part of Systematic Pharmaceutical Chemistry analyzes in detail some classes of drugs used in therapy, with emphasis on the most recent advances in the pharmaceutical literature. The analysis of drug classes will subsequently be completed with the teaching of Pharmaceutical and Toxicological Chemistry II. General part GENERAL PART (16 hours) The course of Pharmaceutical and Toxicological Chemistry I provides the acquisition of concepts related to: i) nomenclature, design and development of drugs and their classification, ii) pharmacokinetics and pharmacodynamics, iii) mechanism of action, iv) metabolism and toxicity. All of this is dealt with in the general part of the programme, which generally takes about 16 hours of lessons. For this part text 1 and files on elearning2 are strongly recommended. Genesis, development, classification and nomenclature of drugs (1 hour) Pharmacokinetics (8 hours) • Drugs absorption. Biological membranes. Drug passage through membrane barriers: convective transport, passive diffusion, Fick's law, influence of ionization, facilitated diffusion and active transport. • Distribution and excretion of drugs. • Drug metabolism. Phase I metabolic reactions: microsomal and non-microsomal oxidation and reduction, hydrolytic reactions. Phase II metabolic reactions: glucuronidation, sulfoconjugation, hippuric conjugation, mercapturic synthesis, acetylation and methylation. Pharmacodynamics (7 hours) • Definition and nature of drug receptors. Concepts of agonist and antagonist. Receptor superfamilies: structure and mechanisms of signal transduction. • Drug-receptor bonds: covalent bonds, electrostatic interactions, hydrophobic and charge transfer bonds. • Enzyme inhibitors: reversible inhibitors, affinity markers, mechanism-based inhibitors. • Stereochemistry and pharmacological activity: concepts of eutomer and distomer, eudismic relationship, Easson-Stedman model, pharmacophore conformation. • Qualitative structure-activity relationships. Molecular modifications. Pharmacophore groups. Dissociation of pharmacological activity. Molecular simplification and complication. Molecular replication, hybridization and addition. Prodrugs: carrier pro-drugs and bioprecursors. Linear and cyclic homology. • Isosterism and bioisosterism: classical and non-classical bioisosteries. Quantitative structure-activity relationships. SYSTEMATIC PHARMACEUTICAL CHEMISTRY (64 hours) The study of some classes of drugs, which are reported in the systematic part of the programme, is deepened. For each class of drugs, notions relating to general properties, classification, mechanism of action, structure-activity relationships and main pharmacological properties are taught. For drugs marked with (s), specific synthesis is required. Approximately 64 hours of lessons are dedicated to this part of the program, divided as follows: SYSTEMATIC PART For all drug classes of the systematic part: general properties, classification, mechanism of action, structure-activity relationships, main pharmacological properties. For drugs marked with (s), specific synthesis is required. ANTIINFECTIVE DRUGS Generalities and classification. Inorganic disinfectants: (1 hour) Hydrogen peroxide, iodine, sodium hypochlorite, quaternary ammonium salts, formaldehyde, alcohols and phenols, silver derivatives, mercury derivatives. For this part, the file on elearning2 is recommended. Chemotherapy: (44 hours) Antibacterials. General information on bacteria. General mechanisms of antibacterial action. Bacteriostatics and bactericides. Antibacterial resistance. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Sulfonamides: Sulfathiazole, sulfamethylthiazole, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfadimethoxine, sulfalene, sulfasalazine (s). Sulfonamide associations: co-trimoxazole (s). • Quinolones: Nalidixic (s) and pipemidic acids, cinoxacin, norfloxacin, pefloxacin, ciprofloxacin (s), ofloxacin (s) and levofloxacin, moxifloxacin, rufloxacin, lomefloxacin, prulifloxacin. Text 2 is particularly recommended for this first part. Antibiotics Biosynthesis of peptidoglycan and protein synthesis in bacteria and effects of antibacterial antibiotics on them. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Penicillins. Narrow-spectrum and beta-lactamase sensitive penicillins: benzylpenicillin. Narrow-spectrum and beta-lactamase resistant penicillins: oxacillin (s), flucloxacillin (s). Broad-spectrum penicillins: Ampicillin (s), amoxicillin (s), bacampicillin, ticarcillin, piperacillin. • Beta-Lactamase inhibitors. Clavulanic acid, sulbactam, tazobactam. Sultamicillin • Cephalosporins. 1st generation cephalosporins: cephalexin, cephalothin, cefazolin. 2nd generation cephalosporins: cefoxitin, cefuroxime, cefamandole, cefachlor, cefonicid. 3rd generation cephalosporins: cefotaxime (s), ceftazidime, ceftriazone, cefixime, cefpodoxime. 4th generation cephalosporins: cefepime. 5th generation cephalosporins • Monobatmi. Aztreonam. • Carbapenems. Imipenem, meropenem, ertapenem. • Tetracyclines. Tetracycline, chlortetracycline, methacycline, meclocycline, doxycycline, minocycline(s), tigecycline, rolitetracycline, lymecycline. • Amphenicols. Chloramphenicol (s, Parke-Davis process), thiamphenicol. • Macrolides. Erythromycin, roxithromycin, azithromycin, clarithromycin, flurithromycin, troleandomycin, midecamycin, josamycin, myocamycin, rokitamycin, spiramycin. • Lincosamides. Clindamycin, lincomycin. • Aminoglycosides. Streptomycin, tobramycin, gentamicin, amikacin, netilmycin, kanamycin, neomycin. • Glycopeptides. Vancomycin, teicoplanin. • Polypeptides. Bacitracin, thyrotricin, polymyxin B, colistin. • Different antibacterials. Fosfomycin, linezolid(s) • Antimycobacterials. General information on mycobacterial infections. For this part, one of the texts in points 3-6 and the files available on elearning2 are recommended. Antituberculars. Isoniazid (s). Pyrazinamide(s). Rifamycins [rifamycin SV, rifampicin, rifabutin] Ethambutol (s). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antileprotics. Dapsone(s). Rifampicin. Clofazimine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antiprotozoans. General information on protozoa. • Antimalarials. Biological cycle of malaria parasites. Alkaloids of cinchona bark. Artemisinin and its derivatives. Atovaquone. Derivatives of 4-aminoquinoline: chloroquine (s). Fluorenylmethanol derivatives: lumefantrine. Quinolinomethanol derivatives: mefloquine. Derivatives of 8-aminoquinoline: primaquine. Antifolics: proguanil (s), pyrimethamine, trimethoprim. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antivirals. General information on viruses. • Vaccines, immunoglobulins, immunomodulatory substances (notes). Interferons. • Antivirals against influenza: amantadine (s), zanamivir, oseltamivir. • Hepatitis B and C antivirals: Idoxuridine. Brivudine. Ribavirin(s). Entecavir and telbivudine. Boceprevir and telaprevir. DAAS, Sofosbuvir. • Antivirals against herpes: Aciclovir (s) and valaciclovir (s). Penciclovir and famciclovir. Ganciclovir (s) and valganciclovir. Foscarnet sodium (s), Adefovir. • Antiretroviral therapy: nucleoside/nucleotide and non-nucleoside reverse transcriptase inhibitors [zidovudine (s), didanosine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, efavirenz (s), etravirine, rilpivirine]; HIV protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, fosamprenavir, lopinavir, atazanavir, tipranavir, darunavir); fusion inhibitors (enfuvirtide); CCR5 antagonists (maraviroc); integrase inhibitors [raltegravir]. Antifungals • Imidazole antifungals: clotrimazole, bifonazole, econazole, miconazole, isoconazole, tioconazole, fenticonazole, sertaconazole, ketoconazole. • Triazole antifungals: itraconazole, posaconazole, fluconazole (s), voriconazole. • Antifungals of various structure: flucytosine (s), terbinafine, cyclopiroxolamine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. ANTINEOPLASTIC DRUGS (16 hours) General information on neoplasms and therapies for neoplastic diseases Cytotoxic. • Alkylating agents: chlorambucil, melphalan, bendamustine, cyclophosphamide (s), busulfan, carmustine, temozolomide (s). • Antimetabolites: methotrexate (s), cytarabine, fluorouracil (s), gemcitabine, mercaptopurine, thioguanine, fludarabine. • Vinca alkaloids: vinblastine, vincristine, vinorelbine. • Podophyllotoxin derivatives: etoposide. • Taxanes: paclitaxel, docetaxel, cabazitaxel. • Cytotoxic antibiotics: anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin), mitoxantrone, bleomycin, mitomycin. • Various cytotoxics: platinum complexes [cisplatin (s), carboplatin (s), oxaliplatin (s)]; trabectedin; camptothecines (irinotecan and topotecan). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Endocrine therapy. • Hormones and related agents: medroxyprogesterone, gonadotropin-releasing hormone analogues and antagonists (buserelin, leuprorelin, goserelin, triptorelin, ganirelix, degarelix). • Hormonal antagonists and related substances: tamoxifen (s), fulvestrant, exemestane, anastrozole (s), abiraterone, flutamide (s), bicalutamide. For this part, one of the texts in points 3-6 is recommended. Biological therapy. • Protein kinase inhibitors: imatinib (s) and derivatives • Biological response modifiers: interferons, aldesleukin (notes), monoclonal antibodies. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. DIGESTIVE SYSTEM DRUGS (3 hours) General information on gastric secretion and its mechanisms. • Anti-ulcer. Antisecretors: H2 antihistamines [cimetidine, ranitidine (s), famotidine, nizatidine, roxatidine]. • H+, K+-ATPase inhibitors [omeprazole (s), lansoprazole, pantoprazole, rabeprazole, esomeprazole]. Prostaglandins: misoprostol. • Other anti-ulcer: sucralfate For this part, one of the texts in the paragraphs 3-6 is recommended and file on elearning2.

For an adequate understanding of the course, it is essential that the student possess sufficient knowledge of: Organic Chemistry, in particular as regards chemical reactions and their mechanism; Biochemistry especially with regard to the synthesis processes of the bacterial cell wall, protein synthesis and DNA; Microbiology especially in relation to the structure of infectious agents such as bacteria, viruses, fungi, plasmodia, mycobacteria, amoebas, etc. Organic chemistry, physiology, biochemistry and microbiology represent the cultural propaedeutics of medicinal chemistry.

1. Greco Giovanni. Farmacocinetica e farmacodinamica su basi chimico-fisiche. Ed. Loghìa 2. Greco Giovanni. Farmaci antibatterici. Ed. Loghìa 3. Costantino, G., Sbardella, G. Chimica farmaceutica, Ed. EdiSES 4. David A. Williams, Thomas L. Lemke, Foye’s principi di chimica farmaceutica. 6° ed, Piccin Ed. 5. David A. Williams, Thomas L. Lemke, Foye’s L’essenziale. Piccin Ed. 6. John M. Beale, Jr, John H. Block. Wilson & Givolds Chimica farmaceutica, 1a Ed. italiana, Casa Ed. Ambrosiana 7. A. Gasco, F. Gualtieri, C. Melchiorre, Chimica Farmaceutica, 1a Ed, CEA Ed. (esce il 9 marzo). 8. E. Stevens, Chimica farmaceutica, Ed. Piccin. 9. File del materiale didattico su elearning2 (https://elearning.uniroma1.it/course/view.php?id=852)

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt

Mandatory and in presence attendance

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The exam consists of four questions, one of which on the general part and three on the systematic part. Each question is assigned the same score, for a total of 30/30. The objective of the exam is to ascertain that the student possesses the chemical knowledge that underlies the therapeutic action of the drug and has acquired the fundamentals of the drug action from a general and systematic point of view as reported in the program, i.e. how and why a drug is distributed in the body, how it interacts with the receptor and why it undergoes a certain type of metabolism and, consequently, elimination. In order to pass the exam, thus obtaining a mark of at least 18/30, the student must demonstrate that he has acquired sufficient knowledge of all the topics covered in the course. To achieve a score of 30/30 cum laude, the student must instead demonstrate that he has acquired an excellent knowledge of all the topics covered during the course.

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt

The subject “Chimica farmaceutica e tossicologica I” leads the student to acquire the basis of knowledge to understand the therapeutic action of the drug at a chemical level. At the end of this subject, the student can understand the sequence of events inside the human body from drug administration to excretion. As a guide to learning fruitful, this subject was splitted into two sections. The general medicinal chemistry guides the student through the general knowledge of drug action. The systematic section analyses in depth some drug classes of therapeutic intervention, with focus on the most recent drugs. The analysis of drug classes will be completed later by the “Chimica farmaceutica e tossicologica II” subject. • General medicinal chemistry (18 h) Aim of the subject is to acquire knowledge of systematic naming of drugs, drug design and development and their catogerization, phamacokinetica and pharmacodinamica, mechanism of action, metabolism and toxicity. • Systematic medicinal chemistry (70 h) Then, each drug class is analysed for the mechanism of action at molecular level, the structure-activity relationships, the metabolism and the synthesis of selected drugs. Sulphamidics, quinolones, nitrofurans and nitroimidazoles (8 h) • Antibiotics petidoglycan synthesis inhibitors. Penicillins, cephalosporins, carbapenams (8 h) • Antibiotics inhibitors of ribosom. Aminoglycosides, macrolides, tetracyclins, chlororamfenicol, ansamicyns (8 h) • Other antibiotics (2 h) • Antimycobacterial agents (4 h) • Antifungal agents (6 h) • Antiparasitic agents (4 h) • Antiviral agents and AIDS treatment (8 h) • Cancer and chemotherapy (8 h) • Antiinfective agents (2 h) • Expectorant and mucolytic agents (2 h) • Tensioactive agents (2 h) • Gastrointestinal agents. Antiacid agents, antiulcer agents and purging agents (8 h)

In view of a fruitful and enjoyable learning, at the start of the subject the student must have knowledge of Organic chemistry regarding in particular the organic reactions and their mechanisms. Moreover, the student must know the 5, 6 and benzofused heterocycle naming and chemistry. Important Phisiology and Biochemistry knowledge include cell replication, protein synthesis, structure and DNA synthesis, biosynthesis of bacterial cell wall and viral replication. Useful knowledge of Microbiology mainly concerns the structure of infective agents, such as bacteria, viruses, fungi, plasmodia, mycobacteria, amoeba etc.

Greco Giovanni. Farmacocinetica e farmacodinamica su basi chimico-fisiche. Ed. Loghìa Greco Giovanni. Farmacoci antibatterici. Ed. Loghìa David A. Williams, Thomas L. Lemke, Foye’s principi di chimica farmaceutica. 7° ed, Piccin Ed. David A. Williams, Thomas L. Lemke, Foye’s L’essenziale. Piccin Ed. John M. Beale, Jr, John H. Block. Wilson & Givolds Chimica farmaceutica, 1a Ed. italiana, Casa Ed. Ambrosiana A. Gasco, F. Gualtieri, C. Melchiorre, Chimica Farmaceutica, 2a Ed, CEA Ed. E. Stevens, Chimica farmaceutica, Ed. Piccin. File delle lezioni scaricabile da e-learning.

The subject “Chimica farmaceutica e tossicologica I” provides front lessons in the classroom. Each chapter can be followed through the indicated new or revised learning books. The teacher shows the student the suitable chapters to follows. Moreover, files of the lessons can be downloaded from the e-learning website. The student can ask the teacher additional explanation on appointment. Lesson attendance is mandatory. Attendance aims to improve the quality of teaching and to give a track record for the exam. Students who can not attend the lessons, download the detailed program and the lesson files from the e-learning website, and receive assistance from the teacher.

Attendance is mandatory

The exam is oral. To this end the capability of the student the explain the teacher the fundamentals of general medicinal chemistry, mechanism of action, structure-activity relationships and therapeutic use is considered. For the questions, refer to the current program downloadable from e-alearning. Goal of the exam is to evaluate the capability of the student to manage the general and specific fundamentals of drug action.

References reported by the teacher at lesson

The subject “Chimica farmaceutica e tossicologica I” provides front lessons in the classroom. Each chapter can be followed through the indicated new or revised learning books. The teacher shows the student the suitable chapters to follows. Moreover, files of the lessons can be downloaded from the e-learning website. The student can ask the teacher additional explanation on appointment. Lesson attendance is mandatory. Attendance aims to improve the quality of teaching and to give a track record for the exam. Students who can not attend the lessons, download the detailed program and the lesson files from the e-learning website, and receive assistance from the teacher.

The Pharmaceutical and Toxicological Chemistry I course provides the student with the foundations for understanding the therapeutic action of drugs at a chemical level. At the end of this course the student will be able to understand the events that take place inside the human body from the administration of the drug to its elimination. To make better use of the notions of this course, the teaching program is shared into two sections: the part of General Pharmaceutical Chemistry leads the student through the general knowledge that underlies the action of the drug; the part of Systematic Pharmaceutical Chemistry analyzes in detail some classes of drugs used in therapy, with emphasis on the most recent advances in the pharmaceutical literature. The analysis of drug classes will subsequently be completed with the teaching of Pharmaceutical and Toxicological Chemistry II. General part GENERAL PART (16 hours) The course of Pharmaceutical and Toxicological Chemistry I provides the acquisition of concepts related to: i) nomenclature, design and development of drugs and their classification, ii) pharmacokinetics and pharmacodynamics, iii) mechanism of action, iv) metabolism and toxicity. All of this is dealt with in the general part of the programme, which generally takes about 16 hours of lessons. For this part text 1 and files on elearning2 are strongly recommended. Genesis, development, classification and nomenclature of drugs (1 hour) Pharmacokinetics (8 hours) • Drugs absorption. Biological membranes. Drug passage through membrane barriers: convective transport, passive diffusion, Fick's law, influence of ionization, facilitated diffusion and active transport. • Distribution and excretion of drugs. • Drug metabolism. Phase I metabolic reactions: microsomal and non-microsomal oxidation and reduction, hydrolytic reactions. Phase II metabolic reactions: glucuronidation, sulfoconjugation, hippuric conjugation, mercapturic synthesis, acetylation and methylation. Pharmacodynamics (7 hours) • Definition and nature of drug receptors. Concepts of agonist and antagonist. Receptor superfamilies: structure and mechanisms of signal transduction. • Drug-receptor bonds: covalent bonds, electrostatic interactions, hydrophobic and charge transfer bonds. • Enzyme inhibitors: reversible inhibitors, affinity markers, mechanism-based inhibitors. • Stereochemistry and pharmacological activity: concepts of eutomer and distomer, eudismic relationship, Easson-Stedman model, pharmacophore conformation. • Qualitative structure-activity relationships. Molecular modifications. Pharmacophore groups. Dissociation of pharmacological activity. Molecular simplification and complication. Molecular replication, hybridization and addition. Prodrugs: carrier pro-drugs and bioprecursors. Linear and cyclic homology. • Isosterism and bioisosterism: classical and non-classical bioisosteries. Quantitative structure-activity relationships. SYSTEMATIC PHARMACEUTICAL CHEMISTRY (64 hours) The study of some classes of drugs, which are reported in the systematic part of the programme, is deepened. For each class of drugs, notions relating to general properties, classification, mechanism of action, structure-activity relationships and main pharmacological properties are taught. For drugs marked with (s), specific synthesis is required. Approximately 64 hours of lessons are dedicated to this part of the program, divided as follows: SYSTEMATIC PART For all drug classes of the systematic part: general properties, classification, mechanism of action, structure-activity relationships, main pharmacological properties. For drugs marked with (s), specific synthesis is required. ANTIINFECTIVE DRUGS Generalities and classification. Inorganic disinfectants: (1 hour) Hydrogen peroxide, iodine, sodium hypochlorite, quaternary ammonium salts, formaldehyde, alcohols and phenols, silver derivatives, mercury derivatives. For this part, the file on elearning2 is recommended. Chemotherapy: (44 hours) Antibacterials. General information on bacteria. General mechanisms of antibacterial action. Bacteriostatics and bactericides. Antibacterial resistance. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Sulfonamides: Sulfathiazole, sulfamethylthiazole, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfadimethoxine, sulfalene, sulfasalazine (s). Sulfonamide associations: co-trimoxazole (s). • Quinolones: Nalidixic (s) and pipemidic acids, cinoxacin, norfloxacin, pefloxacin, ciprofloxacin (s), ofloxacin (s) and levofloxacin, moxifloxacin, rufloxacin, lomefloxacin, prulifloxacin. Text 2 is particularly recommended for this first part. Antibiotics Biosynthesis of peptidoglycan and protein synthesis in bacteria and effects of antibacterial antibiotics on them. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Penicillins. Narrow-spectrum and beta-lactamase sensitive penicillins: benzylpenicillin. Narrow-spectrum and beta-lactamase resistant penicillins: oxacillin (s), flucloxacillin (s). Broad-spectrum penicillins: Ampicillin (s), amoxicillin (s), bacampicillin, ticarcillin, piperacillin. • Beta-Lactamase inhibitors. Clavulanic acid, sulbactam, tazobactam. Sultamicillin • Cephalosporins. 1st generation cephalosporins: cephalexin, cephalothin, cefazolin. 2nd generation cephalosporins: cefoxitin, cefuroxime, cefamandole, cefachlor, cefonicid. 3rd generation cephalosporins: cefotaxime (s), ceftazidime, ceftriazone, cefixime, cefpodoxime. 4th generation cephalosporins: cefepime. 5th generation cephalosporins • Monobatmi. Aztreonam. • Carbapenems. Imipenem, meropenem, ertapenem. • Tetracyclines. Tetracycline, chlortetracycline, methacycline, meclocycline, doxycycline, minocycline(s), tigecycline, rolitetracycline, lymecycline. • Amphenicols. Chloramphenicol (s, Parke-Davis process), thiamphenicol. • Macrolides. Erythromycin, roxithromycin, azithromycin, clarithromycin, flurithromycin, troleandomycin, midecamycin, josamycin, myocamycin, rokitamycin, spiramycin. • Lincosamides. Clindamycin, lincomycin. • Aminoglycosides. Streptomycin, tobramycin, gentamicin, amikacin, netilmycin, kanamycin, neomycin. • Glycopeptides. Vancomycin, teicoplanin. • Polypeptides. Bacitracin, thyrotricin, polymyxin B, colistin. • Different antibacterials. Fosfomycin, linezolid(s) • Antimycobacterials. General information on mycobacterial infections. For this part, one of the texts in points 3-6 and the files available on elearning2 are recommended. Antituberculars. Isoniazid (s). Pyrazinamide(s). Rifamycins [rifamycin SV, rifampicin, rifabutin] Ethambutol (s). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antileprotics. Dapsone(s). Rifampicin. Clofazimine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antiprotozoans. General information on protozoa. • Antimalarials. Biological cycle of malaria parasites. Alkaloids of cinchona bark. Artemisinin and its derivatives. Atovaquone. Derivatives of 4-aminoquinoline: chloroquine (s). Fluorenylmethanol derivatives: lumefantrine. Quinolinomethanol derivatives: mefloquine. Derivatives of 8-aminoquinoline: primaquine. Antifolics: proguanil (s), pyrimethamine, trimethoprim. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antivirals. General information on viruses. • Vaccines, immunoglobulins, immunomodulatory substances (notes). Interferons. • Antivirals against influenza: amantadine (s), zanamivir, oseltamivir. • Hepatitis B and C antivirals: Idoxuridine. Brivudine. Ribavirin(s). Entecavir and telbivudine. Boceprevir and telaprevir. DAAS, Sofosbuvir. • Antivirals against herpes: Aciclovir (s) and valaciclovir (s). Penciclovir and famciclovir. Ganciclovir (s) and valganciclovir. Foscarnet sodium (s), Adefovir. • Antiretroviral therapy: nucleoside/nucleotide and non-nucleoside reverse transcriptase inhibitors [zidovudine (s), didanosine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, efavirenz (s), etravirine, rilpivirine]; HIV protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, fosamprenavir, lopinavir, atazanavir, tipranavir, darunavir); fusion inhibitors (enfuvirtide); CCR5 antagonists (maraviroc); integrase inhibitors [raltegravir]. Antifungals • Imidazole antifungals: clotrimazole, bifonazole, econazole, miconazole, isoconazole, tioconazole, fenticonazole, sertaconazole, ketoconazole. • Triazole antifungals: itraconazole, posaconazole, fluconazole (s), voriconazole. • Antifungals of various structure: flucytosine (s), terbinafine, cyclopiroxolamine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. ANTINEOPLASTIC DRUGS (16 hours) General information on neoplasms and therapies for neoplastic diseases Cytotoxic. • Alkylating agents: chlorambucil, melphalan, bendamustine, cyclophosphamide (s), busulfan, carmustine, temozolomide (s). • Antimetabolites: methotrexate (s), cytarabine, fluorouracil (s), gemcitabine, mercaptopurine, thioguanine, fludarabine. • Vinca alkaloids: vinblastine, vincristine, vinorelbine. • Podophyllotoxin derivatives: etoposide. • Taxanes: paclitaxel, docetaxel, cabazitaxel. • Cytotoxic antibiotics: anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin), mitoxantrone, bleomycin, mitomycin. • Various cytotoxics: platinum complexes [cisplatin (s), carboplatin (s), oxaliplatin (s)]; trabectedin; camptothecines (irinotecan and topotecan). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Endocrine therapy. • Hormones and related agents: medroxyprogesterone, gonadotropin-releasing hormone analogues and antagonists (buserelin, leuprorelin, goserelin, triptorelin, ganirelix, degarelix). • Hormonal antagonists and related substances: tamoxifen (s), fulvestrant, exemestane, anastrozole (s), abiraterone, flutamide (s), bicalutamide. For this part, one of the texts in points 3-6 is recommended. Biological therapy. • Protein kinase inhibitors: imatinib (s) and derivatives • Biological response modifiers: interferons, aldesleukin (notes), monoclonal antibodies. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. DIGESTIVE SYSTEM DRUGS (3 hours) General information on gastric secretion and its mechanisms. • Anti-ulcer. Antisecretors: H2 antihistamines [cimetidine, ranitidine (s), famotidine, nizatidine, roxatidine]. • H+, K+-ATPase inhibitors [omeprazole (s), lansoprazole, pantoprazole, rabeprazole, esomeprazole]. Prostaglandins: misoprostol. • Other anti-ulcer: sucralfate For this part, one of the texts in the paragraphs 3-6 is recommended and file on elearning2.

For an adequate understanding of the course, it is essential that the student possess sufficient knowledge of: Organic Chemistry, in particular as regards chemical reactions and their mechanism; Biochemistry especially with regard to the synthesis processes of the bacterial cell wall, protein synthesis and DNA; Microbiology especially in relation to the structure of infectious agents such as bacteria, viruses, fungi, plasmodia, mycobacteria, amoebas, etc. Organic chemistry, physiology, biochemistry and microbiology represent the cultural propaedeutics of medicinal chemistry.

1. Greco Giovanni. Farmacocinetica e farmacodinamica su basi chimico-fisiche. Ed. Loghìa 2. Greco Giovanni. Farmaci antibatterici. Ed. Loghìa 3. Costantino, G., Sbardella, G. Chimica farmaceutica, Ed. EdiSES 4. David A. Williams, Thomas L. Lemke, Foye’s principi di chimica farmaceutica. 6° ed, Piccin Ed. 5. David A. Williams, Thomas L. Lemke, Foye’s L’essenziale. Piccin Ed. 6. John M. Beale, Jr, John H. Block. Wilson & Givolds Chimica farmaceutica, 1a Ed. italiana, Casa Ed. Ambrosiana 7. A. Gasco, F. Gualtieri, C. Melchiorre, Chimica Farmaceutica, 1a Ed, CEA Ed. (esce il 9 marzo). 8. E. Stevens, Chimica farmaceutica, Ed. Piccin. 9. File del materiale didattico su elearning2 (https://elearning.uniroma1.it/course/view.php?id=852)

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt

Mandatory and in presence attendance

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The exam consists of four questions, one of which on the general part and three on the systematic part. Each question is assigned the same score, for a total of 30/30. The objective of the exam is to ascertain that the student possesses the chemical knowledge that underlies the therapeutic action of the drug and has acquired the fundamentals of the drug action from a general and systematic point of view as reported in the program, i.e. how and why a drug is distributed in the body, how it interacts with the receptor and why it undergoes a certain type of metabolism and, consequently, elimination. In order to pass the exam, thus obtaining a mark of at least 18/30, the student must demonstrate that he has acquired sufficient knowledge of all the topics covered in the course. To achieve a score of 30/30 cum laude, the student must instead demonstrate that he has acquired an excellent knowledge of all the topics covered during the course.

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt

The Pharmaceutical and Toxicological Chemistry I course provides the student with the foundations for understanding the therapeutic action of drugs at a chemical level. At the end of this course the student will be able to understand the events that take place inside the human body from the administration of the drug to its elimination. To make better use of the notions of this course, the teaching program is shared into two sections: the part of General Pharmaceutical Chemistry leads the student through the general knowledge that underlies the action of the drug; the part of Systematic Pharmaceutical Chemistry analyzes in detail some classes of drugs used in therapy, with emphasis on the most recent advances in the pharmaceutical literature. The analysis of drug classes will subsequently be completed with the teaching of Pharmaceutical and Toxicological Chemistry II. General part GENERAL PART (16 hours) The course of Pharmaceutical and Toxicological Chemistry I provides the acquisition of concepts related to: i) nomenclature, design and development of drugs and their classification, ii) pharmacokinetics and pharmacodynamics, iii) mechanism of action, iv) metabolism and toxicity. All of this is dealt with in the general part of the programme, which generally takes about 16 hours of lessons. For this part text 1 and files on elearning2 are strongly recommended. Genesis, development, classification and nomenclature of drugs (1 hour) Pharmacokinetics (8 hours) • Drugs absorption. Biological membranes. Drug passage through membrane barriers: convective transport, passive diffusion, Fick's law, influence of ionization, facilitated diffusion and active transport. • Distribution and excretion of drugs. • Drug metabolism. Phase I metabolic reactions: microsomal and non-microsomal oxidation and reduction, hydrolytic reactions. Phase II metabolic reactions: glucuronidation, sulfoconjugation, hippuric conjugation, mercapturic synthesis, acetylation and methylation. Pharmacodynamics (7 hours) • Definition and nature of drug receptors. Concepts of agonist and antagonist. Receptor superfamilies: structure and mechanisms of signal transduction. • Drug-receptor bonds: covalent bonds, electrostatic interactions, hydrophobic and charge transfer bonds. • Enzyme inhibitors: reversible inhibitors, affinity markers, mechanism-based inhibitors. • Stereochemistry and pharmacological activity: concepts of eutomer and distomer, eudismic relationship, Easson-Stedman model, pharmacophore conformation. • Qualitative structure-activity relationships. Molecular modifications. Pharmacophore groups. Dissociation of pharmacological activity. Molecular simplification and complication. Molecular replication, hybridization and addition. Prodrugs: carrier pro-drugs and bioprecursors. Linear and cyclic homology. • Isosterism and bioisosterism: classical and non-classical bioisosteries. Quantitative structure-activity relationships. SYSTEMATIC PHARMACEUTICAL CHEMISTRY (64 hours) The study of some classes of drugs, which are reported in the systematic part of the programme, is deepened. For each class of drugs, notions relating to general properties, classification, mechanism of action, structure-activity relationships and main pharmacological properties are taught. For drugs marked with (s), specific synthesis is required. Approximately 64 hours of lessons are dedicated to this part of the program, divided as follows: SYSTEMATIC PART For all drug classes of the systematic part: general properties, classification, mechanism of action, structure-activity relationships, main pharmacological properties. For drugs marked with (s), specific synthesis is required. ANTIINFECTIVE DRUGS Generalities and classification. Inorganic disinfectants: (1 hour) Hydrogen peroxide, iodine, sodium hypochlorite, quaternary ammonium salts, formaldehyde, alcohols and phenols, silver derivatives, mercury derivatives. For this part, the file on elearning2 is recommended. Chemotherapy: (44 hours) Antibacterials. General information on bacteria. General mechanisms of antibacterial action. Bacteriostatics and bactericides. Antibacterial resistance. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Sulfonamides: Sulfathiazole, sulfamethylthiazole, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfadimethoxine, sulfalene, sulfasalazine (s). Sulfonamide associations: co-trimoxazole (s). • Quinolones: Nalidixic (s) and pipemidic acids, cinoxacin, norfloxacin, pefloxacin, ciprofloxacin (s), ofloxacin (s) and levofloxacin, moxifloxacin, rufloxacin, lomefloxacin, prulifloxacin. Text 2 is particularly recommended for this first part. Antibiotics Biosynthesis of peptidoglycan and protein synthesis in bacteria and effects of antibacterial antibiotics on them. For this first part, text 2 and the files present on elearning2 are particularly recommended. • Penicillins. Narrow-spectrum and beta-lactamase sensitive penicillins: benzylpenicillin. Narrow-spectrum and beta-lactamase resistant penicillins: oxacillin (s), flucloxacillin (s). Broad-spectrum penicillins: Ampicillin (s), amoxicillin (s), bacampicillin, ticarcillin, piperacillin. • Beta-Lactamase inhibitors. Clavulanic acid, sulbactam, tazobactam. Sultamicillin • Cephalosporins. 1st generation cephalosporins: cephalexin, cephalothin, cefazolin. 2nd generation cephalosporins: cefoxitin, cefuroxime, cefamandole, cefachlor, cefonicid. 3rd generation cephalosporins: cefotaxime (s), ceftazidime, ceftriazone, cefixime, cefpodoxime. 4th generation cephalosporins: cefepime. 5th generation cephalosporins • Monobatmi. Aztreonam. • Carbapenems. Imipenem, meropenem, ertapenem. • Tetracyclines. Tetracycline, chlortetracycline, methacycline, meclocycline, doxycycline, minocycline(s), tigecycline, rolitetracycline, lymecycline. • Amphenicols. Chloramphenicol (s, Parke-Davis process), thiamphenicol. • Macrolides. Erythromycin, roxithromycin, azithromycin, clarithromycin, flurithromycin, troleandomycin, midecamycin, josamycin, myocamycin, rokitamycin, spiramycin. • Lincosamides. Clindamycin, lincomycin. • Aminoglycosides. Streptomycin, tobramycin, gentamicin, amikacin, netilmycin, kanamycin, neomycin. • Glycopeptides. Vancomycin, teicoplanin. • Polypeptides. Bacitracin, thyrotricin, polymyxin B, colistin. • Different antibacterials. Fosfomycin, linezolid(s) • Antimycobacterials. General information on mycobacterial infections. For this part, one of the texts in points 3-6 and the files available on elearning2 are recommended. Antituberculars. Isoniazid (s). Pyrazinamide(s). Rifamycins [rifamycin SV, rifampicin, rifabutin] Ethambutol (s). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antileprotics. Dapsone(s). Rifampicin. Clofazimine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antiprotozoans. General information on protozoa. • Antimalarials. Biological cycle of malaria parasites. Alkaloids of cinchona bark. Artemisinin and its derivatives. Atovaquone. Derivatives of 4-aminoquinoline: chloroquine (s). Fluorenylmethanol derivatives: lumefantrine. Quinolinomethanol derivatives: mefloquine. Derivatives of 8-aminoquinoline: primaquine. Antifolics: proguanil (s), pyrimethamine, trimethoprim. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Antivirals. General information on viruses. • Vaccines, immunoglobulins, immunomodulatory substances (notes). Interferons. • Antivirals against influenza: amantadine (s), zanamivir, oseltamivir. • Hepatitis B and C antivirals: Idoxuridine. Brivudine. Ribavirin(s). Entecavir and telbivudine. Boceprevir and telaprevir. DAAS, Sofosbuvir. • Antivirals against herpes: Aciclovir (s) and valaciclovir (s). Penciclovir and famciclovir. Ganciclovir (s) and valganciclovir. Foscarnet sodium (s), Adefovir. • Antiretroviral therapy: nucleoside/nucleotide and non-nucleoside reverse transcriptase inhibitors [zidovudine (s), didanosine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir, nevirapine, efavirenz (s), etravirine, rilpivirine]; HIV protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, fosamprenavir, lopinavir, atazanavir, tipranavir, darunavir); fusion inhibitors (enfuvirtide); CCR5 antagonists (maraviroc); integrase inhibitors [raltegravir]. Antifungals • Imidazole antifungals: clotrimazole, bifonazole, econazole, miconazole, isoconazole, tioconazole, fenticonazole, sertaconazole, ketoconazole. • Triazole antifungals: itraconazole, posaconazole, fluconazole (s), voriconazole. • Antifungals of various structure: flucytosine (s), terbinafine, cyclopiroxolamine. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. ANTINEOPLASTIC DRUGS (16 hours) General information on neoplasms and therapies for neoplastic diseases Cytotoxic. • Alkylating agents: chlorambucil, melphalan, bendamustine, cyclophosphamide (s), busulfan, carmustine, temozolomide (s). • Antimetabolites: methotrexate (s), cytarabine, fluorouracil (s), gemcitabine, mercaptopurine, thioguanine, fludarabine. • Vinca alkaloids: vinblastine, vincristine, vinorelbine. • Podophyllotoxin derivatives: etoposide. • Taxanes: paclitaxel, docetaxel, cabazitaxel. • Cytotoxic antibiotics: anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin), mitoxantrone, bleomycin, mitomycin. • Various cytotoxics: platinum complexes [cisplatin (s), carboplatin (s), oxaliplatin (s)]; trabectedin; camptothecines (irinotecan and topotecan). For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. Endocrine therapy. • Hormones and related agents: medroxyprogesterone, gonadotropin-releasing hormone analogues and antagonists (buserelin, leuprorelin, goserelin, triptorelin, ganirelix, degarelix). • Hormonal antagonists and related substances: tamoxifen (s), fulvestrant, exemestane, anastrozole (s), abiraterone, flutamide (s), bicalutamide. For this part, one of the texts in points 3-6 is recommended. Biological therapy. • Protein kinase inhibitors: imatinib (s) and derivatives • Biological response modifiers: interferons, aldesleukin (notes), monoclonal antibodies. For this part, one of the texts at points 3-6 and the files available on elearning2 are recommended. DIGESTIVE SYSTEM DRUGS (3 hours) General information on gastric secretion and its mechanisms. • Anti-ulcer. Antisecretors: H2 antihistamines [cimetidine, ranitidine (s), famotidine, nizatidine, roxatidine]. • H+, K+-ATPase inhibitors [omeprazole (s), lansoprazole, pantoprazole, rabeprazole, esomeprazole]. Prostaglandins: misoprostol. • Other anti-ulcer: sucralfate For this part, one of the texts in the paragraphs 3-6 is recommended and file on elearning2.

For an adequate understanding of the course, it is essential that the student possess sufficient knowledge of: Organic Chemistry, in particular as regards chemical reactions and their mechanism; Biochemistry especially with regard to the synthesis processes of the bacterial cell wall, protein synthesis and DNA; Microbiology especially in relation to the structure of infectious agents such as bacteria, viruses, fungi, plasmodia, mycobacteria, amoebas, etc. Organic chemistry, physiology, biochemistry and microbiology represent the cultural propaedeutics of medicinal chemistry.

1. Greco Giovanni. Farmacocinetica e farmacodinamica su basi chimico-fisiche. Ed. Loghìa 2. Greco Giovanni. Farmaci antibatterici. Ed. Loghìa 3. Costantino, G., Sbardella, G. Chimica farmaceutica, Ed. EdiSES 4. David A. Williams, Thomas L. Lemke, Foye’s principi di chimica farmaceutica. 6° ed, Piccin Ed. 5. David A. Williams, Thomas L. Lemke, Foye’s L’essenziale. Piccin Ed. 6. John M. Beale, Jr, John H. Block. Wilson & Givolds Chimica farmaceutica, 1a Ed. italiana, Casa Ed. Ambrosiana 7. A. Gasco, F. Gualtieri, C. Melchiorre, Chimica Farmaceutica, 1a Ed, CEA Ed. (esce il 9 marzo). 8. E. Stevens, Chimica farmaceutica, Ed. Piccin. 9. File del materiale didattico su elearning2 (https://elearning.uniroma1.it/course/view.php?id=852)

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt

Mandatory and in presence attendance

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The exam consists of four questions, one of which on the general part and three on the systematic part. Each question is assigned the same score, for a total of 30/30. The objective of the exam is to ascertain that the student possesses the chemical knowledge that underlies the therapeutic action of the drug and has acquired the fundamentals of the drug action from a general and systematic point of view as reported in the program, i.e. how and why a drug is distributed in the body, how it interacts with the receptor and why it undergoes a certain type of metabolism and, consequently, elimination. In order to pass the exam, thus obtaining a mark of at least 18/30, the student must demonstrate that he has acquired sufficient knowledge of all the topics covered in the course. To achieve a score of 30/30 cum laude, the student must instead demonstrate that he has acquired an excellent knowledge of all the topics covered during the course.

The exam is oral. The aim is verifying the ability of the student to have acquired the bases of the general medicinal chemistry, and the mechanism of action, structure-activity relationships and therapeutic use of drugs. For the examination, topics questions refer to the current program downloadable from e-learning. The goal of the exam is to evaluate the ability of the student to demonstrate the good knowledge of both the general and specific fundamentals of drug action. For on line lessons connect to the following link: https://meet.google.com/uvh-vebj-pkt