MEDICINAL AND TOXICOLOGICAL CHEMISTRY

MODULE A – Lez. 30 h; CFU 4

GENERAL ASPECTS

Unity 1

Introduction. Production of drugs. Pharmaceutical research. Access ways to new drug substances. Development phases of a new drug. Development of a drug into a pharmaceutical agent. Pre-clinic studies: chemical, analytical and galenical development, pharmacodynamics, pharmacokinetics, toxicity, carcinogenicity and mutagenicity. Clinical tests. Patent protection. Good Clinical Practice (GCP). Ethics Committee. Off-label, generic equivalent, Me-too drugs. Innovation. Orphan drugs. Stability.

Unity 2

Phases of a drug action:

- pharmaceutical phase, administration pathways and characteristics.

- pharmacokinetic phase with absorption mechanisms, transport in the bloodstream, distribution, pathways of xenobiotic metabolism, phase I reactions (oxidation, reduction, hydrolysis), phase II (methylation, acetylation, conjugation), enzymatic inhibition and induction, elimination and excretion pathways. Pro-drugs, advantages and combinations. Mutual pro-drugs. Soft-drugs, advantages and soft analogues.

- pharmacodynamic phase: drug-receptor interaction, chemical bonding and theories about the drugs mechanism of action. Dose-response relationships. Antagonism.

Unity 3

Haptophoric and pharmacophoric groups. Structural features and pharmacological activity, optical and geometric isomerism, conformational isomerism and eudismic index, influence of stereoselectivity and stereospecificity on drug-receptor interaction, molecular modifications, chemical isosterism, bioisosterism classical and nonclassical bioisosteres. International drug abbreviations, DC.IT, INN, importance to monitoring and scientific information. Pharmacosurveillance. ATC classification.

MODULE B – Lez. 36 h; CFU 5

SPECIFIC TOPICS

Unity 4

ANTIBIOTICS AND ANTIMICROBIAL AGENTS: general principles, classifications.

BACTERIAL CHEMOTHERAPY: antibacterial classification and mechanism of action. Bacterial resistance.

Sulfonamides: short historical outlines, classification, action spectrum, association, mode of action, synthesis of N-heterocyclic, N-acyl and acylamino derivatives, structure-activity relationships.

- classical: sulfathiazole, sulfamethazine, sulfamethizole, sulfisomidine,sulfisoxazole.

- semiretard: sulfadiazine, sulfamethoxazole, sulfamerazine.

- retard: sulfamethoxypyridazine, sulfadimethoxine, sulfamethoxydiazine.

- ultraretard: sulfadoxine.

- topical action: sulfacetamide, sulfanilamide, sulfaguanidine, phthalylsulfathiazole, succinylsulfathiazole, sulfasalazine.

Nitrofurans: short historical outlines, activity, action spectrum, mode of action, synthesis, structure-activity relationships. Nitrofurazone, nifuroxime, nitrofurantoin, furazolidone, nifuratel.

Nitroimidazoli: short historical outlines, action spectrum, mode of action, metronidazole.

Quinolones: fluoro- and difluoroquinolones, synthesis, mode of action, structure-activity relationships.

- I generation: nalidixic acid, piromidic acid, oxolinic acid.

- II generation: pipemidic acid, cinoxacin.

- III generation: ofloxacin, norfloxacin, ciprofloxacin, enoxacin, pefloxacin mesylate.

Unity 5

ANTIMYCOBACTERIAL AGENTS: general principles, mode of action, synthesis, antimycobacterial therapy.

Diaminodiphenylsulfones: dapsone, acedapsone.

Carboxylic acids and derivatives: 4-aminosalicylic acid, isoniazid, pyrazinamide.

Thioamides: etionamide, protionamide.

Ethylenediamines: ethambutol.

Antibiotics: cycloserine, rifamycin SV, rifampicin,rifabutin, streptomycin.

Unity 6

ANTIBIOTICS: short historical outlines, production pathways: fermentation, synthesis, semisynthesis.

Beta-lactam antibiotics: structure, nomenclature, properties, synthesis, mode of action, antimicrobial spectrum, bacterial resistance.

penicillins: stability, acid lability, acid stability, production of 6-APA, structure-activity relationships, depot penicillins, penicillinase-stable penicillins, broad-spectrum penicillins, antipseudomonas penicillins, ureidopenicillins.

Unity 7

- Cefalosphorins: short historical outlines, activity, production of cephalosporin C, production of 7-ACA, structure-activity relationships, classification. I generation, cefacetrile, cefalotin, cefapirin, cefaloridine; perorally cephalosporins, cefalexin, cefaclor; II generation, cefamandole, cefuroxime, cephamycins, cefoxitin; III generation, cefotaxime, IV generation, cefpirome, cefepime, cefclidine.

- 2-penem: structural features

- carbapenem: structural features, antimicrobial spectrum, thienamycin, imipenem.

- monobactams: chemical and structural features, synthesis, aztreonam, carumonam

Unity 8

Tetracyclines: therapeutic and structural features, classification, structure-activity relationships, chemical properties, stability, synthesis, oxytetracycline, metacycline, doxycycline, minocycline, prodrugs, rolitetracycline, lymecycline, mepicycline.

Amphenicols: therapeutic features, synthesis, structure-activity relationships, Chloramphenicol, thiamphenicol.

Unity 9

Macrolide antibiotics: structural features, classification, mode of action, erythromycin, roxithromycin, azithromycin, oleandomycin, spiramycin.

Carbohydratic antibiotics: lincosamides, lincomycin, structure-activity relationships, clindamycin.

Aminoglycosides: structural and therapeutic features, bacterial resistance, kanamycin B, streptomycin, amikacin, synthesis, gentamicin.

Ansamycins: rifamycins, mode and spectrum of action, structural features, structure-activity relationships, rifampicin, rifapentin.

Polypeptides: classification, mode of action, bacitracin.

Lipopeptides: mode of action, polymyxin, colistin.

Unity 10

ANTIFUNGAL AGENTS: pathogenicity of fungus, mycosis, therapy, classification.

Antibiotics: griseofulvin, nystatin, anphotericin.

Imidazoles: therapeutic features, mode of action and synthesis, clotrimazole, miconazole, econazole, isoconazole, ketoconazole.

Triazoles: terconazole, fluconazole.

Unity 11

ANTIVIRAL AGENTS: features of viruses, viral replication steps, antiviral therapy, chemoterapy, mode of action, spectrum and synthesis.

Thiosemicarbazones: methisazone.

Aminoadamantanes: amantadine, tromantadine.

Nucleosides: pyrimidine, azole, purine analogues, idoxuridine, cytarabine, ribavirin, acyclovir, gancyclovir.

Unity 12

CANCER CHEMOTHERAPY: cancer generalities, classification, carcinogenesis, treatment of cancer, alkylating agents, cisplatin, carboplatin; procarbazine, antibiotics, antimetabolites, Vinca alkaloids.

Unity 13

ANTIPROTOZOAL AGENTS: parasitic diseases, malaria, types of chemotherapy, exoerythrocytic stage antimalarial agents, primaquine and erythrocitic stage antimalarial agents, chloroquine, quinine, pyrimethamine, mefloquine.

1. Materiale Didattico fornito dal docente: http://studium.unict.it/dokeos/2016/index.php?category=409a732f04b0
2. FOYE’S PRINCIPI DI CHIMICA FARMACEUTICA - VI ediz. italiana (2014) - Piccin.
3. PATRICK G.L. - Introduzione alla Chimica Farmaceutica – II ed. (2010) - EdiSES.
4. Wilson & Gisvold -Chimica Farmaceutica- I Ed. (2014) - Casa Editrice Ambrosiana
5. Gasco A. Gualtieri F. Chimica Farmaceutica- I Ed. (2015) - Casa Editrice Ambrosiana
6. G. GRECO - Farmacocinetica e Farmacodinamica su basi chimico-fisiche - (2007) – Loghìa
7. G. GRECO – Farmaci antibatterici - (2009) - Loghìa

Letture consigliate:

- BURGER’S - Medicinal Chemistry and Drug Discovery, vol I - Ed. M.E. Wolff - J. Wiley & Sons.