Catalogo dei Corsi di studio

The student will know the classes of the drugs described (hormones, drugs for nervous system, anti-histamines, local anesthetic, drugs for cardiovascoular system) with particular reference to their structures, the drug discovery process, structure-activity relationships, molecular modification leading to modification of duration of action and administration route, molecular mechanism of action, binding mode, metabolism. The student will also know examples of synthetic pathway for a few drugs described within the lectures, with particular attention to the cost of production of the drug.

Specific Aims

1. Knowledge and understanding (Dublin descriptor 1)
The students will know and will be able to understand all aspects about hormeones and hormonoids, drugs for man’s and woman’s health, drugs acting on autonomic nervous system (adrenergic and cholinergic), drugs for nervous system depressant (drugs for general anaesthesia, ansiolitic, hypnotic and sedative agents, anticonvulsant, anti-Parkinson, neuroleptic agents), narcotic and non-narcotic analgesics, stimulats agents (analeptics , antidepressant) local anaestetics, cardiovascular drugs (analeptics, antiarrhythmics, coronary dilatators, aardiotonic, antihypertensive, diuretic, hypolipidemic agents).

2. Applying knowledge and understanding (Dublin descriptor 2)
At the end of the course the student, applying the aquired knowledge, will be able to identify a drug placing it ina a specific therapeutic class, to evaluate the structural modification useful to improve (or decrease) the activity, modulate the absorption, and the lifetime. The student will be able to plan a synthesis of a specific drug, to apply his/her knowledge to hypotesize the binding mode of a specific drug with its receptor.

3. Making judgements
At the end of the course the student will be able to evaluate the appropriate choise of a drug based on its structure. This critical and judgement ability, will be obtained thanks to continuous interactivity hold during the course. In fact the teacher will ask questions very frequently to stimulate students to link the actual topics to all the topics studied up to that time, so that the study will not be isolated, but integrated matter with the aquired knowledge. At the end of the course the stundent will hold a presentation about an innovative recent drug.

4. Communication skills
Judgment of the student study will be realized by oral exame about all the program topics, testing the communications ability of the student about the matter.

5. Learning skills
The student will find details of lessons on the suggested textbooks and in the scientific literature and will have ability to use them to pursue an indipendent preparation. This will be useful to teh studento to find again topics of the matter also in future time when the memory of the concepts described in the lesson room will be softer. The textbooks will remain the benchmark for student that will be able to find again details of forgotten notions.

Programme

Cholinergic drugs (8 hours)
Cholinergic receptors: type, location and functioning of nicotinic and muscarinic receptors. Biosynthesis, release and biodegradation of ACh and active conformation of ACh (s). Cholinergic agonists: characteristics and SAR starting from the ACh structure. Methacholine, carbacol (s), betanecol. Use of cholinergic agonists. Indirect cholinomimetic agents: AChE, active site interaction mechanism with ACh and hydrolysis mechanism. Fisostigmine, neostigmine. Organophosphates: echothiophate. Organophosphates as insecticides: parathion and malathion and their antidote: 2-PAM. AChE inhibitors as "smart drugs": Tacrina, Donepezil. Muscarinic antagonists. Tropane alkaloids and their derivatives: atropine, hyoscyamine, ioscine, scopalamine methyl bromide, ipratropium. SAR studies on atropine and drugs derived from them: propanteline, pyrenzepine. Nicotinic antagonists: tubocurarine, decametonium, suxamethonium, pancuronium, atracurium. Spasmolytic myotropes: papaverine (s).
Adrenergic drugs. (8 hours)
 Adrenergic receptors. Biosynthesis and catabolism of nor-adrenaline (NA). Direct and indirect drugs. Main therapeutic uses of drugs acting on the adrenergic system. SAR studies on b-phenylethylamine. General ethanolamine adrenergic syntheses. Agonists a1: metaraminol, naphazoline (s). A2 agonists: clonidine. Agonists b: dopamine, dobutamine. Agonists b2: salbutamol, terbutaline. Mixed-acting agonists: ephedrine, pseudo-ephedrine, norepinephrine, epinephrine, amphetamine, methamphetamine. Non-selective antagonists: phenoxybenzamine. Antagonists a1: prazosin. Antagonists a2: yohimbine. Antagonists b: Propranolol, Pindolol, atenolol. SAR b blockers. Ergot alkaloids: simple amides (lysergic acid and derivatives: ergonovine and LSD).
General anesthetics (2 hours):
Halothane (s) and metabolism, methoxyflurane, cyclopropane, etherethyl, chloroform with respective degradation. thiopental, metoexital. eugenol, propanidide.
Local anesthetics: Cocaine: structural and chemical characteristics. Amino-ester derivatives: benzocaine, procaine (s), tetracaine. Lidocaine (s). SAR Studies .

CNS (40 hours):
Sedative Hypnotics:
 Barbiturates. Chemical, chemical-physical and pharmacological characteristics. SAR and isosteric analogues (diprilone, thalidomide, metaqualone). Mechanism of action and degradation in a basic environment. Fenobarbital (s) and tiopental.
Anxiolytics: General. Benzodiazepines: discovery, synthetic aspects, SAR studies, mechanism of action and pharmacological profile. Chlordiazepoxide, diazepam, ossazepam (s), triazolam (s). Classification of GABA receptors. Structural and functional characteristics of the GABAA receptor. Antagonists (flumazenil) and inverse agonists (DMCM).
Psycholeptics: General information on schizophrenia. Dopaminergic theory: localization and functional aspects of dopaminergic neurons. Classification and typology of dopaminergic receptors. Classification of antipsychotic drugs. Typical antipsychotics. Fenotiazine: chlorpromazine, phenmetazine, promazine. Thioxanthene derivatives: chlorprotixene (s) and clotiapine (s). Butyrophenones: haloperidol (s), trifluperidol. Atypical antipsychotics. Dibenzazepine derivatives: clozapine, loxepine. Benzamide derivatives: metoclopramide, sulpiride. Antagonist-DOPA mechanism of action. Reserpine and analogs. General synthesis of the phenothiazine derivatives.
Antiparkinson General. pathology. Drugs: L-DOPA; direct agonists DOPA (apomorphine and bromocriptine); anticholinergics (benzatropine, amantadine). Dopamine biosynthesis.

Antidepressants .Generality. Mechanisms of action . Classification . Tricyclic antidepressants. SAR studies. Imipramine (s), desipramine, amitriptyline, maprotiline. Selective 5-HT uptake inhibitors (SSRIs): fluoxetine (s), sertraline. Inhibitors of MAO (IMAO). Classification of MAOs. Non-selective irreversible inhibitors: iproniazide, tranylycipromine (s), pargilin. Selective irreversible inhibitors: clorgiline, deprenil. Action mechanism. Reversible MAO inhibitors (RIMA): moclobemide. Atypical antidepressants: mianserine, mirtazepine, trazodone, bupropione.

Anticonvulsant. Main targets of antiepileptic drugs. Classification of antiepileptic drugs. phenobarbital, primidone, carbamazepine. Structural analogues of GABA: vigabatrin (specific mechanism of action). Other antiepileptic drugs: valproic acid.
Opioid analgesics. Opium alkaloids . Morphine: structural and pharmacological characteristics. Opioid receptors: classification and localization. Endogenous opioids: enkephalins, endorphins. Morphine SAR studies and its derivatives. Codeine, heroin, hydromorphone,oxymorphone, oxycodone, nalorphin, naloxone, naltrexone, etorfina (s), buprenorphine, diprenorphine. Molecular simplifications. Derivatives of morfinan: levorphanol, butorphanol, dextromethorphan. Benzomorphic derivatives: phenazocin (s) and pentazocine. 4-arylpiperidine derivatives: meperidine (s), fentanyl. Phenylpropylamine derivatives: methadone (s), isomethadone.
FANS
Generality. mechanism of action . Structural characteristics and biological activities of COX. Antipyretic and analgesic effect of NSAIDs and their gastrointestinal side effects. Chemical classification of NSAIDs. Anilides: paracetamol and benorylate. Salicylates: acetylsalicylic acid, salicilamide, diflunisal. Reye's syndrome. Phenamates: mefenamic acid (s) and meclofenamate. Arylalkanoic acids: general characteristics. Indomethacin, sulindac (s), tolmetin (s via TosMic). Arilpropionic acids: ibuprofen, naproxen (s), flurbiprofen, ketorolac and ketoprofen (s). Enolic acids: phenylbutazone (s). Oxicam: piroxicam, meloxicam. COX-2selective: nimesulide, celecoxib, rofecoxib (s).

Analeptics: General. Strychnine. Pentylenetetrazole. Xantine: caffeine (s), theophylline (s), theobromine.

ANTI-H1 DRUGS .Introduction. Chemistry, pharmacophore conformation and histamine metabolism. Histamine receptors. Classification of antihistamine H1 drugs and their therapeutic applications. First generation H1 antihistamines: mepyramine, antazoline. H2 antihistamines: cimetidine (discovery), burinamide, ranitidine.

CARDIOVASCULAR SYSTEM (20 hours)

Antianginal drugs. Classification . Organic nitrates: nitroglycerin and amyl nitrate. Pharmacological effects and mechanism of action. Calcium channel blockers. Pharmacological effects and therapeutic indications. 1,4-Dihydropyridines: nifedipine (s), nitrendipine (s) and nicardipine. SAR and conformational studies. Phenylachylamine derivatives :verapamil (s)) and 1,5-benzothiazepine [diltiazem (s)].

Antiarrhythmic drugs.
Classification of antiarrhythmic drugs according to Vaughan Williams and their mechanism of action. IA class drugs: procainamide. IB class: lidocaine. Class II: propranolol. Class III: amiodarone. Class IV: verapamil.
Diuretics.
 diuretic drugs their classification and mechanism of action. Anhydrase-carbonic inhibitors: acetazolamide. Drastic diuretics: furosemide, ethacrynic acid. Thiazide and analogous drugs: clortiazide, hydroclortiazide. General thiazide and dihydrotiazide synthesis. spironolactone (s).
Drugs acting on the renin-angiotensin system. General information on hypertension and possible therapeutic approaches. Renin-angiotensin system, its involvement in the regulation of arterial pressure and possible pharmacological interventions. Features and role of angiotensin II. Development of ACE inhibitors. Captopril (s). Dicarboxylic derivatives and their structural peculiarities: enalaprilat, enalapril. Main therapeutic applications of ACE inhibitors. Features of angiotensin II receptors and development of their antagonists. Losartan (s). Renin inhibitors: aliskiren.
HMG CoA reductase inhibitors. Lipoprotein: classification and role in disorders of hyperlipoproteinemias. Classification of lipid-lowering drugs. Bile acid sequestrants. HMG CoA reductase inhibitors and related SAR studies. Lovastatin, simvastatin, pravastatin, atorvastatin. Fibrates: clofibrate (s). Nicotinic acid.

Drugs of Erectile Dysfunction. Sildenafil (s). Tadaladil.

HORMONES (hours10 )
Peptide hormones. General features, mechanism of action and metabolism. Oral hypoglycemic agents. Arylsulphonylureas: SAR, carbutamide, gliburide, glimepride. Bisguanidine derivatives, pentaminidine and metformin. Glitazone derivatives: troglitazone, rosiglitazone, pioglitazone.

Thyroid hormones. Generality. Endogenous biosynthesis T3 and T4. SAR. Hyperthyroid drugs: iodide, thyrostatic (tiobarbital and propylthiouracil) salts, imidazole derivatives (methimazole and carbimazole).

 Steroid hormones. Classification, nomenclature, structure and biosynthesis of steroid hormones. Receptors and mechanism of action. Neuroendocrine control of the production and secretion of steroid hormones. Natural estrogens and their derivatives, conjugated and semisynthetic estrogens. Progestin: progesterone and derivatives, analogs of 19-nortestosterone, various progestins, progesterone antagonists (mifepristone). Hormonal contraceptives: main associations and mechanism of action. Levonorgestrel (s). Hormonal replacement therapies (in menopause). Gonadotropin-releasing hormone (GnRH) and its analogs and antagonists. Selective modulators of estrogen receptors. Tamoxifen (s). Antiestrogens (fulvestrant). Aromatase inhibitors (exemestane, anastrousimidazole). Exemestane (s). Androgens and anabolics. Endogenous androgens. Testosterone metabolism. Semi-synthetic analogues. Antiandrogens (flutamide and bicalutamide) Inhibitors of 17a-hydroxylase and 17,20-lyase (abiraterone). Testosterone 5a-reductase inhibitors (fìnasteride and dutasteride). Finasteride (s). Corticosteroids. Mineral- and endogenous glucocorticoids. Structure-activity relationships of corticosteroids. Synthesis glucocorticoids. Anti-inflammatory mechanisms of glucocorticoids.

Adopted texts

W.O. Foye, T.L. Lemke, D.A. Williams: Principi di Chimica Farmaceutica, Piccin
G. L. Patrick: An Introduction to Medicinal Chemistry, Oxford University Press
Gasco A Gualtieri F Melchiorre C, Chimica farmaceutica I Ed. Casa Editrice Ambrosiana, 2015.

Programme

1. HORMONES (3 CFU)
Introduction
a- Thyroid hormones and thyreostatics. Thyreoglobulin, T3 e T4 biogenesis, SAR, binding mode. Drugs for hypothyroidism (natural and synthetic). Drugs for hyperithyroidism - thyreostatics (propylthiouracil, methimazole, thiamazole, carbimazole).
b-Insulin structure, stability, manifacturing. Oral hypoglicaemic agents (Arylsulfonylureas: carbutamide, tolbutamide, phenbutamide, chlorpropamide, glyburide, glymepiride. Repaglinide. Biguanides: metformin, buformin, phenformin. Glitazons: troglitazone, rosiglitazone, pioglitazone).
c-Steroid hormones and related drugs. Introduction: sterols, gonane. Nomenclature, stereochemistry.
c1-Sex hormones. Struttures: androstane, estrane, pregnane.
Men’s health.
Androgens: testosterone (s), metabolism, esters, androsterone, dehydroepiandrosterone. Synthetic androgens: methyltestosterone (s). Anabolic agents: clostebol, stanozolol, nandrolone (SAR). Andropause. Replacement therapy. SARM: N-arylpropionammides, bicalutammide. Benign Prostatic Hyperplasia: 5-redutctase inhibitors: medrogesterone, finasteride, dutasteride. Mechanism of action. 1-adrenergic antagonists: doxazosin, terazosin, prazosin, alfuzosin, tamsulosin. Fitotherapy, Serenoa repens and further plants. Treatment of Prostatitis. Treatment of prostatic cancer (refer to Medicinal and Toxicological Chemistry I schedule). Erectile Dysfunction. Introduction, penile protheses, vacuum constriction devices. Intracavernosal injection therapy. Papaverina, Phentolamine, PGE1. PDE5 inhibitors, meccanism of action. Sildenafil (s), vardenafil, tadalafil.
Women’s health.
Progestins: progesterone (s), metabolism. Synthetic Progestins: progesterone derivatives, ethisterone (s), derivatives and SAR.
Progestin Antagonists. RU-486, mifepristone.
Estrogens: estrone (s), estradiol (s), estriol. Structures. SAR. Estrogen receptors. Binding mode. Estrone Esters (prodrugs). Enterohepatic recycling. Conjugated estrogens. Synthetic Estrogens: ethynylestradiol (s), mestranol (s), quinestrol (s). Estradiol metabolism. Nonsteroidal Estrogens: diethylstibestrol, hexestrol, dienestrol, chlorotrianisene, clomifene.
Antiestrogen agents. Estrogen Receptor Modulators (SERM): tamoxifen, toremifene, nafoxidine, ospemifene, raloxifene, arzoxifene. Raloxifene binding mode and comparison with the estradiol. Inhibitors of estradiol bioshyntesis. Steroids. Azoles (anastrozole, letrozole).
Oral Contraceptives: estrogen-progestin oral combination; long-acting contraceptives; progestin-only oral contraceptives; emergency contraception. Toxicity.
Infertility.
Menopause.
Breast Cancer. (refer to Medicinal and Toxicological Chemistry I schedule).
c2-Mineralcorticoids and glucocorticoids. Desoxicorticosterone, aldosterone, hydrocortisone, cortisone. Biogenesis. Metabolism. Anti-inflammatory steroids: SAR. Prednisone, prednisolone, fludrocortisone, betametazone.
d-Provitamin D: ergosterin, 7-dehydrocolesterol and transformation in D2 e D3 vitamins.

2. NERVOUS SYSTEM AGENTS
2a. Central Nervous System (3 CFU)
A. Non-selective Depressants.
a- General Anaesthesia. Introduction. SAR, activity, metabolism, administration route and toxicity. Inhalational anaesthetics: meccanism of action, nitrogen protoxide, diethyl ether, chloroform, halogenated compounds, halothane (metabolism). Injection anaesthetics: introduction and meccanism of action, ketamine, barbiturates, benzodiazepines, Narcotic analgesics.
b-Hypnotic and sedative agents. Introduction. Alcohols and carbammates: mefenesina, meprobamate. Barbiturates: barbital, phenobarbital (s), SAR, metabolism, toxicity. Isosteric analogs: glutetimide, talidomid. Benzodiazepines. Refer to ansiolitic agents.
c- Narcotic Analgesics. Introduction. Syntheses, SAR, activity, metabolism, administration routes and toxicity. Enkephalins, endorphins. Morphine, codeine, thebaine, heroin. Hydromorphone, oxymorphone, Agonist and antagonist agents: nalorphine, naloxone. Molecular simplification: levorphanol, butorphanol, phenazocine (s), pentazocine, meperidine (s), methadone (s). Molecular complication: Etorphine (s) buprenorphine. Opioid receptor: models. Binding modes. Krokodil: history, industrial manufacturing and “in house” preparation.
d- Non Narcotic Analgesics (analgesic-antipyretic-antiinflammatory agents). Introduction. Inflammation, autacoids, PG, arachidonic acid cascade. Use of AAA agents. Chemical classification. Benzoic acids: Aspirin (s) meccanism of action, diflunisal, fenamates (s); arylacetic acids: indomethacin (s), binding mode, active conformation; sulindac (s), SAR, binding mode, metabolism; tolmetin (s); arylpropionic acids, general structure, SAR, ibuprofen, ketoprofen, naproxen (s). Pyrazolone derivatives: struttures and metabolism, aminophenazone, metamizole (s). Pyrazolidinedione derivatives: phenylbutazone, metabolism, SAR and analogs. Oxicams: pyroxycam, SAR and analogs. p-Aminophenol derivatives: paracetamole, phenacetin, acetanilide, metabolism.
COX-2 Selective Inhibitors. COX-1, COX-2 and their active sites. Binding modes, selective (celecoxib and other coxibs) and non-selective agents (diflunisal, indomethacin). Sulides (nimesulide and analogs). "Tricyclic" inhibitors, celecoxib, rofecoxib.

B. Selective C.N.S. Depressing Agents
a-Antiparkinson Drugs. Introduction. Anticholinergic agents. Amantadine. Dopamine Agonists. Direct agonists. Apomorphine. Bromocriptine. Carbidopa. DOPA decarboxylase inhibitors.
b-Anticonvulsant Agents. Introduction. Barbiturates (Phenobarbital, mefobarbital, etobarbital, metabolism), primidons (metabolism), hydantoins, succinimides (carbamazepine, etosuccinimide), acylureas, SAR. Diltiazem, oxazolidinediones (trimetadione, metabolism), valproic acid, carbonic anhydrase inhibitors (acetazolamide).
c-Neuroleptic agents. Introduction. Chemical classes. Reserpine and derivatives. Tricyclic compounds: phenothiazine: chlorpromazine discovery (s), metabolism, superimposition with dopamine, triflupromazine, side chain modification: perazines, phenazines (s), piperacetazine, pecazine, thioridazine. Thioxantenes. Chlorprothixene, thiothixene, chlopenthixol. SAR. 6,7,6 Tricyclic composti: chlothiapine, loxapine, chlozapine. Fluorobutyrophenones: haloperidol (s), droperidol. Benzamides: sulpiride, remoxipride. Poldinger graph. Activities and side effects for each class.
d-Ansiolitic Agents. Introduction. Benzodiazepines: chlordiazepoxide discovery (s), nomenclature, SAR, binding mode, metabolism, toxicity, general synthetic pathways, demoxepam, diazepam, nordiazepam, oxazepam (s), triazolam (s). Benzodiazepine receptor. Agonists, antagonists and reverse agonista, Ro 15-1788 DMCM (-carboline). Centrally acting muscle relaxant agents: meprobamate.
C. C.N.S. Stimulants
Antidepressants: a-Timoleptic agents Introduction. Structures. Imipramine (s), desipramine, chlomipramine, opipramolo, protriptilina, amitriptilina, nortriptilina, maprotilina, dimetacrina, butriptilina, dossepina, dibenzepina. SAR.
b-Timeretici. Metabolismo della NA, farmaci anti-MAO: idrazidi; idrazine: fenelzina, feniprazina; ammine: tranylcypromine, propargylamines, pargyline, chlorgylina and deprenyl, meccanism of action.
2b. Drugs acting on Autonomic Nervous System (2 CFU)
Introduction. Receptors. Pharmacological activities. Nomenclature.
a- Adrenergic receptors ligands.
Adrenergic agents: Direct simpaticomimetics: agonists: epinephrine, norepinephrine (biogenesis, metabolism), phenylephrine, metaraminol, synephrine, metoxamine; amphetamine, methamphetamine, MDMA, ephedrine. Selectivity: -agonists: isoprenaline, salbutamole, dobutamine, isoxisuprine. SAR. Activity – side effects on CNS and approaches to limit them. Non-phenethylamine adrenergics: naphazoline. General synthetic pathways. Drugs that interfere with the synthesis, metabolism, stockage and uptake of epinephrine and norepinephrine.
Adrenergic Antagonists. Alpha-blockers: phenoxybenzamine, imidazolines (phentolamine and tolazoline), prazosin, Ergot alcaloids. Beta-blockersi: structural elements leading to beta-selectivity. Examples. See also drugs acting on cardiovascular system.
b- Cholinergic receptor ligands. Cholinergic synapse. Biogenesis and metabolism of acetylcholine (acetylcholine esterase). Muscarinic and nicotinic receptors. Acetylcholine active conformazions on muscarinic and nicotinic receptors, respectively.
Cholinergic agents. Direct acting cholinergic agents. Acetylcholine, methacholine, carbachol, bethanechol. Acetylcholine esterase, mechanism of hydrolysis. Metabolism and duration of action. SAR. Syntheses of acetylcholine and carbacholo. Indirect acting cholinergic agents. Reversibile, irreversibile and partially-reversibile acetylcholine esterase inhibitors. Edrofonium, neostigmine, pyridostigmine, physostigmine, organophosphoric derivatives. Acetylcholine esterase reactivators: pralidoxime.
Cholinergic receptors blockers. Antimuscarinic agents. Chemical Classes. Belladonna Alcaloids. Adiphenine, piperidolate, mepenzolate. Binding mode.
Neuromuscular blockers. Curares, tubocurarine. Depolarizing agents: decamethonium, sussamethonium.
Miotropic spasmolytic agents: papaverine (s), ethaverine. Meccanism of action.
2c. Local Anaesthetics. (0,5 CFU)
Introduction. Syntheses, SAR, pharmacological activity, metabolisms, nomenclature, administration route and toxicity. Cocaine (strutture, ecgonine), procaine (metabolism), tetracaine. Lidocaine (s), pyrrocaine, mepivacaine, bupivacaine. SAR, pKa.
3. HISTAMINE AND ANTIHISTAMINE AGENTS. (0,5 CFU)
Introduction. Histamine: strutture, conformations, physical and chemical properties and biogenesis. Mepyramine and analogs, clemizole, antazoline, chlorphenamine, diphenhydramine, chlorcyclizine, phenothiazines: promethazine. SAR, pharmacological activity and toxicity. Binding mode of histamine to H1 receptor. Binding mode of histamine to H2 receptor and activation. H2 receptor antagonists, discovery of burimamide, thiaburimamide, cimetidine, ranitidine.
4. DRUGS ACTING ON CARDIOVASCULAR SYSTEM. (2 CFU)
3a. Analeptics. Introduction. Strychnine, pentamethylene tetrazole, xanthines: theophylline, caffeine. Meccanism of action.
3b. Antiarrhythmic agents. Properties and classification. Class 1. Procainamide, metabolism; lidocaine. Class 2. Beta-blockers. SAR. Class 3. amiodarone. Class 4: calcium antangonist. Verapamil, dihydropyridines, dilthiazem.
3c. Coronary dilatators. Introduction. Nitrites and nitrates. Betablockers. Calcium-antagonists: dihydropyridines: SAR, nifedipina, nitrendipine, metabolism. Verapamil, metabolism, related drugs; benzothiazepines: dilthiazem (s). Khelline analogs: methylchromone, amiodarone (s). Coenzymes and vitamins: carnitine.
3d. Cardiotonic heterosides. Structures, isolation and purification. Aglycones and glycosides properties. Heterosides from digitalis purpurea and lanata. Heterosides from strofantus. Heterosides from scylla. Meccanism, binding mode, toxicity, uses.
3e. Cardiotonic Agents. Agonista of beta adrenergic receptor. Inhibitors of cAMP phosphodiesterase: amrinone (s), milrinone, SAR and binding mode.
3f. Hypolipidemic agents. Introduction. Fibrates: chlofibrate and analogs. Chlofibrate metabolism. Nicotinic acid. Dextrothyroxine. Pyridinol carbamate (s). Statins (HMG-CoA reductase inhibitors): lovastatin and congeners. Resins: cholestyramine.
3g. Antihypertensive agents. Alfa-blockersi: prazosin. Beta-blockers: SAR. Direct action dilatators: nitroprussiate, diazoxide, dihydralazine, minoxidil (s). Calcium antagonists. Central acting dilatators: clonidine and congenere, SAR, binding mode. Alfa-methyl DOPA (s). Reserpine, rescinamine and derivatives. ACE inhibitors: Drugs acting on sul renin-angiotensin system: captopril (s), enalapril (s), enaprilate. ACE model from Cushman and from Petrillo-Ondetti. SAR for ACE inhibitors. Captopril metabolism. Angiotensina II Receptor Antagonists: Saralasina, sartani: losartan (s). Renin Inhibitors: Aliskiren.
3h. Drugs for DE treatment. See above: Men’s health.
3i. Diuretic agents. Introduction. Arylsulfonamides: acetazolamide, SAR. Thiazides and dihydrothiazides, properties and SAR. Loop diuretics: etacrinic acid. Aldosterone blocking diuretics: canrenone, canrenoic acid, spironolattone.

Adopted texts

Gasco, Gualtieri, Melchiorre – Chimica Farmaceutica, SEA Editore
Foye – Principi di Chimica Farmaceutica, Piccin Editore
Artico – Lezioni di Chimica Farmaceutica, CISU Editore